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Aarogya, can you share information about a health condition involving Chorioamnionitis

Chorioamnionitis

Chorioamnionitis, also known as intra-amniotic infection (IAI), is inflammation of the fetal membranes (amnion and chorion), usually due to bacterial infection. In 2015, a National Institute of Child Health and Human Development Workshop expert panel recommended use of the term "triple I" to address the heterogeneity of this disorder. The term triple I refers to intrauterine infection or inflammation or both and is defined by strict diagnostic criteria, but this terminology has not been commonly adopted although the criteria are used.Chorioamnionitis results from an infection caused by bacteria ascending from the vagina into the uterus and is associated with premature or prolonged labor. It triggers an inflammatory response to release various inflammatory signaling molecules, leading to increased prostaglandin and metalloproteinase release. These substances promote uterine contractions and cervical ripening, causations of premature birth. The risk of developing chorioamnionitis increases with number of vaginal examinations performed in the final month of pregnancy, including labor. Tobacco and alcohol use also puts mothers at risk for chorioamnionitis development.Chorioamnionitis is caught early by looking at signs and symptoms such as fever, abdominal pain, or abnormal vaginal excretion. Administration of antibiotics if the amniotic sac bursts prematurely can prevent chorioamnionitis occurrence. Signs and symptoms The signs and symptoms of clinical chorioamnionitis include fever, leukocytosis (>15,000 cells/mm³), maternal (>100 bpm) or fetal (>160 bpm) tachycardia, uterine tenderness and preterm rupture of membranes. Causes Causes of chorioamnionitis stem from bacterial infection as well as obstetric and other related factors. Microorganisms Bacterial, viral, and even fungal infections can cause chorioamnionitis. Most commonly from Ureaplasma, Fusobacterium, and Streptococcus bacteria species. Less commonly, Gardnerella, Mycoplasma, and Bacteroides bacteria species. Sexually transmitted infections, chlamydia and gonorrhea, can cause development of the condition as well. Studies are continuing to identify other microorganism classes and species as infection sources. Obstetric and other Birthing-related events, lifestyle, and ethnic background have been linked to an increase in the risk of developing chorioamnionitis apart from bacterial causation. Premature deliveries, ruptures of the amniotic sac membranes, prolonged labor, and primigravida childbirth are associated with this condition. At term mothers who experience a combination of pre-labor membrane ruptures and multiple invasive vaginal examinations, prolonged labor, or have meconium appear in the amniotic fluid are at higher risk than at term mothers experiencing just one of those events. In other studies, smoking, alcohol use and drug use are noted as risk factors. Those of African American ethnicity are noted to be at higher risk. Anatomy The amniotic sac consists of two parts: The outer membrane is the chorion. It is closest to the mother and physically supports the much thinner amnion. The chorion is the last and outermost of the membranes that make up the amniotic sac. The inner membrane is the amnion. It is in direct contact with the amniotic fluid, which surrounds the fetus. The amniotic fluid exists within the amnion, and is where the fetus is able to grow and develop. The swelling of the amnion and chorion is characteristic of chorioamnionitis, occurring when bacteria makes its way into the amniotic fluid and creates an infection within the amniotic fluid. Diagnosis Pathologic Chorioamnionitis is diagnosed from a histologic (tissue) examination of the fetal membranes. Confirmed histologic chorioamnionitis without any clinical symptoms is termed subclinical chorioamnionitis and is more common than symptomatic clinical chorioamnionitis.Infiltration of the chorionic plate by neutrophils is diagnostic of (mild) chorioamnionitis. More severe chorioamnionitis involves subamniotic tissue and may have fetal membrane necrosis and/or abscess formation.Severe chorioamnionitis may be accompanied by vasculitis of the umbilical blood vessels due to the fetus inflammatory cells. If very severe, funisitis, inflammation of the umbilical cord connective tissue, occurs. Suspected clinical diagnosis The presence of fever between 38.0°C and 39.0°C alone is insufficient to indicate chorioamnionitis and is termed isolated maternal fever. Isolated maternal fever may not have an infectious cause and does not required antibiotic treatment.When intrapartum (during delivery) fever is higher than 39.0°C, suspected diagnosis of chorioamnionitis can be made. Alternatively, if intrapartum fever is between 38.0°C and 39.0°C, an additional risk factor must be present to make a presumptive diagnosis of chorioamnionitis. Additional risk factors include: Fetal tachycardia Maternal leukocytosis (>15,000 cells/mm³) Purulent cervical drainage Confirmed diagnosis Diagnosis is typically not confirmed until after delivery. However, people with confirmed diagnosis and suspected diagnosis have the same post-delivery treatment regardless of diagnostic status. Diagnosis can be confirmed histologically or through amniotic fluid tests such as gram staining, glucose levels, or other culture results consistent with infection. Prevention If the amniotic sac breaks early into pregnancy, the potential of introducing bacteria in the amniotic fluid can increase. Administering antibiotics maternally can potentially prevent chorioamnionitis and allow for a longer pregnancy. In addition, it has been shown that it is not necessary to deliver the fetus quickly after chorioamnionitis is diagnosed, so a C-section is not necessary unless maternal health concern is present. However, research has found that beginning labor early at approximately 34 weeks can lessen the likelihood of fetal death, and reduce the potential for excessive infection within the mother.In addition, providers should interview people suspected to have chorioamnionitis about whether they are experiencing signs and symptoms at scheduled obstetrics visits during pregnancy, including whether the individual has experienced excretion vaginally, febrile, or abdominal pain. Treatment The American College of Obstetricians and Gynecologists Committee Opinion proposes the use of antibiotic treatment in intrapartum mothers with suspected or confirmed chorioamnionitis and maternal fever without an identifiable cause.Intrapartum antibiotic treatment consists of: Standard Ampicillin + gentamicin Alternative Ampicillin/sulbactam Ticarcillin/clavulanate Cefoxitine Cefotetan Piperacillin/tazobactam Ertapenem Cesarean delivery Ampicillin and gentamicin plus either clindamycin or metronidazole Penicillin-allergy Vancomycin + gentamicin Gentamicin + clindamycinHowever, there is not enough evidence to support the most efficient antimicrobial regimen. Starting the treatment during the intrapartum period is more effective than starting it postpartum; it shortens the hospital stay for the mother and the neonate. There is currently not enough evidence to dictate how long antibiotic therapy should last. Completion of treatment/cure is only considered after delivery. Supportive measures Acetaminophen is often used for treating fevers and may be beneficial for fetal tachycardia. There can be increased likelihood for neonatal encephalopathy when mothers have intrapartum fever. Outcomes Chorioamnionitis has possible associations with numerous neonatal conditions. Intrapartum (during labor) chorioamnionitis may be associated with neonatal pneumonia, meningitis, sepsis, and death. Long-term infant complications like bronchopulmonary dysplasia, cerebral palsy, and Wilson-Mikity syndrome have been associated to the bacterial infection. Furthermore, histological chorioamnionitis may increase the likelihood of newborn necrotizing enterocolitis, where one or more sections of the bowel die. This occurs when the fetal gut barrier becomes compromised and is more susceptible to conditions like infection and sepsis. In addition, chorioamnionitis can act as a risk factor for premature birth and periventricular leukomalacia. Complications For mother and fetus, chorioamnionitis may lead to short-term and long-term issues when microbes move to different areas or trigger inflammatory responses due to infection. Maternal complications Higher risk for C-section Postpartum hemorrhage Endometritis Bacteremia (often due to Group B streptococcus and Escherichia coli) Pelvic abscessMothers with chorioamnionitis who undergo a C-section may be more likely to develop pelvic abscesses, septic pelvic thrombophlebitis, and infections at the surgical site. Fetal complications Fetal death Neonatal sepsis Neonatal complications Perinatal death Asphyxia Early onset neonatal sepsis Septic shock Neonatal pneumonia Infant respiratory distressIn the long-term, infants may be more likely to experience cerebral palsy or neurodevelopmental disabilities. Disability development is related to the activation of the fetal inflammatory response syndrome (FIRS) when the fetus is exposed to infected amniotic fluid or other foreign entities. This systemic response results in neutrophil and cytokine release that can impair the fetal brain and other vital organs. Compared to infants with clinical chorioamnionitis, it appears cerebral palsy may occur at a higher rate for those with histologic chorioamnionitis. However, more research needs to be done to examine this association. There is also concern about the impact of FIRS on infant immunity as this is a critical time for growth and development. For instance, it may be linked to chronic inflammatory disorders, such as asthma. Epidemiology Chorioamnionitis is approximated to occur in about 4% of births in the United States. However, many other factors can increase the risk of chorioamnionitis. For example, in births with premature rupture of membranes (PROM), between 40 and 70% involve chorioamnionitis. Furthermore, clinical chorioamnionitis is implicated in 12% of all cesarean deliveries. Some studies have shown that the risk of chorioamnionitis is higher in those of African American ethnicity, those with immunosuppression, and those who smoke, use alcohol, or abuse drugs. See also Chronic deciduitis Funisitis Placentitis Whartons jelly Notes References External links Overview at Cleveland Clinic. Cerebral palsy inflammation link (29 November 2003) at BBC.

Aarogya , Do you know what is Gray baby syndrome,

Gray baby syndrome

Gray baby syndrome (also termed Gray or Grey syndrome) is a rare but serious, even fatal, side effect that occurs in newborn infants (especially premature babies) following the accumulation of antibiotic chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic that has been used to treat a variety of bacteria infections like Streptococcus pneumoniae as well as typhoid fever, meningococcal sepsis, cholera, and eye infections. Chloramphenicol works by binding to ribosomal subunits which blocks transfer ribonucleic acid and prevents the synthesis of bacterial proteins. Chloramphenicol has also been used to treat neonates born before 37 weeks of the gestational period for prophylaxis purposes. In 1958, newborns born prematurely due to rupture of the amniotic sac were given chloramphenicol to prevent possible infections, and it was noticed that these newborns had a higher mortality rate compared with those who were not treated with the antibiotic. Over the years, chloramphenicol has been used less in clinical practices due to the risks of toxicity not only to neonates, but also to adults due to the risk of aplastic anemia. Chloramphenicol is now reserved to treat certain severe bacteria infections that were not successfully treated with other antibiotic medications. Signs and symptoms are summarized in the WHO Model Formulary for Children 2010 under the rare adverse effect section of chloramphenicol. Signs and symptoms Since the syndrome is due to the accumulation of chloramphenicol, the signs and symptoms are dose related. According to Kastens review published in the Mayo Clinic Proceedings, a serum concentration of more than 50 μg/mL is a warning sign, while Hammett-Stabler and John states that the common therapeutics peak level is 10-20 μg/mL and is expected to achieve after 0.5-1.5 hours of intravenous administration in their review of antimicrobial drugs. The common onset of signs and symptoms are 2 to 9 days after the initiation of the medication, which allows the serum concentration to build up to reach the toxic concentration above. Common signs and symptoms include loss of appetite, fussiness, vomiting, ashen gray color of the skin, hypotension (low blood pressure), cyanosis (blue discoloration of lips and skin), hypothermia, cardiovascular collapse, hypotonia (muscle stiffness), abdominal distension, irregular respiration, and increased blood lactate. Pathophysiology Two pathophysiologic mechanisms are thought to play a role in the development of gray baby syndrome after exposure to chloramphenicol. This condition is due to a lack of glucuronidation reactions occurring in the baby (phase II hepatic metabolism), thus leading to an accumulation of toxic chloramphenicol metabolites: Metabolism: The UDP-glucuronyl transferase enzyme system in infants, especially premature infants, is not fully developed and incapable of metabolizing the excessive drug load needed to excrete chloramphenicol. Elimination: Insufficient renal excretion of the unconjugated drug.Insufficient metabolism and excretion of chloramphenicol leads to increased blood concentrations of the drug, causing blockade of the electron transport of the liver, myocardium, and skeletal muscles. Since the electron transport is an essential part of cellular respiration, its blockade can result in cell damage. In addition, the presence of chloramphenicol weakens the binding of bilirubin and albumin, so increased levels of the drug can lead to high levels of free bilirubin in the blood, resulting in brain damage or kernicterus. If left untreated, possible bleeding, renal (kidney) and/or hepatic (liver) failure, anemia, infection, confusion, weakness, blurred vision, or eventually death are expected. Additionally, chloramphenicol is significantly insoluble due to an absence of acidic and basic groups in its molecular compound. As a result, larger amounts of the medication are required to achieve the desired therapeutic effect. High volumes of a medication that can cause various toxicities is another avenue how chloramphenicol can potentially lead to grey baby syndrome. Diagnosis Gray baby syndrome should be suspected in a new born with abdominal distension, progressive pallid cyanosis, irregular respirations, and refusal to breastfeed. The cause of gray baby syndrome can come from the direct use of intravenous or oral chloramphenicol in neonates. Direct chronological relation between the use of the medication and signs and symptoms of the syndrome should be found in the previous medical history. In terms of the possible route of chloramphenicol, gray baby syndrome may not come from the mothers use of chloramphenicol during pregnancy or breastfeeding. According to the Drug and Lactation database (LactMed), it states that "milk concentrations are not sufficient to induce gray baby syndrome". It is also reported that the syndrome may not develop in infants when their mothers use the medication in their late period of pregnancy. According to the Oxford Review, chloramphenicol given to mothers during their pregnancy did not result in gray baby syndrome, but was caused by infants receiving supra-therapeutic doses of chloramphenicol after birth. The presentation of symptoms can depend on the level of exposure of the drug to the baby, given its dose-related nature. A broad diagnosis is usually needed for babies who present with cyanosis. To support the diagnosis, blood work should be done to determine the level of serum chloramphenicol, and to further evaluate chloramphenicol toxicity, a complete blood panel including levels of serum ketones, glucose (due to the risk of hypoglycemia), metabolic panel should be completed to help determine if an infant has the syndrome. Other tools used to help with diagnosis include CT scans, ultrasound, and electrocardiogram. Prevention Since the syndrome is a side effect of chloramphenicol, the prevention is primarily related to the proper use of the medication. The WHO Model Formulary for Children 2010 recommends to reserve chloramphenicol for life-threatening infections. As well as using chloramphenicol only when necessary, it should also be used in short periods of time to also prevent the potential for toxicity. In particular, this medication should not be prescribed especially in neonates less than one week old due to the significant risk of toxicity. Preterm infants especially should not be administered chloramphenicol. Gray baby syndrome has been noted to be dose-dependent as it typically occurs in neonates who have received a daily dose greater than 200 milligrams.When chloramphenicol is necessary, the condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels, or alternatively, third generation cephalosporins can be effectively substituted for the drug, without the associated toxicity. Also, repeated course of administration and prolonged treatment should be avoided as much as possible. In terms of hepatic development in neonates, it take only weeks from birth for them to develop their UDPGT expression and function to be at an adult-like level, while the function is only about 1% in the late pregnancy, even right before birth-giving. According to MSD Manuals, chloramphenicol should not be given to neonates with younger than 1 month of age with more than a dose of 25 mg/kg/day to start with. The serum concentration of the medication should be monitored to titrate to a therapeutic level and to prevent toxicity. Medication reconciliation of other medications that neonates may be taking that can decrease blood cell count should be monitored because of this medications ability to suppress bone marrow activity. Rifampicin and trimethoprim are examples of medications with bone marrow suppression abilities and are contraindicated for concomitant use with chloramphenicol. In regards to bone marrow suppression, chloramphenicol has two major etiological manifestations. The first mechanism of bone marrow suppression affects the formation of blood cells such as erythrocytes, and this can be reversible since it is an early sign up toxicity. The second form of bone marrow suppression is bone marrow aplasia, which is associated with being late into toxicity and cannot be reversed in some cases. Chloramphenicol is contraindicated in persons who are breastfeeding due to the risk of toxic effects in the baby, but if maternal use of chloramphenicol cannot be avoided, close monitoring of the babys symptoms such as feeding difficulties, and blood work is recommended. Treatment Chloramphenicol therapy should be stopped immediately if objective or subjective signs of gray baby syndrome are suspected since gray baby syndrome can be fatal for the infant if it is not diagnosed early on as it can lead to anemia, shock, and end-organ damage. After discontinuing the antibiotic, the side effects caused by the toxicity should be treated. This includes treating hypoglycemia to help prevent hemodynamic instability, as well as increasing the temperature of the infant if they have developed hypothermia. Since symptoms of gray baby syndrome are correlated with elevated serum chloramphenicol concentrations, exchange transfusion may be required to remove the drug, charcoal column hemoperfusion is a type of transfusion that has shown significant effects but is associated with numerous side effects. The associated side effects isnt the only reason why this method of treatment is not a first line therapy. According to the American Journal of Kidney Diseases, elevated cartridge prices and viable lifespan of the product are deterring factors to consider. Phenobarbital and theophylline are two drugs in particular that have shown significant efficacy with charcoal hemoperfusion, aside from its most significant indication for chronic aluminum toxicity in people with end-stage renal disease (ESRD) traditionally. Sometimes, phenobarbital is used to induce UDP-glucuronyl transferase enzyme function. For hemodynamically unstable neonates, supportive care measures such as resuscitation, oxygenation, and treatment for hypothermia are common practices when cessation of chloramphenicol alone is insufficient. With sepsis being a complication of severe gray baby syndrome, usage of broad-spectrum antibiotics such as vancomycin, for example, is a recommended treatment option. Third generation antibiotics have also proven efficacy in treating gray baby-induced sepsis. References Further reading == External links ==

Hey Aarogya!, what is Spasticity

Spasticity

Spasticity (from Greek spasmos- drawing, pulling) is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. Clinically, spasticity results from the loss of inhibition of motor neurons, causing excessive velocity-dependent muscle contraction. This ultimately leads to hyperreflexia, an exaggerated deep tendon reflex. Spasticity is often treated with the drug baclofen, which acts as an agonist at GABA receptors, which are inhibitory. Spastic cerebral palsy is the most common form of cerebral palsy, which is a group of permanent movement problems that do not get worse over time. GABAs inhibitory actions contribute to baclofens efficacy as an anti-spasticity agent. Cause Spasticity mostly occurs in disorders of the central nervous system (CNS) affecting the upper motor neurons in the form of a lesion, such as spastic diplegia, or upper motor neuron syndrome, and can also be present in various types of multiple sclerosis, where it occurs as a symptom of the progressively-worsening attacks on myelin sheaths and is thus unrelated to the types of spasticity present in neuromuscular cerebral palsy rooted spasticity disorders.The cause of spasticity is thought to be where an imbalance occurs in the excitatory and inhibitory input to α motor neurons caused by damage to the spinal cord and/or central nervous system. The damage causes a change in the balance of signals between the nervous system and the muscles, leading to increased excitability in muscles. This is common in people who have cerebral palsy, brain injuries or a spinal cord injury, but it can happen to anybody e.g. having a stroke.One factor that is thought to be related to spasticity is the stretch reflex. This reflex is important in coordinating normal movements in which muscles are contracted and relaxed and in keeping the muscle from stretching too far. Although the result of spasticity is problems with the muscles, spasticity is actually caused by an injury to a part of the central nervous system (the brain or spinal cord) that controls voluntary movements. The damage causes a change in the balance of signals between the nervous system and the muscles. This imbalance leads to increased activity (excitability) in the muscles. Receptors in the muscles receive messages from the nervous system, which sense the amount of stretch in the muscle and sends that signal to the brain. The brain responds by sending a message back to reverse the stretch by contracting or shortening.Overall, a defining feature of spasticity is that the increased resistance to passive stretch is velocity-dependent. Lance (1980) describes it this way: "...a motor disorder, characterised by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex as one component of the upper motor neurone (UMN) syndrome".Spasticity is found in conditions where the brain and/or spinal cord are damaged or fail to develop normally; these include cerebral palsy, multiple sclerosis, spinal cord injury and acquired brain injury including stroke. Damage to the CNS as a result of stroke or spinal cord injury, alter the [net inhibition] of peripheral nerves in the affected region. This change in input to bodily structures tends to favor excitation and therefore increase nerve excitability. CNS damage also causes nerve cell membranes to rest in a more [depolarized] state. The combination of decreased inhibition and an increased depolarized state of cell membranes, decreases action potential threshold for nerve signal conduction, and thus increases activity of structures innervated by the affected nerves (spasticity). Muscles affected in this way have many other potential features of altered performance in addition to spasticity, including muscle weakness; decreased movement control; clonus (a series of involuntary rapid muscle contractions often symptomatic of muscle over-exertion and/or muscle fatigue); exaggerated deep tendon reflexes; and decreased endurance. Spasticity and clonus Clonus (i.e. involuntary, rhythmic, muscular contractions and relaxations) tends to co-exist with spasticity in many cases of stroke and spinal cord injury likely due to their common physiological origins. Some consider clonus as simply an extended outcome of spasticity. Although closely linked, clonus is not seen in all patients with spasticity. Clonus tends to not be present with spasticity in patients with significantly increased muscle tone, as the muscles are constantly active and therefore not engaging in the characteristic on/off cycle of clonus. Clonus results due to an increased motor neuron excitation (decreased action potential threshold) and is common in muscles with long conduction delays, such as the long reflex tracts found in distal muscle groups. Clonus is commonly seen in the ankle but may exist in other distal structures as well, such as the knee or spine. Diagnosis The clinical underpinnings of two of the most common spasticity conditions, spastic cerebral palsy and multiple sclerosis, can be described as follows: in spastic diplegia, the upper motor neuron lesion arises often as a result of neonatal asphyxia, while in conditions like multiple sclerosis, spasticity is thought by some to be as a result of the autoimmune destruction of the myelin sheaths around nerve endings—which in turn can mimic the gamma amino butyric acid deficiencies present in the damaged nerves of spastic cerebral palsy children, leading to roughly the same presentation of spasticity, but which clinically is fundamentally different from the latter.Spasticity is assessed by feeling the resistance of the muscle to passive lengthening in its most relaxed state. A spastic muscle will have immediately noticeable, often quite forceful, increased resistance to passive stretch when moved with speed and/or while attempting to be stretched out, as compared to the non-spastic muscles in the same persons body (if any exist). As there are many features of the upper motor neuron syndrome, there are likely to be multiple other changes in affected musculature and surrounding bones, such as progressive malalignments of bone structure around the spastic muscles (leading for example to the scissor gait and tip-toeing gait due to ankle equinus or ankle planter flexion deformity in spastic cerebral palsy children. scissor gait is caused by spasticity of the hip adductor muscles while tip-toeing gait is caused by spasticity of the gastrocnemius-soleus muscle complex or calf musculature. Also, following an upper motor neuron lesion, there may be multiple muscles affected, to varying degrees, depending on the location and severity of the upper motor neuron damage. The result for the affected individual, is that they may have any degree of impairment, ranging from a mild to a severe movement disorder. A relatively mild movement disorder may contribute to a loss of dexterity in an arm, or difficulty with high level mobility such as running or walking on stairs. A severe movement disorder may result in marked loss of function with minimal or no volitional muscle activation. There are several scales used to measure spasticity, such as the Kings hypertonicity scale, the Tardieu, and the modified Ashworth. Of these three, only the Kings hypertonicity scale measures a range of muscle changes from the UMN lesion, including active muscle performance as well as passive response to stretch.Assessment of a movement disorder featuring spasticity may involve several health professionals depending on the affected individuals situation, and the severity of their condition. This may include physical therapists, physicians (including neurologists and rehabilitation physicians), orthotists and occupational therapists. Assessment is needed of the affected individuals goals, their function, and any symptoms that may be related to the movement disorder, such as pain. A thorough assessment will include analysis of posture, active movement, muscle strength, movement control and coordination, and endurance, as well as spasticity (response of the muscle to stretch). Spastic muscles typically demonstrate a loss of selective movement, including a loss of eccentric control (decreased ability to actively lengthen). While multiple muscles in a limb are usually affected in the upper motor neuron syndrome, there is usually an imbalance of activity, such that there is a stronger pull in one direction, such as into elbow flexion. Decreasing the degree of this imbalance is a common focus of muscle strengthening programs. Spastic movement disorders also typically feature a loss of stabilisation of an affected limb or the head from the trunk, so a thorough assessment requires this to be analysed as well.Secondary effects are likely to impact on assessment of spastic muscles. If a muscle has impaired function following an upper motor neuron lesion, other changes such as increased muscle stiffness are likely to affect the feeling of resistance to passive stretch. Other secondary changes such as loss of muscle fibres following acquired muscle weakness are likely to compound the weakness arising from the upper motor neuron lesion. In severely affected spastic muscles, there may be marked secondary changes, such as muscle contracture, particularly if management has been delayed or absent. Treatment Treatment should be based on assessment by relevant health professionals. For spastic muscles with mild-to-moderate impairment, exercise should be the mainstay of management, and is likely needed to be prescribed by a Physiatrist (Doctor specialized in Rehabilitation medicine), occupational therapist, physical therapist, accredited exercise physiologist (AEP) or other health professional skilled in neurological rehabilitation.Muscles with severe spasticity are likely to be more limited in their ability to exercise, and may require help to do this. In spastic cerebral palsy children the main treatment modality of spasticity is conservative in the form of botulinum toxin A injection and various physical therapy modalities such as serial casting, sustained stretching and medical pharmacologic treatment. Spasticity in cerebral palsy children is usually generalized although with varying degrees of severity across the affected extremities and trunk musculature. Neglected or inappropriately treated spasticity can eventually lead to joint contractures. Both spasticity and contractures can cause joint subluxations or dislocations and severe gait difficulties. In the event of contracture there is no role for conservative treatment. Hip dislocation and ankle equinus deformity are known to arise from muscle spasticity primarily. Orthopedic surgical reconstruction of the hip is commonly practiced to improve sitting balance, nursing care and relief hip pain. Treatment should be done with firm and constant manual contact positioned over nonspastic areas to avoid stimulating the spastic muscle(s). Alternatively, rehabilitation robotics can be used to provide high volumes of passive or assisted movement, depending on the individuals requirements; this form of therapy can be useful if therapists are at a premium, and has been found effective at reducing spasticity in patients with strokes. For muscles that lack any volitional control, such as after complete spinal cord injury, exercise may be assisted, and may require equipment, such as using a standing frame to sustain a standing position. A general treatment guideline can be followed that involves: The initial focus on first activating contraction of antagonist muscles to provide reciprocal inhibition and lengthen spastic muscles Reciprocal actions are attempted. Agonist contractions are performed first in small ranges progressing to larger arcs of movement Highly stressful activities be minimized early in training Functional skills are targeted for training Patients and family/caregivers should be educated about the importance of maintaining range of motion and doing daily exercisesMedical interventions may include such medications as baclofen, diazepam, dantrolene, or clonazepam. Phenol injections can be used, or botulinum toxin injections into the muscle belly, to attempt to dampen the signals between nerve and muscle. The effectiveness of medications vary between individuals, and vary based on location of the upper motor neuron lesion (in the brain or the spinal cord). Medications are commonly used for spastic movement disorders, but research has not shown functional benefit for some drugs. Some studies have shown that medications have been effective in decreasing spasticity, but that this has not been accompanied by functional benefits. Surgery could be required for a tendon release in the case of a severe muscle imbalance leading to contracture. In spastic CP, selective dorsal rhizotomy has also been used to decrease muscle overactivity.Incorporating hydrotherapy in the treatment program may help decrease spasm severity, promote functional independence, improve motor recovery and decrease medication required for spasticity, which may help reduce the side effects that are possible with oral drug treatments. A 2004 study compared the effects of hydrotherapy on spasticity, oral baclofen dosage and Functional Independence Measure (FIM) scores of patients with a spinal cord injury (SCI). It was found that subjects who received hydrotherapy treatment obtained increased FIM scores and a decreased intake of oral baclofen medication. A 2009 study looked at the effect of hydrotherapy to decrease spasticity on post-stroke, hemiparetic patients with limited mobility and concluded that there was a significantly larger increase in FIM scores compared to the control group that did not receive hydrotherapy. Prognosis The prognosis for those with spastic muscles depends on multiple factors, including the severity of the spasticity and the associated movement disorder, access to specialised and intensive management, and ability of the affected individual to maintain the management plan (particularly an exercise program). Most people with a significant UMN lesion will have ongoing impairment, but most of these will be able to make progress. The most important factor to indicate ability to progress is seeing improvement, but improvement in many spastic movement disorders may not be seen until the affected individual receives help from a specialised team or health professional. Research Doublecortin positive cells, similar to stem cells, are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. The treatment using them would take some time to be available for general public use, as it has to clear regulations and trials. History Historical progression of spasticity and the upper motor neuron lesion on which it is based has progressed considerably in recent decades. However, the term "spasticity" is still often used interchangeably with "upper motor neuron syndrome" in the clinical settings, and it is not unusual to see patients labeled as "spastic" who actually demonstrate not just spasticity alone, but also an array of upper motor neuron findings.Research has clearly shown that exercise is beneficial for spastic muscles, even though in the very early days of research it was assumed that strength exercise would increase spasticity. Also, from at least the 1950s through at least the 1980s, there was a strong focus on other interventions for spastic muscles, particularly stretching and splinting, but the evidence does not support these as effective. While splinting is not considered effective for decreasing spasticity, a range of different orthotics are effectively used for preventing muscle contractures on patients with spasticity. In the case of spastic diplegia there is also a permanent neurosurgical treatment for spasticity, selective dorsal rhizotomy, that directly targets nerves in the spine that cause the spasticity, and destroys them, so that the spasticity cannot be activated at all. See also References Further reading Lance JW: Symposium synopsis, in Feldman RG, Young RR, Koella WP (eds): Spasticity: Disordered Motor Control. Chicago, Yearbook Medical Publishers, 1980 "Other Complications of Spinal Cord Injury: Spasticity." (Louis Calder Memorial Library of the University of Miami/Jackson Memorial Medical Center, October 3, 2002), http://calder.med.miami.edu/pointis/spasticity.html Maureen E. Neistadt; Elizabeth Blesedell Crepeau, eds. (1998). Willard and Spackmans occupational therapy. Philadelphia: Lippincott-Raven Publishers. pp. 233. ISBN 978-0-397-55192-7. This article contains text from the public domain document at http://www.ninds.nih.gov/health_and_medical/disorders/spasticity_doc.htm Douglas, Wallace M.; Bruce H Ross; Christine K. Thomas (Aug 25, 2005). "Motor unit behaviour during clonus". Journal of Applied Physiology. 99 (6): 2166–2172. CiteSeerX 10.1.1.501.9581. doi:10.1152/japplphysiol.00649.2005. PMID 16099891. S2CID 8598394. Hilder, Joseph M.; Zev W. Rymer (September 1999). "A Stimulation Study of Reflex Instability in Spasticity: Origins of Clonus". IEEE Transactions on Rehabilitation Engineering. 7 (3): 327–340. doi:10.1109/86.788469. PMID 10498378. S2CID 18315004. == External links ==

What does Standing mean Aarogya

Standing

Standing, also referred to as orthostasis, is a position in which the body is held in an erect ("orthostatic") position and supported only by the feet. Although seemingly static, the body rocks slightly back and forth from the ankle in the sagittal plane. The sagittal plane bisects the body into right and left sides. The sway of quiet standing is often likened to the motion of an inverted pendulum.Standing at attention is a military standing posture, as is stand at ease, but these terms are also used in military-style organisations and in some professions which involve standing, such as modeling. At ease refers to the classic military position of standing with legs slightly apart, not in as formal or regimented a pose as standing at attention. In modeling, model at ease refers to the model standing with one leg straight, with the majority of the weight on it, and the other leg tucked over and slightly around. Control Standing posture relies on dynamic rather than static balance. The human center of mass is in front of the ankle, and unlike in tetrapods, the base of support is narrow, consisting of only two feet. A static pose would cause humans to fall forward onto the face. In addition, there are constant external perturbations, such as breezes, and internal perturbations that come from respiration. Erect posture requires adjustment and correction. There are many mechanisms in the body that are suggested to control this, e.g. a spring action in muscles, higher control from the nervous system or core muscles. Humans begin to stand between 8 and 12 months of age. Spring action Traditionally, such correction was explained by the spring action of the muscles, a local mechanism taking place without the intervention of the central nervous system (C.N.S.). Recent studies, however, show that this spring action by itself is insufficient to prevent a forward fall. Also, human sway is too complicated to be adequately explained by spring action. Nervous system According to current theory, the nervous system continually and unconsciously monitors our direction and velocity. The vertical body axis alternates between tilting forward and backward. Before each tilt reaches the tipover point the nervous system counters with a signal to reverse direction. Sway also occurs in the hip and there is a slight winding and unwinding of the lower back.An analogy would be a ball that volleys back and forth between two players without touching the ground. The muscle exertion required to maintain an aligned standing posture is crucial but minimal. Electromyography has detected slight activity in the muscles of the calves, hips and lower back. Core muscles The core muscles play a role in maintaining stability. The core muscles are deep muscle layers that lie close to the spine and provide structural support. The transverse abdominals wrap around the spine and function as a compression corset. The multifidi are intersegmental muscles. Dysfunction in the core muscles has been implicated in back pain. Expansion of pendulum model Some investigators have replaced the ankle inverted pendulum analogy with a model of double linked pendulums involving both hip and ankle sway. Neither model is accepted as more than an approximation. Analysis of postural sway shows much more variation than is seen in a physical pendulum or even a pair of coupled pendulums. Furthermore, quiet standing involves activity in all joints, not just the ankles or hips.In the past the variation was attributed to random effects. A more recent interpretation is that sway has a fractal structure. A fractal pattern consists of a motif repeated at varying levels of magnification. The levels are related by a ratio called the fractal dimension. It is believed that the fractal pattern offers a range of fine and gross control tuning. Fractal dimension is altered in some motor dysfunctions. In other words, the body cannot compensate well enough for imbalances. Pathology Although standing per se is not dangerous, there are pathologies associated with it. One short term condition is orthostatic hypotension, and long term conditions are sore feet, stiff legs and low back pain. Orthostatic hypotension Orthostatic hypotension is characterized by an unusually low blood pressure when the patient is standing up. It can cause dizziness, lightheadedness, headache, blurred or dimmed vision and fainting, because the brain does not get sufficient blood supply. This, in turn, is caused by gravity, pulling the blood into the lower part of the body. Normally, the body compensates, but in the presence of other factors, e.g. hypovolemia, diseases and medications, this response may not be sufficient. There are medications to treat hypotension. In addition, there are many lifestyle advices. Many of them, however, are specific for a certain cause of orthostatic hypotension, e.g. maintaining a proper fluid intake in dehydration. Orthostatic hypercoagulability Prolonged still standing significantly activates the coagulation cascade, called orthostatic hypercoagulability. Overall, it causes an increase in transcapillary hydrostatic pressure. As a result, approximately 12% of blood plasma volume crosses into the extravascular compartment. This plasma shift causes an increase in the concentration of coagulation factors and other proteins of coagulation, in turn causing hypercoagulability. Orthostatic tremor Characterized by fast (12–18 Hz) rhythmic muscle contractions that occur in the legs and trunk immediately after standing. No other clinical signs or symptoms are present and the shaking ceases when the patient sits or is lifted off the ground. The high frequency of the tremor often makes the tremor look like rippling of leg muscles while standing. Long-term complications Standing per se does not pose any harm. In the long term, however, complications may arise. See also At attention Agonoclita, a former Christian group that said prayers standing Human position Prostration Standing desk Bowing (social) References External links Dizziness-and-balance.com – Description apta.org – The Secret of Good Posture

Hey Aarogya!, what is Pituitary apoplexy

Pituitary apoplexy

Pituitary apoplexy is bleeding into or impaired blood supply of the pituitary gland. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously. The most common initial symptom is a sudden headache, often associated with a rapidly worsening visual field defect or double vision caused by compression of nerves surrounding the gland. This is often followed by acute symptoms caused by lack of secretion of essential hormones, predominantly adrenal insufficiency.The diagnosis is achieved with magnetic resonance imaging and blood tests. Treatment is by the timely correction of hormone deficiencies. In many cases, surgical decompression is required. Many people who have had a pituitary apoplexy develop pituitary hormone deficiencies and require long-term hormone supplementation. The first case of the disease was recorded in 1898. Signs and symptoms Acute symptoms The initial symptoms of pituitary apoplexy are related to the increased pressure in and around the pituitary gland. The most common symptom, in over 95% of cases, is a sudden-onset headache located behind the eyes or around the temples. It is often associated with nausea and vomiting. Occasionally, the presence of blood leads to irritation of the lining of the brain, which may cause neck rigidity and intolerance to bright light, as well as a decreased level of consciousness. This occurs in 24% of cases. Pressure on the part of the optic nerve known as the chiasm, which is located above the gland, leads to loss of vision on the outer side of the visual field on both sides, as this corresponds to areas on the retinas supplied by these parts of the optic nerve; it is encountered in 75% of cases. Visual acuity is reduced in half, and over 60% have a visual field defect. The visual loss depends on which part of the nerve is affected. If the part of the nerve between the eye and the chiasm is compressed, the result is vision loss in one eye. If the part after the chiasm is affected, visual loss on one side of the visual field occurs.Adjacent to the pituitary lies a part of the skull base known as the cavernous sinus. This contains a number of nerves that control the eye muscles. 70% of people with pituitary apoplexy experience double vision due to compression of one of the nerves. In half of these cases, the oculomotor nerve (the third cranial nerve), which controls a number of eye muscles, is affected. This leads to diagonal double vision and a dilated pupil. The fourth (trochlear) and sixth (abducens) cranial nerves are located in the same compartment and can cause diagonal or horizontal double vision, respectively. The oculomotor nerve is predominantly affected as it lies closest to the pituitary. The cavernous sinus also contains the carotid artery, which supplies blood to the brain; occasionally, compression of the artery can lead to one-sided weakness and other symptoms of stroke. Endocrine dysfunction The pituitary gland consists of two parts, the anterior (front) and posterior (back) pituitary. Both parts release hormones that control numerous other organs. In pituitary apoplexy, the main initial problem is a lack of secretion of adrenocorticotropic hormone (ACTH, corticotropin), which stimulates the secretion of cortisol by the adrenal gland. This occurs in 70% of those with pituitary apoplexy. A sudden lack of cortisol in the body leads to a constellation of symptoms called "adrenal crisis" or "Addisonian crisis" (after a complication of Addisons disease, the main cause of adrenal dysfunction and low cortisol levels). The main problems are low blood pressure (particularly on standing), low blood sugars (which can lead to coma) and abdominal pain; the low blood pressure can be life-threatening and requires immediate medical attention.Hyponatremia, an unusually low level of sodium in the blood that may cause confusion and seizures, is found in 40% of cases. This may be caused by low cortisol levels or by inappropriate release of antidiuretic hormone (ADH) from the posterior pituitary. Several other hormonal deficiencies may develop in the subacute phase. 50% have a deficiency in thyroid-stimulating hormone (TSH), leading to hyposecretion of thyroid hormone by the thyroid gland and characteristic symptoms such as fatigue, weight gain, and cold intolerance. 75% develop a deficiency to gonadotropins (LH and FSH), which control the reproductive hormone glands. This leads to a disrupted menstrual cycle, infertility, and decreased libido. Causes Almost all cases of pituitary apoplexy arise from a pituitary adenoma, a benign tumor of the pituitary gland. In 80%, the patient has been previously unaware of this (although some will retrospectively report associated symptoms). It was previously thought that particular types of pituitary tumors were more prone to apoplexy than others, but this has not been confirmed. In absolute terms, only a very small proportion of pituitary tumors eventually undergoes apoplexy. In an analysis of incidentally found pituitary tumors, apoplexy occurred in 0.2% annually, but the risk was higher in tumors larger than 10 mm ("macroadenomas") and tumors that were growing more rapidly; in a meta-analysis, not all these associations achieved statistical significance.The majority of cases (60–80%) are not precipitated by a particular cause. A quarter has a history of high blood pressure, but this is a common problem in the general population, and it is not clear whether it significantly increase the risk of apoplexy. A number of cases has been reported in association with particular conditions and situations; it is uncertain whether these were in fact causative. Amongst reported associations are surgery (especially coronary artery bypass graft, where there are significant fluctuations in the blood pressure), disturbances in blood coagulation or medication that inhibits coagulation, radiation therapy to the pituitary, traumatic brain injury, pregnancy (during which the pituitary enlarges) and treatment with estrogens. Hormonal stimulation tests of the pituitary have been reported to provoke episodes. Treatment of prolactinomas (pituitary adenomas that secrete prolactin) with dopamine agonist drugs, as well as withdrawal of such treatment, has been reported to precipitate apoplexy.Hemorrhage from a Rathkes cleft cyst, a remnant of Rathkes pouch that normally regresses after embryological development, may cause symptoms that are indistinguishable from pituitary apoplexy. Pituitary apoplexy is regarded by some as distinct from Sheehans syndrome, where the pituitary undergoes infarction as a result of prolonged very low blood pressure, particularly when caused by bleeding after childbirth. This condition usually occurs in the absence of a tumor. Others regard Sheehans syndrome as a form of pituitary apoplexy. Mechanism The pituitary gland is located in a recess in the skull base known as the sella turcica ("Turkish saddle", after its shape). It is attached to the hypothalamus, a part of the brain, by a stalk that also contains the blood vessels that supply the gland. It is unclear why pituitary tumors are five times more likely to bleed than other tumors in the brain. There are various proposed mechanisms by which a tumor can increase the risk of either infarction (insufficient blood supply leading to tissue dysfunction) or hemorrhage. The pituitary gland normally derives its blood supply from vessels that pass through the hypothalamus, but tumors develop a blood supply from the nearby inferior hypophyseal artery that generates a higher blood pressure, possibly accounting for the risk of bleeding. Tumors may also be more sensitive to fluctuations in blood pressure, and the blood vessels may show structural abnormalities that make them vulnerable to damage. It has been suggested that infarction alone causes milder symptoms than either hemorrhage or hemorrhagic infarction (infarction followed by hemorrhage into the damaged tissue). Larger tumors are more prone to bleeding, and more rapidly growing lesions (as evidenced by detection of increased levels of the protein PCNA) may also be at a higher risk of apoplexy.After an apoplexy, the pressure inside the sella turcica rises, and surrounding structures such as the optic nerve and the contents of the cavernous sinus are compressed. The raised pressure further impairs the blood supply to the pituitary hormone-producing tissue, leading to tissue death due to insufficient blood supply. Diagnosis It is recommended that magnetic resonance imaging (MRI) scan of the pituitary gland is performed if the diagnosis is suspected; this has a sensitivity of over 90% for detecting pituitary apoplexy; it may demonstrate infarction (tissue damage due to a decreased blood supply) or hemorrhage. Different MRI sequences can be used to establish when the apoplexy occurred, and the predominant form of damage (hemorrhage or infarction). If MRI is not suitable (e.g. due to claustrophobia or the presence of metal-containing implants), a computed tomography (CT) scan may demonstrate abnormalities in the pituitary gland, although it is less reliable. Many pituitary tumors (25%) are found to have areas of hemorrhagic infarction on MRI scans, but apoplexy is not said to exist unless it is accompanied by symptoms.In some instances, lumbar puncture may be required if there is a suspicion that the symptoms might be caused by other problems (meningitis or subarachnoid hemorrhage). This is the examination of the cerebrospinal fluid that envelops the brain and the spinal cord; the sample is obtained with a needle that is passed under local anesthetic into the spine. In pituitary apoplexy the results are typically normal, although abnormalities may be detected if blood from the pituitary has entered the subarachnoid space. If there is remaining doubt about the possibility of subarachnoid hemorrhage (SAH), a magnetic resonance angiogram (MRI with a contrast agent) may be required to identify aneurysms of the brain blood vessels, the most common cause of SAH.Professional guidelines recommend that if pituitary apoplexy is suspected or confirmed, the minimal blood tests performed should include a complete blood count, urea (a measure of renal function, usually performed together with creatinine), electrolytes (sodium and potassium), liver function tests, routine coagulation testing, and a hormonal panel including IGF-1, growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, thyroid hormone, and either testosterone in men or estradiol in women.Visual field testing is recommended as soon as possible after diagnosis, as it quantifies the severity of any optic nerve involvement, and may be required to decide on surgical treatment. Treatment The first priority in suspected or confirmed pituitary apoplexy is stabilization of the circulatory system. Cortisol deficiency can cause severe low blood pressure. Depending on the severity of the illness, admission to a high dependency unit (HDU) may be required.Treatment for acute adrenal insufficiency requires the administration of intravenous saline or dextrose solution; volumes of over two liters may be required in an adult. This is followed by the administration of hydrocortisone, which is pharmaceutical grade cortisol, intravenously or into a muscle. The drug dexamethasone has similar properties, but its use is not recommended unless it is required to reduce swelling in the brain around the area of hemorrhage. Some are well enough not to require immediate cortisol replacement; in this case, blood levels of cortisol are determined at 9:00 AM (as cortisol levels vary over the day). A level below 550 nmol/l indicates a need for replacement.The decision on whether to surgically decompress the pituitary gland is complex and mainly dependent on the severity of visual loss and visual field defects. If visual acuity is severely reduced, there are large or worsening visual field defects, or the level of consciousness falls consistently, professional guidelines recommend that surgery is performed. Most commonly, operations on the pituitary gland are performed through transsphenoidal surgery. In this procedure, surgical instruments are passed through the nose towards the sphenoid bone, which is opened to give access to the cavity that contains the pituitary gland. Surgery is most likely to improve vision if there was some remaining vision before surgery, and if surgery is undertaken within a week of the onset of symptoms.Those with relatively mild visual field loss or double vision only may be managed conservatively, with close observation of the level of consciousness, visual fields, and results of routine blood tests. If there is any deterioration, or expected spontaneous improvement does not occur, surgical intervention may still be indicated. If the apoplexy occurred in a prolactin-secreting tumor, this may respond to dopamine agonist treatment.After recovery, people who have had pituitary apoplexy require follow-up by an endocrinologist to monitor for long-term consequences. MRI scans are performed 3–6 months after the initial episode and subsequently on an annual basis. If after surgery some tumor tissue remains, this may respond to medication, further surgery, or radiation therapy with a "gamma knife". Prognosis In larger case series, the mortality was 1.6% overall. In the group of patients who were unwell enough to require surgery, the mortality was 1.9%, with no deaths in those who could be treated conservatively.After an episode of pituitary apoplexy, 80% of people develop hypopituitarism and require some form of hormone replacement therapy. The most common problem is growth hormone deficiency, which is often left untreated but may cause decreased muscle mass and strength, obesity and fatigue. 60–80% require hydrocortisone replacement (either permanently or when unwell), 50–60% need thyroid hormone replacement, and 60–80% of men require testosterone supplements. Finally, 10–25% develop diabetes insipidus, the inability to retain fluid in the kidneys due to a lack of the pituitary antidiuretic hormone. This may be treated with the drug desmopressin, which can be applied as a nose spray or taken by mouth. Epidemiology Pituitary apoplexy is rare. Even in people with a known pituitary tumor, only 0.6–10% experience apoplexy; the risk is higher in larger tumors. Based on extrapolations from existing data, one would expect 18 cases of pituitary apoplexy per one million people every year; the actual figure is probably lower.The average age at onset is 50; cases have reported in people between 15 and 90 years old. Men are affected more commonly than women, with a male-to-female ratio of 1.6. The majority of the underlying tumors are "null cell" or nonsecretory tumors, which do not produce excessive amounts of hormones; this might explain why the tumor has often gone undetected prior to an episode of apoplexy. History The first case description of pituitary apoplexy has been attributed to the American neurologist Pearce Bailey in 1898. This was followed in 1905 by a further report from the German physician Bleibtreu. Surgery for pituitary apoplexy was described in 1925. Before the introduction of steroid replacement, the mortality from pituitary apoplexy approximated 50%.The name of the condition was coined in 1950 in a case series by physicians from Boston City Hospital and Harvard Medical School. The term "apoplexy" was applied as it referred to both necrosis and bleeding into pituitary tumors. References == External links ==

Hi Aarogya, explain a situation where Cholestasis occurs

Cholestasis

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications. Classification is further divided into acute or chronic and extrahepatic or intrahepatic. Signs and symptoms The signs and symptoms of cholestasis vary according to the cause. In case of sudden onset, the disease is likely to be acute, while the gradual appearance of symptoms suggests chronic pathology. In many cases, patients may experience pain in the abdominal area. Localization of pain to the upper right quadrant can be indicative of cholecystitis or choledocholithiasis, which can progress to cholestasis.Pruritus or itching is often present in many patients with cholestasis. Patients may present with visible scratch marks as a result of scratching. Pruritus is often misdiagnosed as a dermatological condition, especially in patients that do not have jaundice as an accompanying symptom. In a typical day, pruritus worsens as the day progresses, particularly during the evening time. Overnight, pruritus dramatically improves. This cycle can be attributed to an increase in the concentration of biliary elements during the day due to food consumption, and a decline at night. Pruritus is mostly localized to the limbs, but can also be more generalized. The efficacy of naltrexone for cholestatic pruritus suggests involvement of the endogenous opioid system. Many patients may experience jaundice as a result of cholestasis. This is usually evident after physical examination as yellow pigment deposits on the skin, in the oral mucosa, or conjunctiva. Jaundice is an uncommon occurrence in intrahepatic (metabolic) cholestasis, but is common in obstructive cholestasis. The majority of patients with chronic cholestasis also experience fatigue. This is likely a result of defects in the corticotrophin hormone axis or other abnormalities with neurotransmission. Some patients may also have xanthomas, which are fat deposits that accumulate below the skin. These usually appear waxy and yellow, predominantly around the eyes and joints. This condition results from an accumulation of lipids within the blood. If gallstones prevent bile flowing from the pancreas to the small intestine, it can lead to gallstone pancreatitis. Physical symptoms include nausea, vomiting, and abdominal pain. Bile is required for the absorption of fat-soluble vitamins. As such, patients with cholestasis may present with a deficiency in vitamins A, D, E, or K due to a decline in bile flow. Patients with cholestasis may also experience pale stool and dark urine. Causes Possible causes: pregnancy androgens birth control pills antibiotics (such as TMP/SMX) abdominal mass (e.g. cancer) pediatric liver diseases biliary trauma congenital anomalies of the biliary tract gallstones biliary dyskinesia acute hepatitis cystic fibrosis primary biliary cholangitis, an autoimmune disorder primary sclerosing cholangitis, associated with inflammatory bowel disease some drugs (e.g. flucloxacillin and erythromycin): 208  secondary syphilis, albeit rarelyDrugs such as gold salts, nitrofurantoin, anabolic steroids, sulindac, chlorpromazine, erythromycin, prochlorperazine, cimetidine, estrogen, and statins can cause cholestasis and may result in damage to the liver.: 208 Drug-induced cholestasis Acute and chronic cholestasis can be caused by certain drugs or their metabolites. Drug-induced cholestasis (DIC) falls under drug-induced liver injury (DILI), specifically the cholestatic or mixed type. While some drugs (e.g., acetaminophen) are known to cause DILI in a predictable dose-dependent manner (intrinsic DILI), most cases of DILI are idiosyncratic, i.e., affecting only a minority of individuals taking the medication. Seventy-three percent of DIC cases can be attributed to a single prescription medication, commonly antibiotics & antifungals, anti-diabetics, anti-inflammatory, & cardiovascular drugs, psychotropic drugs. The exact pathomechanism may vary for different drugs and requires further elucidation.Typical symptoms of DIC include pruritus and jaundice, nausea, fatigue, and dark urine, which usually resolve after discontinuation of the offending medication.Clinically, DIC can manifest as acute bland (pure) cholestasis, acute cholestatic hepatitis, secondary sclerosing cholangitis (involving bile duct injury), or vanishing bile duct syndrome (loss of intrahepatic bile ducts).: 17  Bland cholestasis occurs when there is obstruction to bile flow in the absence of inflammation or biliary and hepatic injury, whereas these features are present in cholestatic hepatitis.: 17 Bland cholestasis is almost always caused by anabolic steroids or estrogen contraceptive use, while many drugs may cause cholestatic hepatitis, including penicillins, sulfonamides, rifampin, cephalosporins, fluoroquinolones, tetracyclines, and methimazole, among others.Antibiotics and antifungals that commonly cause DIC are penicillins, macrolides, trimethoprim/sulfamethoxazole, and tetracyclines. Due to its clavulanic acid component, penicillin amoxicillin-clavulanate is the most common culprit of cholestatic liver injury. Flucloxacillin, which is commonly prescribed in the UK, Sweden, and Australia, is another penicillin frequently implicated in DIC. Cholestasis induced by penicillins usually resolves after withdrawal. Macrolides with cholestatic potential include erythromycin, clarithromycin, and azithromycin, and prognosis is likewise favorable with these drugs. Trimethoprim/sulfamethoxazole (via its sulfonamide component) is the fourth most common antibiotic responsible for DILI in North America. However, DIC is comparatively less common with low-dose tetracyclines like doxycycline. Other cholestatic antimicrobials include the antifungal terbinafine, notable for its potential to cause life-threatening cholestatic injury, and quinolones (ciprofloxacin, levofloxacin), which have been linked to cholestatic hepatitis and vanishing bile duct syndrome.Among psychotropic drugs, chlorpromazine is known to cause cholestatic hepatitis. Tricyclic antidepressants (imipramine, amitriptyline) and SSRIs (duloxetine) causing cholestasis have also been reported. Anti-inflammatory drugs with cholestatic potential include the immunosuppressant azathioprine, which has been reported to cause fatal cholestatic hepatitis, and the NSAID diclofenac. Rare causes of cholestasis The causes of cholestasis are diverse, and some feature more prominently than others. Some rare causes include primary sclerosing cholangitis, primary biliary cholangitis, familial intrahepatic cholestasis, Alagille syndrome, sepsis, total parenteral nutrition-based cholestasis, benign recurrent intrahepatic cholestasis, biliary atresia, and intrahepatic cholestasis of pregnancy. Primary biliary cholangitis Chronic cholestasis occurs in primary biliary cholangitis (PBC). PBC is a progressive autoimmune liver disease in which small intrahepatic bile ducts are selectively destroyed, leading to cholestasis, biliary fibrosis, cirrhosis, and eventually liver failure that requires transplantation. Prevalence of PBC ranges from 19 to 402 cases/million depending on geographic location, with a 9:1 female preponderance and median ages of diagnosis of 68.5 years for females and 54.5 years for males.At diagnosis, 50% of PBC patients are asymptomatic, indicative of an early stage of disease, while another 50% report fatigue and daytime sleepiness. Other symptoms include pruritus and skin lesions, and in prolonged cholestasis, malabsorption and steatorrhea leading to fat-soluble vitamin deficiency. Disease progression is accompanied by intensifying portal hypertension and hepatosplenomegaly. Clinically, diagnosis generally requires a 1:40 or greater titer of anti-mitochondrial antibody (AMA) against PDC-E2 and elevated alkaline phosphatase persisting for 6+ months.Ursodeoxycholic acid (UDCA) is an FDA-approved first-line treatment for PBC. At moderate doses, UDCA has been demonstrated to slow disease progression and improve transplant-free survival. A complete response is achieved in 25-30% patients, and similar survival as the general population is expected in 2/3 of patients on UDCA. For the 1/3 non-responders, obeticholic acid (OCA) is approved by the FDA as a second-line treatment.The precise etiology of PBC remains poorly understood, though a clearer picture is starting to emerge. A loss of immune tolerance is indicated by the presence of AMAs and autoreactive CD4+ and CD8+ T cells targeting cholangiocytes that line the bile ducts. Cholangiocytes are normally responsible for 40% of bile flow, mostly through secretion of bicarbonate into bile via anion exchanger 2 (AE2) on their apical membrane. The resulting bicarbonate "umbrella" that forms over cholangiocytes provides protection from toxic bile salts. However, in PBC there is repression of AE2 activity due to upregulation of miR-506. This results in decreased biliary bicarbonate secretion and consequently, cholestasis and injury to cholangiocytes by bile salts. Injury may induce cholangiocytes to undergo apoptosis, and during this process, the unique way in which cholangiocytes handle the degradation of PDC-E2 (the E2 subunit of mitochondrial pyruvate dehydrogenase complex) may be a trigger for PSC. Specifically, PDC-E2 in apoptotic cholangiocytes undergo a covalent modification that may render them recognizable to antibodies and thereby trigger a break in self-tolerance. The problem is compounded by cholangiocytes peculiarly abundant expression of HLA-II and HLA-I, as well as adhesion and chemoattractant molecules, which recruit aid in recruitment of mononuclear immune cells.Both genetic and environmental factors probably contribute to PBC pathogenesis. Genetic predisposition is suggested by high concordance between identical twins, higher incidence among relatives, and a strong association of disease with certain HLA variants. Disease is likely triggered in the genetically predisposed by some environmental factor, such as pollutants, xenobiotics (e.g., chemicals in makeup), diet, drugs, stress, and infectious agents. Urinary tract infection with E. coli is a particularly strong risk factor for PBC. A possible explanation is that E. coli possess a similar PDC-E2 as humans which could trigger autoimmunity via molecular mimicry. Primary sclerosing cholangitis Chronic cholestasis is a feature in primary sclerosing cholangitis (PSC). PSC is a rare and progressive cholestatic liver disease characterized by narrowing, fibrosis, and inflammation of intrahepatic or extrahepatic bile ducts, leading to reduced bile flow or formation (i.e., cholestasis). The pathogenesis of PSC remains unclear but probably involves a combination of environmental factors and genetic predisposition. Notably, 70-80% of patients with PSC are comorbid with inflammatory bowel disease (e.g., ulcerative colitis or Crohns colitis), suggesting there exists a link between the two.PSC predominantly affects males (60-70%) of 30–40 years of age. The disease has an incidence is 0.4-2.0 cases/100,000 and a prevalence of 16.2 cases/100,000, making it a rare disease. Nonetheless, PSC accounts for 6% of liver transplants in the US due to its eventual progression to end-stage liver disease, with a mean transplant-free survival of 21.3 year.Though 40-50% of patients are asymptomatic, commonly reported symptoms include abdominal pain in the right upper quadrant, pruritus, jaundice, fatigue, and fever. The most common signs are hepatomegaly and splenomegaly. Prolonged cholestasis in PSC may cause fat-soluble vitamin deficiency leading to osteoporosisDiagnosis requires elevated serum alkaline phosphatase persisting for at least 6 months and the presence of bile duct strictures on cholangiogram. Unlike primary biliary cholangitis, PSC lacks a diagnostic autoantibody or reliable biomarker of disease progression. Although a liver biopsy is not required for diagnosis, the characteristic histological finding is concentric periductal fibrosis resembling onion skin.PSC is associated with increased risk of several cancers, most notably, a 400 times greater risk for cholangiocarcinoma compared to the general population. Patients with PSC also face elevated risk of pancreatic and colorectal cancer. Therefore, regular screening is recommended.No drugs are currently approved for treating PSC specifically. Although commonly given, ursodeoxycholic acid at moderate doses failed to improve transplant-free survival in randomized controlled trials. Due to disease progression, 40% of patients eventually require liver transplantation, which has survival rates (91% at 1 year, 82% at 5 years, and 74% at 10 years). However, the disease recurs in at least 25% of transplant recipients, particularly in those with IBD and an intact colon. Clinical trials are underway for several novel therapies, including obeticholic acid (a bile acid analogue), simtuzumab (a monoclonal antibody), and 24-norursodeoxycholic acid (a synthetic bile acid). Although the pathogenesis of PSC is poorly understood, three dominant theories have been proposed: 1) aberrant immune response, 2) increased intestinal permeability, and 3) dysbiosis of gut microbiota. The first theory involves immune-mediated damage to bile ducts by T cells. In PSC, cholangiocytes and hepatocytes display aberrant expression of adhesion molecules, which facilitate homing of intestinal T cells to the liver. Additionally, intestinal microbiota may produce pathogen-associated molecular patterns that stimulate cholangiocytes and hepatic macrophages to produce proinflammatory cytokines, which promote recruitment of immune cells to the bile ducts, fibrosis, cholangiocyte apoptosis and senescence, and ultimately destruction of the bile ducts. In support of T cell involvement, certain human leukocyte antigen (HLA) variants are strongly associated with PSC risk. Further evidence for genetic predisposition include the identification of 23 non-HLA susceptibility loci and a higher disease risk among siblings, though environmental factors appear to play a much greater role in pathogenesis.Another theory postulates that increased intestinal permeability contributes to PSC. Tight junctions, which normally maintain the integrity of the intestinal epithelium, may become disrupted in inflammation. Leaky tight junctions could allow commensal bacteria and toxins to enter portal circulation and reach the liver, where they can trigger inflammation and fibrosis.The intestinal dysbiosis theory hypothesizes that yet unidentified environmental triggers (e.g., diet, medication, inflammation) reduce microbiota diversity and/or alter the population of specific species. The resulting imbalance between primary and secondary bile acids may lead to PSC via the gut-liver axis. The primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) are synthesized in the liver and undergo conjugation before being released into the small intestine to aid digestion. In the distal ileum, 95% of these conjugated BAs are actively reabsorbed via ASBT but 5% enter the colon and are converted by gut microbes into deconjugated secondary bile acids, predominantly deoxycholic acid (DCA) and lithocholic acid (LCA). DCA and LCA are then reabsorbed into portal circulation and reach the liver, where they serve as signaling molecules that maintain bile acid homeostasis. Specifically, DCA and LCA and potent agonists of farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), both of which mediate anti-inflammatory and cholangioprotective effects upon activation. On cholangiocytes, TGR5 activation induces CFTR to secrete chloride into bile ducts, which then drives anion exchanger 2 to secrete bicarbonate into bile canaliculi. Bicarbonate serves to protect the apical surface of cholangiocytes from damage by bile acids. On macrophages, activation of FXR and TGR5 inhibits NF-κB, thereby reducing production of proinflammatory cytokines. Therefore, it is hypothesized that a reduction in secondary bile acid production, as a result of dysbiosis, could lead to bile duct damage via decreased activation of FXR and TGR5. Indeed, lower levels of secondary bile acids were found in PSC patients, but a causal relationship is yet to be confirmed. Familial intrahepatic cholestasis Familial intrahepatic cholestasis (FIH) is a group of disorders that lead to intrahepatic cholestasis in children. Most often, FIH occurs during the first year of life, with an incidence rate of 1/50,000 to 1/100,000. There are three different versions of FIH, with each causing a different severity of jaundice. Typically, children exhibit recurrent jaundice episodes, which eventually become permanent. Diagnosis usually occurs by analyzing laboratory features, liver biopsy results, DNA/RNA sequences, and biliary lipid analysis. The definitive treatment for FIH is liver transplant which usually results in a high recovery rate. Each type of FIH is a result of a different mutation. The three genes thought to be involved include APT8B1, which encodes for the FIC1 protein. The ABCB11 gene encodes for the bile salt export pump (BSEP) protein, and the ABCB4 gene encodes for the multidrug resistance 3 (MDR3) protein. BSEP and MDR3 are respectively responsible for transporting bile salt and phospholipid, two major constituents of bile, across the apical membrane of hepatocytes. Alagille syndrome Alagille syndrome is an autosomal dominant disorder that impacts five systems, including the liver, heart, skeleton, face, and eyes. In the early part of life (within the first three months), patients with Alagille syndrome exhibit conjugated hyperbilirubinemia, severe pruritus, and jaundice. Bile duct obliteration usually worsens over time, causing cirrhosis of the liver and eventual failure. Diagnosis usually occurs using the classic criteria by looking at changes associated with the five systems discussed earlier. Like FIH, the definitive treatment is a liver transplant. Almost all patients with Alagille syndrome have mutations of the genes involved in the Notch signaling pathway. Most have a mutation of the JAG1 gene, while a small minority have a mutation of the NOTCH2 gene. Sepsis A variety of factors associated with sepsis may cause cholestasis. Typically, patients have conjugated hyperbilirubinemia and alkaline phosphatase (ALP) elevation but not to extreme levels. Sepsis-induced cholestasis may occur due to increased serum lipopolysaccharide levels. Lipopolysaccharides can inhibit and down-regulate bile salt transporters in hepatocytes, thereby leading to cholestasis. As such, in the case of sepsis, cholestasis occurs not as a result of impaired obstruction but rather the disruption of bile flow. Ischemic liver injury resulting from sepsis can also cause cholestasis. Importantly, jaundice is not indicative of cholestasis in all cases. Widespread hemolysis resulting from sepsis may release bilirubin, thereby overwhelming bilirubin reabsorption and excretion mechanism. TPN-based cholestasis Total parenteral nutrition (TPN) is given to patients with intestinal failure or a variety of other gastrointestinal problems. Under normal settings, TPN causes a slight elevation of ALP levels. However, this does not indicate cholestasis alone. In the case of TPN-induced cholestasis, there is an excessive elevation of ALP, gamma-glutamyltransferase (GGT), and conjugated bilirubin. Without appropriate intervention, symptoms can quickly exacerbate, leading to liver cirrhosis and failure. Cholestasis arising from TPN has a diverse range of causes, including toxicity to TPN components, underlying disorders, or a lack of enteral nutrition. Without enteral food consumption, gallbladder function is greatly inhibited, leading to gallstone formation, subsequent blockage, and eventually cholestasis. Cholestasis resulting from TPN may also be a result of reduced bile flow from portal endotoxins. With TPN, there is a reduction in gastrointestinal motility, immunity, with an increase in permeability. These changes facilitate bacteria growth and increase the amount of circulating endotoxin. Moreover, given that patients using TPN often have underlying health problems, drugs being used with known liver toxicity may also cause cholestasis. Lipids in TPN may cause cholestasis and liver damage by overwhelming clearage mechanisms. Intravenous glucose can also cause cholestasis as a result of increased fatty acid synthesis and decreased breakdown, which facilitates the accumulation of fats. Intrahepatic cholestasis of pregnancy (obstetric cholestasis) Intrahepatic cholestasis of pregnancy (ICP) is an acute cause of cholestasis that manifests most commonly in the third trimester of pregnancy. It affects 0.5-1.5% of pregnancies in Europe and the US and up to 28% in women of Mapuche ethnicity in Chile. ICP is characterized by severe pruritus and elevated serum levels of bile acids as well as transaminases and alkaline phosphatase. These signs and symptoms resolve on their own shortly after delivery, though they may reappar in subsequent pregnancies for 45-70% of women. In the treatment of ICP, current evidence suggests ursodeoxycholic acid (UDCA), a minor secondary bile acid in humans, is the most effective drug for reducing pruritus and improving liver function.The etiology of ICP is multifactorial and likely involves hormonal, genetic, and environmental factors. Several observations suggest estrogen plays a major role: ICP begins in the third trimester, when estrogen levels are highest, resolves after estrogen levels return to normal post-delivery, and occurs with higher incidence in multiple pregnancies, where estrogen levels are more elevated than usual. Although estrogens exact pathomechanism in ICP remains unclear, several explanations have been offered. Estrogen may induce a decrease in the fluidity of the hepatic sinusoidal membrane, leading to a decrease in the activity of basolateral Na+/K+-ATPase. A weaker Na+ gradient results in diminished sodium-dependent uptake of bile acids from venous blood into hepatocytes by the sodium/bile acid cotransporter. More recent evidence suggests that estrogen promotes cholestasis via its metabolite estradiol-17-β-D-glucuronide (E2). E2 secreted into the canaliculi by MRP2 was found to repress the transcription of bile salt export pump (BSEP), the apical ABC transporter responsible for exporting monoanionic conjugated bile acids from hepatocytes into bile canaliculi. E2 was also found to upregulate miR-148a, which represses expression of the pregnane X receptor (PXR). PXR is a nuclear receptor in hepatocytes that senses intracellular bile acid concentrations and regulates gene expression accordingly to increase bile efflux.Genetic predisposition for ICP is suggested by familial and regional clustering of cases. Several studies have implicated heterozygous mutations of the genes ABCB11 and ABCB4 in ICP, which respectively encode the canalicular transport proteins BSEP and multidrug resistance protein 3 (MDR3). MDR3 is responsible for exporting phosphatidylcholine, the major lipid component of bile, into bile canaliculi where it forms micelles with bile salts to prevent the latter from damaging luminal epithelium. Bile flow requires canalicular secretion of both bile salts and phosphatidylcholine. MDR3 mutations are an established predisposing factor, found in 16% of ICP cases. More recently, studies have demonstrated involvement of BSEP mutations in at least 5% of cases. The V444A polymorphism of ABCB11 in particular may lead to ICP by causing a reduction in hepatic BSEP expression and consequently decreased bile salt export. Other notable mutations identified in ICP patients include ones in the farnesoid X receptor (FXR), a nuclear receptor in hepatocytes which activates transcription of MDR3 and BSEP upon binding intracellular bile acids, thereby increasing canalicular bile efflux. Mechanism Bile is secreted by the liver to aid in the digestion of fats. Bile formation begins in bile canaliculi that form between two adjacent surfaces of liver cells (hepatocytes) similar to the terminal branches of a tree. The canaliculi join each other to form larger and larger structures, sometimes referred to as the canals of Hering, which themselves join to form small bile ductules that have an epithelial surface. The ductules join to form bile ducts that eventually form either the right main hepatic duct that drains the right lobe of the liver, or the left main hepatic duct draining the left lobe of the liver. The two ducts join to form the common hepatic duct, which in turn joins the cystic duct from the gall bladder, to give the common bile duct. This duct then enters the duodenum at the ampulla of Vater. In cholestasis, bile accumulates in the hepatic parenchyma.One of the most common causes of extrahepatic, or obstructive cholestasis, is biliary obstruction. This is better known as choledocholithiasis where gallstones become stuck in the common bile duct. Mechanisms of drug-induced cholestasis Drugs may induce cholestasis by interfering with 1) hepatic transporters, 2) bile canaliculi dynamics, and/or 3) cell structure and protein localization. Hepatic transporters are essential for maintaining enterohepatic bile flow and bile acid homeostasis. Therefore, their direct inhibition by certain drugs may lead to cholestasis. Relevant transporters implicated include BSEP, MDR3, MRP2-4, and NTCP.Cholestasis can result from competitive inhibition of BSEP by several drugs, including cyclosporine A, rifampicin, nefazodone, glibenclamide, troglitazone, and bosentan. BSEP is the main transporter in hepatocytes responsible for exporting bile salts across the apical membrane into bile canaliculi. Therefore, inhibiting BSEP should cause cytotoxic bile salts to accumulate in hepatocytes, leading to liver injury and impaired bile flow. Indeed, there is a strong association between BSEP inhibition and cholestasis in humans, and BSEP inhibitors are shown to induce cholestasis in vitro. However, hepatocytes have safety mechanisms that can compensate for impaired canalicular bile efflux. In response to cholestasis, MRP3 and MRP4 on the basolateral membrane are upregulated to allow efflux of accumulated bile salts into portal blood. Similarly, MRP2 can accommodate additional bile flow across the apical membrane in cholestatic conditions. These compensatory mechanisms explain why some BSEP inhibitors do not cause cholestasis. On the contrary, contrast, drugs that inhibit both MRP3/4 and BSEP (e.g., rifampicin, troglitazone, bosentan) pose greater risk for cholestasisMDR3 is another key canalicular efflux transporter that is the target of inhibition by certain drugs. MDR3 secretes phosphatidylcholine into bile canaliculi, where it form micelles with bile salts to dissolve cholesterol as well as protect hepatocyte and cholangiocytes from damage by bile salts. MDR3 inhibition leads to low phospholipid concentrations in bile that damages cholangiocytes and leads to cholestasis. Antifungal azoles such itraconazole have been shown to inhibit both MDR3 and BSEP, thus giving them higher cholestatic potential. Other MDR3-inhibiting drugs are chlorpromazine, imipramine, haloperidol, ketoconazole, saquinavir, clotrimazole, ritonavir, and troglitazone.Another target for inhibition, MRP2 is an apical efflux transporter that mainly exports bilirubin glucuronide and glutathione into bile. However, MRP2 is also the preferential route of export for certain sulfated conjugated BAs (taurolithocholic acid and glycolithocholic acid), so its inhibition could contribute to cholestasis.On the hepatocyte basolateral membrane, Na+-taurocholate cotransporting peptide (NTCP) is the major transporter of conjugated bile acids. Enterohepatic bile flow requires the concerted activity of both NTCP and BSEP, which form the major route by which BAs enter and exit hepatocytes respectively. Therefore, NTCP inhibitors, such as cyclosporine A, ketoconazole, propranolol, furosemide, rifamycin, saquinavir, and ritonavir, should theoretically cause cholestasis by decreasing hepatocyte BA uptake. However, no relationship was found between NTCP inhibition and DIC risk, possibly because basolateral sodium-independent OATPs can partially compensate for bile salt uptake. Therefore, NTCP inhibition alone seems to be insufficient for causeing cholestasis. Indeed, the cholestatic effect of cyclosporine A relies on its inhibition of both NTCP and the compensatory OATP1B1.In addition to direct inhibition, drugs can also induce cholestasis by promoting downregulation and internalization of transporters. For example, cyclosporine A in rats was shown to induce BSEP internalization in addition to inhibition. Furthermore, human hepatocytes showed decreased expression of BSEP mRNA and protein following long-term exposure to metformin and tamoxifen, neither of which are direct BSEP inhibitors.Bile canaliculi dynamics refers to the contractile motion of bile canaliculi (ducts) required for bile flow. Cholestasis can result when drugs constrict or dilate bile canaliculi. Constrictors include chlorpromazine, nefazodone, troglitazone, perhexiline, metformin, cyclosporin A. These drugs activate the RhoA/Rho-kinase pathway, which inhibits myosin light chain phosphatase (MLCP), and in turn, increases myosin light chain phosphorylation by MLC kinase leading to constriction of bile canaliculi. Drugs that dilate canaliculi work by inhibiting MLCK or RhoA/Rho-kinase and include diclofenac, bosentan, entacapone, tacrolimus, cimetidine, and flucloxacillin. Constriction is more serious than dilation, as the former causes irreversible cell damage and death.Minor mechanisms that may contribute to DIC include aberrant paracellular permeability, membrane fluidity, and transporter localization. Tight junctions normally seal the gap between hepatocytes to prevent bile from diffusing out of the canaliculi. If a drug causes internalization of hepatocyte tight junctions, like rifampicin does in mice, bile flow may become impaired due to paracellular leakage. Membrane fluidity can affect bile flow by regulating the activity of hepatocyte Na+/K+-ATPase, which maintains the inwardly-directed Na+ gradient that drives BA uptake by apical NTCP. In rats, cyclosporine A was found to increase canalicular membrane fluidity and consequently reduce bile secretion. Bile flow was similarly reduced in rats as a result of alterations to basolateral membrane fluidity by ethinylestradiol and chlorpromazine. Lastly, some agents (rimpaficin and 17β-estradiol) were shown to hinder proper localization of hepatocyte transporters by interfering with the microtubules required for their insertion into plasma membranes. Diagnosis Cholestasis can be suspected when there is an elevation of both 5-nucleotidase and ALP enzymes. With a few exceptions, the optimal test for cholestasis would be elevations of serum bile acid levels. However, this is not normally available in most clinical settings necessitating the use of other biomarkers. If 5 nucleosidase and ALP enzymes are elevated, imaging studies such as computed tomography (CT) scan, ultrasound, and magnetic resonance imaging (MRI) are used to differentiate intrahepatic cholestasis from extrahepatic cholestasis. Additional imaging, laboratory testing, and biopsies might be conducted to identify the cause and extent of cholestasis. Biomarkers ALP enzymes are found abundantly within the bile canaliculi and bile. If a duct is obstructed, tight junctions permit migration of the ALP enzymes until the polarity is reversed and the enzymes are found on the whole of the cell membrane. Serum ALP levels exceeding 2-3 times the upper baseline value may be due to a variety of liver diseases. However, an elevation that exceeds 10 times the upper baseline limit is strongly indicative of either intrahepatic or extrahepatic cholestasis and requires further investigation. Cholestasis can be differentiated from other liver disorders by measuring the proportion of ALP to serum aminotransferases, where a greater proportion indicates a higher likelihood of cholestasis. Typically, aminotransferase enzymes are localized within hepatocytes and leak across the membrane upon damage. However, measurement of serum aminotransferase levels alone is not a good marker to determine cholestasis. In up to a third of patients, ALP levels may be elevated without the presence of cholestasis. As such, other biomarkers should be measured to corroborate findings. Measurement of 5 nucleosidase levels may be used to identify cholestasis in conjunction with ALP. Levels of ALP may rise within a few hours of cholestasis onset while 5 nucleosidase levels may take a few days. Many labs cannot measure 5 nucleosidase and ALP levels so, GGT may be measured in some cases. Abnormal GGT elevation may be attributable to a variety of factors. As such, GGT elevations lack the necessary specificity to be a useful confirmatory test for cholestasis.Importantly, conjugated hyperbilirubinemia is present in 80% of patients with extrahepatic cholestasis and 50% of patients with intrahepatic cholestasis. Given that many patients with hyperbilirubinemia may not have cholestasis, the measurement of bilirubin levels is not a good diagnostic tool for identifying cholestasis. In a later stage of cholestasis aspartate transaminase (AST), alanine transaminase (ALT) and unconjugated bilirubin may be elevated due to hepatocyte damage as a secondary effect of cholestasis. Imaging After determination using biomarkers, a variety of imaging studies may be used to differentiate between intrahepatic or extrahepatic cholestasis. Ultrasound is often used to identify the location of the obstruction but, is often insufficient in determining the level of biliary obstruction or its cause because it can pick up bowel gas that may interfere with readings. CT scans are not impacted by bowel gas and may also be more suitable for overweight patients. Typically, the cause of cholestasis and magnitude of obstruction is better diagnosed with CT compared to ultrasound. MRI scans provide similar information to CT scans but are more prone to interference from breathing or other bodily functions.Although CT, ultrasound, and MRI may help differentiate intrahepatic and extrahepatic cholestasis, the cause and extent of obstruction is best determined by cholangiography. Potential causes of extrahepatic cholestasis include obstructions outside the wall of the lumen, those outside the duct, and obstructions found in the duct lumen. Endoscopic retrograde cholangiography may be useful to visualize the extrahepatic biliary ducts. In case of anatomical anomalies, or if endoscopic retrograde cholangiography is unsuccessful, percutaneous transhepatic cholangiography may be used. CT or MRI-based cholangiography may also be useful, particularly in cases where additional interventions are not anticipated. Histopathology There is a significant overlap between cholestasis resulting from a hepatocellular origin and cholestasis caused by bile duct obstruction. Due to this, obstructive cholestasis can only be diagnosed after finding additional diagnostic signs that are specific to obstructive changes to the bile ducts or portal tracts. In both non-obstructive and obstructive cholestasis, there is an accumulation of substances that are typically secreted in the bile, as well as degeneration of hepatocytes. The most significant feature from a histopathological perspective includes pigmentation resulting from the retention of bilirubin. Under a microscope, the individual hepatocytes will have a brownish-green stippled appearance within the cytoplasm, representing bile that cannot get out of the cell. Pigmentation can involve regurgitation of bile into the sinusoidal spaces caused by phagocytosis from Kupffer cells, an accumulation of bilirubin within hepatocytes, and inspissated bile in the canaliculi. Most pigmentation and canaliculi dilation occurs in the perivenular region of the hepatic lobule. In chronic cases, this may extend into the periportal area.Hepatocyte necrosis is not a significant feature of cholestasis; however, apoptosis may often occur. Under the microscope, hepatocytes in the perivenular zone appear enlarged and flocculent. In cases of obstructive cholestasis, bile infarcts may be produced during the degeneration and necrosis of hepatocytes. Bile infarcts are marked by a large amount of pigmented tissue surrounded by a ring of necrotic hepatocytes. In some cases, hepatocyte degeneration is uncommon. E.g., with Alagille syndrome limited degeneration occurs, however, there may be a small amount of apoptosis and enlarged hepatocytes.Cholestasis is often marked by cholate statis, which are a set of changes that occur in the periportal hepatocytes. Cholate statis is more common in obstructive cholestasis compared to non-obstructive cholestasis. During the cholate statis process, hepatocytes first undergo swelling and then degeneration. Under the microscope, this is evident as a lucent cell periphery and enlarged cytoplasm around the nucleus. Oftentimes, Mallory bodies may also be found in the periportal areas. Due to the retention of bile, which contains copper, stains made for staining copper-associated protein can be used to visualize bile accumulation in the hepatocytes.Cholestatic liver cell rosettes may occur in children with chronic cholestasis. Histologically, this is evident as two or more hepatocytes in a pseudotubular fashion that encircle a segment of enlarged bile canaliculi. Children may also have giant hepatocytes present, which are characterized by a pigmented spongy appearance. Giant cell formation is likely caused by the detergent properties of bile salts causing a loss of the lateral membrane and joining of hepatocytes. In the case of Alagille syndrome, hepatocyte degeneration is uncommon. However, there may be a small amount of apoptosis and enlarged hepatocytes.In non-obstructive cholestasis, changes to the portal tracts are unlikely. However, it may occur in some unique situations. In the case of neutrophilic pericholangitis, neutrophils surround the portal ducts and obstruct them. Neutrophilic pericholangitis has a variety of causes including endotoxemia, Hodgkins disease, among others. Cholangitis lenta can also cause changes to the portal tracts. This occurs during chronic cases of sepsis and results in dilation of the bile ductules. Cholangitis lenta is likely a result of a stoppage of bile secretion and bile flow through the ductules. Back pressure created from obstructive cholestasis can cause dilation of the bile duct and biliary epithelial cell proliferation, mainly in the portal tracts. Portal tract edema may also occur as a result of bile retention, as well as periductular infiltration of neutrophils. If the obstruction is left untreated, it can lead to a bacterial infection of the biliary tree. Infection is mostly caused by coliforms and enterococci and is evident from a large migration of neutrophils to the duct lumina. This can result in the formation of a cholangitic abscess. With treatment, many of the histological features of cholestasis can be corrected once the obstruction is removed. If the obstruction is not promptly resolved, portal tract fibrosis can result. Even with treatment, some fibrosis may remain. Management Surgical management In cases involving obstructive cholestasis, the primary treatment includes biliary decompression. If bile stones are present in the common bile duct, an endoscopic sphincterotomy can be conducted either with or without placing a stent. To do this, a duodenoscope is placed by the endoscopist in the second portion of the duodenum. A catheter and guidewire is moved up into the common bile duct. A sphincterotome can then enlarge the ampulla of Vater and release the stones. Later, the endoscopist can place a stent in the common bile duct to soften any remaining stones and allow for bile drainage. If needed, a balloon catheter is available to remove any leftover stones. If these stones are too large with these methods, surgical removal may be needed. Patients can also request an elective cholecystectomy to prevent future cases of choledocholithiasis. In case of narrowing of the common bile duct, a stent can be placed after dilating the constriction to resolve the obstruction.The treatment approach for patients with obstructive cholestasis resulting from cancer varies based on whether they are a suitable candidate for surgery. In most cases, surgical intervention is the best option. For patients whom complete removal of the biliary obstruction is not possible, a combination of a gastric bypass and hepaticojejunostomy can be used. This can reestablish bile flow into the small intestine, thereby bypassing the blockage. In cases where a patient is not a suitable candidate for surgery, an endoscopic stent can be placed. If this is not possible or successful, a percutaneous transhepatic cholangiogram and percutaneous biliary drainage can be used to visualize the blockage and re-establish bile flow. Medical management A significant portion of patients with cholestasis (80%) will experience pruritus at some point during their disease. This is a condition that can severely decrease a patients quality of life as it can impact sleep, concentration, work ability, and mood. Many treatments exist, but how effective each option is depends on the patient and their condition. Assessment using a scale, such as a visual analogue scale or a 5-D itch scale will be useful to identify an appropriate treatment. Possible treatment options include antihistamines, ursodeoxycholic acid, and phenobarbital. Nalfurafine hydrochloride can also be used to treat pruritus caused by chronic liver disease and was recently approved in Japan for this purpose.Bile acid binding resins like cholestyramine are the most common treatment. Side effects of this treatment are limited and include constipation and bloating. Other commonly used treatments include rifampin, naloxone, and sertraline. In cholestatic liver disease, when bilirubin concentration starts to build up, a deficiency of fat soluble vitamins may also occur. To manage this, doses of vitamin A, D, E, and K are recommended to retain appropriate vitamin levels. Cholestatic liver disease can impact lipids, and possibly lead to dyslipidemia, which may present a risk for coronary artery disease. Statins and fibrates are generally used as lipid lowering therapy to treat patients with cholestatic liver disease. For intrahepatic cholestasis in pregnant women, S-adenosylmethionine has proven to be an effective treatment. Dexamethasone is a viable treatment in regards to the symptom of intensive itching. Research directions Primary sclerosing cholangitis (PSC) is one of the most common cholestatic liver diseases, yet treatment options remain limited. Treatment for primary biliary cholangitis (PBC) is often done with ursodeoxycholic acid (UDCA) and with no other suitable alternative, it poses a problem for those that are not responsive to (UDCA). However, with advancing technology in the molecular biochemistry field and higher understanding of bile acid regulation, novel pharmacological treatments have been considered. For patients with primary biliary cholangitis, current guidelines recommend about 13–15 mg/kg of ursodeoxycholic acid as a first line treatment. This drug stimulates biliary bicarbonate secretion, improves survival without having to resort to a liver transplantation, and is very well tolerated— making it an ideal treatment. However, around 40% of patients with primary biliary cholangitis are not responsive to UDCA.Obeticholic acid has been approved by the US Food and Drug Administration for PBC in 2016 after experiments found beneficial improvements for the liver in half of patients with inadequate response to UDCA.Primary sclerosing cholangitis is a challenging liver disease as treatment options are limited. There is still uncertainty about the efficacy of ursodeoxycholic acid for PSC and researchers offer conflicting recommendations. One study found UDCA had improved biochemical functions but did lower the rate for death or transplant-free survival. Peroxisomes receptor agonists An important regulator in bile acid homeostasis is the alpha and delta isoforms of the peroxisome proliferator-activated receptor (PPARα, PPARδ). The function of PPARα is that it promotes bile acid excretion and lowers inflammation by acting on nuclear transcription factors. A well known agonist are fibrates and in the clinical trials, there was a significant biochemical response in most patients. A combination therapy with bezafibrate showed remarkable biochemical improvement, with 67% of patients normalizing their alkaline phosphatase levels. Another study of 48 patients with PBC found a combination of bezafibrate and UDCA showed a decrease of alkaline phosphatase in all patients. Further, the study found those treated had a marked relief in pruritus.However, fibrates are associated with a number of adverse effects including arthritis, leg edema, polydipsia, and myalgias. Elevations of creatinine and creatinine phosphokinase were also found over a long term use. Farnesoid X-receptor agonist A new novel treatment option is the farnesoid X receptor is responsible for regulating bile acid homeostasis. An agonist of this nuclear hormone receptor is seen as a possible treatment as it can downregulate bile acid synthesis and reabsorption. Further the farnesoid X receptor is partly responsible for lipid and glucose homeostasis, as well as pathogen recognition. An agonist for the farnesoid X receptor can therefore lead to an anti-cholestatic environment to minimize the effect of toxic bile acids on the liver. A candidate agonist for the farnesoid X receptor is obeticholic acid with experiments showing it has very strong affinity. A worry though is despite benefits in the biochemical pathways, pruritus was more intense and prevalent than the placebo. A titration strategy may help to mitigate pruritus, but FDA approval for obeticholic acid is currently unlikely. In fact, in February 2018, the FDA gave a black box warning for OCA. A recent study did find that if the drug is given with UDCA, the incidence for cirrhosis and liver transplants decreases.Another target that is being looked into is the All-trans retinoic acid (ATRA), an activator for the retinoid X receptor. In vitro and animal studies found ATRA had lowered the amount of bile acid and decreased hepatic inflammation. 24-norursodeoxycholic acid A recent scientific breakthrough for cholestasis that has allowed us to evaluate a new treatment option is that a hydrophilic environment and bicarbonate production protects hepatocytes from bile acid. The novel agent norUDCA (24-norursodeoxycholic acid) can be passively absorbed by cholangiocytes. This leads to bicarbonate production and an environment that is less toxic. Mouse models have found promising results with norUDCA with the drug showing antiproliferative and anti-inflammatory properties. A recent clinical trial found norUDCA had significant dose-dependent reductions for ALP levels. This makes norUDCA a viable possibility to look into as it clearly plays a significant role in the treatment of cholestasis. Immunomodulatory treatments In PBC, the liver is filled with T cells and B cells that contribute to a worsening condition. Therefore, some treatments are looking into targeting the antigens of these immune cells. The monoclonal antibody Rituximab targets the CD20 antigen on the B cells, and is already used in a wide array of other rheumatologic diseases. In an open-label study, six patients that were unresponsive to UDCA had improvement in ALP levels after rituximab infusions. However, the efficacy of rituximab is still uncertain, and awaits further studies and trials. PBC can also lead to higher levels of interleukin 12 and interleukin 23. This was what motivated researches to look at the viability of ustekinumab, a monoclonal antibody targeted against interleukin 12 and 23. An experiment found though it did not significantly improve serum ALP levels. The researchers were further even criticized for placing patients at risk by allowing them to move to advanced disease stages where immunomodulatory therapies may not even be an option. Gut microbiome In several chronic liver diseases, the gut microbiome, which regulates both the innate and adaptive immune systems, is implicated. This can result in abnormal immunological development and an accumulation of primary bile acids. Using this information a bile-acid–intestinal-microbiota–cholestasis triangle is thought to be involved in the pathogenesis of PBC and PSC. After all, bile acids do modulate the gut microbiota; a disturbance here can result in development and progression of cholestasis. This information has prompted researchers into manipulating the microbiota via antibiotics and probiotics for new treatment options. Some antibiotics examined for PSC include vancomycin, which has extensively studied and reviewed. The usage of the drug is found along with a significant decrease in ALP levels, although the long term clinical benefit is unknown.As biochemistry technology becomes more advanced, promising targets have appeared, prompting numerous studies and trials to evaluate the feasibility. Fibrates, FXR agonists, and norUDCA are all innovative therapies for cholestasis. See also Jaundice Liver function tests Lipoprotein-X - an abnormal low density lipoprotein found in cholestasis Intrahepatic cholestasis of pregnancy Progressive familial intrahepatic cholestasis Feathery degeneration - a histopathologic finding associated with cholestasis References == External links ==

Can you describe Cerebral infarction, to me Aarogya

Cerebral infarction

A cerebral infarction is the pathologic process that results in an area of necrotic tissue in the brain (cerebral infarct). It is caused by disrupted blood supply (ischemia) and restricted oxygen supply (hypoxia), most commonly due to thromboembolism, and manifests clinically as ischemic stroke. In response to ischemia, the brain degenerates by the process of liquefactive necrosis. Classification There are various classification systems for a cerebral infarction, some of which are described below. The Oxford Community Stroke Project classification (OCSP, also known as the Bamford or Oxford classification) relies primarily on the initial symptoms. Based on the extent of the symptoms, the stroke episode is classified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of the stroke, the area of the brain affected, the underlying cause, and the prognosis. The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinical symptoms as well as results of further investigations; on this basis, a stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) embolism of cardiac origin, (3) occlusion of a small blood vessel, (4) other determined cause, (5) undetermined cause (two possible causes, no cause identified, or incomplete investigation). Symptoms Symptoms of cerebral infarction are determined by the parts of the brain affected. If the infarct is located in the primary motor cortex, contralateral hemiparesis is said to occur. With brainstem localization, brainstem syndromes are typical: Wallenbergs syndrome, Webers syndrome, Millard–Gubler syndrome, Benedikt syndrome or others. Infarctions will result in weakness and loss of sensation on the opposite side of the body. Physical examination of the head area will reveal abnormal pupil dilation, light reaction and lack of eye movement on opposite side. If the infarction occurs on the left side brain, speech will be slurred. Reflexes may be aggravated as well. Risk factors Major risk factors for cerebral infarction are generally the same as for atherosclerosis. These include high blood pressure, diabetes mellitus, tobacco smoking, obesity, and dyslipidemia. The American Heart Association/American Stroke Association (AHA/ASA) recommends controlling these risk factors in order to prevent stroke. The AHA/ASA guidelines also provide information on how to prevent stroke if someone has more specific concerns, such as sickle-cell disease or pregnancy. It is also possible to calculate the risk of stroke in the next decade based on information gathered through the Framingham Heart Study. Pathophysiology Cerebral infarction is caused by a disruption to blood supply that is severe enough and long enough in duration to result in tissue death. The disruption to blood supply can come from many causes, including: Thrombosis (obstruction of a blood vessel by a blood clot forming locally) Embolism (obstruction due to an embolus from elsewhere in the body), Systemic hypoperfusion (general decrease in blood supply, e.g., in shock) Cerebral venous sinus thrombosis. Unusual causes such as gas embolism from rapid ascents in scuba diving.Even in cases where there is a complete blockage to blood flow of a major blood vessel supplying the brain, there is typically some blood flow to the downstream tissue through collateral blood vessels, and the tissue can typically survive for some length of time that is dependent upon the level of remaining blood flow. If blood flow is reduced enough, oxygen delivery can decrease enough to cause the tissue to undergo the ischemic cascade. The ischemic cascade leads to energy failure that prevents neurons from sufficiently moving ions through active transport which leads the neurons to first cease firing, then depolarize leading to ion imbalances that cause fluid inflows and cellular edema, then undergo a complex chain of events that can lead to cell death through one or more pathways. Diagnosis Computed tomography (CT) and MRI scanning will show damaged area in the brain, showing that the symptoms were not caused by a tumor, subdural hematoma or other brain disorder. The blockage will also appear on the angiogram. In people who die of cerebral infarction, an autopsy of stroke may give a clue about the duration from the infarction onset until the time of death. Treatment In the last decade, similar to myocardial infarction treatment, thrombolytic drugs were introduced in the therapy of cerebral infarction. The use of intravenous rtPA therapy can be advocated in patients who arrive to stroke unit and can be fully evaluated within 3 hours of the onset. If cerebral infarction is caused by a thrombus occluding blood flow to an artery supplying the brain, definitive therapy is aimed at removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). The more rapidly blood flow is restored to the brain, the fewer brain cells die. In increasing numbers of primary stroke centers, pharmacologic thrombolysis with the drug tissue plasminogen activator (tPA), is used to dissolve the clot and unblock the artery. Another intervention for acute cerebral ischaemia is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. Mechanical embolectomy devices have been demonstrated effective at restoring blood flow in patients who were unable to receive thrombolytic drugs or for whom the drugs were ineffective, though no differences have been found between newer and older versions of the devices. The devices have only been tested on patients treated with mechanical clot embolectomy within eight hours of the onset of symptoms. Angioplasty and stenting have begun to be looked at as possible viable options in treatment of acute cerebral ischaemia. In a systematic review of six uncontrolled, single-center trials, involving a total of 300 patients, of intra-cranial stenting in symptomatic intracranial arterial stenosis, the rate of technical success (reduction to stenosis of <50%) ranged from 90 to 98%, and the rate of major peri-procedural complications ranged from 4-10%. The rates of restenosis and/or stroke following the treatment were also favorable. This data suggests that a large, randomized controlled trial is needed to more completely evaluate the possible therapeutic advantage of this treatment. If studies show carotid stenosis, and the patient has residual function in the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after cerebral infarction. Carotid endarterectomy is also indicated to decrease the risk of cerebral infarction for symptomatic carotid stenosis (>70 to 80% reduction in diameter).In tissue losses that are not immediately fatal, the best course of action is to make every effort to restore impairments through physical therapy, cognitive therapy, occupational therapy, speech therapy and exercise. Permissive hypertension - allowing for higher than normal blood pressures in the acute phase of cerebral infarction - can be used to encourage perfusion to the penumbra. References == External links ==

Aarogya, Please give me a short description about Barretts esophagus

Barretts esophagus

Barretts esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells that are normally present only in the small intestine and large intestine. This change is considered to be a premalignant condition because it is associated with a high incidence of further transition to esophageal adenocarcinoma, an often-deadly cancer.The main cause of Barretts esophagus is thought to be an adaptation to chronic acid exposure from reflux esophagitis. Barretts esophagus is diagnosed by endoscopy: observing the characteristic appearance of this condition by direct inspection of the lower esophagus; followed by microscopic examination of tissue from the affected area obtained from biopsy. The cells of Barretts esophagus are classified into four categories: nondysplastic, low-grade dysplasia, high-grade dysplasia, and frank carcinoma. High-grade dysplasia and early stages of adenocarcinoma may be treated by endoscopic resection or radiofrequency ablation. Later stages of adenocarcinoma may be treated with surgical resection or palliation. Those with nondysplastic or low-grade dysplasia are managed by annual observation with endoscopy, or treatment with radiofrequency ablation. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.The incidence of esophageal adenocarcinoma has increased substantially in the Western world in recent years. The condition is found in 5–15% of patients who seek medical care for heartburn (gastroesophageal reflux disease, or GERD), although a large subgroup of patients with Barretts esophagus are asymptomatic. The condition is named after surgeon Norman Barrett (1903–1979) even though the condition was originally described by Philip Rowland Allison in 1946. Signs and symptoms The change from normal to premalignant cells indicate Barretts esophagus does not cause any particular symptoms. Barretts esophagus, however, is associated with these symptoms: frequent and longstanding heartburn trouble swallowing (dysphagia) vomiting blood (hematemesis) pain under the sternum where the esophagus meets the stomach pain when swallowing (odynophagia), which can lead to unintentional weight lossThe risk of developing Barretts esophagus is increased by central obesity (vs. peripheral obesity). The exact mechanism is unclear. The difference in distribution of fat among men (more central) and women (more peripheral) may explain the increased risk in males. Pathophysiology Barretts esophagus occurs due to chronic inflammation. The principal cause of chronic inflammation is gastroesophageal reflux disease, GERD (UK: GORD). In this disease, acidic stomach, bile, and small intestine and pancreatic contents cause damage to the cells of the lower esophagus. In turn, this provokes an advantage for cells more resistant to these noxious stimuli in particular HOXA13-expressing stem cells that are characterised by distal (intestinal) characteristics and outcompete the normal squamous cells.This mechanism also explains the selection of HER2/neu (also called ERBB2) and the overexpressing (lineage-addicted) cancer cells during the process of carcinogenesis, and the efficacy of targeted therapy against the Her-2 receptor with trastuzumab (Herceptin) in the treatment of adenocarcinomas at the gastroesophageal junction. Researchers are unable to predict who with heartburn will develop Barretts esophagus. While no relationship exists between the severity of heartburn and the development of Barretts esophagus, a relationship does exist between chronic heartburn and the development of Barretts esophagus. Sometimes, people with Barretts esophagus have no heartburn symptoms at all. Some anecdotal evidence indicates those with the eating disorder bulimia are more likely to develop Barretts esophagus because bulimia can cause severe acid reflux, and because purging also floods the esophagus with acid. However, a link between bulimia and Barretts esophagus remains unproven.During episodes of reflux, bile acids enter the esophagus, and this may be an important factor in carcinogenesis. Individuals with GERD and BE are exposed to high concentrations of deoxycholic acid that has cytotoxic effects and can cause DNA damage. Diagnosis Both macroscopic (from endoscopy) and microscopic positive findings are required to make a diagnosis. Barretts esophagus is marked by the presence of columnar epithelia in the lower esophagus, replacing the normal squamous cell epithelium—an example of metaplasia. The secretory columnar epithelium may be more able to withstand the erosive action of the gastric secretions; however, this metaplasia confers an increased risk of adenocarcinoma. Screening Screening endoscopy is recommended among males over the age of 60 who have reflux symptoms that are of long duration and not controllable with treatment. Among those not expected to live more than 5 years screening is not recommended.The Seattle protocol is used commonly in endoscopy to obtain endoscopic biopsies for screening, taken every 1 to 2 cm from the gastroesophageal junction. Since the COVID-19 pandemic In Scotland, the local NHS started using a swallowable sponge (Cytosponge) in hospitals to collect cell samples for diagnosis. Preliminary studies have shown this diagnostic test to be a useful tool for screening people with heartburn symptoms and improved diagnosis. Intestinal metaplasia The presence of goblet cells, called intestinal metaplasia, is necessary to make a diagnosis of Barretts esophagus. This frequently occurs in the presence of other metaplastic columnar cells, but only the presence of goblet cells is diagnostic. The metaplasia is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope to determine whether cells are gastric or colonic in nature. Colonic metaplasia is usually identified by finding goblet cells in the epithelium and is necessary for the true diagnosis.Many histologic mimics of Barretts esophagus are known (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar [gastric] type mucin simulates the acid mucin true goblet cells). Assessment of relationship to submucosal glands and transitional-type epithelium with examination of multiple levels through the tissue may allow the pathologist to reliably distinguish between goblet cells of submucosal gland ducts and true Barretts esophagus (specialized columnar metaplasia). The histochemical stain Alcian blue pH 2.5 is also frequently used to distinguish true intestinal-type mucins from their histologic mimics. Recently, immunohistochemical analysis with antibodies to CDX-2 (specific for mid and hindgut intestinal derivation) has also been used to identify true intestinal-type metaplastic cells. The protein AGR2 is elevated in Barretts esophagus and can be used as a biomarker for distinguishing Barrett epithelium from normal esophageal epithelium.The presence of intestinal metaplasia in Barretts esophagus represents a marker for the progression of metaplasia towards dysplasia and eventually adenocarcinoma. This factor combined with two different immunohistochemical expression of p53, Her2 and p16 leads to two different genetic pathways that likely progress to dysplasia in Barretts esophagus. Also intestinal metaplastic cells can be positive for CK 7+/CK20-. Epithelial dysplasia After the initial diagnosis of Barretts esophagus is rendered, affected persons undergo annual surveillance to detect changes that indicate higher risk to progression to cancer: development of epithelial dysplasia (or "intraepithelial neoplasia"). Among all metaplastic lesions, around 8% were associated with dysplasia. particularly a recent study demonstrated that dysplastic lesions were located mainly in the posterior wall of the esophagus.Considerable variability is seen in assessment for dysplasia among pathologists. Recently, gastroenterology and GI pathology societies have recommended that any diagnosis of high-grade dysplasia in Barrett be confirmed by at least two fellowship-trained GI pathologists prior to definitive treatment for patients. For more accuracy and reproducibility, it is also recommended to follow international classification systems, such as the "Vienna classification" of gastrointestinal epithelial neoplasia (2000). Management Many people with Barretts esophagus do not have dysplasia. Medical societies recommend that if a patient has Barretts esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.Endoscopic surveillance of people with Barretts esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).The risk of malignancy is highest in the United States in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barretts esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barretts esophagus and dysplasia and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation is at least 90% effective to completely clear Barretts esophagus and dysplasia, with durability of up to five years and a favorable safety profile.Anti-reflux surgery has not been proven to prevent esophageal cancer. However, the indication is that proton pump inhibitors are effective in limiting the progression of esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. A recent five-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor.There is presently no reliable way to determine which patients with Barretts esophagus will go on to develop esophageal cancer, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.In a variety of studies, nonsteroidal anti-inflammatory drugs (NSAIDS) such as low-dose aspirin (75-300 mg/day) have shown evidence of preventing esophageal cancer in people with Barretts esophagus. Prognosis Barretts esophagus is a premalignant condition, not a malignant one. Its malignant sequela, esophagogastric junctional adenocarcinoma, has a mortality rate of over 85%. The risk of developing esophageal adenocarcinoma in people who have Barretts esophagus has been estimated to be 6–7 per 1000 person-years, but a cohort study of 11,028 patients from Denmark published in 2011 showed an incidence of only 1.2 per 1000 person-years (5.1 per 1000 person-years in patients with dysplasia, 1.0 per 1000 person-years in patients without dysplasia).The relative risk of esophageal adenocarcinoma is about ten times higher in those with Barretts esophagus than the general population. Most patients with esophageal carcinoma survive less than one year. Epidemiology The incidence in the United States among Caucasian men is eight times the rate among Caucasian women and five times greater than African American men. Overall, the male to female ratio of Barretts esophagus is 10:1. Several studies have estimated the prevalence of Barretts esophagus in the general population to be 1.3% to 1.6% in two European populations (Italian and Swedish), and 3.6% in a Korean population. History The condition is named after Australian thoracic surgeon Norman Barrett (1903–1979), who in 1950 argued that "ulcers are found below the squamocolumnar junction ... represent gastric ulcers within a pouch of stomach … drawn up by scar tissue into the mediastinum ... representing an example of a congenital short esophagus". In contrast, Philip Rowland Allison and Alan Johnstone argued that the condition related to the "esophagus lined with gastric mucous membrane and not intra-thoracic stomach as Barrett mistakenly believed." Philip Allison, cardiothoracic surgeon and Chair of Surgery at the University of Oxford, suggested "calling the chronic peptic ulcer crater of the esophagus a Barretts ulcer", but added this name did not imply agreement with "Barretts description of an esophagus lined with gastric mucous membrane as stomach." Bani-Hani KE and Bani-Hani KR argue that the terminology and definition of Barretts esophagus is surrounded by extraordinary confusion unlike most other medical conditions and that [t]he use of the eponym “Barrett’s” to describe [the condition] is not justified from a historical point of view. Bani-Hani KE and Bani-Hani KR investigated the historical aspects of the condition and found they could establish how little Norman Barrett had contributed to the core concept of this condition in comparison to the contributions of other investigators, particularly the contribution of Philip Allison.A further association was made with adenocarcinoma in 1975. References External links Barretts esophagus at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Barretts esophagus Video Overview Archived 2012-05-10 at the Wayback Machine and Barretts esophagus Health Information at Mayo Clinic

Do you know what is Neutropenic enterocolitis, Aarogya

Neutropenic enterocolitis

Neutropenic enterocolitis is inflammation of the cecum (part of the large intestine) that may be associated with infection. It is particularly associated with neutropenia, a low level of neutrophil granulocytes (the most common form of white blood cells) in the blood. Signs and symptoms Signs and symptoms of typhlitis may include diarrhea, a distended abdomen, fever, chills, nausea, vomiting, and abdominal pain or tenderness. Cause The condition is usually caused by Gram-positive enteric commensal bacteria of the gut (gut flora). Clostridium difficile is a species of Gram-positive bacteria that commonly causes severe diarrhea and other intestinal diseases when competing bacteria are wiped out by antibiotics, causing pseudomembranous colitis, whereas Clostridium septicum is responsible for most cases of neutropenic enterocolitis.Typhlitis most commonly occurs in immunocompromised patients, such as those undergoing chemotherapy, patients with AIDS, kidney transplant patients, or the elderly. Diagnosis Typhlitis is diagnosed with a radiograph CT scan showing thickening of the cecum and "fat stranding". Treatment Typhlitis is a medical emergency and requires prompt management. Untreated typhlitis has a poor prognosis, particularly if associated with pneumatosis intestinalis (air in the bowel wall) and/or bowel perforation, and has significant morbidity unless promptly recognized and aggressively treated.Successful treatment hinges on: Early diagnosis provided by a high index of suspicion and the use of CT scanning Nonoperative treatment for uncomplicated cases Empiric antibiotics, particularly if the patient is neutropenic or at other risk of infection.In rare cases of prolonged neutropenia and complications such as bowel perforation, neutrophil transfusions can be considered but have not been studied in a randomized control trial. Elective right hemicolectomy may be used to prevent recurrence but is generally not recommended"...The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however," as based on studies from the 1980s Prognosis Inflammation can spread to other parts of the gut in patients with typhlitis. The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation. More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death . See also Colitis References == External links ==

Give me a short description about Hemorrhagic gastroenteritis , Aarogya

Hemorrhagic gastroenteritis

Hemorrhagic gastroenteritis (HGE) is a disease of dogs characterized by sudden vomiting and bloody diarrhea. The symptoms are usually severe, and HGE can be fatal if not treated. HGE is most common in young adult dogs of any breed, but especially small dogs such as the Toy Poodle and Miniature Schnauzer. It is not contagious. Cause The cause is uncertain. Suspected causes include abnormal responses to bacteria or bacterial endotoxin, or a hypersensitivity to food. Pathologically there is an increase in the permeability of the intestinal lining and a leakage of blood and proteins into the bowel. Clostridium perfringens has been found in large numbers in the intestines of many affected dogs. Clinical signs Profuse vomiting is usually the first symptom, followed by depression and bloody diarrhea with a foul odor. Severe hypovolemia (low blood volume) is one of the hallmarks of the disease, and severe hemoconcentration (concentrated blood) is considered necessary for diagnosis. The progression of HGE is so rapid that hypovolemic shock and death can occur within 24 hours. Disseminated intravascular coagulation (DIC) is a possible sequela of HGE. As a result, this disease can cause severe damage. Diagnosis Clinical signs of HGE and canine parvovirus (CPV) are similar enough that they need to be differentiated. It may or may not be detected by a high or low white blood cell count, and there may be a low hematocrit. A negative fecal parvovirus test is sometimes necessary to completely rule out CPV. Other potential causes of vomiting and diarrhea, white foam from the mouth include gastrointestinal parasites, bacterial infections including E. coli, Campylobacter, or Salmonella, protozoal infections such as coccidiosis or giardiasis, and gastrointestinal cancer. Treatment The most important aspect of treatment of HGE is intravenous fluid therapy to replace lost fluid volume. The vomiting and diarrhea are treated symptomatically and will usually resolve after one to two days. Antibiotics targeting C. perfringens are also used but recent studies have shown no difference in outcome or survival rate between patients given antibiotics and those not when no signs of sepsis were present. In other words, if there are no signs of sepsis, antibiotics will not hasten a recovery or improve outcome. With prompt, aggressive treatment, the prognosis is good. There is less than 10 percent mortality with treatment, but 10 to 15 percent of cases will recur. See also Gastroenteritis == References ==

Hi Aarogya, could you help me understand about Wheal

Wheal

Wheal may refer to: Wheals, a type of skin lesion Brad Wheal (born 1996), British cricketer Donald James Wheal (1931–2008), British British television writer, novelist and non-fiction writer David John Wheal, Australian businessman "The Wheal", a 1987 song by Coil See also All pages with titles containing Wheal Mining in Cornwall and Devon, includes mines whose names include Wheal Wheel (disambiguation)

Would you describe Fasciculation, to me Aarogya

Fasciculation

A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions. When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome. Diagnosis The most effective way to detect fasciculations may be surface electromyography (EMG). Surface EMG is more sensitive than needle electromyography and clinical observation in the detection of fasciculation in people with amyotrophic lateral sclerosis.Deeper areas of contraction can be detected by electromyography (EMG) testing, though they can happen in any skeletal muscle in the body. Fasciculations arise as a result of spontaneous depolarization of a lower motor neuron leading to the synchronous contraction of all the skeletal muscle fibers within a single motor unit. An example of normal spontaneous depolarization is the constant contractions of cardiac muscle, causing the heart to beat. Usually, intentional movement of the involved muscle causes fasciculations to cease immediately, but they may return once the muscle is at rest again. Tics must also be distinguished from fasciculations. Small twitches of the upper or lower eyelid, for example, are not tics, because they do not involve a whole muscle, rather are twitches of a few muscle fibre bundles, that are not suppressible. Causes Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons. They are encountered by up to 70% of all healthy people, though for most, it is quite infrequent. In some cases, the presence of fasciculations can be annoying and interfere with quality of life. If a neurological examination is otherwise normal and EMG testing does not indicate any additional pathology, a diagnosis of benign fasciculation syndrome is usually made. Risk factors Risk factors for benign fasciculations are age, stress, fatigue, and strenuous exercise. Fasciculations can be caused by anxiety, caffeine or alcohol and thyroid disease. Magnesium deficiency is a common cause of fasciculation.Other factors may include the use of anticholinergic drugs over long periods. In particular, these include ethanolamines such as diphenhydramine (brand names Benadryl, Dimedrol, Daedalon and Nytol), used as an antihistamine and sedative, and dimenhydrinate (brand names Dramamine, Driminate, Gravol, Gravamin, Vomex, and Vertirosan) for nausea and motion sickness. Persons with benign fasciculation syndrome (BFS) may experience paraesthesia (especially numbness) shortly after taking such medication; fasciculation episodes begin as the medication wears off. Stimulants can cause fasciculations directly. These include caffeine, pseudoephedrine (Sudafed), amphetamines, and the asthma bronchodilator salbutamol (brand names Proventil, Combivent, Ventolin). Medications used to treat attention deficit disorder (ADHD) often contain stimulants as well, and are common causes of benign fasciculations. Since asthma and ADHD are much more serious than the fasciculations themselves, this side effect may have to be tolerated by the patient after consulting a physician or pharmacist. The depolarizing neuromuscular blocker succinylcholine causes fasciculations. It is a normal side effect of the drugs administration, and can be prevented with a small dose of a nondepolarizing neuromuscular blocker prior to the administration of succinylcholine, often 10% of a nondepolarizing NMBs induction dose. Even if a drug such as caffeine causes fasciculations, that does not necessarily mean it is the only cause. For example, a very slight magnesium deficiency by itself (see below) might not be enough for fasciculations to occur, but when combined with caffeine, the two factors together could be enough. Treatment Reducing stress and anxiety is therefore another useful treatment.There is no proven treatment for fasciculations in people with ALS. Among patients with ALS, fasciculation frequency is not associated with the duration of ALS and is independent of the degree of limb weakness and limb atrophy. No prediction of ALS disease duration can be made based on fasciculation frequency alone. Epidemiology Fasciculations are observed more often in males, and clinicians are overrepresented in study samples. See also Blepharospasm Carnitine palmitoyltransferase II deficiency Myokymia References == External links ==

Aarogya what is Colorectal polyp

Colorectal polyp

A colorectal polyp is a polyp (fleshy growth) occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer.Colorectal polyps are often classified by their behaviour (i.e. benign vs. malignant) or cause (e.g. as a consequence of inflammatory bowel disease). They may be benign (e.g. hyperplastic polyp), pre-malignant (e.g. tubular adenoma) or malignant (e.g. colorectal adenocarcinoma). Signs and symptoms Colorectal polyps are not usually associated with symptoms. When they occur, symptoms include bloody stools; changes in frequency or consistency of stools (such as a week or more of constipation or diarrhoea); and fatigue arising from blood loss. Anemia arising from iron deficiency can also present due to chronic blood loss, even in the absence of bloody stools. Another symptom may be an increased mucus production especially those involving villous adenomas. Copious production of mucous causes loss of potassium that can occasionally result in symptomatic hypokalemia. Occasionally, if a polyp is big enough to cause a bowel obstruction, there may be nausea, vomiting and severe constipation. Structure Polyps are either pedunculated (attached to the intestinal wall by a stalk) or sessile (grow directly from the wall).: 1342  In addition to the gross appearance categorization, they are further divided by their histologic appearance as tubular adenoma which are tubular glands, villous adenoma which are long finger like projections on the surface, and tubulovillous adenoma which has features of both.: 1342 Genetics Hereditary syndromes causing increased colorectal polyp formation include: Familial adenomatous polyposis (FAP) Hereditary nonpolyposis colorectal cancer Peutz–Jeghers syndrome Juvenile polyposis syndromeSeveral genes have been associated with polyposis, such as GREM1, MSH3, MLH3, NTHL1, RNF43 and RPS20. Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is a form of hereditary cancer syndrome involving the APC gene located on chromosome q521. The syndrome was first described in 1863 by Virchow on a 15-year-old boy with multiple polyps in his colon. The syndrome involves development of multiple polyps at an early age and those left untreated will all eventually develop cancer. The gene is expressed 100% in those with the mutation and it is autosomal dominant. 10% to 20% of patients have negative family history and acquire the syndrome from spontaneous germline mutation. The average age of newly diagnosed patient is 29 and the average age of newly discovered colorectal cancer is 39. It is recommended that those affected undergo colorectal cancer screening at younger age with treatment and prevention are surgical with removal of affected tissues. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) is a hereditary colorectal cancer syndrome. It is the most common hereditary form of colorectal cancer in the United States and accounts for about 3% of all cases of cancer. It was first recognized by Alder S. Warthin in 1885 at the University of Michigan. It was later further studied by Henry Lynch who recognized an autosomal dominant transmission pattern with those affected having relatively early onset of cancer (mean age 44 years), greater occurrence of proximal lesions, mostly mucinous or poorly differentiated adenocarcinoma, greater number of synchronous and metachronous cancer cells, and good outcome after surgical intervention. The Amsterdam Criteria was initially used to define Lynch syndrome before the underlying genetic mechanism had been worked out. The Criteria required that the patient has three family members all first-degree relatives with colorectal cancer that involves at least two generations with at least one affected person being younger than 50 years of age when the diagnosis was made. The Amsterdam Criteria is too restrictive and was later expanded to include cancers of endometrial, ovarian, gastric, pancreatic, small intestinal, ureteral, and renal pelvic origin. The increased risk of cancer seen in patients with by the syndrome is associated with dysfunction of DNA repair mechanism. Molecular biologists have linked the syndrome to specific genes such as hMSH2, hMSH1, hMSH6, and hPMS2. Peutz–Jeghers syndrome Peutz–Jeghers syndrome is an autosomal dominant syndrome that presents with hamartomatous polyps, which are disorganized growth of tissues of the intestinal tract, and hyperpigmentation of the interlining of the mouth, lips and fingers. The syndrome was first noted in 1896 by Hutchinson, and later separately described by Peutz, and then again in 1940 by Jeghers. The syndrome is associated with malfunction of serine-threonine kinase 11 or STK 11 gene, and has a 2% to 10% increase in risk of developing cancer of the intestinal tract. The syndrome also causes increased risk of extraintestinal cancer such as that involving breast, ovary, cervix, fallopian tubes, thyroid, lung, gallbladder, bile ducts, pancreas, and testicles. The polyps often bleeds and may cause obstruction that would require surgery. Any polyps larger than 1.5 cm needs removal and patients should be monitored closely and screen every 2 years for malignancy. Juvenile polyposis syndrome Juvenile polyposis syndrome is an autosomal dominant syndrome characterized by increased risk of cancer of intestinal tract and extraintestinal cancer. It often presents with bleeding and obstruction of the intestinal tract along with low serum albumin due to protein loss in the intestine. The syndrome is linked to malfunction of SMAD4 a tumor suppression gene that is seen in 50% of cases. Individuals with multiple juvenile polyps have at least 10% chance of developing malignancy and should undergo abdominal colectomy with ileorectal anastomosis, and close monitoring via endoscopy of rectum. For individuals with few juvenile polyps, patients should undergo endoscopic polypectomy. Types Colorectal polyps can broadly be classified as follows: hyperplastic, neoplastic (adenomatous & malignant), hamartomatous and, inflammatory. Comparison table Hyperplastic polyp Most hyperplastic polyps are found in the distal colon and rectum. They have no malignant potential, which means that they are no more likely than normal tissue to eventually become a cancer. Neoplastic polyp A neoplasm is a tissue whose cells have lost normal differentiation. They can be either benign growths or malignant growths. The malignant growths can either have primary or secondary causes. Adenomatous polyps are considered precursors to cancer and cancer becomes invasive once malignant cells cross the muscularis mucosa and invade the cells below. Any cellular changes seen above the lamina propria are considered non-invasive and are labeled atypia or dysplasia. Any invasive carcinoma that has penetrated the muscularis mocos has the potential for lymph node metastasis and local recurrence which will require more aggressive and extensive resection. The Haggitts criteria is used for classification of polyps containing cancer and is based on the depth of penetration. The Haggitts criteria has level 0 through level 4, with all invasive carcinoma of sessile polyp variant by definition being classified as level 4. Level 0: Cancer does not penetrate through the muscularis mucosa. Level 1: Cancer penetrates through the muscularis mucosa and invades the submucosa below but is limited to the head of the polyp. Level 2: Cancer invades through with involvement of the neck of polyp. Level 3: Cancer invades through with involvement of any parts of the stalk. Level 4: Cancer invades through the submucosa below the stalk of the polyp but above the muscularis propria of the bowel wall. Adenomas Neoplastic polyps of the bowel are often benign hence called adenomas. An adenoma is a tumor of glandular tissue, that has not (yet) gained the properties of cancer.The common adenomas of the colon (colorectal adenoma) are the tubular, tubulovillous, villous, and sessile serrated (SSA). A large majority (65% to 80%) are of the benign tubular type with 10% to 25% being tubulovillous, and villous being the most rare at 5% to 10%.As is evident from their name, sessile serrated and traditional serrated adenomas (TSAs) have a serrated appearance and can be difficult to distinguish microscopically from hyperplastic polyps. Making this distinction is important, however, since SSAs and TSAs have the potential to become cancers, while hyperplastic polyps do not.The villous subdivision is associated with the highest malignant potential because they generally have the largest surface area. (This is because the villi are projections into the lumen and hence have a bigger surface area.) However, villous adenomas are no more likely than tubular or tubulovillous adenomas to become cancerous if their sizes are all the same. Hamartomatous polyp Hamartomatous polyps are tumours, like growths found in organs as a result of faulty development. They are normally made up of a mixture of tissues. They contain mucus-filled glands, with retention cysts, abundant connective tissue, and chronic cellular infiltration of eosinophils. They grow at the normal rate of the host tissue and rarely cause problems such as compression. A common example of a hamartomatous lesion is a strawberry naevus. Hamartomatous polyps are often found by chance; occurring in syndromes such as Peutz–Jegher syndrome or Juvenile polyposis syndrome. Peutz–Jeghers syndrome is associated with polyps of the GI tract and also increased pigmentation around the lips, genitalia, buccal mucosa feet and hands. People are often diagnosed with Peutz-Jegher after presenting at around the age of 9 with an intussusception. The polyps themselves carry little malignant potential but because of potential coexisting adenomas there is a 15% chance of colonic malignancy. Juvenile polyps are hamartomatous polyps that often become evident before twenty years of age, but can also be seen in adults. They are usually solitary polyps found in the rectum which most commonly present with rectal bleeding. Juvenile polyposis syndrome is characterised by the presence of more than five polyps in the colon or rectum, or numerous juvenile polyps throughout the gastrointestinal tract, or any number of juvenile polyps in any person with a family history of juvenile polyposis. People with juvenile polyposis have an increased risk of colon cancer. Inflammatory polyp These are polyps that are associated with inflammatory conditions such as ulcerative colitis and Crohns disease. Prevention Diet and lifestyle are believed to play a large role in whether colorectal polyps form. Studies show there to be a protective link between consumption of cooked green vegetables, brown rice, legumes, and dried fruit and decreased incidence of colorectal polyps. Diagnosis Colorectal polyps can be detected using a faecal occult blood test, flexible sigmoidoscopy, colonoscopy, virtual colonoscopy, digital rectal examination, barium enema or a pill camera.Malignant potential is associated with degree of dysplasia Type of polyp (e.g. villous adenoma): Tubular Adenoma: 5% risk of cancer Tubulovillous adenoma: 20% risk of cancer Villous adenoma: 40% risk of cancer Size of polyp: <1 cm =<1% risk of cancer 1–2 cm=10% risk of cancer >2 cm=50% risk of cancerNormally an adenoma that is greater than 0.5 cm is treated. Gallery NICE classification In colonoscopy, colorectal polyps can be classified by NICE (Narrow-band imaging International Colorectal Endoscopic): Treatment Polyps can be removed during a colonoscopy or sigmoidoscopy using a wire loop that cuts the stalk of the polyp and cauterises it to prevent bleeding. Many "defiant" polyps—large, flat, and otherwise laterally spreading adenomas—may be removed endoscopically by a technique called endoscopic mucosal resection (EMR), which involves injection of fluid underneath the lesion to lift it and thus facilitate endoscopic resection. Saline water may be used to generate lift, though some injectable solutions such as SIC 8000 may be more effective. Minimally invasive surgery is indicated for polyps that are too large or in unfavorable locations, such as the appendix, that cannot be removed endoscopically. These techniques may be employed as an alternative to the more invasive colectomy. Follow-up By United States guidelines, the following follow-up is recommended: References External links Villous Adenoma – Medscape

Give me a short description about Mammary tumor , Aarogya

Mammary tumor

A mammary tumor is a neoplasm originating in the mammary gland. It is a common finding in older female dogs and cats that are not spayed, but they are found in other animals as well. The mammary glands in dogs and cats are associated with their nipples and extend from the underside of the chest to the groin on both sides of the midline. There are many differences between mammary tumors in animals and breast cancer in humans, including tumor type, malignancy, and treatment options. The prevalence in dogs is about three times that of women. In dogs, mammary tumors are the second most common tumor (after skin tumors) over all and the most common tumor in female dogs with a reported incidence of 3.4%. Multiple studies have documented that spaying female dogs when young greatly decreases their risk of developing mammary neoplasia when aged. Compared with female dogs left intact, those spayed before puberty have 0.5% of the risk, those spayed after one estrous cycle have 8.0% of the risk, and dogs spayed after two estrous cycles have 26.0% of the risk of developing mammary neoplasia later in life. Overall, unspayed female dogs have a seven times greater risk of developing mammary neoplasia than do those that are spayed. While the benefit of spaying decreases with each estrous cycle, some benefit has been demonstrated in female dogs even up to 9 years of age. There is a much lower risk (about 1 percent) in male dogs and a risk in cats about half that of dogs. In dogs Causes The exact causes for the development of canine mammary tumors are not fully understood. However, hormones of the estrous cycle seem to be involved. Female dogs who are not spayed or who are spayed later than the first heat cycle are more likely to develop mammary tumors. Dogs have an overall reported incidence of mammary tumors of 3.4 percent. Dogs spayed before their first heat have 0.5 percent of this risk, and dogs spayed after just one heat cycle have 8 percent of this risk. The tumors are often multiple. The average age of dogs with mammary tumors is ten to eleven years old. Obesity at one year of age and eating red meat have also been associated with an increased risk for these tumors, as has the feeding of high fat homemade diets. There are several hypotheses on the molecular mechanisms involved in the development of canine mammary tumors but a specific genetic mutation has not been identified. Biology Historically, about 50 percent of mammary tumors in dogs were found to be malignant, although taking into account tumor behavior, one study has estimated true malignancy in mammary tumors to be 21 to 22 percent. Adenomas and fibroadenomas make up the benign types. Malignant mammary tumors are divided into sarcomas, carcinosarcomas, inflammatory carcinomas (usually anaplastic carcinomas), and carcinomas (including adenocarcinomas), which are the most common. Inflammatory carcinomas describe tumors that are fast growing and have bruising, edema, and pain, and can also cause disseminated intravascular coagulation. They are the most malignant type of canine mammary tumor.Malignant tumors are also subdivided histopathologically into those showing blood vessel wall invasion and those that do not. Without blood vessel wall invasion there is a better prognosis. Dogs with noninvasive adenocarcinomas have an average survival time of two years, while dogs with invasive adenocarcinomas have an average survival time of one year. Tumor size also affects the prognosis, in that dogs with tumors greater than five centimeters have a greater chance of lymph node metastasis. Tumor type is also important. Sarcomas and carcinosarcomas carry an average survival time of nine to twelve months. Inflammatory carcinomas have a very poor prognosis, and have usually metastasized by the time of diagnosis. Metastasis for any malignant mammary tumor is usually to the regional lymph nodes and lungs.The molecular carcinogenesis of canine mammary tumors are not completely understand. However, the increasing information on molecular pathways involved in the carcinogenesis of this canine tumor has potential to complement and refine the current diagnostic and therapeutic approach to this tumor type. Furthermore, current data show that significant similarities and differences exist between canine and human mammary tumors at the molecular level. Diagnosis and treatment Appearance and location of the tumor is enough to identify it as a mammary tumor. Biopsy will give type and invasiveness of the tumor. In addition, newer studies showed that certain gene expression patterns are associated with malignant behaviour of canine mammary tumors.Surgical removal is the treatment of choice, but chest x-rays should be taken first to rule out metastasis. Removal should be with wide margins to prevent recurrence, taking the whole mammary gland if necessary. Because 40 to 50 percent of dog mammary tumors have estrogen receptors, spaying is recommended by many veterinarians. A recent study showed a better prognosis in dogs that are spayed at the time of surgery or that had been recently spayed. However, several other studies found no improvement of disease outcome when spaying was performed after the tumor had developed. Chemotherapy is rarely used. Breeds at increased risk Chihuahua Poodle Brittany Spaniel English Setter Pointer Fox Terrier Boston Terrier Cocker Spaniel Lhasa Apso In cats Mammary tumors are the third most common neoplasia in cats, following lymphoid and skin cancers. The incidence of mammary tumors in cats is reduced by 91 percent in cats spayed prior to six months of age and by 86 percent in cats spayed prior to one year, according to one study. Siamese cats and Japanese breeds seem to have increased risk, and obesity also appears to be a factor in tumor development. Malignant tumors make up 80 to 96 percent of mammary tumors in cats, almost all adenocarcinomas. Male cats may also develop mammary adenocarcinoma, albeit rarely, and the clinical course is similar to female cats. As in dogs, tumor size is an important prognostic factor, although for tumors less than three centimeters the individual size is less predictive. According to one study, cats with tumors less than three cm had an average survival time of 21 months, and cats with tumors greater than three cm had an average survival of 12 months. About 10 percent of cat mammary tumors have estrogen receptors, so spaying at the time of surgery has little effect on recurrence or survival time. Metastasis tends to be to the lungs and lymph nodes, and rarely to bone. Diagnosis and treatment is similar to the dog. There is a better prognosis with bilateral radical surgery (removing both mammary chains) than with more conservative surgery. Doxorubicin has shown some promise in treatment. In rats Most mammary tumors in rats are benign fibroadenomas, which are also the most common tumor in the rat. Less than 10 percent are adenocarcinomas. They occur in male and female rats. The tumors can be large and occur anywhere on the trunk. There is a good prognosis with surgery. Spayed rats have a decreased risk of developing mammary tumors. In mice Most mammary tumors in mice are adenocarcinomas. They can be caused by viral infection. Recurrence rates are high, and therefore there is a poor prognosis. There is frequently local tissue invasion and metastasis to the lungs. A well known tumor virus of the mouse is the mouse mammary tumor virus, which may be the most common cause of this tumor in mice. In other animals Ferrets: Mammary tumors are rare in ferrets. Appearance tends to be a soft, dark colored lump. Most seem to be benign and occur most frequently in neutered males. Surgery is recommended. Guinea pigs: Mammary tumors in guinea pigs occur in males and females. Most are benign, but 30 percent are adenocarcinomas. They usually do not metastasize, but aggressive surgery is necessary to prevent recurrence. Hamsters and gerbils: Mammary tumors tend to be benign in hamsters and malignant in gerbils. Hedgehogs: Mammary gland adenocarcinoma is the most common tumor of the hedgehog. == References ==

Hey Aarogya, could you help me understand about Fasciculation

Fasciculation

A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions. When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome. Diagnosis The most effective way to detect fasciculations may be surface electromyography (EMG). Surface EMG is more sensitive than needle electromyography and clinical observation in the detection of fasciculation in people with amyotrophic lateral sclerosis.Deeper areas of contraction can be detected by electromyography (EMG) testing, though they can happen in any skeletal muscle in the body. Fasciculations arise as a result of spontaneous depolarization of a lower motor neuron leading to the synchronous contraction of all the skeletal muscle fibers within a single motor unit. An example of normal spontaneous depolarization is the constant contractions of cardiac muscle, causing the heart to beat. Usually, intentional movement of the involved muscle causes fasciculations to cease immediately, but they may return once the muscle is at rest again. Tics must also be distinguished from fasciculations. Small twitches of the upper or lower eyelid, for example, are not tics, because they do not involve a whole muscle, rather are twitches of a few muscle fibre bundles, that are not suppressible. Causes Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons. They are encountered by up to 70% of all healthy people, though for most, it is quite infrequent. In some cases, the presence of fasciculations can be annoying and interfere with quality of life. If a neurological examination is otherwise normal and EMG testing does not indicate any additional pathology, a diagnosis of benign fasciculation syndrome is usually made. Risk factors Risk factors for benign fasciculations are age, stress, fatigue, and strenuous exercise. Fasciculations can be caused by anxiety, caffeine or alcohol and thyroid disease. Magnesium deficiency is a common cause of fasciculation.Other factors may include the use of anticholinergic drugs over long periods. In particular, these include ethanolamines such as diphenhydramine (brand names Benadryl, Dimedrol, Daedalon and Nytol), used as an antihistamine and sedative, and dimenhydrinate (brand names Dramamine, Driminate, Gravol, Gravamin, Vomex, and Vertirosan) for nausea and motion sickness. Persons with benign fasciculation syndrome (BFS) may experience paraesthesia (especially numbness) shortly after taking such medication; fasciculation episodes begin as the medication wears off. Stimulants can cause fasciculations directly. These include caffeine, pseudoephedrine (Sudafed), amphetamines, and the asthma bronchodilator salbutamol (brand names Proventil, Combivent, Ventolin). Medications used to treat attention deficit disorder (ADHD) often contain stimulants as well, and are common causes of benign fasciculations. Since asthma and ADHD are much more serious than the fasciculations themselves, this side effect may have to be tolerated by the patient after consulting a physician or pharmacist. The depolarizing neuromuscular blocker succinylcholine causes fasciculations. It is a normal side effect of the drugs administration, and can be prevented with a small dose of a nondepolarizing neuromuscular blocker prior to the administration of succinylcholine, often 10% of a nondepolarizing NMBs induction dose. Even if a drug such as caffeine causes fasciculations, that does not necessarily mean it is the only cause. For example, a very slight magnesium deficiency by itself (see below) might not be enough for fasciculations to occur, but when combined with caffeine, the two factors together could be enough. Treatment Reducing stress and anxiety is therefore another useful treatment.There is no proven treatment for fasciculations in people with ALS. Among patients with ALS, fasciculation frequency is not associated with the duration of ALS and is independent of the degree of limb weakness and limb atrophy. No prediction of ALS disease duration can be made based on fasciculation frequency alone. Epidemiology Fasciculations are observed more often in males, and clinicians are overrepresented in study samples. See also Blepharospasm Carnitine palmitoyltransferase II deficiency Myokymia References == External links ==

Aarogya, explain a scenario commonly referred as Lymphedema

Lymphedema

Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the bodys immune system and returns interstitial fluid to the bloodstream. Lymphedema is most frequently a complication of cancer treatment or parasitic infections, but it can also be seen in a number of genetic disorders. Though incurable and progressive, a number of treatments may improve symptoms. Tissues with lymphedema are at high risk of infection because the lymphatic system has been compromised.While there is no cure, treatment may improve outcomes. This commonly include compression therapy, good skin care, exercise, and manual lymphatic drainage (MLD), which together are known as combined decongestive therapy. Diuretics are not useful. Signs and symptoms The most common manifestation of lymphedema is soft tissue swelling, edema. As the disorder progresses, worsening edema and skin changes including discoloration, verrucous (wart-like) hyperplasia, hyperkeratosis, papillomatosis, dermal thickening, and ulcers may be seen. Additionally, there is increased risk of infection of the skin, known as Erysipelas. Complications When the lymphatic impairment becomes so great that the lymph fluid exceeds the lymphatic systems ability to transport it, an abnormal amount of protein-rich fluid collects in the tissues. Left untreated, this stagnant, protein-rich fluid causes tissue channels to increase in size and number, reducing oxygen availability. This interferes with wound healing and provides a rich culture medium for bacterial growth that can result in infections, cellulitis, lymphangitis, lymphadenitis, and, in severe cases, skin ulcers. It is vital for lymphedema patients to be aware of the symptoms of infection and to seek immediate treatment, since recurrent infections or cellulitis, in addition to their inherent danger, further damage the lymphatic system and set up a vicious circle.In rare cases, lymphedema may lead to a form of cancer called lymphangiosarcoma, although the mechanism of carcinogenesis is not understood. Lymphedema-associated lymphangiosarcoma is called Stewart-Treves syndrome. Lymphangiosarcoma most frequently occurs in cases of long-standing lymphedema. The incidence of angiosarcoma is estimated to be 0.45% in patients living five years after radical mastectomy. Lymphedema is also associated with a low grade form of cancer called retiform hemangioendothelioma (a low grade angiosarcoma).Lymphedema can be disfiguring, and may result in a poor body image, which can cause psychological distress. Complications of lymphedema can cause difficulties in activities of daily living. Causes Lymphedema may be inherited (primary) or caused by injury to the lymphatic vessels (secondary). Lymph node damage It is most frequently seen after lymph node dissection, surgery and/or radiation therapy, in which damage to the lymphatic system is caused during the treatment of cancer, most notably breast cancer. In many patients with cancer, this condition does not develop until months or even years after therapy has concluded. Lymphedema may also be associated with accidents or certain diseases or problems that may inhibit the lymphatic system from functioning properly. In tropical endemic areas of the world, a common cause of secondary lymphedema is filariasis, a parasitic infection. It can also be caused by damage to the lymphatic system from infections such as cellulitis.Primary lymphedema may be congenital or arise sporadically. Multiple syndromes are associated with primary lymphedema, including Turner syndrome, Milroys disease, and Klippel-Trenaunay-Weber syndrome. It is generally thought to occur as a result of absent or malformed lymph nodes and/or lymphatic channels. Lymphedema may be present at birth, develop at the onset of puberty (praecox), or not become apparent for many years into adulthood (tarda). In men, lower-limb primary lymphedema is most common, occurring in one or both legs. Some cases of lymphedema may be associated with other vascular abnormalities.Secondary lymphedema affects both men and women. In women, it is most prevalent in the upper limbs after breast cancer surgery, in particular after axillary lymph node dissection, occurring in the arm on the side of the body in which the surgery is performed. Breast and trunk lymphedema can also occur but go unrecognised as there is swelling in the area after surgery, and its symptoms (peau dorange and/or an inverted nipple) can be confused with post surgery fat necrosis. In Western countries, secondary lymphedema is most commonly due to cancer treatment. Between 38 and 89% of breast cancer patients have lymphedema due to axillary lymph node dissection and/or radiation. Unilateral lymphedema occurs in up to 41% of patients after gynecologic cancer. For men, a 5-66% incidence of lymphedema has been reported in patients treated with incidence depending on whether staging or radical removal of lymph glands was done in addition to radiotherapy.Head and neck lymphedema can be caused by surgery or radiation therapy for tongue or throat cancer. It may also occur in the lower limbs or groin after surgery for colon, ovarian or uterine cancer, in which removal of lymph nodes or radiation therapy is required. Surgery or treatment for prostate, colon and testicular cancers may result in secondary lymphedema, particularly when lymph nodes have been removed or damaged.The onset of secondary lymphedema in patients who have had cancer surgery has also been linked to aircraft flight (likely due to decreased cabin pressure or relative immobility). For cancer survivors, therefore, wearing a prescribed and properly fitted compression garment may help decrease swelling during air travel.Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to the blood clots and deep vein thrombosis (DVT) that can be associated with this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.Infectious causes include lymphatic filariasis. At birth Hereditary lymphedema is a primary lymphedema – swelling that results from abnormalities in the lymphatic system that are present from birth. Swelling may be present in a single affected limb, several limbs, genitalia, or the face. It is sometimes diagnosed prenatally by a nuchal scan or post-natally by lymphoscintigraphy. The most common form is Meige disease that usually presents at puberty. Another form of hereditary lymphedema is Milroys disease caused by mutations in the VEGFR3 gene. Hereditary lymphedema is frequently syndromic and is associated with Turner syndrome, lymphedema–distichiasis syndrome, yellow nail syndrome, and Klippel–Trénaunay–Weber syndrome.One defined genetic cause for hereditary lymphedema is GATA2 deficiency. This deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the genes product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, and/or other disorders. GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema which is primarily located in the lower extremities but may also occur in other places such as the face or testes (i.e. hydrocele). This form of the deficiency, when coupled with sensorineural hearing loss which may also be due to faulty development of the lymphatic system, is sometimes termed the Emberger syndrome.Primary lymphedema has a quoted incidence of approximately 1-3 births out of every 10,000 births, with a particular female preponderance to male ratio of 3.5:1 In North America, the incidence of primary lymphedema is approximately 1.15 births out of every 100,000 births Compared to secondary lymphedema, primary lymphedema is relatively rare. Inflammatory lymphedema Bilateral lower extremity inflammatory lymphedema (BLEIL) is a distinct type of lymphedema occurring in a setting of acute and prolonged standing, such as in new recruits during basic training. The possible underlying mechanisms are thought to be venous congestion and inflammatory vasculitis. Physiology Lymph is formed from the fluid that filters out of the blood circulation and contains proteins, cellular debris, bacteria, etc. The collection of this fluid is carried out by the initial lymph collectors that are blind-ended endothelial-lined vessels with fenestrated openings that allow fluids and particles as large as cells to enter. Once inside the lumen of the lymphatic vessels, the fluid is guided along increasingly larger vessels, first with rudimentary valves to prevent backflow, which later develops into complete valves similar to the venous valve. Once the lymph enters the fully valved lymphatic vessels, it is pumped by a rhythmic peristaltic-like action by smooth muscle cells within the lymphatic vessel walls. This peristaltic action is the primary driving force, moving lymph within its vessel walls. The regulation of the frequency and power of contraction is regulated by the sympathetic nervous system. Lymph movement can be influenced by the pressure of nearby muscle contraction, arterial pulse pressure and the vacuum created in the chest cavity during respiration, but these passive forces contribute only a minor percentage of lymph transport. The fluids collected are pumped into continually larger vessels and through lymph nodes, which remove debris and police the fluid for dangerous microbes. The lymph ends its journey in the thoracic duct or right lymphatic duct, which drain into the blood circulation. Diagnosis Diagnosis is generally based on signs and symptoms, with testing used to rule out other potential causes. An accurate diagnosis and staging may help with management. A swollen limb can result from different conditions that require different treatments. Diagnosis of lymphedema is currently based on history, physical exam, and limb measurements. Imaging studies such as lymphoscintigraphy and indocyanine green lymphography are only required when surgery is being considered. However, the ideal method for lymphedema staging to guide the most appropriate treatment is controversial because of several different proposed protocols. Lymphedema can occur in both the upper and lower extremities, and in some cases, the head and neck. Assessment of the extremities first begins with a visual inspection. Color, presence of hair, visible veins, size and any sores or ulcerations are noted. Lack of hair may indicate an arterial circulation problem. Given swelling, the extremities circumference is measured for reference as time continues. In early stages of lymphedema, elevating the limb may reduce or eliminate the swelling. Palpation of the wrist or ankle can determine the degree of swelling; assessment includes a check of the pulses. The axillary or inguinal nodes may be enlarged due to the swelling. Enlargement of the nodes lasting more than three weeks may indicate infection or other illnesses such as sequela from breast cancer surgery requiring further medical attention.Diagnosis or early detection of lymphedema is difficult. The first signs may be subjective observations such as a feeling of heaviness in the affected extremity. These may be symptomatic of early-stage lymphedema where accumulation of lymph is mild and not detectable by changes in volume or circumference. As lymphedema progresses, definitive diagnosis is commonly based upon an objective measurement of differences between the affected or at-risk limb at the opposite unaffected limb, e.g. in volume or circumference. No generally accepted criterion is definitively diagnostic, although a volume difference of 200 ml between limbs or a 4-cm difference (at a single measurement site or set intervals along the limb) is often used. Bioimpedance measurement (which measures the amount of fluid in a limb) offers greater sensitivity than existing methods.Chronic venous stasis changes can mimic early lymphedema, but the changes in venous stasis are more often bilateral and symmetric. Lipedema can also mimic lymphedema, however lipedema characteristically spares the feet beginning abruptly at the medial malleoli (ankle level). As a part of the initial work-up before diagnosing lymphedema, it may be necessary to exclude other potential causes of lower extremity swelling such as kidney failure, hypoalbuminemia, congestive heart-failure, protein-losing nephropathy, pulmonary hypertension, obesity, pregnancy and drug-induced edema. Classification According to the Fifth WHO Expert Committee on Filariasis the most common method of classification of lymphedema is as follows: (The same classification method can be used for both primary and secondary lymphedema) The International Society of Lymphology (ISL) Staging System is based solely on subjective symptoms, making it prone to substantial observer bias. Imaging modalities have been suggested as useful adjuncts to the ISL staging to clarify the diagnosis. The lymphedema expert Dr. Ming-Huei Cheng developed a Chengs Lymphedema Grading tool to assess the severity of extremity lymphedema based on objective limb measurements and providing appropriate options for management. I. Grading Grade 1: Spontaneously reversible on elevation. Mostly pitting edema. Grade 2: Non-spontaneously reversible on elevation. Mostly non-pitting edema. Grade 3: Gross increase in volume and circumference of Grade 2 lymphedema, with eight stages of severity given below based on clinical assessments. II. Staging As described by the Fifth WHO Expert Committee on Filariasis, and endorsed by the American Society of Lymphology., the staging system helps to identify the severity of lymphedema. With the assistance of medical imaging apparatus, such as MRI or CT, staging can be established by the physician, and therapeutic or medical interventions may be applied: Stage 0: The lymphatic vessels have sustained some damage that is not yet apparent. Transport capacity is sufficient for the amount of lymph being removed. Lymphedema is not present. Stage 1 : Swelling increases during the day and disappears overnight as the patient lies flat in bed. Tissue is still at the pitting stage: when pressed by the fingertips, the affected area indents and reverses with elevation. Usually, upon waking in the morning, the limb or affected area is normal or almost normal in size. Treatment is not necessarily required at this point. Stage 2: Swelling is not reversible overnight, and does not disappear without proper management. The tissue now has a spongy consistency and is considered non-pitting: when pressed by the fingertips, the affected area bounces back without indentation. Fibrosis found in Stage 2 lymphedema marks the beginning of the hardening of the limbs and increasing size. Stage 3: Swelling is irreversible and usually the limb(s) or affected area becomes increasingly large. The tissue is hard (fibrotic) and unresponsive; some patients consider undergoing reconstructive surgery, called "debulking". This remains controversial, however, since the risks may outweigh the benefits and the further damage done to the lymphatic system may in fact make the lymphedema worse. Stage 4: The size and circumference of the affected limb(s) become noticeably large. Bumps, lumps, or protrusions (also called knobs) on the skin begin to appear. Stage 5: The affected limb(s) become grossly large; one or more deep skin folds is prevalent among patients in this stage. Stage 6: Knobs of small elongated or small rounded sizes cluster together, giving mossy-like shapes on the limb. Mobility of the patient becomes increasingly difficult. Stage 7: The person becomes "handicapped", and is unable to independently perform daily routine activities such as walking, bathing and cooking. Assistance from the family and health care system is needed. Grades Lymphedema can also be categorized by its severity (usually referenced to a healthy extremity): Grade 1 (mild edema): Involves the distal parts such as a forearm and hand or a lower leg and foot. The difference in circumference is less than 4 cm and other tissue changes are not yet present. Grade 2 (moderate edema): Involves an entire limb or corresponding quadrant of the trunk. Difference in circumference is 4–6 cm. Tissue changes, such as pitting, are apparent. The patient may experience erysipelas. Grade 3a (severe edema): Lymphedema is present in one limb and its associated trunk quadrant. Circumferential difference is greater than 6 centimeters. Significant skin alterations, such as cornification or keratosis, cysts and/or fistulae, are present. Additionally, the patient may experience repeated attacks of erysipelas. Grade 3b (massive edema): The same symptoms as grade 3a, except that two or more extremities are affected. Grade 4 (gigantic edema): In this stage of lymphedema, the affected extremities are huge, due to almost complete blockage of the lymph channels. Differential Lymphedema should not be confused with edema arising from venous insufficiency, which is caused by compromise of the venous drainage rather than lymphatic drainage. However, untreated venous insufficiency can progress into a combined venous/lymphatic disorder. Treatment While there is no cure, treatment may improve outcomes. This commonly include compression therapy, good skin care, exercise, and manual lymphatic drainage (MLD), which together is known as combined decongestive therapy. MLD is most effective in mild to moderate disease. In breast cancer-related lymphedema, MLD is safe and may offer added benefit to compression bandages for reducing swelling. Most people with lymphedema can be medically managed with conservative treatment. Diuretics are not useful. Surgery is generally only used in those who are not improved with other measures. Compression Garments Once a person is diagnosed with lymphedema, compression becomes imperative in the management of the condition. Garments are often intended to be worn all day but may be taken off for sleeping unless otherwise prescribed. Elastic compression garments are worn on the affected limb following complete de-congestive therapy to maintain edema reduction. Inelastic garments provide containment and reduction. Available styles, options, and prices vary widely. A professional garment fitter or certified lymphedema therapist can help determine the best option for the patient. Bandaging Compression bandaging, also called wrapping, is the application of layers of padding and short-stretch bandages to the involved areas. Short-stretch bandages are preferred over long-stretch bandages (such as those normally used to treat sprains), as the long-stretch bandages cannot produce the proper therapeutic tension necessary to safely reduce lymphedema and may in fact end up producing a tourniquet effect. Compression bandages provide resistance that assists in pumping fluid out of the affected area during exercise. This counter-force results in increased lymphatic drainage and therefore a decrease in size of the swollen area. Intermittent pneumatic compression therapy Intermittent pneumatic compression therapy (IPC) utilizes a multi-chambered pneumatic sleeve with overlapping cells to promote movement of lymph fluid. Pump therapy should be used in addition to other treatments such as compression bandaging and manual lymph drainage. Pump therapy has been used a lot in the past to help with controlling lymphedema. In some cases, pump therapy helps soften fibrotic tissue and therefore potentially enable more efficient lymphatic drainage. However, reports link pump therapy to increased incidence of edema proximal to the affected limb, such as genital edema arising after pump therapy in the lower limb. Current literature has suggested the use of IPC treatment in conjunction with Kinesiotape (KT) is more effective in the overall reduction of lymphedema as well as increasing shoulder ROM than the traditional treatment of IPC paired with complete decongestive therapy. Kinesiotape (KT) is an elastic cotton strip with an acrylic adhesive that is used commonly used to relieve the discomfort and disability associated with sports injuries, but in the context of lymphedema, this increases the space between the dermis and the muscle which increases the opportunity for lymphatic fluid to flow out naturally. The use of IPC treatments with KT tape as well as subsequent lymphatic drainage has proven to significantly reduce the circumference of lymphatic limbs in patients experiencing lymphedema secondary to breast cancer postmastectomy. Exercise In those with lymphedema or at risk of developing lymphedema, following breast cancer treatment, resistance training did not increase swelling and decreases in some, in addition to other potential beneficial effects on cardiovascular health. Moreover, resistance training and other forms of exercise were not associated with an increased risk of developing lymphedema in people who previously received breast cancer-related treatment. Compression garments should be worn during exercise (with the possible exception of swimming).Physical therapy treatment of patients with lymphedema may include trigger point release, soft tissue massage, postural improvement, patient education on condition management, strengthening, and stretching exercises. Exercises may increase in intensity and difficulty over time, beginning with passive movements to increase range of motion and progressing towards using external weights and resistance in various postures. Surgery The treatment of lymphedema is usually conservative, however the use of surgery is proposed for some cases.Suction assisted lipectomy (SAL), also known as liposuction for lymphedema, may help improve chronic non pitting edema if present. The procedure removes fat and protein and is done along with continued compression therapy.Vascularized lymph node transfers (VLNT) and lymphovenous bypass are supported by tentative evidence as of 2017 but is associated with a number of complications. Laser therapy Low-level laser therapy (LLLT) was cleared by the US Food and Drug Administration (FDA) for the treatment of lymphedema in November 2006.According to the US National Cancer Institute, LLLT may be effective in reducing lymphedema in some women. Two cycles of laser treatment were found to be reduce the volume of the affected arm in approximately one-third of people with postmastectomy lymphedema at three months post-treatment. Epidemiology Lymphedema affects approximately 200 million people worldwide. References == External links ==

Hi Aarogya, could you help me understand about Gastroesophageal reflux disease

Gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or complications. Symptoms include dental corrosion, dysphagia, heartburn, odynophagia, regurgitation, non-cardiac chest pain, extraesophageal symptoms such as chronic cough, hoarseness, reflux-induced laryngitis, or asthma. On the long term, and when not treated, complications such as esophagitis, esophageal stricture, and Barretts esophagus may arise.Risk factors include obesity, pregnancy, smoking, hiatal hernia, and taking certain medications. Medications that may cause or worsen the disease include benzodiazepines, calcium channel blockers, tricyclic antidepressants, NSAIDs, and certain asthma medicines. Acid reflux is due to poor closure of the lower esophageal sphincter, which is at the junction between the stomach and the esophagus. Diagnosis among those who do not improve with simpler measures may involve gastroscopy, upper GI series, esophageal pH monitoring, or esophageal manometry.Treatment options include lifestyle changes, medications, and sometimes surgery for those who do not improve with the first two measures. Lifestyle changes include not lying down for three hours after eating, lying down on the left side, raising the pillow/bedhead height, losing weight, and stopping smoking. Foods that may precipitate GERD symptoms and could be avoided include coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods. Medications include antacids, H2 receptor blockers, proton pump inhibitors, and prokinetics.In the Western world, between 10 and 20% of the population is affected by GERD. It is highly prevalent in North America with 18% to 28% of the population suffering from the condition. Occasional gastroesophageal reflux without troublesome symptoms or complications is even more common. The classic symptoms of GERD were first described in 1925, when Friedenwald and Feldman commented on heartburn and its possible relationship to a hiatal hernia. In 1934 gastroenterologist Asher Winkelstein described reflux and attributed the symptoms to stomach acid. Signs and symptoms Adults The most common symptoms of GERD in adults are an acidic taste in the mouth, regurgitation, and heartburn. Less common symptoms include pain with swallowing/sore throat, increased salivation (also known as water brash), nausea, chest pain, coughing, and globus sensation. The acid reflux can induce asthma attack symptoms like shortness of breath, cough, and wheezing in those with underlying asthma.GERD sometimes causes injury to the esophagus. These injuries may include one or more of the following: Reflux esophagitis – inflammation of esophageal epithelium which can cause ulcers near the junction of the stomach and esophagus Esophageal strictures – the persistent narrowing of the esophagus caused by reflux-induced inflammation Barretts esophagus – intestinal metaplasia (changes of the epithelial cells from squamous to intestinal columnar epithelium) of the distal esophagus Esophageal adenocarcinoma – a form of cancerGERD sometimes causes injury of the larynx (LPR). Other complications can include aspiration pneumonia. Children and babies GERD may be difficult to detect in infants and children since they cannot describe what they are feeling and indicators must be observed. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems, such as wheezing. Inconsolable crying, refusing food, crying for food and then pulling off the bottle or breast only to cry for it again, failure to gain adequate weight, bad breath, and burping are also common. Children may have one symptom or many; no single symptom is universal in all children with GERD. Of the estimated 4 million babies born in the US each year, up to 35% of them may have difficulties with reflux in the first few months of their lives, known as spitting up. About 90% of infants will outgrow their reflux by their first birthday. Mouth Acid reflux into the mouth can cause breakdown of the enamel, especially on the inside surface of the teeth. A dry mouth, acid or burning sensation in the mouth, bad breath and redness of the palate may occur. Other not so common symptoms of GERD include difficulty in swallowing, water brash which is flooding of the mouth with saliva, chronic cough, hoarse voice, nausea and vomiting.Signs of enamel erosion are the appearance of a smooth, silky-glazed, sometimes dull, enamel surfaces with the absence of perikymata, together with intact enamel along the gum margin. It will be evident in people with restorations as tooth structure typically dissolves much faster than the restorative material, causing it to seem as if it “stands above” the surrounding tooth structure. Barretts esophagus GERD may lead to Barretts esophagus, a type of intestinal metaplasia, which is in turn a precursor condition for esophageal cancer. The risk of progression from Barretts to dysplasia is uncertain, but is estimated at 20% of cases. Due to the risk of chronic heartburn progressing to Barretts, EGD every five years is recommended for people with chronic heartburn, or who take drugs for chronic GERD. Causes Acid reflux is due to poor closure of the lower esophageal sphincter, which is at the junction between the stomach and the esophagus. Factors that can contribute to GERD: Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors. Obesity: increasing body mass index is associated with more severe GERD. In a large series of 2,000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.Factors that have been linked with GERD, but not conclusively: Obstructive sleep apnea Gallstones, which can impede the flow of bile into the duodenum, which can affect the ability to neutralize gastric acidIn 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection. The eradication of H. pylori can lead to an increase in acid secretion, leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity. Diagnosis The diagnosis of GERD is usually made when typical symptoms are present. Reflux can be present in people without symptoms and the diagnosis requires both symptoms or complications and reflux of stomach content.Other investigations may include esophagogastroduodenoscopy (EGD). Barium swallow X-rays should not be used for diagnosis. Esophageal manometry is not recommended for use in the diagnosis, being recommended only prior to surgery. Ambulatory esophageal pH monitoring may be useful in those who do not improve after PPIs and is not needed in those in whom Barretts esophagus is seen. Investigation for H. pylori is not usually needed.The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and allows monitoring GERD patients in their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton-pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. Short-term treatment with proton-pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD. Endoscopy Endoscopy, the looking down into the stomach with a fibre-optic scope, is not routinely needed if the case is typical and responds to treatment. It is recommended when people either do not respond well to treatment or have alarm symptoms, including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate either once-in-a-lifetime or 5- to 10-yearly endoscopy for people with longstanding GERD, to evaluate the possible presence of dysplasia or Barretts esophagus.Biopsies performed during gastroscopy may show: Edema and basal hyperplasia (nonspecific inflammatory changes) Lymphocytic inflammation (nonspecific) Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis) Eosinophilic inflammation (usually due to reflux): The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE. Goblet cell intestinal metaplasia or Barretts esophagus Elongation of the papillae Thinning of the squamous cell layer Dysplasia CarcinomaReflux changes that are not erosive in nature lead to "nonerosive reflux disease". Severity Severity may be documented with the Johnson-DeMeesters scoring system: 0 - None 1 - Minimal - occasional episodes 2 - Moderate - medical therapy visits 3 - Severe - interference with daily activities Differential diagnosis Other causes of chest pain such as heart disease should be ruled out before making the diagnosis. Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or "extraesophageal reflux disease" (EERD). Unlike GERD, LPR rarely produces heartburn, and is sometimes called silent reflux. Differential diagnosis of GERD can also include dyspepsia, peptic ulcer disease, esophageal and gastric cancer, and food allergies. Treatment The treatments for GERD may include food choices, lifestyle changes, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole. In some cases, a person with GERD symptoms can manage them by taking over-the-counter drugs. This is often safer and less expensive than taking prescription drugs. Some guidelines recommend trying to treat symptoms with an H2 antagonist before using a proton-pump inhibitor because of cost and safety concerns. Medical Nutrition Therapy and Lifestyle Changes Medical nutrition therapy plays an essential role in managing the symptoms of the disease by preventing reflux, preventing pain and irritation, and decreasing gastric secretions.Some foods such as chocolate, mint, high fat food , and alcohol showed to relax the lower esophageal sphincter increasing the risk of reflux. It is also recommended to lose weight if overweight or obese, Avoid eating bedtime snacks or lying down immediately after meals, Consume meals 2–3 hours before bedtime, Elevate head of bed on 6-inch blocks, Avoid smoking, Avoid wearing tight clothing that increases pressure in the stomach, avoid spices, citrus juices, tomatoes and soft drinks, as well as consume small frequent meals and drink liquids between meals . Some evidence suggests that reduced sugar intake and increased fiber intake can help. Although moderate exercise may improve symptoms in people with GERD, vigorous exercise may worsen them. Breathing exercises may relieve GERD symptoms. Medications The primary medications used for GERD are proton-pump inhibitors, H2 receptor blockers and antacids with or without alginic acid. The use of acid suppression therapy is a common response to GERD symptoms and many people get more of this kind of treatment than their case merits. The overuse of acid suppression is a problem because of the side effects and costs. Proton-pump inhibitors Proton-pump inhibitors (PPIs), such as omeprazole, are the most effective, followed by H2 receptor blockers, such as ranitidine. If a once-daily PPI is only partially effective they may be used twice a day. They should be taken one half to one hour before a meal. There is no significant difference between PPIs. When these medications are used long term, the lowest effective dose should be taken. They may also be taken only when symptoms occur in those with frequent problems. H2 receptor blockers lead to roughly a 40% improvement. Antacids The evidence for antacids is weaker with a benefit of about 10% (NNT=13) while a combination of an antacid and alginic acid (such as Gaviscon) may improve symptoms by 60% (NNT=4). Metoclopramide (a prokinetic) is not recommended either alone or in combination with other treatments due to concerns around adverse effects. The benefit of the prokinetic mosapride is modest. Other agents Sucralfate has similar effectiveness to H2 receptor blockers; however, sucralfate needs to be taken multiple times a day, thus limiting its use. Baclofen, an agonist of the GABAB receptor, while effective, has similar issues of needing frequent dosing in addition to greater adverse effects compared to other medications. Surgery The standard surgical treatment for severe GERD is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. It is recommended only for those who do not improve with PPIs. Quality of life is improved in the short term compared to medical therapy, but there is uncertainty in the benefits of surgery versus long-term medical management with proton pump inhibitors. When comparing different fundoplication techniques, partial posterior fundoplication surgery is more effective than partial anterior fundoplication surgery, and partial fundoplication has better outcomes than total fundoplication.Esophagogastric dissociation is an alternative procedure that is sometimes used to treat neurologically impaired children with GERD. Preliminary studies have shown it may have a lower failure rate and a lower incidence of recurrent reflux.In 2012 the U.S. Food and Drug Administration (FDA) approved a device called the LINX, which consists of a series of metal beads with magnetic cores that are placed surgically around the lower esophageal sphincter, for those with severe symptoms that do not respond to other treatments. Improvement of GERD symptoms is similar to those of the Nissen fundoplication, although there is no data regarding long-term effects. Compared to Nissen fundoplication procedures, the procedure has shown a reduction in complications such as gas bloat syndrome that commonly occur. Adverse responses include difficulty swallowing, chest pain, vomiting, and nausea. Contraindications that would advise against use of the device are patients who are or may be allergic to titanium, stainless steel, nickel, or ferrous iron materials. A warning advises that the device should not be used by patients who could be exposed to, or undergo, magnetic resonance imaging (MRI) because of serious injury to the patient and damage to the device.In those with symptoms that do not improve with PPIs surgery known as transoral incisionless fundoplication may help. Benefits may last for up to six years. Special populations Pregnancy GERD is a common condition that develops during pregnancy, but usually resolves after delivery. The severity of symptoms tend to increase throughout the pregnancy. In pregnancy, dietary modifications and lifestyle changes may be attempted, but often have little effect. Some lifestyle changes that can be implemented are elevating the head of the bed, eating small portions of food at regularly scheduled intervals, reduce fluid intake with a meal, avoid eating 3 hours before bedtime, and refrain from lying down after eating. Calcium-based antacids are recommended if these changes are not effective, aluminum- and magnesium hydroxide -based antacids are also safe. Antacids that contain sodium bicarbonate or magnesium trisilicate should be avoided in pregnancy. Sucralfate has been studied in pregnancy and proven to be safe as is ranitidine and PPIs. Babies Babies may see relief with smaller, more frequent feedings, more frequent burping during feedings, holding the baby in an upright position 30 minutes after feeding, keeping the babys head elevated while laying on the back, removing milk and soy from the mothers diet or feeding the baby milk protein-free formula. They may also be treated with medicines such as ranitidine or proton pump inhibitors. Proton pump inhibitors however have not been found to be effective in this population and there is a lack of evidence for safety. The role of an Occupational Therapist with an infant with GERD includes positioning during and after feeding. One technique used is called “the log roll technique” which is practiced when changing an infants clothing or diapers. Placing an infant on their back while having their legs lifted is not recommended since it causes the acid to flow back up the esophagus. Instead, the occupational therapist would suggest rolling the child on the side, keeping the shoulders and hips aligned to avoid acid rising up the babys esophagus. Another technique used is feeding the baby on their side with an upright position instead of lying flat on their back. The final positioning technique used for infants is to keep them on their tummy or upright for 20 minutes after feeding. Epidemiology In Western populations, GERD affects approximately 10% to 20% of the population and 0.4% newly develop the condition. For instance, an estimated 3.4 million to 6.8 million Canadians have GERD. The prevalence rate of GERD in developed nations is also tightly linked with age, with adults aged 60 to 70 being the most commonly affected. In the United States 20% of people have symptoms in a given week and 7% every day. No data supports sex predominance with regard to GERD. History An obsolete treatment is vagotomy ("highly selective vagotomy"), the surgical removal of vagus nerve branches that innervate the stomach lining. This treatment has been largely replaced by medication. Vagotomy by itself tended to worsen contraction of the pyloric sphincter of the stomach, and delayed stomach emptying. Historically, vagotomy was combined with pyloroplasty or gastroenterostomy to counter this problem. Research A number of endoscopic devices have been tested to treat chronic heartburn. Endocinch, puts stitches in the lower esophogeal sphincter (LES) to create small pleats to help strengthen the muscle. However, long-term results were disappointing, and the device is no longer sold by Bard. Stretta procedure, uses electrodes to apply radio-frequency energy to the LES. A 2015 systematic review and meta-analysis in response to the systematic review (no meta-analysis) conducted by SAGES did not support the claims that Stretta was an effective treatment for GERD. A 2012 systematic review found that it improves GERD symptoms. NDO Surgical Plicator creates a plication, or fold, of tissue near the gastroesophageal junction, and fixates the plication with a suture-based implant. The company ceased operations in mid-2008, and the device is no longer on the market. Transoral incisionless fundoplication, which uses a device called Esophyx, may be effective. See also Acid perfusion test Esophageal motility disorder Esophageal motility study References Further reading Lichtenstein DR, Cash BD, Davila R, et al. (August 2007). "Role of endoscopy in the management of GERD" (PDF). Gastrointestinal Endoscopy. 66 (2): 219–24. doi:10.1016/j.gie.2007.05.027. PMID 17643692. Lay summary. {{cite journal}}: Cite uses deprecated parameter |lay-url= (help) Hirano I, Richter JE (March 2007). "ACG practice guidelines: esophageal reflux testing". American Journal of Gastroenterology. 102 (3): 668–85. CiteSeerX 10.1.1.619.3818. doi:10.1111/j.1572-0241.2006.00936.x. PMID 17335450. S2CID 10854440. Katz PO, Gerson LB, Vela MF (March 2013). "Guidelines for the diagnosis and management of gastroesophageal reflux disease". American Journal of Gastroenterology. 108 (3): 308–28. doi:10.1038/ajg.2012.444. PMID 23419381.

Give me a short description about Neoplasm , Aarogya

Neoplasm

A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor.ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek νέος- neo new and πλάσμα plasma formation, creation. Types A neoplasm can be benign, potentially malignant, or malignant (cancer). Benign tumors include uterine fibroids, osteophytes and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer. Potentially-malignant neoplasms include carcinoma in situ. They are localised, do not invade and destroy but in time, may transform into a cancer. Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and, if untreated or unresponsive to treatment, will generally prove fatal. Secondary neoplasm refers to any of a class of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy. Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin. Clonality Neoplastic tumors are often heterogeneous and contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are presumed to be monoclonal – that is, they are derived from the same cell, and all carry the same genetic or epigenetic anomaly – evident of clonality. For lymphoid neoplasms, e.g. lymphoma and leukemia, clonality is proven by the amplification of a single rearrangement of their immunoglobulin gene (for B cell lesions) or T cell receptor gene (for T cell lesions). The demonstration of clonality is now considered to be necessary to identify a lymphoid cell proliferation as neoplastic.It is tempting to define neoplasms as clonal cellular proliferations but the demonstration of clonality is not always possible. Therefore, clonality is not required in the definition of neoplasia. Neoplasm vs. tumor The word tumor or tumour comes from the Latin word for swelling, which is one of the cardinal signs of inflammation. The word originally referred to any form of swelling, neoplastic or not. In modern English, tumor is used as a synonym for neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size. Some neoplasms do not form a tumor - these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant. The terms mass and nodule are often used synonymously with tumor. Generally speaking, however, the term tumor is used generically, without reference to the physical size of the lesion. More specifically, the term mass is often used when the lesion has a maximal diameter of at least 20 millimeters (mm) in greatest direction, while the term nodule is usually used when the size of the lesion is less than 20 mm in its greatest dimension (25.4 mm = 1 inch). Causes Tumors in humans occur as a result of accumulated genetic and epigenetic alterations within single cells, which cause the cell to divide and expand uncontrollably. A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of neoplasms cause a tumorous overgrowth of tissue, however (such as leukemia or carcinoma in situ) and similarities between neoplasmic growths and regenerative processes, e.g., dedifferentiation and rapid cell proliferation, have been pointed out.Tumor growth has been studied using mathematics and continuum mechanics. Vascular tumors such as hemangiomas and lymphangiomas (formed from blood or lymph vessels) are thus looked at as being amalgams of a solid skeleton formed by sticky cells and an organic liquid filling the spaces in which cells can grow. Under this type of model, mechanical stresses and strains can be dealt with and their influence on the growth of the tumor and the surrounding tissue and vasculature elucidated. Recent findings from experiments that use this model show that active growth of the tumor is restricted to the outer edges of the tumor and that stiffening of the underlying normal tissue inhibits tumor growth as well.Benign conditions that are not associated with an abnormal proliferation of tissue (such as sebaceous cysts) can also present as tumors, however, but have no malignant potential. Breast cysts (as occur commonly during pregnancy and at other times) are another example, as are other encapsulated glandular swellings (thyroid, adrenal gland, pancreas). Encapsulated hematomas, encapsulated necrotic tissue (from an insect bite, foreign body, or other noxious mechanism), keloids (discrete overgrowths of scar tissue) and granulomas may also present as tumors. Discrete localized enlargements of normal structures (ureters, blood vessels, intrahepatic or extrahepatic biliary ducts, pulmonary inclusions, or gastrointestinal duplications) due to outflow obstructions or narrowings, or abnormal connections, may also present as a tumor. Examples are arteriovenous fistulae or aneurysms (with or without thrombosis), biliary fistulae or aneurysms, sclerosing cholangitis, cysticercosis or hydatid cysts, intestinal duplications, and pulmonary inclusions as seen with cystic fibrosis. It can be dangerous to biopsy a number of types of tumor in which the leakage of their contents would potentially be catastrophic. When such types of tumors are encountered, diagnostic modalities such as ultrasound, CT scans, MRI, angiograms, and nuclear medicine scans are employed prior to (or during) biopsy or surgical exploration/excision in an attempt to avoid such severe complications. Malignant neoplasms DNA damage DNA damage is considered to be the primary underlying cause of malignant neoplasms known as cancers. Its central role in progression to cancer is illustrated in the figure in this section, in the box near the top. (The central features of DNA damage, epigenetic alterations and deficient DNA repair in progression to cancer are shown in red.) DNA damage is very common. Naturally occurring DNA damages (mostly due to cellular metabolism and the properties of DNA in water at body temperatures) occur at a rate of more than 60,000 new damages, on average, per human cell, per day [also see article DNA damage (naturally occurring) ]. Additional DNA damages can arise from exposure to exogenous agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the likely cause of lung cancer due to smoking. UV light from solar radiation causes DNA damage that is important in melanoma. Helicobacter pylori infection produces high levels of reactive oxygen species that damage DNA and contributes to gastric cancer. Bile acids, at high levels in the colons of humans eating a high fat diet, also cause DNA damage and contribute to colon cancer. Katsurano et al. indicated that macrophages and neutrophils in an inflamed colonic epithelium are the source of reactive oxygen species causing the DNA damages that initiate colonic tumorigenesis. Some sources of DNA damage are indicated in the boxes at the top of the figure in this section. Individuals with a germ line mutation causing deficiency in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) are at increased risk of cancer. Some germ line mutations in DNA repair genes cause up to 100% lifetime chance of cancer (e.g., p53 mutations). These germ line mutations are indicated in a box at the left of the figure with an arrow indicating their contribution to DNA repair deficiency. About 70% of malignant neoplasms have no hereditary component and are called "sporadic cancers". Only a minority of sporadic cancers have a deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce or silence DNA repair gene expression. For example, of 113 sequential colorectal cancers, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration). Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.In further examples, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in expression of ERCC1, XPF or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR).During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing. DNA repair deficiencies (level 4 in the figure) cause increased DNA damages (level 5 in the figure) which result in increased somatic mutations and epigenetic alterations (level 6 in the figure). Field defects, normal appearing tissue with multiple alterations (and discussed in the section below), are common precursors to development of the disordered and improperly proliferating clone of tissue in a malignant neoplasm. Such field defects (second level from bottom of figure) may have multiple mutations and epigenetic alterations. Once a cancer is formed, it usually has genome instability. This instability is likely due to reduced DNA repair or excessive DNA damage. Because of such instability, the cancer continues to evolve and to produce sub clones. For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumor heterogeneity (i.e. present in all areas of the cancer), 59 mutations shared by some (but not all areas), and 29 “private” mutations only present in one of the areas of the cancer. Field defects Various other terms have been used to describe this phenomenon, including "field effect", "field cancerization", and "field carcinogenesis". The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. Since then, the terms "field cancerization" and "field defect" have been used to describe pre-malignant tissue in which new cancers are likely to arise.Field defects are important in progression to cancer. However, in most cancer research, as pointed out by Rubin “The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion. Similarly, Vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to patient death.In the colon, a field defect probably arises by natural selection of a mutant or epigenetically altered cell among the stem cells at the base of one of the intestinal crypts on the inside surface of the colon. A mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. Thus, a patch of abnormal tissue may arise. The figure in this section includes a photo of a freshly resected and lengthwise-opened segment of the colon showing a colon cancer and four polyps. Below the photo, there is a schematic diagram of how a large patch of mutant or epigenetically altered cells may have formed, shown by the large area in yellow in the diagram. Within this first large patch in the diagram (a large clone of cells), a second such mutation or epigenetic alteration may occur so that a given stem cell acquires an advantage compared to other stem cells within the patch, and this altered stem cell may expand clonally forming a secondary patch, or sub-clone, within the original patch. This is indicated in the diagram by four smaller patches of different colors within the large yellow original area. Within these new patches (sub-clones), the process may be repeated multiple times, indicated by the still smaller patches within the four secondary patches (with still different colors in the diagram) which clonally expand, until stem cells arise that generate either small polyps or else a malignant neoplasm (cancer).In the photo, an apparent field defect in this segment of a colon has generated four polyps (labeled with the size of the polyps, 6mm, 5mm, and two of 3mm, and a cancer about 3 cm across in its longest dimension). These neoplasms are also indicated, in the diagram below the photo, by 4 small tan circles (polyps) and a larger red area (cancer). The cancer in the photo occurred in the cecal area of the colon, where the colon joins the small intestine (labeled) and where the appendix occurs (labeled). The fat in the photo is external to the outer wall of the colon. In the segment of colon shown here, the colon was cut open lengthwise to expose the inner surface of the colon and to display the cancer and polyps occurring within the inner epithelial lining of the colon.If the general process by which sporadic colon cancers arise is the formation of a pre-neoplastic clone that spreads by natural selection, followed by formation of internal sub-clones within the initial clone, and sub-sub-clones inside those, then colon cancers generally should be associated with, and be preceded by, fields of increasing abnormality reflecting the succession of premalignant events. The most extensive region of abnormality (the outermost yellow irregular area in the diagram) would reflect the earliest event in formation of a malignant neoplasm.In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also shown to occur in the field defects surrounding those cancers. The Table, below, gives examples for which the DNA repair deficiency in a cancer was shown to be caused by an epigenetic alteration, and the somewhat lower frequencies with which the same epigenetically caused DNA repair deficiency was found in the surrounding field defect. Some of the small polyps in the field defect shown in the photo of the opened colon segment may be relatively benign neoplasms. Of polyps less than 10mm in size, found during colonoscopy and followed with repeat colonoscopies for 3 years, 25% were unchanged in size, 35% regressed or shrank in size while 40% grew in size. Genome instability Cancers are known to exhibit genome instability or a mutator phenotype. The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA. Within this protein-coding DNA (called the exome), an average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations. However, the average number of DNA sequence mutations in the entire genome (including non-protein-coding regions) within a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. This compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans.The high frequencies of mutations in the total nucleotide sequences within cancers suggest that often an early alteration in the field defects giving rise to a cancer (e.g. yellow area in the diagram in this section) is a deficiency in DNA repair. The large field defects surrounding colon cancers (extending to at about 10 cm on each side of a cancer) were shown by Facista et al. to frequently have epigenetic defects in 2 or 3 DNA repair proteins (ERCC1, XPF or PMS2) in the entire area of the field defect. Deficiencies in DNA repair cause increased mutation rates. A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epimutations. These new mutations or epimutations may provide a proliferative advantage, generating a field defect. Although the mutations/epimutations in DNA repair genes do not, themselves, confer a selective advantage, they may be carried along as passengers in cells when the cells acquire additional mutations/epimutations that do provide a proliferative advantage. Etymology The term neoplasm is a synonym of tumor. Neoplasia denotes the process of the formation of neoplasms/tumors, and the process is referred to as a neoplastic process. The word neoplastic itself comes from Greek neo new and plastic formed, molded.The term tumor derives from the Latin noun tumor a swelling, ultimately from the verb tumēre to swell. In the British Commonwealth, the spelling tumour is commonly used, whereas in the U.S. the word is usually spelled tumor.In its medical sense, tumor has traditionally meant an abnormal swelling of the flesh. The Roman medical encyclopedist Celsus (c. 30 BC–38 AD) described the four cardinal signs of acute inflammation as tumor, dolor, calor, and rubor (swelling, pain, increased heat, and redness). (His treatise, De Medicina, was the first medical book printed in 1478 following the invention of the movable-type printing press.) In contemporary English, the word tumor is often used as a synonym for a cystic (liquid-filled) growth or solid neoplasm (cancerous or non-cancerous), with other forms of swelling often referred to as "swellings".Related terms occur commonly in the medical literature, where the nouns tumefaction and tumescence (derived from the adjective tumescent) are current medical terms for non-neoplastic swelling. This type of swelling is most often caused by inflammation caused by trauma, infection, and other factors. Tumors may be caused by conditions other than an overgrowth of neoplastic cells, however. Cysts (such as sebaceous cysts) are also referred to as tumors, even though they have no neoplastic cells. This is standard in medical-billing terminology (especially when billing for a growth whose pathology has yet to be determined). See also Somatic evolution in cancer List of biological development disorders Epidemiology of cancer Pleomorphism References == External links ==

Aarogya, give me a short description about Autosensitization dermatitis

Autosensitization dermatitis

Autosensitization dermatitis presents with the development of widespread dermatitis or dermatitis distant from a local inflammatory focus, a process referred to as autoeczematization.: 81 See also Id reaction List of cutaneous conditions References == External links ==

Hi Aarogya , Do you know what is Human skin,

Human skin

The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective cutaneous literally means "of the skin" (from Latin cutis, skin). Because it interfaces with the environment, skin plays an important immunity role in protecting the body against pathogens and excessive water loss. Its other functions are insulation, temperature regulation, sensation, synthesis of vitamin D, and the protection of vitamin B folates. Severely damaged skin will try to heal by forming scar tissue. This is often discoloured and depigmented. In humans, skin pigmentation (affected by melanin) varies among populations, and skin type can range from dry to non-dry and from oily to non-oily. Such skin variety provides a rich and diverse habitat for bacteria that number roughly 1000 species from 19 phyla, present on the human skin. Structure Human skin shares anatomical, physiological, biochemical and immunological properties with other mammalian lines, especially pig skin. Pig skin shares similar epidermal and dermal thickness ratios to human skin; pig and human skin share similar hair follicle and blood vessel patterns; biochemically the dermal collagen and elastic content is similar in pig and human skin; and pig skin and human skin have similar physical responses to various growth factors.Skin has mesodermal cells, pigmentation, such as melanin provided by melanocytes, which absorb some of the potentially dangerous ultraviolet radiation (UV) in sunlight. It also contains DNA repair enzymes that help reverse UV damage, such that people lacking the genes for these enzymes have high rates of skin cancer. One form predominantly produced by UV light, malignant melanoma, is particularly invasive, causing it to spread quickly, and can often be deadly. Human skin pigmentation varies among populations in a striking manner. This has led to the classification of people(s) on the basis of skin colour.In terms of surface area, the skin is the second largest organ in the human body (the inside of the small intestine is 15 to 20 times larger). For the average adult human, the skin has a surface area of from 1.5–2.0 square metres (16–22 sq ft). The thickness of the skin varies considerably over all parts of the body, and between men and women and the young and the old. An example is the skin on the forearm which is on average 1.3 mm in the male and 1.26 mm in the female. One average square inch (6.5 cm2) of skin holds 650 sweat glands, 20 blood vessels, 60,000 melanocytes, and more than 1,000 nerve endings. The average human skin cell is about 30 micrometres (μm) in diameter, but there are variants. A skin cell usually ranges from 25 to 40 μm2, depending on a variety of factors. Skin is composed of three primary layers: the epidermis, the dermis and the hypodermis. Epidermis Epidermis, "epi" coming from the Greek meaning "over" or "upon", is the outermost layer of the skin. It forms the waterproof, protective wrap over the bodys surface which also serves as a barrier to infection and is made up of stratified squamous epithelium with an underlying basal lamina. The epidermis contains no blood vessels, and cells in the deepest layers are nourished almost exclusively by diffused oxygen from the surrounding air and to a far lesser degree by blood capillaries extending to the outer layers of the dermis. The main type of cells that make up the epidermis are Merkel cells, keratinocytes, with melanocytes and Langerhans cells also present. The epidermis can be further subdivided into the following strata (beginning with the outermost layer): corneum, lucidum (only in palms of hands and bottoms of feet), granulosum, spinosum, and basale. Cells are formed through mitosis at the basale layer. The daughter cells (see cell division) move up the strata changing shape and composition as they die due to isolation from their blood source. The cytoplasm is released and the protein keratin is inserted. They eventually reach the corneum and slough off (desquamation). This process is called "keratinization". This keratinized layer of skin is responsible for keeping water in the body and keeping other harmful chemicals and pathogens out, making skin a natural barrier to infection. The epidermis contains no blood vessels and is nourished by diffusion from the dermis. The main type of cells that make up the epidermis are keratinocytes, melanocytes, Langerhans cells, and Merkel cells. The epidermis helps the skin regulate body temperature. Layers The skin has up to seven layers of ectodermal tissue and guards the underlying muscles, bones, ligaments and internal organs. The epidermis is divided into several layers, where cells are formed through mitosis at the innermost layers. They move up the strata changing shape and composition as they differentiate and become filled with keratin. After reaching the top layer stratum corneum they are eventually sloughed off, or desquamated. This process is called keratinization and takes place within weeks. It was previously believed that the stratum corneum was "a simple, biologically inactive, outer epidermal layer comprising a fibrillar lattice of dead keratin". It is now understood that this is not true, and that the stratum corneum should be considered to be a live tissue. While it is true that the stratum corneum is mainly composed of terminally differentiated keratinocytes called corneocytes that are anucleated, these cells remain alive and metabolically functional until desquamated. Sublayers The epidermis is divided into the following 5 sublayers or strata: Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale (also called "stratum germinativum")Blood capillaries are found beneath the epidermis and are linked to an arteriole and a venule. Arterial shunt vessels may bypass the network in ears, the nose and fingertips. Genes and proteins expressed in the epidermis About 70% of all human protein-coding genes are expressed in the skin. Almost 500 genes have an elevated pattern of expression in the skin. There are fewer than 100 genes that are specific for the skin, and these are expressed in the epidermis. An analysis of the corresponding proteins show that these are mainly expressed in keratinocytes and have functions related to squamous differentiation and cornification. Dermis The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbours many nerve endings that provide the sense of touch and heat. It contains the hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic vessels and blood vessels. The blood vessels in the dermis provide nourishment and waste removal from its own cells as well as from the stratum basale of the epidermis. The dermis is structurally divided into two areas: a superficial area adjacent to the epidermis, called the papillary region, and a deep thicker area known as the reticular region. Papillary region The papillary region is composed of loose areolar connective tissue. It is named for its finger-like projections called papillae, which extend toward the epidermis. The papillae provide the dermis with a "bumpy" surface that interdigitates with the epidermis, strengthening the connection between the two layers of skin. In the palms, fingers, soles, and toes, the influence of the papillae projecting into the epidermis forms contours in the skins surface. These epidermal ridges occur in patterns (see: fingerprint) that are genetically and epigenetically determined and are therefore unique to the individual, making it possible to use fingerprints or footprints as a means of identification. Reticular region The reticular region lies deep in the papillary region and is usually much thicker. It is composed of dense irregular connective tissue, and receives its name from the dense concentration of collagenous, elastic, and reticular fibres that weave throughout it. These protein fibres give the dermis its properties of strength, extensibility, and elasticity. Also located within the reticular region are the roots of the hairs, sebaceous glands, sweat glands, receptors, nails, and blood vessels. Tattoo ink is held in the dermis. Stretch marks, often from pregnancy and obesity, are also located in the dermis. Subcutaneous tissue The subcutaneous tissue (also hypodermis and subcutis) is not part of the skin, but lies below the dermis of the cutis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It consists of loose connective tissue, adipose tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes (subcutaneous tissue contains 50% of body fat). Fat serves as padding and insulation for the body. Cross-section Development Skin colour Human skin shows high skin colour variety from the darkest brown to the lightest pinkish-white hues. Human skin shows higher variation in colour than any other single mammalian species and is the result of natural selection. Skin pigmentation in humans evolved to primarily regulate the amount of ultraviolet radiation (UVR) penetrating the skin, controlling its biochemical effects.The actual skin colour of different humans is affected by many substances, although the single most important substance determining human skin colour is the pigment melanin. Melanin is produced within the skin in cells called melanocytes and it is the main determinant of the skin colour of darker-skinned humans. The skin colour of people with light skin is determined mainly by the bluish-white connective tissue under the dermis and by the haemoglobin circulating in the veins of the dermis. The red colour underlying the skin becomes more visible, especially in the face, when, as consequence of physical exercise or the stimulation of the nervous system (anger, fear), arterioles dilate.There are at least five different pigments that determine the colour of the skin. These pigments are present at different levels and places. Melanin: It is brown in colour and present in the basal layer of the epidermis. Melanoid: It resembles melanin but is present diffusely throughout the epidermis. Carotene: This pigment is yellow to orange in colour. It is present in the stratum corneum and fat cells of dermis and superficial fascia. Hemoglobin (also spelled haemoglobin): It is found in blood and is not a pigment of the skin but develops a purple colour. Oxyhemoglobin: It is also found in blood and is not a pigment of the skin. It develops a red colour.There is a correlation between the geographic distribution of UV radiation (UVR) and the distribution of indigenous skin pigmentation around the world. Areas that highlight higher amounts of UVR reflect darker-skinned populations, generally located nearer towards the equator. Areas that are far from the tropics and closer to the poles have lower concentration of UVR, which is reflected in lighter-skinned populations.In the same population it has been observed that adult human females are considerably lighter in skin pigmentation than males. Females need more calcium during pregnancy and lactation, and vitamin D which is synthesized from sunlight helps in absorbing calcium. For this reason it is thought that females may have evolved to have lighter skin in order to help their bodies absorb more calcium.The Fitzpatrick scale is a numerical classification schema for human skin colour developed in 1975 as a way to classify the typical response of different types of skin to ultraviolet (UV) light: Ageing As skin ages, it becomes thinner and more easily damaged. Intensifying this effect is the decreasing ability of skin to heal itself as a person ages. Among other things, skin ageing is noted by a decrease in volume and elasticity. There are many internal and external causes to skin ageing. For example, ageing skin receives less blood flow and lower glandular activity. A validated comprehensive grading scale has categorized the clinical findings of skin ageing as laxity (sagging), rhytids (wrinkles), and the various facets of photoageing, including erythema (redness), and telangiectasia, dyspigmentation (brown discolouration), solar elastosis (yellowing), keratoses (abnormal growths) and poor texture.Cortisol causes degradation of collagen, accelerating skin ageing.Anti-ageing supplements are used to treat skin ageing. Photoageing Photoageing has two main concerns: an increased risk for skin cancer and the appearance of damaged skin. In younger skin, sun damage will heal faster since the cells in the epidermis have a faster turnover rate, while in the older population the skin becomes thinner and the epidermis turnover rate for cell repair is lower, which may result in the dermis layer being damaged. Types Though most human skin is covered with hair follicles, some parts can be hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective cutaneous means "of the skin" (from Latin cutis, skin). Functions Skin performs the following functions: Protection: an anatomical barrier from pathogens and damage between the internal and external environment in bodily defence; Langerhans cells in the skin are part of the adaptive immune system. Perspiration contains lysozyme that break the bonds within the cell walls of bacteria. Sensation: contains a variety of nerve endings that react to heat and cold, touch, pressure, vibration, and tissue injury; see somatosensory system and haptics. Heat regulation: the skin contains a blood supply far greater than its requirements which allows precise control of energy loss by radiation, convection and conduction. Dilated blood vessels increase perfusion and heat loss, while constricted vessels greatly reduce cutaneous blood flow and conserve heat. Control of evaporation: the skin provides a relatively dry and semi-impermeable barrier to fluid loss. Loss of this function contributes to the massive fluid loss in burns. Aesthetics and communication: others see our skin and can assess our mood, physical state and attractiveness. Storage and synthesis: acts as a storage centre for lipids and water, as well as a means of synthesis of vitamin D by action of UV on certain parts of the skin. Excretion: sweat contains urea, however its concentration is 1/130th that of urine, hence excretion by sweating is at most a secondary function to temperature regulation. Absorption: the cells comprising the outermost 0.25–0.40 mm of the skin are "almost exclusively supplied by external oxygen", although the "contribution to total respiration is negligible". In addition, medicine can be administered through the skin, by ointments or by means of adhesive patch, such as the nicotine patch or iontophoresis. The skin is an important site of transport in many other organisms. Water resistance: The skin acts as a water-resistant barrier so essential nutrients are not washed out of the body. Skin flora The human skin is a rich environment for microbes. Around 1000 species of bacteria from 19 bacterial phyla have been found. Most come from only four phyla: Actinomycetota (51.8%), Bacillota (24.4%), Pseudomonadota (16.5%), and Bacteroidota (6.3%). Propionibacteria and Staphylococci species were the main species in sebaceous areas. There are three main ecological areas: moist, dry and sebaceous. In moist places on the body Corynebacteria together with Staphylococci dominate. In dry areas, there is a mixture of species but dominated by Betaproteobacteria and Flavobacteriales. Ecologically, sebaceous areas had greater species richness than moist and dry ones. The areas with least similarity between people in species were the spaces between fingers, the spaces between toes, axillae, and umbilical cord stump. Most similarly were beside the nostril, nares (inside the nostril), and on the back. Reflecting upon the diversity of the human skin researchers on the human skin microbiome have observed: "hairy, moist underarms lie a short distance from smooth dry forearms, but these two niches are likely as ecologically dissimilar as rainforests are to deserts."The NIH conducted the Human Microbiome Project to characterize the human microbiota which includes that on the skin and the role of this microbiome in health and disease.Microorganisms like Staphylococcus epidermidis colonize the skin surface. The density of skin flora depends on region of the skin. The disinfected skin surface gets recolonized from bacteria residing in the deeper areas of the hair follicle, gut and urogenital openings. Clinical significance Diseases of the skin include skin infections and skin neoplasms (including skin cancer). Dermatology is the branch of medicine that deals with conditions of the skin.The skin is also valuable for diagnosis of other conditions, since many medical signs show through the skin. Skin color affects the visibility of these signs, a source of misdiagnosis in unaware medical personnel. Society and culture Hygiene and skin care The skin supports its own ecosystems of microorganisms, including yeasts and bacteria, which cannot be removed by any amount of cleaning. Estimates place the number of individual bacteria on the surface of 6.5 square centimetres (1 sq in) of human skin at 50 million, though this figure varies greatly over the average 1.9 square metres (20 sq ft) of human skin. Oily surfaces, such as the face, may contain over 78 million bacteria per square centimetre (500 million per square inch). Despite these vast quantities, all of the bacteria found on the skins surface would fit into a volume the size of a pea. In general, the microorganisms keep one another in check and are part of a healthy skin. When the balance is disturbed, there may be an overgrowth and infection, such as when antibiotics kill microbes, resulting in an overgrowth of yeast. The skin is continuous with the inner epithelial lining of the body at the orifices, each of which supports its own complement of microbes. Cosmetics should be used carefully on the skin because these may cause allergic reactions. Each season requires suitable clothing in order to facilitate the evaporation of the sweat. Sunlight, water and air play an important role in keeping the skin healthy. Oily skin Oily skin is caused by over-active sebaceous glands, that produce a substance called sebum, a naturally healthy skin lubricant. A high glycemic-index diet and dairy products (except for cheese) consumption increase IGF-1 generation, which in turn increases sebum production. Overwashing the skin does not cause sebum overproduction but may cause dryness.When the skin produces excessive sebum, it becomes heavy and thick in texture, known as oily skin. Oily skin is typified by shininess, blemishes and pimples. The oily-skin type is not necessarily bad, since such skin is less prone to wrinkling, or other signs of ageing, because the oil helps to keep needed moisture locked into the epidermis (outermost layer of skin). The negative aspect of the oily-skin type is that oily complexions are especially susceptible to clogged pores, blackheads, and buildup of dead skin cells on the surface of the skin. Oily skin can be sallow and rough in texture and tends to have large, clearly visible pores everywhere, except around the eyes and neck. Permeability Human skin has a low permeability; that is, most foreign substances are unable to penetrate and diffuse through the skin. Skins outermost layer, the stratum corneum, is an effective barrier to most inorganic nanosized particles. This protects the body from external particles such as toxins by not allowing them to come into contact with internal tissues. However, in some cases it is desirable to allow particles entry to the body through the skin. Potential medical applications of such particle transfer has prompted developments in nanomedicine and biology to increase skin permeability. One application of transcutaneous particle delivery could be to locate and treat cancer. Nanomedical researchers seek to target the epidermis and other layers of active cell division where nanoparticles can interact directly with cells that have lost their growth-control mechanisms (cancer cells). Such direct interaction could be used to more accurately diagnose properties of specific tumours or to treat them by delivering drugs with cellular specificity. Nanoparticles Nanoparticles 40 nm in diameter and smaller have been successful in penetrating the skin. Research confirms that nanoparticles larger than 40 nm do not penetrate the skin past the stratum corneum. Most particles that do penetrate will diffuse through skin cells, but some will travel down hair follicles and reach the dermis layer. The permeability of skin relative to different shapes of nanoparticles has also been studied. Research has shown that spherical particles have a better ability to penetrate the skin compared to oblong (ellipsoidal) particles because spheres are symmetric in all three spatial dimensions. One study compared the two shapes and recorded data that showed spherical particles located deep in the epidermis and dermis whereas ellipsoidal particles were mainly found in the stratum corneum and epidermal layers. Nanorods are used in experiments because of their unique fluorescent properties but have shown mediocre penetration. Nanoparticles of different materials have shown skins permeability limitations. In many experiments, gold nanoparticles 40 nm in diameter or smaller are used and have shown to penetrate to the epidermis. Titanium oxide (TiO2), zinc oxide (ZnO), and silver nanoparticles are ineffective in penetrating the skin past the stratum corneum. Cadmium selenide (CdSe) quantum dots have proven to penetrate very effectively when they have certain properties. Because CdSe is toxic to living organisms, the particle must be covered in a surface group. An experiment comparing the permeability of quantum dots coated in polyethylene glycol (PEG), PEG-amine, and carboxylic acid concluded the PEG and PEG-amine surface groups allowed for the greatest penetration of particles. The carboxylic acid coated particles did not penetrate past the stratum corneum. Increasing permeability Scientists previously believed that the skin was an effective barrier to inorganic particles. Damage from mechanical stressors was believed to be the only way to increase its permeability.Recently, simpler and more effective methods for increasing skin permeability have been developed. Ultraviolet radiation (UVR) slightly damages the surface of skin and causes a time-dependent defect allowing easier penetration of nanoparticles. The UVRs high energy causes a restructuring of cells, weakening the boundary between the stratum corneum and the epidermal layer. The damage of the skin is typically measured by the transepidermal water loss (TEWL), though it may take 3–5 days for the TEWL to reach its peak value. When the TEWL reaches its highest value, the maximum density of nanoparticles is able to permeate the skin. While the effect of increased permeability after UVR exposure can lead to an increase in the number of particles that permeate the skin, the specific permeability of skin after UVR exposure relative to particles of different sizes and materials has not been determined.There are other methods to increase nanoparticle penetration by skin damage: tape stripping is the process in which tape is applied to skin then lifted to remove the top layer of skin; skin abrasion is done by shaving the top 5–10 μm off the surface of the skin; chemical enhancement applies chemicals such as polyvinylpyrrolidone (PVP), dimethyl sulfoxide (DMSO), and oleic acid to the surface of the skin to increase permeability; electroporation increases skin permeability by the application of short pulses of electric fields. The pulses are high voltage and on the order of milliseconds when applied. Charged molecules penetrate the skin more frequently than neutral molecules after the skin has been exposed to electric field pulses. Results have shown molecules on the order of 100 μm to easily permeate electroporated skin. Applications A large area of interest in nanomedicine is the transdermal patch because of the possibility of a painless application of therapeutic agents with very few side effects. Transdermal patches have been limited to administer a small number of drugs, such as nicotine, because of the limitations in permeability of the skin. Development of techniques that increase skin permeability has led to more drugs that can be applied via transdermal patches and more options for patients.Increasing the permeability of skin allows nanoparticles to penetrate and target cancer cells. Nanoparticles along with multi-modal imaging techniques have been used as a way to diagnose cancer non-invasively. Skin with high permeability allowed quantum dots with an antibody attached to the surface for active targeting to successfully penetrate and identify cancerous tumours in mice. Tumour targeting is beneficial because the particles can be excited using fluorescence microscopy and emit light energy and heat that will destroy cancer cells. Sunblock and sunscreen Sunblock and sunscreen are different important skin-care products though both offer full protection from the sun.Sunblock—Sunblock is opaque and stronger than sunscreen, since it is able to block most of the UVA/UVB rays and radiation from the sun, and does not need to be reapplied several times in a day. Titanium dioxide and zinc oxide are two of the important ingredients in sunblock.Sunscreen—Sunscreen is more transparent once applied to the skin and also has the ability to protect against UVA/UVB rays, although the sunscreens ingredients have the ability to break down at a faster rate once exposed to sunlight, and some of the radiation is able to penetrate to the skin. In order for sunscreen to be more effective it is necessary to consistently reapply and use one with a higher sun protection factor. Diet Vitamin A, also known as retinoids, benefits the skin by normalizing keratinization, downregulating sebum production which contributes to acne, and reversing and treating photodamage, striae, and cellulite. Vitamin D and analogues are used to downregulate the cutaneous immune system and epithelial proliferation while promoting differentiation. Vitamin C is an antioxidant that regulates collagen synthesis, forms barrier lipids, regenerates vitamin E, and provides photoprotection. Vitamin E is a membrane antioxidant that protects against oxidative damage and also provides protection against harmful UV rays. Several scientific studies confirmed that changes in baseline nutritional status affects skin condition. The Mayo Clinic lists foods they state help the skin: fruits and vegetables, whole-grains, dark leafy greens, nuts, and seeds. See also Acid mantle Anthropodermic bibliopegy Artificial skin Callus, thick area of skin List of cutaneous conditions Cutaneous structure development Fingerprint, skin on fingertips Hyperpigmentation, about excess skin colour Intertriginous Meissners corpuscle Pacinian corpuscle Polyphenol antioxidant Skin cancer Skin lesion Skin repair References External links Media related to Human skin at Wikimedia Commons MedlinePlus Skin Conditions National Library of Medicine retrieved 12 November 2013.

Hey Aarogya, explain a situation where Salicylate poisoning occurs

Salicylate poisoning

Salicylate poisoning, also known as aspirin poisoning, is the acute or chronic poisoning with a salicylate such as aspirin. The classic symptoms are ringing in the ears, nausea, abdominal pain, and a fast breathing rate. Early on, these may be subtle, while larger doses may result in fever. Complications can include swelling of the brain or lungs, seizures, low blood sugar, or cardiac arrest.While usually due to aspirin, other possible causes include oil of wintergreen and bismuth subsalicylate. Excess doses can be either on purpose or accidental. Small amounts of oil of wintergreen can be toxic. Diagnosis is generally based on repeated blood tests measuring aspirin levels and blood gases. While a type of graph has been created to try to assist with diagnosis, its general use is not recommended. In overdose maximum blood levels may not occur for more than 12 hours.Efforts to prevent poisoning include child-resistant packaging and a lower number of pills per package. Treatment may include activated charcoal, intravenous sodium bicarbonate with dextrose and potassium chloride, and dialysis. Giving dextrose may be useful even if the blood sugar is normal. Dialysis is recommended in those with kidney failure, decreased level of consciousness, blood pH less than 7.2, or high blood salicylate levels. If a person requires intubation, a fast respiratory rate may be required.The toxic effects of salicylates have been described since at least 1877. In 2004, more than 20,000 cases with 43 deaths were reported in the United States. About 1% of those with an acute overdose die, while chronic overdoses may have severe outcomes. Older people are at higher risks of toxicity for any given dose. Signs and symptoms Salicylate toxicity has potentially serious consequences, sometimes leading to significant morbidity and death. Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, ringing in the ears, and dizziness. More significant signs and symptoms occur in more severe poisonings and include high body temperature, fast breathing rate, respiratory alkalosis, metabolic acidosis, low blood potassium, low blood glucose, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.High doses of salicylate can cause salicylate-induced tinnitus. Severity The severity of toxicity depends on the amount of aspirin taken. Pathophysiology High levels of salicylates stimulate peripheral chemoreceptors and the central respiratory centers in the medulla causing increased ventilation and a respiratory alkalosis. The increased pH secondary to hyperventilation with respiratory alkalosis causes an increase in lipolysis and ketogenesis which causes the production of lactate and organic keto-acids (such as beta-hydroxybutyrate). The accumulation of these organic acids can cause an acidosis with an increased anion-gap as well as a decreased buffering capacity of the body. Salicylate toxicity also causes an uncoupling of oxidative phosphorylation and a decrease in citric acid cycle activity in the mitochondria. This decrease in aerobic production of adenosine triphosphate (ATP) is accompanied by an increase in anaerobic production of ATP through glycolysis which leads to glycogen depletion and hypoglycemia. The inefficient ATP production through anaerobic metabolism causes the body to shift to a catabolic predominant mode for energy production which consists of increased oxygen consumption, increased heat production (often manifesting as sweating), liver glycogen utilization and increased carbon dioxide production. This increased catabolism accompanied by hyperventilation can lead to severe insensible water losses, dehydration and hypernatremia.Acute aspirin or salicylates overdose or poisoning can cause initial respiratory alkalosis though metabolic acidosis ensues thereafter. The acid-base, fluid, and electrolyte abnormalities observed in salicylate toxicity can be grouped into three broad phases: Phase I is characterized by hyperventilation resulting from direct respiratory center stimulation, leading to respiratory alkalosis and compensatory alkaluria. Potassium and sodium bicarbonate are excreted in the urine. This phase may last as long as 12 hours. Phase II is characterized by paradoxic aciduria in the presence of continued respiratory alkalosis occurs when sufficient potassium has been lost from the kidneys. This phase may begin within hours and may last 12–24 hours. Phase III is characterized by dehydration, hypokalemia, and progressive metabolic acidosis. This phase may begin 4–6 hours after ingestion in a young infant or 24 hours or more after ingestion in an adolescent or adult. Diagnosis The acutely toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass. Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 and 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg. Chronic toxicity may occur following doses of 100 mg/kg per day for two or more days.Monitoring of biochemical parameters such as electrolytes and solutes, liver and kidney function, urinalysis, and complete blood count is undertaken along with frequent checking of salicylate and blood sugar levels. Arterial blood gas assessments typically find respiratory alkalosis early in the course of the overdose due to hyperstimulation of the respiratory center, and may be the only finding in a mild overdose. An anion-gap metabolic acidosis occurs later in the course of the overdose, especially if it is a moderate to severe overdose, due to the increase in protons (acidic contents) in the blood. The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels generally range from 30–100 mg/L (3–10 mg/dL) after usual therapeutic doses, 50–300 mg/L in patients taking high doses, and 700–1400 mg/L following acute overdose. Patients may undergo repeated testing until their peak plasma salicylate level can be estimated. Optimally, plasma levels should be assessed four hours after ingestion and then every two hours after that to allow calculation of the maximum level, which can then be used as a guide to the degree of toxicity expected. Patients may also be treated according to their individual symptoms. Prevention Efforts to prevent poisoning include child-resistant packaging and a lower number of pills per package. Treatment There is no antidote for salicylate poisoning. Initial treatment of an overdose involves resuscitation measures such as maintaining an adequate airway and adequate circulation followed by gastric decontamination by administering activated charcoal, which adsorbs the salicylate in the gastrointestinal tract. Stomach pumping is no longer routinely used in the treatment of poisonings, but is sometimes considered if the patient has ingested a potentially lethal amount less than one hour before presentation. Inducing vomiting with syrup of ipecac is not recommended. Repeated doses of activated charcoal have been proposed to be beneficial in cases of salicylate poisoning, especially in ingestion of enteric coated and extended release salicylic acid formulations which are able to remain in the gastrointestinal (GI) tract for longer periods of time. Repeated doses of activated charcoal are also useful to re-adsorb salicylates in the GI tract that may have desorbed from the previous administration of activated charcoal. The initial dose of activated charcoal is most useful if given within 2 hours of initial ingestion. Contraindications to the use of activated charcoal include altered mental status (due to the risk of aspiration), GI bleeding (often due to salicylates) or poor gastric motility. Whole bowel irrigation using the laxative polyethylene glycol can be useful to induce the gastrointestinal elimination of salicylates, particularly if there is partial or diminished response to activated charcoal.Alkalinization of the urine and plasma, by giving a bolus of sodium bicarbonate then adding sodium bicarbonate to maintenance fluids, is an effective method to increase the clearance of salicylates from the body. Alkalinization of the urine causes salicylates to be trapped in renal tubules in their ionized form and then readily excreted in the urine. Alkalinization of the urine increases urinary salicylate excretion by 18 fold. Alkalinization of the plasma decreases the lipid soluble form of salicylates facilitating movement out of the central nervous system. Oral sodium bicarbonate is contra-indicated in salicylate toxicity as it can cause dissociation of salicylate tablets in the GI tract and subsequent increased absorption. Intravenous fluids Intravenous fluids containing dextrose such as dextrose 5% in water (D5W) are recommended to keep a urinary output between 1 and 1.5 millilitres per kilogram per hour.Sodium bicarbonate is given in a significant aspirin overdose (salicylate level greater than 35 mg/dL 6 hours after ingestion) regardless of the serum pH, as it enhances elimination of aspirin in the urine. It is given until a urine pH between 7.5 and 8.0 is achieved. Dialysis Hemodialysis can be used to enhance the removal of salicylate from the blood, usually in those who are severely poisoned. Examples of severe poisoning include people with high salicylate blood levels: 7.25 mmol/L (100 mg/dL) in acute ingestions or 40 mg/dL in chronic ingestions, significant neurotoxicity (agitation, coma, convulsions), kidney failure, pulmonary edema, or cardiovascular instability. Hemodialysis also has the advantage of restoring electrolyte and acid-base abnormalities while removing salicylate.Salicylic acid has a small size (low molecular mass), has a low volume of distribution (is more water soluble), has low tissue binding and is largely free (and not protein bound) at toxic levels in the body; all of which make it easily removable from the body by hemodialysis.Indication for dialysis: Salicylate level higher than 90 mg/dL Severe acid base imbalance Severe cardiac toxicity Acute respiratory distress syndrome Cerebral involvement/ neurological signs and symptoms Rising serum salicylate level despite alkalinization/multidose activated charcoal, or people in which standard approaches to treatment ave failed Unable to tolerate fluids with fluid overload Epidemiology Acute salicylate toxicity usually occurs after an intentional ingestion by younger adults, often with a history of psychiatric disease or previous overdose, whereas chronic toxicity usually occurs in older adults who experience inadvertent overdose while ingesting salicylates therapeutically over longer periods of time.During the latter part of the 20th century, the number of poisonings from salicylates declined, mainly because of the increased popularity of other over-the-counter analgesics such as paracetamol (acetaminophen). Fifty-two deaths involving single-ingredient aspirin were reported in the United States in 2000; however, in all but three of these cases, the reason for the ingestion of lethal doses was intentional—predominantly suicidal. History Aspirin poisoning has controversially been cited as a possible cause of the high mortality rate during the 1918 flu pandemic, which killed 50 to 100 million people. See also NSAID hypersensitivity reactions Reye syndrome Salicylate sensitivity References External links Reingardiene, D; Lazauskas, R (2006). "[Acute salicylate poisoning]". Medicina (Kaunas, Lithuania). 42 (1): 79–83. PMID 16467617.

Hello Aarogya , Do you know what is Anorexia (symptom),

Anorexia (symptom)

Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others indicate a serious clinical condition or pose a significant risk. Anorexia is a symptom, not a diagnosis. Anorexia is not to be confused with the mental health disorder anorexia nervosa. Because the term anorexia is often used as a short-form of anorexia nervosa, to avoid confusion a provider must clarify to a patient whether they are simply referring to a decreased appetite or the mental health disorder. Anyone can manifest anorexia as a loss of appetite, regardless of their gender, age, or weight. The symptom also occurs in other animals, such as cats, dogs, cattle, goats, and sheep. In these species, anorexia may be referred to as inappetence. As in humans, loss of appetite can be due to a range of diseases and conditions, as well as environmental and psychological factors. Etymology The term is from Ancient Greek: ανορεξία (ἀν-, without + όρεξις, spelled órexis, meaning appetite). Common manifestations Anorexia simply manifests as a decreased or loss of appetite. This can present as not feeling hungry or lacking the desire to eat. Sometimes people do not even notice they lack an appetite until they begin to lose weight from eating less. In other cases, it can be more noticeable, such as when a person becomes nauseated from just the thought of eating. Any form of decreased appetite that leads to changes in the body (such as weight loss or muscle loss) that is not done intentionally as part of dieting is clinically significant. Physiology of anorexia Appetite stimulation and suppression is a complex process involving many different parts of the brain and body by the use of various hormones and signals. Appetite is thought to be stimulated by interplay between peripheral signals to the brain (taste, smell, sight, gut hormones) as well as the balance of neurotransmitters and neuropeptides in the hypothalamus. Examples of these signals or hormones include neuropeptide Y, leptin, ghrelin, insulin, serotonin, and orexins (also called hypocretins). Anything that causes an imbalance of these signals or hormones can lead to the symptom of anorexia. While it is known that these signals and hormones help control appetite, the complicated mechanisms regarding a pathological increase or decrease in appetite are still being explored. Common causes Acute radiation syndrome Addisons disease Alcoholism Alcohol withdrawal Anemia Anorexia nervosa Anxiety Appendicitis Babesiosis Benzodiazepine withdrawal Bipolar disorder Cancer Cannabinoid hyperemesis syndrome Cannabis withdrawal Celiac disease Chronic kidney disease Chronic pain Common cold Constipation COPD COVID-19 Crohns disease Dehydration Dementia Depression Ebola Fatty liver disease Fever Food poisoning Gastroparesis Hepatitis HIV/AIDS Hypercalcemia Hyperglycemia Hypervitaminosis D Hypothyroidism and sometimes hyperthyroidism Irritable bowel syndrome Ketoacidosis Kidney failure Low blood pressure Mania Metabolic disorders, particularly urea cycle disorders MELAS syndrome Nausea Opioid use disorder Pancreatitis Pernicious anemia Psychosis Schizophrenia Side effect of drugs Stimulant use disorder Stomach flu Stress Sickness behavior Superior mesenteric artery syndrome Syndrome of inappropriate antidiuretic hormone secretion Tuberculosis Thalassemia Ulcerative colitis Uremia Vitamin B12 deficiency Zinc deficiency Infection: Anorexia of infection is part of the acute phase response (APR) to infection. The APR can be triggered by lipopolysaccharides and peptidoglycans from bacterial cell walls, bacterial DNA, and double-stranded viral RNA, and viral glycoproteins, which can trigger production of a variety of proinflammatory cytokines. These can have an indirect effect on appetite by a number of means, including peripheral afferents from their sites of production in the body, by enhancing production of leptin from fat stores. Inflammatory cytokines can also signal to the central nervous system more directly by specialized transport mechanisms through the blood–brain barrier, via circumventricular organs (which are outside the barrier), or by triggering production of eicosanoids in the endothelial cells of the brain vasculature. Ultimately, the control of appetite by this mechanism is thought to be mediated by the same factors normally controlling appetite, such as neurotransmitters (serotonin, dopamine, histamine, norepinephrine, corticotropin releasing factor, neuropeptide Y, and α-melanocyte-stimulating hormone). Drugs Stimulants, such as ephedrine, amphetamine, methamphetamine, MDMA, cathinone, methylphenidate, nicotine, cocaine, caffeine, etc. Narcotics, such as heroin, morphine, codeine, hydrocodone, oxycodone, etc. Antidepressants can have anorexia as a side effect, primarily selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Byetta, a type II diabetes drug, will cause moderate nausea and loss of appetite. Abruptly stopping appetite-increasing drugs, such as cannabis and corticosteroids. Chemicals that are members of the phenethylamine group. (Individuals with anorexia nervosa may seek them to suppress appetite.) Topiramate may cause anorexia as a side effect. Other drugs may be used to intentionally cause anorexia in order to help a patient preoperative fasting prior to general anesthesia. It is important to avoid food before surgery to mitigate the risk of pulmonary aspiration, which can be fatal. Other During the post-operative recovery period for a tonsillectomy or adenoidectomy, it is common for adult patients to experience a lack of appetite until their throat significantly heals (usually 10–14 days). Altitude sickness Significant emotional pain caused by an event (rather than a mental disorder) can cause an individual to temporarily lose all interest in food. Several Twelve-step programs including Overeaters Anonymous tackle psychological issues members believe lead to forms of deprivation Psychological stress Experiencing grotesque or unappealing thoughts or conversations, or viewing similar images Being in the presence of unappealing things such as waste matter, dead organisms, or bad smells Complications Complications of anorexia may result due to poor food intake. Poor food intake can lead to dehydration, electrolyte imbalances, anemia and nutritional deficiencies. These imbalances will worsen the longer that food is avoided. Sudden cardiac death Anorexia is a relatively common condition that can lead patients to have dangerous electrolyte imbalances, leading to acquired long QT syndrome which can result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Refeeding syndrome Care must be taken when a patient begins to eat after prolonged starvation to avoid the potentially fatal complications of refeeding syndrome. The initial signs of refeeding syndrome are minimal, but can rapidly progress to death. Thus, the reinitiation of food or oral intake is usually started slowly and requires close observation under supervision by trained healthcare professionals. This is usually done in a hospital or nutritional rehabilitation center. Management Anorexia can be treated with the help of orexigenic drugs. "Anorexia" vs "anorexic" vs anorexia nervosa Anorexic is a description of somebody with the stereotypical thin, frail, malnourished appearance. The appearance is classically associated with anorexia, although in rare cases do patients end up becoming anorexic. An anorexic or anorectic is also a description given to substances that cause anorexia for weight loss purposes. Anorexia nervosa is an eating disorder characterized by food restriction due to the strong desire to remain thin. It is considered a mental health diagnosis where people see themselves as obese regardless of their weight or appearance. The person does not necessarily exhibit anorexia as a symptom in their quest to restrict food intake. References == External links ==

Aarogya , Do you know what is Crystalluria,

Crystalluria

Crystalluria refers to crystals found in the urine when performing a urine test. Crystalluria is considered often as a benign condition and as one of the side effects of sulfonamides and penicillins. The main reason for the identification of urinary crystals is to detect the presence of the relatively few abnormal types that may represent a disease. Clinical significance It can be an indication of urolithiasis. It may be relevant when there is presence of specific abnormal types of crystals (cystine, cholesterol, leucine, tyrosine, etc.) and that may be a sign of metabolic or liver disorders such as cystinuria. It leads to formation of stones. References == External links ==

Aarogya, What does Adhesion (medicine) mean

Adhesion (medicine)

Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connects tissues not normally connected. Pathophysiology Adhesions form as a natural part of the bodys healing process after surgery in a similar way that a scar forms. The term "adhesion" is applied when the scar extends from within one tissue across to another, usually across a virtual space such as the peritoneal cavity. Adhesion formation post-surgery typically occurs when two injured surfaces are close to one another. According to the "classical paradigm" of adhesion formation, the pathogenesis starts with inflammation and activation of the coagulation system which causes fibrin deposits onto the damaged tissues. The fibrin then connects the two adjacent structures where damage of the tissues occurred. The fibrin acts like a glue to seal the injury and builds the fledgling adhesion, said at this point to be "fibrinous." In body cavities such as the peritoneal, pericardial, and synovial cavities, a family of fibrinolytic enzymes may act to limit the extent of the initial fibrinous adhesion, and may even dissolve it. In many cases, the production or activity of these enzymes are compromised because of inflammation following injury or infection, however, and the fibrinous adhesion persists. A more recent study suggested that the formation of "fibrinous" adhesions is preceded by the aggregation of cavity macrophages, that can act like extravascular platelets in the abdominal cavity.If this is allowed to happen, tissue repair cells such as macrophages, fibroblasts, and blood vessel cells penetrate into the fibrinous adhesion and lay down collagen and other matrix substances to form a permanent fibrous adhesion. In 2002, Giuseppe Martucciellos research group showed a possible role could be played by microscopic foreign bodies (FB) inadvertently contaminating the operative field during surgery. These data suggested that two different stimuli are necessary for adhesion formation: a direct lesion of the mesothelial layers and a solid substrate foreign body (FB). While some adhesions do not cause problems, others may prevent muscle and other tissues and organs from moving freely, sometimes causing organs to become twisted or pulled from their normal positions. Regions affected Adhesive capsulitis In the case of adhesive capsulitis of the shoulder (also known as frozen shoulder), adhesions grow between the shoulder joint surfaces, restricting motion. Abdominal adhesions Abdominal adhesions (or intra-abdominal adhesions) are most commonly caused by abdominal surgical procedures. The adhesions start to form within hours of surgery and may cause internal organs to attach to the surgical site or to other organs in the abdominal cavity. Adhesion-related twisting and pulling of internal organs may result in complications such as abdominal pain or intestinal obstruction. Small bowel obstruction (SBO) is a significant consequence of post-surgical adhesions. A SBO may be caused when an adhesion pulls or kinks the small intestine and prevents the flow of content through the digestive tract. Obstruction may occur 20 years or more after the initial surgical procedure, if a previously benign adhesion allows the small bowel to twist spontaneously around itself and obstruct. Without immediate medical attention, SBO is an emergent, possibly fatal, condition. According to statistics provided by the National Hospital Discharge Survey approximately 2,000 people die every year in the US from obstruction due to adhesions. Depending on the severity of the obstruction, a partial obstruction may relieve itself with conservative medical intervention. Many obstructive events require surgery, however, to loosen or dissolve the offending adhesion(s) or to resect the affected small intestine. Pelvic adhesions Pelvic adhesions are a form of abdominal adhesions in the pelvis. In women they typically affect reproductive organs and thus are of concern in reproduction or as a cause of chronic pelvic pain. Other than surgery, endometriosis and pelvic inflammatory disease are typical causes. Surgery inside the uterine cavity (e.g., suction dilation and curettage, myomectomy, endometrial ablation) may result in Ashermans syndrome (also known as intrauterine adhesions, intra uterine synechiae), a cause of infertility. The impairment of reproductive performance from adhesions may happen through many mechanisms, all of which usually stem from the distortion of the normal tubo-ovarian relationship. This distortion may prevent an ovum from traveling to the fimbriated end of the Fallopian tube.A meta-analysis in 2012 came to the conclusion that there is only little evidence for the surgical principle that using less invasive techniques, introducing fewer foreign bodies, or causing less ischemia reduces the extent and severity of adhesions in pelvic surgery. Pericardial adhesions Adhesions forming between the heart and the sternum after cardiac surgery place the heart at risk of catastrophic injury during re-entry for a subsequent procedure. Peridural adhesions Adhesions and scarring as epidural fibrosis may occur after spinal surgery that restricts the free movement of nerve roots, causing tethering and leading to pain. Peritendinous adhesions Adhesions and scarring occurring around tendons after hand surgery restrict the gliding of tendons in their sheaths and compromise digital mobility. Association with surgical procedures Applying adhesion barriers during surgery may help to prevent the formation of adhesions. There are two methods that are approved by the U.S. Food and Drug Administration (FDA) for adhesion prevention: Intercede and Seprafilm. One study found that Seprafilm is twice as effective at preventing adhesion formation when compared to just surgical technique alone. Surgical humidification therapy may also minimise the incidence of adhesion formation. Laparoscopic surgery has a reduced risk for creating adhesions. Steps may be taken during surgery to help prevent adhesions such as handling tissues and organs gently, using starch-free and latex-free gloves, not allowing tissues to dry out, and shortening surgery time.An unfortunate fact is, that adhesions are unavoidable in surgery and the main treatment for adhesions is more surgery. Besides intestinal obstructions caused by adhesions that may be seen in an X-ray, there are no diagnostic tests available to accurately diagnose an adhesion. Abdominal surgery A study showed that more than 90% of people develop adhesions following open abdominal surgery and that 55–100% of women develop adhesions following pelvic surgery. Adhesions from prior abdominal or pelvic surgery may obscure visibility and access at subsequent abdominal or pelvic surgery. In a very large study (29,790 participants) published in British medical journal The Lancet, 35% of patients who underwent open abdominal or pelvic surgery were readmitted to the hospital an average of two times after their surgery, due to adhesion-related or adhesion-suspected complications. Over 22% of all readmissions occurred in the first year after the initial surgery. Adhesion-related complexity at reoperation adds significant risk to subsequent surgical procedures.Certain organs and structures in the body are more prone to adhesion formation than others. The omentum is particularly susceptible to adhesion formation; one study found that 92% of post-operative adhesions were found in the omentum. It appears that the omentum is the chief organ responsible for "spontaneous" adhesion formation (i.e. no prior history of surgery). In another study, 100% of spontaneous adhesion formations were associated with the omentum.One method to reduce the formation of adhesions following abdominal surgery is hydroflotation, in which the organs are separated from one another by being floated in a solution. Carpal tunnel surgery The long-term use of a wrist splint during recovery from carpal tunnel surgery may cause adhesion formation. For that reason, it is advised that wrist splints be used only for short-term protection in work environments, but otherwise, splints do not improve grip strength, lateral pinch strength, or bowstringing. Beyond adhesion they also may cause stiffness or flexibility problems. Types There are three general types of adhesions: filmy, vascular, and cohesive, however, their pathophysiology is similar. Filmy adhesions usually do not pose problems. Vascular adhesions are problematic. References External links eMedicineHealth: Adhesions, General and After Surgery Smith, Orla M., Getting adhesions unstuck, Science, November 30, 2018, volume 362, issue 6418, pp. 1014-1016

Hello Aarogya , Do you know what is Renal osteodystrophy,

Renal osteodystrophy

Renal osteodystrophy/adynamic bone disease is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.The traditional types of renal osteodystrophy have been defined on the basis of turnover and mineralization as follows: 1) mild, slight increase in turnover and normal mineralization; 2) osteitis fibrosa, increased turnover and abnormal mineralization; 3) osteomalacia, decreased turnover and abnormal mineralization; 4) adynamic, decreased turnover and acellularity; and, 5) mixed, increased turnover with abnormal mineralization. A Kidney Disease: Improving Global Outcomes report has suggested that bone biopsies in patients with CKD should be characterized by determining bone turnover, mineralization, and volume (TMV system).On the other hand, CKD-MBD is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: 1) abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (renal osteodystrophy); and 3) vascular or other soft-tissue calcification. Signs and symptoms Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they include: Bone pain Joint pain Bone deformation Bone fracture The broader concept of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not only associated with fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). These clinical consequences are acquiring such an importance that scientific working groups (such as the ERA-EDTA CKD-MBD Working Group) or international initiatives are trying to promote research in the field including basic, translational and clinical research. Pathogenesis Renal osteodystrophy has been classically described to be the result of hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney.Low activated vitamin D3 levels are a result of the damaged kidneys inability to convert vitamin D3 into its active form, calcitriol, and result in further hypocalcemia. High levels of fibroblast growth factor 23 seem now to be the most important cause of decreased calcitriol levels in CKD patients.In CKD, the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed excessively by a multitude of factors, including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease.Both high and low bone turnover diseases are currently observed equally in CKD patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes. Diagnosis Renal osteodystrophy is usually diagnosed after treatment for end-stage kidney disease begins; however the CKD-MBD starts early in the course of CKD. In advanced stages, blood tests will indicate decreased calcium and calcitriol (vitamin D) and increased phosphate, and parathyroid hormone levels. In earlier stages, serum calcium, phosphate levels are normal at the expense of high parathyroid hormone and fibroblast growth factor-23 levels. X-rays will also show bone features of renal osteodystrophy (subperiostic bone resorption, chondrocalcinosis at the knees and pubic symphysis, osteopenia and bone fractures) but may be difficult to differentiate from other conditions. Since the diagnosis of these bone abnormalities cannot be obtained correctly by current clinical, biochemical, and imaging methods (including measurement of bone-mineral density), bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy. Differential diagnosis To confirm the diagnosis, renal osteodystrophy must be characterized by determining bone turnover, mineralization, and volume (TMV system) (bone biopsy). All forms of renal osteodystrophy should also be distinguished from other bone diseases which may equally result in decreased bone density (related or unrelated to CKD): osteoporosis osteopenia osteomalacia brown tumor should be considered as the top-line diagnosis if a mass-forming lesion is present. Treatment Treatment for renal osteodystrophy includes the following: calcium and/or native vitamin D supplementation restriction of dietary phosphate (especially inorganic phosphate contained in additives) phosphate binders such as calcium carbonate, calcium acetate, sevelamer hydrochloride or carbonate, lanthanum carbonate, sucroferric oxyhydroxide, ferric citrate among others active forms of vitamin D (calcitriol, alfacalcidol, paricalcitol, maxacalcitol, doxercalciferol, among others) cinacalcet renal transplantation haemodialysis five times a week is thought to be of benefit parathyroidectomy for symptomatic medication refractive end stage disease Prognosis Recovery from renal osteodystrophy has been observed following kidney transplantation. Renal osteodystrophy is a chronic condition with a conventional hemodialysis schedule. Nevertheless, it is important to consider that the broader concept of CKD-MBD, which includes renal osteodystrophy, is not only associated with bone disease and increased risk of fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). Actually, bone may now be considered a new endocrine organ at the heart of CKD-MBD. References External links Renal Osteodystrophy - NKUDIC, NIH

Aarogya, explain a scenario commonly referred as Bowel infarction

Bowel infarction

Bowel infarction or gangrenous bowel represents an irreversible injury to the intestine resulting from insufficient blood flow. It is considered a medical emergency because it can quickly result in life-threatening infection and death. Any cause of bowel ischemia, the earlier reversible form of injury, may ultimately lead to infarction if uncorrected. The causes of bowel ischemia or infarction include primary vascular causes (for example, mesenteric ischemia) and other causes of bowel obstruction. Causes Primary vascular causes of bowel infarction, also known as mesenteric ischemia, are due to blockages in the arteries or veins that supply the bowel. Types of mesenteric ischemia are generally separated into acute and chronic processes, because this helps determine treatment and prognosis.Bowel obstruction is most often caused by intestinal adhesions, which frequently form after abdominal surgeries, or by chronic infections such as diverticulitis, hepatitis, and inflammatory bowel disease. The condition may be difficult to diagnose, as the symptoms may resemble those of other bowel disorders. Bowel volvulus describes a specific form of bowel obstruction, where the intestine and/or mesentery are twisted, resulting in ischemia. Management An infarcted or dead intestinal segment is a serious medical problem because intestines contain non-sterile contents within the lumen. Although the fecal content and high bacterial loads of the intestine are normally safely contained, progressive ischemia causes tissue breakdown and inevitably leads to bacteria spreading to the bloodstream. Untreated bowel infarction quickly leads to life-threatening infection and sepsis, and may be fatal.The only treatment for bowel infarction is immediate surgical repair and eventually removal of the dead bowel segment.Patients who have undergone extensive resection of the small bowel may develop malabsorption, indicating the need for dietary supplements. Additional images See also Adhesions Ischemic colitis Volvulus References == External links ==

Could you describe Adrenal insufficiency, to me Aarogya

Adrenal insufficiency

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.Addisons disease and congenital adrenal hyperplasia can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in abdominal pains, vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis). An adrenal crisis may occur if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow.Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary or tertiary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus, respectively. Types There are three major types of adrenal insufficiency. Primary adrenal insufficiency is due to impairment of the adrenal glands. 80% are due to an autoimmune disease called Addisons disease or autoimmune adrenalitis. One subtype is called idiopathic, meaning of unknown cause. It can also be due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland. Other causes include; Infections (TB, CMV, histoplasmosis, paracoccidioidomycosis), vascular (hemorrhage from sepsis, adrenal vein thrombosis, HIT), deposition disease (hemochromatosis, amyloidosis, sarcoidosis), drugs (azole anti-fungals, etomidate (even one dose), rifampin, anticonvulsants) Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. Its principal causes include pituitary adenoma (which can suppress production of adrenocorticotropic hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced; secondary adrenal insufficiency can be caused by steroids, inhaled steroids such as Flovent; and Sheehans syndrome, which is associated with impairment of only the pituitary gland. Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone (CRH). Causes can include brain tumors and sudden withdrawal from long-term exogenous steroid use (which is the most common cause overall). Signs and symptoms Signs and symptoms include: hypoglycemia, hyperpigmentation, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addisons disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present. Eosinophilia may also occur. Hyponatremia is a sign of secondary insufficiency. Causes Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse–Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addisons Disease), tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimotos thyroiditis, and Hashimotos disease). Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.X-Linked Recessive Adrenoleukodystrophy can also cause adrenal insufficiency.Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage). Corticosteroid withdrawal Use of high-dose steroids for more than a week begins to produce suppression of the persons adrenal glands because the exogenous glucocorticoids suppress release of hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the person is vulnerable to adrenal insufficiency during times of stress, such as illness, due to both adrenal atrophy and suppression of CRH and ACTH release. Use of steroids joint injections may also result in adrenal suppression after discontinuation. Adrenal dysgenesis All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia due to DAX-1 gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes. Impaired steroidogenesis To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia.Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin). Adrenal destruction Autoimmune adrenalitis is the most common cause of Addisons disease in the industrialised world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.Adrenal destruction is also a feature of adrenoleukodystrophy (ALD), and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis. Pathophysiology Hyponatremia can be caused by glucocorticoid deficiency. Low levels of glucocorticoids leads to systemic hypotension (one of the effects of cortisol is to increase peripheral resistance), which results in a decrease in stretch of the arterial baroreceptors of the carotid sinus and the aortic arch. This removes the tonic vagal and glossopharyngeal inhibition on the central release of ADH: high levels of ADH will ensue, which will subsequently lead to increase in water retention and hyponatremia.Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance (in fact a positive sodium balance may occur). Diagnosis The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be experiencing an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patients health can deteriorate rapidly and result in death without replacing the corticosteroids.Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addisons Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies. Effects Treatment Adrenal crisis Intravenous fluids Intravenous steroid (Solu-Cortef/injectable hydrocortisone) later hydrocortisone, prednisone or methylpredisolone tablets Rest Cortisol deficiency (primary and secondary) Hydrocortisone (Cortef) Prednisone (Deltasone) Prednisolone (Delta-Cortef) Methylprednisolone (Medrol) Dexamethasone (Decadron) Hydrocortisone granules in capsules for opening (Alkindi) Mineralocorticoid deficiency (low aldosterone) Fludrocortisone acetate(To balance sodium, potassium and increase water retention) See also Addisons disease – primary adrenocortical insufficiency Cushings syndrome – overproduction of cortisol Insulin tolerance test – another test used to identify sub-types of adrenal insufficiency Adrenal fatigue (hypoadrenia) – a term used in alternative medicine to describe a believed exhaustion of the adrenal glands References Further reading Bornstein, Stefan R.; Allolio, Bruno; Arlt, Wiebke; Barthel, Andreas; Don-Wauchope, Andrew; Hammer, Gary D.; Husebye, Eystein S.; Merke, Deborah P.; Murad, M. Hassan; Stratakis, Constantine A.; Torpy, David J. (February 2016). "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 101 (2): 364–389. doi:10.1210/jc.2015-1710. PMC 4880116. PMID 26760044. == External links ==

Hello Aarogya, could you help me understand about Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems.People who have HCM may have a range of symptoms. People may be asymptomatic, or may have fatigue, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Symptoms may be worse when the person is dehydrated. Complications may include heart failure, an irregular heartbeat, and sudden cardiac death.HCM is most commonly inherited from a persons parents in an autosomal dominant pattern. It is often due to mutations in certain genes involved with making heart muscle proteins. Other inherited causes of left ventricular hypertrophy may include Fabry disease, Friedreichs ataxia, and certain medications such as tacrolimus. Other considerations for causes of enlarged heart are athletes heart and hypertension (high blood pressure). Making the diagnosis of HCM often involves a family history or pedigree, an electrocardiogram, echocardiogram, and stress testing. Genetic testing may also be done. HCM can be distinguished from other inherited causes of cardiomyopathy by its autosomal dominant pattern, whereas Fabry disease is X-linked and Friedreichs Ataxia is inherited in an autosomal recessive pattern.Treatment may depend on symptoms and other risk factors. Medications may include the use of beta blockers or disopyramide. An implantable cardiac defibrillator may be recommended in those with certain types of irregular heartbeat. Surgery, in the form of a septal myectomy or heart transplant, may be done in those who do not improve with other measures. With treatment, the risk of death from the disease is less than one percent per year.HCM affects about one in 500 people. Rates in men and women are about equal. People of all ages may be affected. The first modern description of the disease was by Donald Teare in 1958. Signs and symptoms The cause of HCM is variable. Many people are asymptomatic or mildly symptomatic, and many of those carrying disease genes for HCM do not have clinically detectable disease. The symptoms of HCM include shortness of breath due to stiffening and decreased blood filling of the ventricles, exertional chest pain (sometimes known as angina) due to reduced blood flow to the coronary arteries, uncomfortable awareness of the heart beat (palpitations), as well as disruption of the electrical system running through the abnormal heart muscle, lightheadedness, weakness, fainting and sudden cardiac death.Shortness of breath is largely due to increased stiffness of the left ventricle (LV), which impairs filling of the ventricles, but also leads to elevated pressure in the left ventricle and left atrium, causing back pressure and interstitial congestion in the lungs. Symptoms are not closely related to the presence or severity of an outflow tract gradient. Often, symptoms mimic those of congestive heart failure (esp. activity intolerance and dyspnea), but treatment of each is different. Beta blockers are used in both cases, but treatment with diuretics, a mainstay of CHF treatment, will exacerbate symptoms in hypertrophic obstructive cardiomyopathy by decreasing ventricular preload volume and thereby increasing outflow resistance (less blood to push aside the thickened obstructing tissue).Major risk factors for sudden death in individuals with HCM include prior history of cardiac arrest or ventricular fibrillation, spontaneous sustained ventricular tachycardia, abnormal exercise blood pressure and non-sustained ventricular tachycardia, unexplained syncope, family history of premature sudden death, and LVW thickness greater than 15 mm to 30 mm, on echocardiogram. "Spike and dome" pulse and "triple ripple apical impulse" are two other signs that can be discovered in physical examination. Genetics Familial hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for the sarcomere proteins. Currently, about 50–60% of people with a high index of clinical suspicion for HCM will have a mutation identified in at least one of nine sarcomeric genes. Approximately 40% of these mutations occur in the β-myosin heavy chain gene on chromosome 14 q11.2-3, and approximately 40% involve the cardiac myosin-binding protein C gene. Since HCM is typically an autosomal dominant trait, children of a single HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever such a mutation is identified, family-specific genetic testing can be used to identify relatives at-risk for the disease, although clinical severity and age of onset cannot be predicted.An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes.Some mutations could have more harmful potential compared to others (β-myosin heavy chain). For example, troponin T mutations were originally associated with a 50% mortality before the age of 40. However, a more recent and larger study found a similar risk to other sarcomeric protein mutations. The age at disease onset of HCM with MYH7 is earlier and leads to more severe symptoms. Moreover, mutations on troponin C can alter Ca+2 sensibility on force development in cardiac muscle, these mutations are named after the amino acid that was changed after the location in which it happened, such as A8V, A31S, C84Y and D145E. Diagnosis A diagnosis of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there is use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other important considerations include ECG, genetic testing (although not primarily used for diagnosis), and any family history of HCM or unexplained sudden death in otherwise healthy individuals. In about 60 to 70% of the cases, cardiac MRI shows thickening of more than 15 mm of the lower part of the ventricular septum. T1-weighted imaging may identify scarring of cardiac tissues while T2-weighted imaging may identify oedema and inflammation of cardiac tissue which is associated with acute clinical signs of chest pain and fainting episodes.Pulsus bisferiens may occasional be found during examination. Variants Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, HCM can be classified as obstructive or non-obstructive. The obstructive variant of HCM is hypertrophic obstructive cardiomyopathy (HOCM), also historically known as idiopathic hypertrophic subaortic stenosis(IHSS) or asymmetric septal hypertrophy (ASH). The diagnosis of left ventricular outflow tract obstruction is usually made by echocardiographic assessment and is defined as a peak left ventricular outflow tract gradient of ≥ 30 mmHg.Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy (AHC), also called Yamaguchi syndrome. It was first described in individuals of Japanese descent. Cardiac catheterization Upon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle.The Brockenbrough–Braunwald–Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient.While the Brockenbrough–Braunwald–Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM. Screening Although HCM may be asymptomatic, affected individuals may present with symptoms ranging from mild to critical heart failure and sudden cardiac death at any point from early childhood to seniority. HCM is the leading cause of sudden cardiac death in young athletes in the United States, and the most common genetic cardiovascular disorder. One study found that the incidence of sudden cardiac death in young competitive athletes declined in the Veneto region of Italy by 89% since the 1982 introduction of routine cardiac screening for athletes, from an unusually high starting rate. As of 2010, however, studies have shown that the incidence of sudden cardiac death, among all people with HCM, has declined to one percent or less. Screen-positive individuals who are diagnosed with cardiac disease are usually told to avoid competitive athletics.HCM can be detected with an echocardiogram (ECHO) with 80%+ accuracy, which can be preceded by screening with an electrocardiogram (ECG) to test for heart abnormalities. Cardiac magnetic resonance imaging (CMR), considered the gold standard for determining the physical properties of the left ventricular wall, can serve as an alternative screening tool when an echocardiogram provides inconclusive results. For example, the identification of segmental lateral ventricular hypertrophy cannot be accomplished with echocardiography alone. Also, left ventricular hypertrophy may be absent in children under thirteen years of age. This undermines the results of pre-adolescents echocardiograms. Researchers, however, have studied asymptomatic carriers of an HCM-causing mutation through the use of CMR and have been able to identify crypts in the interventricular septal tissue in these people. It has been proposed that the formation of these crypts is an indication of myocyte disarray and altered vessel walls that may later result in the clinical expression of HCM. A possible explanation for this is that the typical gathering of family history only focuses on whether sudden death occurred or not. It fails to acknowledge the age at which relatives had had sudden cardiac death, as well as the frequency of the cardiac events. Furthermore, given the several factors necessary to be considered at risk for sudden cardiac death, while most of the factors do not have strong predictive value individually, there exists ambiguity regarding when to implement special treatment. United States There are several potential challenges associated with routine screening for HCM in the United States. First, the U.S. athlete population of 15 million is almost twice as large as Italys estimated athlete population. Second, these events are rare, with fewer than 100 deaths in the U.S. due to HCM in competitive athletes per year, or about 1 death per 220,000 athletes. Lastly, genetic testing would provide a definitive diagnosis; however, due to the numerous HCM-causing mutations, this method of screening is complex and is not cost-effective. Therefore, genetic testing in the United States is limited to individuals who exhibit clear symptoms of HCM, and their family members. This ensures that the test is not wasted on detecting other causes of ventricular hypertrophy (due to its low sensitivity), and that family members of the individual are educated on the potential risk of being carriers of the mutant gene(s). Canada Canadian genetic testing guidelines and recommendations for individuals diagnosed with HCM are as follows: The main purpose of genetic testing is for screening family members. According to the results, at-risk relatives may be encouraged to undergo extensive testing. Genetic testing is not meant for confirming a diagnosis. If the diagnosed individual has no relatives that are at risk, then genetic testing is not required. Genetic testing is not intended for risk assessment or treatment decisions. Evidence only supports clinical testing in predicting the progression and risk of developing complications of HCM.For individuals suspected of having HCM: Genetic testing is not recommended for determining other causes of left ventricular hypertrophy (such as "athletes heart", hypertension, and cardiac amyloidosis). HCM may be differentiated from other hypertrophy-causing conditions using clinical history and clinical testing. Treatment Asymptomatic people A significant number of people with hypertrophic cardiomyopathy do not have any symptoms and will have a normal life expectancy, although they should avoid particularly strenuous activities or competitive athletics. Asymptomatic people should be screened for risk factors for sudden cardiac death. In people with resting or inducible outflow obstructions, situations that will cause dehydration or vasodilation (such as the use of vasodilatory or diuretic blood pressure medications) should be avoided. Septal reduction therapy is not recommended in asymptomatic people. Medications The primary goal of medications is to relieve symptoms such as chest pain, shortness of breath, and palpitations. Beta blockers are considered first-line agents, as they can slow down the heart rate and decrease the likelihood of ectopic beats. For people who cannot tolerate beta blockers, nondihydropyridine calcium channel blockers such as verapamil can be used, but are potentially harmful in people who also have low blood pressure or severe shortness of breath at rest. These medications also decrease the heart rate, though their use in people with severe outflow obstruction, elevated pulmonary artery wedge pressure, and low blood pressures should be done with caution. Dihydropyridine calcium channel blockers should be avoided in people with evidence of obstruction. For people whose symptoms are not relieved by the above treatments, disopyramide can be considered for further symptom relief. Diuretics can be considered for people with evidence of fluid overload, though cautiously used in those with evidence of obstruction. People who continue to have symptoms despite drug therapy can consider more invasive therapies. Intravenous phenylephrine (or another pure vasoconstricting agent) can be used in the acute setting of low blood pressure in those with obstructive hypertrophic cardiomyopathy who do not respond to fluid administration.Mavacamten was approved for medical use in the United States in April 2022. Surgical septal myectomy Surgical septal myectomy is an open-heart operation done to relieve symptoms in people who remain severely symptomatic despite medical therapy. It has been performed successfully since the early 1960s. Surgical septal myectomy uniformly decreases left ventricular outflow tract obstruction and improves symptoms, and in experienced centers has a surgical mortality of less than 1%, as well as 85% success rate. It involves a median sternotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum. Surgical myectomy resection that focuses just on the subaortic septum, to increase the size of the outflow tract to reduce Venturi forces, may be inadequate to abolish systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. With this limited resection, the residual mid-septal bulge still redirects flow posteriorly; SAM persists because flow still gets behind the mitral valve. It is only when the deeper portion of the septal bulge is resected that flow is redirected anteriorly away from the mitral valve, abolishing SAM. With this in mind, a modification of the Morrow myectomy termed extended myectomy, mobilization and partial excision of the papillary muscles has become the excision of choice. In people with particularly large redundant mitral valves, anterior leaflet plication may be added to complete separation of the mitral valve and outflow. Complications of septal myectomy surgery include possible death, arrhythmias, infection, incessant bleeding, septal perforation/defect, and stroke. Alcohol septal ablation Alcohol septal ablation, introduced by Ulrich Sigwart in 1994, is a percutaneous technique that involves injection of alcohol into one or more septal branches of the left anterior descending artery. This is a catheter technique with results similar to the surgical septal myectomy procedure but is less invasive, since it does not involve general anaesthesia and opening of the chest wall and pericardium (which are done in a septal myectomy). In a select population with symptoms secondary to a high outflow tract gradient, alcohol septal ablation can reduce the symptoms of HCM. In addition, older individuals and those with other medical problems, for whom surgical myectomy would pose increased procedural risk, would likely benefit from the less-invasive septal ablation procedure.When performed properly, an alcohol septal ablation induces a controlled heart attack, in which the portion of the interventricular septum that involves the left ventricular outflow tract is infarcted and will contract into a scar. There is debate over which people are best served by surgical myectomy, alcohol septal ablation, or medical therapy. Mitral clip Since 2013, mitral clips have been implanted via catheter as a new strategy to correct the motion of the mitral valve in people with severe obstructive HCM. The device fastens together the mitral valve leaflets to improve the hearts blood outflow. The mitral clip has not yet established the long-term reliability of septal myectomy or alcohol septal ablation, but HCM specialists are increasingly offering the clip as a less-invasive treatment option. Implantable pacemaker or defibrillator The use of a pacemaker has been advocated in a subset of individuals, in order to cause asynchronous contraction of the left ventricle. Since the pacemaker activates the interventricular septum before the left ventricular free wall, the gradient across the left ventricular outflow tract may decrease. This form of treatment has been shown to provide less relief of symptoms and less of a reduction in the left ventricular outflow tract gradient when compared to surgical myectomy. Technological advancements have also led to the development of a dual-chamber pacemaker, which is only turned on when needed (in contrast to a regular pacemaker which provides a constant stimulus). Although the dual-chamber pacemaker has shown to decrease ventricular outflow tract obstruction, experimental trials have found only a few individuals with improved symptoms. Researchers suspect that these reports of improved symptoms are due to a placebo effect.The procedure includes an incision on the anterolateral area below the clavicle. Two leads are then inserted; one into the right atrium and the other into the right ventricular apex via the subclavian veins. Once in place, they are secured and attached to the generator which will remain inside the fascia, anterior to the pectoral muscle. Complications of this procedure include infection, electrical lead and generator malfunction which will require replacement.For people with HCM who exhibit one or more of the major risk factors for sudden cardiac death, an implantable cardioverter-defibrillator (ICD) or a combination pacemaker/ICD all-in-one unit may be recommended as an appropriate precaution. In 2014, European Society of Cardiology suggested a practical risk score to calculate that risk. Cardiac transplantation In cases that are unresponsive to all other forms of treatment, cardiac transplantation is one option. It is also the only treatment available for end-stage heart failure. However, transplantation must occur before the onset of symptoms such as pulmonary vessel hypertension, kidney malfunction, and thromboembolism in order for it to be successful. Studies have indicated a seven-year survival rate of 94% in people with HCM after transplantation. Prognosis A systematic review from 2002 concluded that: "Overall, HCM confers an annual mortality rate of about 1%... HCM may be associated with important symptoms and premature death but more frequently with no or relatively mild disability and normal life expectancy." Children Even though hypertrophic cardiomyopathy (HCM) may be present early in life and is most likely congenital, it is one of the most-uncommon cardiac malformations encountered in pediatric cardiology, largely because the presentation of symptoms is usually absent, incomplete, or delayed into adulthood. Most of the current information pertaining to HCM arises from studies in adult populations, and the implication of these observations for pediatric population is often uncertain. Nonetheless, recent studies in pediatric cardiology have revealed that HCM accounts for 42% of childhood cardiomyopathies, with an annual incidence rate of 0.47/100,000 in children. Further, in asymptomatic cases, sudden death is considered one of the most-feared complications associated with the disease in select pediatric populations. Consequently, the recommended practice is to screen children of affected individuals throughout childhood to detect cardiac abnormalities at an early stage, in the hope of preventing further complications of the disease.Generally, the diagnosis of HCM in a pediatric population is made during assessment for murmur, congestive heart failure, physical exhaustion, and genetic testing of children of affected individuals. Specifically, echocardiogram (ECHO) has been used as a definitive noninvasive diagnostic tool in nearly all children. ECHO assesses cardiac ventricular size, wall thickness, systolic and diastolic function, and outflow obstruction. Thus, ECHO has been chosen as an ideal means to detect excessive wall thickening of cardiac muscle in HCM.For children with HCM, treatment strategies aim to reduce disease symptoms and lower the risk of sudden death. Due to the heterogeneity of the disease, treatment is usually modified according to individuals needs. β-blockers improve left ventricular filling and relaxation and thereby improve symptoms. In some children, β–blockers (e.g., propranolol) were shown effective to reduce the risk of sudden death. Further, calcium channel blockers (verapamil) and antiarrhythmic drugs may be used as an adjunct therapy to β-blockers in symptomatic children. Nonetheless, further testing is needed to determine their definitive benefits. Other animals Cats Feline hypertrophic cardiomyopathy (HCM) is the most common heart disease in domestic cats; the disease process and genetics are believed to be similar to the disease in humans. In Maine Coon cats, HCM has been confirmed as an autosomal dominant inherited trait. Numerous cat breeds have HCM as a problem in the breed. The first genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was discovered in 2005 in Maine Coon cats. A test for this mutation (A31P) is available. About one-third of Maine Coon cats tested for the mutation are either heterozygous or homozygous for the mutation, although many of the cats that are heterozygous have no overt evidence of the disease on an echocardiogram (low penetrance). Some Maine Coon cats with clinical evidence of hypertrophic cardiomyopathy test negative for this mutation, strongly suggesting that another cause exists in the breed. The cardiac myosin binding protein C mutation identified in Maine Coon cats has not been found in any other breed of cat with HCM, but more recently another myosin binding protein C mutation has been identified in Ragdoll cats with HCM. As in humans, feline HCM is not present at birth but develops over time. It has been identified for the first time in cats as young as 6 months of age and at least as old as 7 years of age.Clinically, cats with hypertrophic cardiomyopathy commonly have a systolic anterior motion (SAM) of the mitral valve (see graphic). Cats with severe HCM often develop left heart failure (pulmonary edema; pleural effusion) because of severe diastolic dysfunction of the left ventricle. They may also develop a left atrial thrombus that embolizes, most commonly, to the terminal aorta creating acute pain and rear limb paralysis (see below). Sudden death can also occur but appears to be uncommon.Ultrasound of the heart (echocardiography) is necessary to diagnose HCM in cats. Measurement of circulating cardiac biomarkers, like N‐terminal‐proBNP (NT‐proBNP) and troponin I (TnI) may be used in cats to strengthen the suspicion of cardiac disease. There is a Point-of-care test for feline NT-proBNP available which can be used at the veterinary clinic when echocardiography is not possible to perform.There is no cure for feline HCM. Many but not all cats have a heart murmur. Many cats that have a heart murmur do not have HCM. Frequently the first signs that a cat has HCM are tachypnea/dyspnea due to heart failure or acute pain and paralysis due to systemic thromboembolism. While medication is commonly given to cats with HCM that have no clinical signs, no medication has been shown to be helpful at this stage and it has been shown that an ACE inhibitor is not beneficial until heart failure is present (at which time a diuretic is most beneficial). Diltiazem generally produces no demonstrable benefit. Atenolol is commonly administered when a severe systolic anterior motion of the mitral valve is present.Feline arterial thromboembolism (FATE) is a relatively common and devastating complication of feline HCM and other feline cardiomyopathies. The thrombus generally forms in the left atrium, most commonly the left auricle. The formation is thought to be primarily due to blood flow stasis. Classically, the thromboembolism lodges at the iliac trifurcation of the aorta, occluding either one or both of the common iliac arteries. Because this split is called the saddle, and is the most frequent location for the thrombus, FATE is commonly known as saddle thrombus. Clinically this presents as a cat with complete loss of function in one or both hind limbs. The hind limbs are cold and the cat is in considerable pain. Emboli may, rarely, lodge in other locations, most commonly the right front limb and the renal arteries.Clopidogrel is used to try to prevent left atrial thrombus formation in cats with HCM and a large left atrium. The FATCAT study at Purdue University demonstrated that it is superior to aspirin for the prevention of a second thrombus from forming in cats that have already experienced a clot. Thrombolytic agents (e.g., tissue plasminogen activator) have been used with some success to break down an existing aortic thromboembolism, but their cost is high and outcome appears to be no better than giving a cat time (48–72 hours) to break down its own clot. Pain management is extremely important. The prognosis for cats with FATE is often poor as they are likely to have significant HCM already and a recurrent bout of FATE is likely. For this reason, euthanasia is often a valid consideration. Gorillas In July 2013, Rigo, a 42-year-old western lowland gorilla, resident in Melbourne Zoo and father of Mzuri, the first gorilla born by artificial insemination, died unexpectedly as a result of HCM. The condition is not uncommon in male gorillas over the age of 30, and in many cases, there is no sign of the disease until the individuals sudden death. References External links Hypertrophic cardiomyopathy at Curlie GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview National Heart, Blood, and Lung Institute Cardiomyopathy Page

Aarogya what is Linear IgA bullous dermatosis

Linear IgA bullous dermatosis

Linear IgA bullous dermatosis is a rare immune-mediated blistering skin disease frequently associated with medication exposure, especially vancomycin, with men and women being equally affected.: 135  It was first described by Tadeusz Chorzelski in 1979 and may be divided into two types:: 587  Adult linear IgA disease is an acquired, autoimmune blistering disease that may present with a clinical pattern of vesicles indistinguishable from dermatitis herpetiformis, or with vesicles and bullae in a bullous pemphigoid-like appearance. This disease can often be difficult to treat even with usually effective medications such as rituximab. Childhood linear IgA disease (also known as "Chronic bullous disease of childhood") is an acquired, self-limited bullous disease that may begin by the time the patient is age 2 to 3 and usually remits by age 13. See also Skin lesion List of cutaneous conditions List of target antigens in pemphigoid List of immunofluorescence findings for autoimmune bullous conditions References == External links ==

Do you know what is Burping, Aarogya

Burping

Burping (also called belching and eructation) is the release of gas from the upper digestive tract (esophagus and stomach) of animals through the mouth. It is usually audible. In humans, burping can be caused by normal eating processes, or as a side effect of other medical conditions. There is a range of levels of social acceptance for burping: within certain context and cultures, burping is acceptable, while in others it is offensive or unacceptable. Failure to burp can cause pain or other negative effects. Humans are not the only animals that burp: it is very common among other mammals. In particular, burping by domesticated ruminants, such as cows or sheep, is a major contributor of methane emissions which cause climate change and negatively impacts animal agriculture on the environment. Significant research is being done to find mitigation strategies for ruminant burping, i.e. modifying the animals diets with Asparagopsis taxiformis (red seaweed). Causes Burping is usually caused by swallowing air when eating or drinking and subsequently expelling it, in which case the expelled gas is mainly a mixture of nitrogen and oxygen. Burps can be caused by drinking beverages containing carbon dioxide, such as beer and soft drinks, in which case the expelled gas is mainly carbon dioxide. Diabetes drugs such as metformin and exenatide can cause burping, especially at higher doses. This often resolves in a few weeks. Burping combined with other symptoms such as dyspepsia, nausea and heartburn may be a sign of an ulcer or hiatal hernia, and should be reviewed by a physician. Other causes of burping include food allergies, gallbladder diseases, H. pylori, acid reflux disease and gastritis. Complications In microgravity environments, burping is frequently associated with regurgitation. With reduced gravity, the stomach contents are more likely to rise up into the esophagus when the gastroesophageal sphincter is relaxed, along with the expelled air. Disorders Inability to burp is uncommon. Chest pain associated with burping can occur, but is rare. Retrograde cricopharyngeus dysfunction (R-CPD) involves the cricopharyngeus muscle not being able to relax. R-CPD was first discovered in 2015 when a user inquired with symptoms on Reddit. Several other users found the post online, mentioning they had a similar condition. Common symptoms include gurgling noises, bloating, flatulence, lesser but common symptoms can be potentially painful hiccups, nausea, constipation, hypersalivation, or shortness of breath. 80% of patients were successfully treated with Botox after a single injection. An alternative if the injection is unsuccessful is to undergo partial cricopharyngeal myotomy. Society and culture Acceptance Some South Asian cultures view burping as acceptable in particular situations. For example, a burping guest can be a sign to the host that the meal satisfied them and they are full.In Japan, burping during a meal is considered bad manners. Burping during a meal is also considered unacceptable in Western cultures, such as North America and Europe. In Middle Eastern countries, it is not acceptable to burp out loud in public, and one should silence ones burp, or at least attempt to do so.Despite virtually no scientific research on the subject, small online communities exist for burping as a sexual fetish. Online, both men and women of any sexual orientation anecdotally report some attraction to burping, with what appears to be psychological and/or behavioural overlaps with other sexual fetishes including body inflation, feederism, vorarephilia, and farting fetishes. Anecdotally, the loudness aspect appears to be an important element to burp fetishists. Despite being a rather uncommon fetish, it continues to follow a general well-known pattern of sexual behaviour where hearing influences sexual arousal and response, noting that "it is the noise made rather than the action itself that appears to be what is sexualized and/or interpreted by the fetishist as sexually pleasurable and arousing". Infants Babies are likely to accumulate gas in the stomach while feeding and experience considerable discomfort (and agitation) until assisted. Burping an infant involves placing the child in a position conducive to gas expulsion (for example against the adults shoulder, with the infants stomach resting on the adults chest) and then lightly patting the lower back. Because burping can cause vomiting, a "burp cloth" or "burp pad" is sometimes employed on the shoulder to protect clothing. Contest The Guinness World Record for the loudest burp is 109.9 dB, set by Paul Hunn at Butlins Bognor Regis, United Kingdom, on 23 August 2009. This is louder than a jackhammer at a distance of 1 m (3 ft 3 in). Burped speech It is possible to voluntarily induce burping through swallowing air and then expelling it, and by manipulation of the vocal tract produce burped speech. While this is often employed as a means of entertainment or competition, it can also act as an alternative means of vocalisation for people who have undergone a laryngectomy, with the burp replacing laryngeal phonation. This is known as esophageal speech. Other animals Many other mammals, such as cows, dogs and sheep, also burp. Ruminants Much of the gas expelled is produced as a byproduct of the ruminants digestive process. These gases notably include a large volume of methane, produced exclusively by a narrow cohort of methanogenic archaea in the animals gut; Escherichia coli (E. coli) and other bacteria lack the enzymes and cofactors required for methane production. A lactating cow produces about 322g of methane per day, i.e. more than 117 kg per year through burping and exhalation, making commercially farmed cows a major (37%) contributor to anthropogenic methane emissions, and hence to the greenhouse effect. 95% of this gas (wind) is emitted through burping. This has led scientists at the Commonwealth Scientific and Industrial Research Organisation of Perth, Australia, to develop an anti-methanogen vaccine to minimize methane in cow burps.One reason why cows burp so much is that they are often fed foods that their digestive systems cannot fully process, such as corn and soy. Some farmers have reduced burping in their cows by feeding them alfalfa and flaxseed, which are closer to the grasses that they had eaten in the wild before they were domesticated.The failure to burp successfully can be fatal. This is particularly common among domesticated ruminants that are allowed to gorge themselves on spring clover or alfalfa. The condition, known as ruminal tympany, is a high-pressure buildup of gas in the stomach(s) and requires immediate treatment to expel the gas, usually the insertion of a flexible rubber hose down the esophagus, or in extreme cases the lancing of the animals side with a trochar and cannula. Birds There is no documented evidence that birds burp, though ornithologists believe that there is nothing which physiologically prevents them from doing so. However, since the microbiota of birds do not include the same set of gas-producing bacteria that mammals have to aid in digestion, gas rarely builds up in the gastrointestinal tracts of birds. See also Flatulence Hiccup Penelope and the Humongous Burp References == External links ==

Aarogya, elaborate on Cardiac fibrosis

Cardiac fibrosis

Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle. Fibrocyte cells normally secrete collagen, and function to provide structural support for the heart. When over-activated this process causes thickening and fibrosis of the valve, with white tissue building up primarily on the tricuspid valve, but also occurring on the pulmonary valve. The thickening and loss of flexibility eventually may lead to valvular dysfunction and right-sided heart failure. Types Following are types of myocardial fibrosis: Interstitial fibrosis, which is unspecific, and has been described in congestive heart failure, hypertension, and normal aging. Subepicardial fibrosis, also unspecific, and is associated with non-infarction diagnoses such as myocarditis and non-ischemic cardiomyopathy. Replacement fibrosis, which indicates an older infarction. Connection with excess blood serotonin (5-HT) Certain diseases such as neuroendocrine tumor of the small intestine (also known by the obsolete term carcinoid), which sometimes release large amounts of 5-hydroxytryptamine, commonly known as 5-HT or serotonin into the blood, may produce a characteristic pattern of mostly right-sided cardiac fibrosis which can be identified with echocardiography. Cardiac fibrosis is a significant source of morbidity and mortality in patients with functional neuroendocrine tumors. This pathology has also been seen in certain East-African tribes who eat foods (Matoke —a green banana) containing excess amounts of serotonin. Connection with direct serotonergic agonist drugs Elevated prevalence of cardiac fibrosis and related valvopathies was found to be associated with use of a number of unrelated drugs following long-term statistical analysis once the drugs had been on the market for some time. The cause of this was unknown at the time, but eventually it was realised that all the implicated drugs acted as agonists at 5-HT2B receptors in the heart in addition to their intended sites of action elsewhere in the body.The precise mechanisms involved remain elusive however, as while the cardiotoxicity shows some dose–response relationship, it does not always develop, and consistent daily use over an extended period tends to be most strongly predictive of development of valvopathy.The drugs most classically associated with the condition are weight loss drugs such as fenfluramine and chlorphentermine, and antiparkinson drugs such as pergolide and cabergoline, which are prescribed for chronic use.The heart valve changes seen with moderate and intermittent use can result in permanent damage and life-threatening heart problems if use of the causative drug is increased or continued, however longitudinal studies of former patients suggest that the damage will heal over time to some extent at least. Anorectics Some appetite suppressant drugs such as fenfluramine (which in combination with phentermine was marketed as Pondimin and commonly referred to as fen-phen), chlorphentermine, and aminorex (along with its analogue 4-Methylaminorex which has seen sporadic use as a recreational drug) induce a similar pattern of cardiac fibrosis (and pulmonary hypertension), apparently by overstimulating 5HT2B receptors on the cardiac fibroblast cells.These drugs consequently tend to cause increased risk of heart valve damage and subsequent heart failure, which eventually led to them being withdrawn from the market. Antimigraine drugs Certain antimigraine drugs which are targeted at serotonin receptors as vasoconstrictive agents, have long been known to be associated with pulmonary hypertension and Raynauds phenomenon (both vasoconstrictive effects), as well as retroperitoneal fibrosis (a fibrotic cell/fibrocyte proliferation effect, thought to be similar to cardiac valve fibrosis).These drugs include ergotamine and methysergide and both drugs can also cause cardiac fibrosis. Antiparkinson drugs Certain antiparkinson drugs, although targeted at dopaminergic receptors, cross-react with serotoninergic 5-HT2B receptors as well, and have been reported to cause cardiac fibrosis. These drugs include pergolide and cabergoline. Antihypertensive drugs Guanfacine may be a 5-HT2B agonist, based on the results of theoretical modeling and high-throughput screening. Pergolide Pergolide was an antiparkinson medications that was in decreasing use since reported in 2003 to be associated with cardiac fibrosis. In March 2007, pergolide was withdrawn from the U.S. market due to serious valvular damage that was shown in two independent studies. Cabergoline Like pergolide, cabergoline has been linked to cardiac damage. Among similar antiparkinsonian drugs, cabergoline exhibits the same type of serotonin receptor binding as pergolide. Although lisuride, a related drug, also binds to the 5-HT2B receptor, it acts as an antagonist rather than as an agonist.In January 2007, cabergoline (Dostinex) was reported also to be associated with valvular proliferation heart damage. Recreational drugs Several serotonergic recreational drugs, including the empathogens MDA and MDMA ("ecstasy"), and some hallucinogens such as DOI and Bromo-DragonFLY, have all been shown to act as 5-HT2B agonists in vitro, but how significant this may be as a risk factor associated with their recreational use is unclear. The piperazine derivative mCPP (a major metabolite of trazodone) is a 5-HT2B agonist in animal models, but actually behaves as a 5-HT2B antagonist in humans. MDMA One study of human users of MDMA ("ecstasy") found that they did have heart valve changes suggestive of early cardiac fibrosis, which were not present in non-MDMA using controls, suggesting that MDMA use certainly has the potential to cause this kind of heart damage.On the other hand, there is as yet no statistical evidence to establish or negate significant increases in rates of cardiac valvopathies in current or former MDMA users. Absent studies on point, it may be speculated that as with other 5-HT2B agonists, development of heart valve damage may be dependent on the frequency and duration of use and the total cumulative exposure over time. If that is the case, then the heaviest users are likely to face the greatest risk of heart damage. Other serotonergic pharmacologics in question The SSRI antidepressants raise blood serotonin levels, and thus may be capable of the same risks, though it is thought that the risk is substantially lower with such drugs. The amino acid L-tryptophan also raises blood serotonin, and may present the same risk as well; though, again, the risk is considered to be low.However, the tryptophan derivative 5-HTP (5-hydroxytryptophan), used in the treatment of depression, raises blood serotonin level considerably. It has yet to be reported to be associated with valve disease or other fibrosis, but for the previous theoretical reasons, it has been suggested as a possible danger.When 5-HTP is used in medicine, it is generally administered along with carbidopa, which prevents the peripheral decarboxylation of 5-HTP to serotonin and so ensures that only brain serotonin levels are increased without producing peripheral side effects, however 5-HTP is also sold without carbidopa as a dietary supplement, and may have increased risks when taken by itself without carbidopa. In non-human great apes Cardiac fibrosis is common in non-human great apes in human care. The term idiopathic myocardial fibrosis was coined to emphasize this disease is likely different from the above described forms of cardiac fibrosis in humans. The etiology is not known, though vitamin D deficiency is a potential suspected cause at least in chimpanzees. Possible treatments The most obvious treatment for cardiac valve fibrosis or fibrosis in other locations, consists of stopping the stimulatory drug or production of serotonin. In the case of a functional neuroendocrine tumor, somatostatin analogs such as octreotide are used to reduce the production of serotonin by tumor cells, which often highly express inhibitory somatostatin receptors.Surgical tricuspid valve replacement, sometimes combined with a pulmonary valve replacement, can be necessary in some patients.A compound found in red wine, resveratrol has been found to slow the development of cardiac fibrosis. More sophisticated approaches of countering cardiac fibrosis like microRNA inhibition (miR-21, for example) are being tested in animal models. == References ==

Aarogya, elaborate on Fasciculation

Fasciculation

A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions. When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome. Diagnosis The most effective way to detect fasciculations may be surface electromyography (EMG). Surface EMG is more sensitive than needle electromyography and clinical observation in the detection of fasciculation in people with amyotrophic lateral sclerosis.Deeper areas of contraction can be detected by electromyography (EMG) testing, though they can happen in any skeletal muscle in the body. Fasciculations arise as a result of spontaneous depolarization of a lower motor neuron leading to the synchronous contraction of all the skeletal muscle fibers within a single motor unit. An example of normal spontaneous depolarization is the constant contractions of cardiac muscle, causing the heart to beat. Usually, intentional movement of the involved muscle causes fasciculations to cease immediately, but they may return once the muscle is at rest again. Tics must also be distinguished from fasciculations. Small twitches of the upper or lower eyelid, for example, are not tics, because they do not involve a whole muscle, rather are twitches of a few muscle fibre bundles, that are not suppressible. Causes Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons. They are encountered by up to 70% of all healthy people, though for most, it is quite infrequent. In some cases, the presence of fasciculations can be annoying and interfere with quality of life. If a neurological examination is otherwise normal and EMG testing does not indicate any additional pathology, a diagnosis of benign fasciculation syndrome is usually made. Risk factors Risk factors for benign fasciculations are age, stress, fatigue, and strenuous exercise. Fasciculations can be caused by anxiety, caffeine or alcohol and thyroid disease. Magnesium deficiency is a common cause of fasciculation.Other factors may include the use of anticholinergic drugs over long periods. In particular, these include ethanolamines such as diphenhydramine (brand names Benadryl, Dimedrol, Daedalon and Nytol), used as an antihistamine and sedative, and dimenhydrinate (brand names Dramamine, Driminate, Gravol, Gravamin, Vomex, and Vertirosan) for nausea and motion sickness. Persons with benign fasciculation syndrome (BFS) may experience paraesthesia (especially numbness) shortly after taking such medication; fasciculation episodes begin as the medication wears off. Stimulants can cause fasciculations directly. These include caffeine, pseudoephedrine (Sudafed), amphetamines, and the asthma bronchodilator salbutamol (brand names Proventil, Combivent, Ventolin). Medications used to treat attention deficit disorder (ADHD) often contain stimulants as well, and are common causes of benign fasciculations. Since asthma and ADHD are much more serious than the fasciculations themselves, this side effect may have to be tolerated by the patient after consulting a physician or pharmacist. The depolarizing neuromuscular blocker succinylcholine causes fasciculations. It is a normal side effect of the drugs administration, and can be prevented with a small dose of a nondepolarizing neuromuscular blocker prior to the administration of succinylcholine, often 10% of a nondepolarizing NMBs induction dose. Even if a drug such as caffeine causes fasciculations, that does not necessarily mean it is the only cause. For example, a very slight magnesium deficiency by itself (see below) might not be enough for fasciculations to occur, but when combined with caffeine, the two factors together could be enough. Treatment Reducing stress and anxiety is therefore another useful treatment.There is no proven treatment for fasciculations in people with ALS. Among patients with ALS, fasciculation frequency is not associated with the duration of ALS and is independent of the degree of limb weakness and limb atrophy. No prediction of ALS disease duration can be made based on fasciculation frequency alone. Epidemiology Fasciculations are observed more often in males, and clinicians are overrepresented in study samples. See also Blepharospasm Carnitine palmitoyltransferase II deficiency Myokymia References == External links ==

Aarogya, share information about a health condition involving Goodpasture syndrome

Goodpasture syndrome

Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis, and kidney failure. It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpastures antigen. Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with medications that suppress the immune system such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood. The disease was first described by an American pathologist Ernest Goodpasture of Vanderbilt University in 1919 and was later named in his honor. Signs and symptoms The anti–glomerular basement membrane (GBM) antibodies primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever, and chills are also common, as are joint aches and pains. 60 to 80% of those with the condition experience both lung and kidney involvement; 20-40% have kidney involvement alone, and less than 10% have lung involvement alone. Lung symptoms usually antedate kidney symptoms and usually include: coughing up blood, chest pain (in less than 50% of cases overall), cough, and shortness of breath. Kidney symptoms usually include blood in the urine, protein in the urine, unexplained swelling of limbs or face, high amounts of urea in the blood, and high blood pressure. Cause While the exact cause is unknown, the genetic predisposition to GPS involves the human leukocyte antigen (HLA) system, specifically HLA-DR15. In addition to genetic susceptibility, an initial environmental insult to the pulmonary vasculature is needed to allow the anti-glomerular basement membrane (anti-GBM) antibodies to reach the alveolar capillaries. Examples of such an insult include: exposure to organic solvents (e.g. chloroform) or hydrocarbons, exposure to tobacco smoke, infection (such as influenza A), cocaine inhalation, metal dust inhalation, bacteremia, sepsis, high-oxygen environments, and antilymphocyte therapies (especially with monoclonal antibodies). Exposure to dry cleaning chemicals and Paraquat brand weed killer have also been implicated as potential insults. In GPS, anti-GBM antibodies are produced and circulated throughout the bloodstream, damaging the membranes lining the lungs and kidneys as well as targeting their capillaries. Pathophysiology GPS is caused by abnormal plasma cell production of anti-GBM antibodies. The major target of these abnormal antibodies is the non-collagen domain of the alpha-3 chain of type 4 collagen, which is mostly found in the basal membranes of glomerular and alveolar capillaries, explaining the obscurely specific symptoms of this condition. This preferred targeting of these alpha-3 collagen chains specifically in the basal membranes of glomerular and alveolar capillaries can be explained by the higher accessible exposure of epitopes, a larger expansion of the alpha-3 collagen units, and because these alpha-3 collagen chains structurally provide higher accessibility for the targeting antibodies. These antibodies bind their reactive epitopes to the basement membranes and activate the complement cascade, leading to the death of tagged cells. A specific antibody and epitope binding that shows the highest affinity and is pathogenic occurs between GPA antibodies and the anti-GBM epitope region, designated EA, which is residues 17-31 of the alpha 3 subunit of non-collagenous domain of type IV collagen. T cells are also implicated, though it is generally considered a type II hypersensitivity reaction. Diagnosis The diagnosis of GPS is often difficult, as numerous other diseases can cause the various manifestations of the condition and the condition itself is rare. The most accurate means of achieving the diagnosis is testing the affected tissues by means of a biopsy, especially the kidney, as it is the best-studied organ for obtaining a sample for the presence of anti-GBM antibodies. On top of the anti-GBM antibodies implicated in the disease, about one in three of those affected also has cytoplasmic antineutrophilic antibodies in their bloodstream, which often predates the anti-GBM antibodies by about a few months or even years. The later the disease is diagnosed, the worse the outcome is for the affected person.In addition, if there is substantial suspicion of the disease, seralogic testing for ELISA assay is usually done by looking for alpha3 NC1 domain area of collagen IV in order to avoid false positives. Treatment The major mainstay of treatment for GPS is plasmapheresis, a procedure in which the affected persons blood is sent through a centrifuge and the various components separated based on weight. The plasma contains the anti-GBM antibodies that attack the affected persons lungs and kidneys, and is filtered out. The other parts of the blood (the red blood cells, white blood cells, and platelets) are recycled and intravenously reinfused. Most individuals affected by the disease also need to be treated with immunosuppressant drugs, especially cyclophosphamide, prednisone, and rituximab, to prevent the formation of new anti-GBM antibodies so as to prevent further damage to the kidneys and lungs. Other, less toxic immunosuppressants such as azathioprine may be used to maintain remission. Prognosis With treatment, the five-year survival rate is >80% and fewer than 30% of affected individuals require long-term dialysis. A study performed in Australia and New Zealand demonstrated that in patients requiring renal replacement therapy (including dialysis) the median survival time is 5.93 years. Without treatment, virtually every affected person will die from either advanced kidney failure or lung hemorrhages. Epidemiology GPS is rare, affecting about 0.5–1.8 per million people per year in Europe and Asia. It is also unusual among autoimmune diseases in that it is more common in males than in females and is also less common in blacks than whites, but more common in the Māori people of New Zealand. The peak age ranges for the onset of the disease are 20–30 and 60–70 years. See also HLA-DR § DR2 Pulmonary-renal syndrome References External links GBM antibodies: immunofluorescence image

Do you know what is Water intoxication, Aarogya

Water intoxication

Water intoxication, also known as water poisoning, hyperhydration, overhydration, or water toxemia, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside safe limits by excessive water intake. Under normal circumstances, accidentally consuming too much water is exceptionally rare. Nearly all deaths related to water intoxication in normal individuals have resulted either from water-drinking contests, in which individuals attempt to consume large amounts of water, or from long bouts of exercise during which excessive amounts of fluid were consumed. In addition, water cure, a method of torture in which the victim is forced to consume excessive amounts of water, can cause water intoxication.Water, just like any other substance, can be considered a poison when over-consumed in a brief period of time. Water intoxication mostly occurs when water is being consumed in a high quantity without adequate electrolyte intake.Excess of body water may also be a result of a medical condition or improper treatment; see "hyponatremia" for some examples. Water is considered one of the least toxic chemical compounds, with an LD50 of over 150 ml/kg in rats. Risk factors Low body mass (infants) It can be very easy for children under one year old (especially those under nine months) to absorb too much water. Because of their small body mass, it is easy for them to take in a large amount of water relative to body mass and total body sodium stores. Endurance sports Marathon runners are susceptible to water intoxication if they drink too much while running. This is caused when sodium levels drop below 135 mmol/L when athletes consume large amounts of fluid. This has been noted to be the result of the encouragement of excessive fluid replacement by various guidelines. This has largely been identified in marathon runners as a dilutional hyponatremia. A study conducted on runners completing the 2002 Boston Marathon found that thirteen percent finished the race with hyponatremia. The study concluded that the strongest predictor of hyponatremia was weight gain while racing (over-hydration), and hyponatremia was just as likely to occur in runners who chose sports drinks as those who chose water. Military training Hyponatremia and other physical conditions associated with water intoxication are more often seen in those participating in military training. One US Army study found 17 trainees were admitted to hospital over a years period for water intoxication while another found that three soldiers had died, leading to a recommendation that no more than 1-1.5L of water should be consumed per hour of heavy sweating. Overexertion and heat stress Any activity or situation that promotes heavy sweating can lead to water intoxication when water is consumed to replace lost fluids. Persons working in extreme heat and/or humidity for long periods must take care to drink and eat in ways that help to maintain electrolyte balance. People using drugs such as MDMA (often referred to colloquially as "Ecstasy") may overexert themselves, perspire heavily, feel increased thirst, and then drink large amounts of water to rehydrate, leading to electrolyte imbalance and water intoxication – this is compounded by MDMA use increasing the levels of antidiuretic hormone (ADH), decreasing the amount of water lost through urination. Even people who are resting quietly in extreme heat or humidity may run the risk of water intoxication if they drink large amounts of water over short periods for rehydration. Psychiatric conditions Psychogenic polydipsia is the psychiatric condition in which patients feel compelled to drink large quantities of water, thus putting them at risk of water intoxication. This condition can be especially dangerous if the patient also exhibits other psychiatric indications (as is often the case), as the care-takers might misinterpret the hyponatremic symptoms. Iatrogenic When an unconscious person is being fed intravenously (for example, total parenteral nutrition) or via a nasogastric tube, the fluids given must be carefully balanced in composition to match fluids and electrolytes lost. These fluids are typically hypertonic, and so water is often co-administered. If the electrolytes are not monitored (even in an ambulatory patient), either hypernatremia or hyponatremia may result.Some neurological/psychiatric medications (oxcarbazepine, among others) have been found to cause hyponatremia in some patients. Patients with diabetes insipidus are particularly vulnerable due to rapid fluid processing. Pathophysiology At the onset of this condition, fluid outside the cells has an excessively low amount of solutes, such as sodium and other electrolytes, in comparison to fluid inside the cells, causing the fluid to move into the cells to balance its osmotic concentration. This causes the cells to swell. The swelling increases intracranial pressure in the brain, which leads to the first observable symptoms of water intoxication: headache, personality changes, changes in behavior, confusion, irritability, and drowsiness. These are sometimes followed by difficulty breathing during exertion, muscle weakness & pain, twitching, or cramping, nausea, vomiting, thirst, and a dulled ability to perceive and interpret sensory information. As the condition persists, papillary and vital signs may result including bradycardia and widened pulse pressure. The cells in the brain may swell to the point where blood flow is interrupted resulting in cerebral edema. Swollen brain cells may also apply pressure to the brain stem causing central nervous system dysfunction. Both cerebral edema and interference with the central nervous system are dangerous and could result in seizures, brain damage, coma or death. Prevention Water intoxication can be prevented if a persons intake of water does not grossly exceed their losses. Healthy kidneys are able to excrete approximately 800 millilitres to one litre of fluid water (0.84–1.04 quarts) per hour. However, stress (from prolonged physical exertion), as well as disease states, can greatly reduce this amount. Treatment Mild intoxication may remain asymptomatic and require only fluid restriction. In more severe cases, treatment consists of: Diuretics to increase urination, which are most effective for excess blood volume. Vasopressin receptor antagonists Notable cases 1097: During the First Crusade, according to at least one chronicle, many crusaders died after drinking too much from a river while marching to Antioch. 1991, Andy Warhol: Five years after his death, Warhols family publicly accused the hospital where he had his gallbladder removed of causing his death by water intoxication administered post-operatively. A claimed autopsy weight of 68 kg (150 lb), with his weight being 58 kg (128 lb) when admitted, was cited as evidence that too much fluid had been given. October 24, 1995: Anna Wood, a 15-year-old Australian schoolgirl, died from the effects of water intoxication. November 16, 1995: Leah Betts, a British schoolgirl, died as the result of drinking too much water, though in the media her death was mistakenly attributed to taking an ecstasy tablet at her 18th birthday party. 2003: British actor Anthony Andrews survived a case of water intoxication. He was performing as Henry Higgins in a revival of the musical My Fair Lady at the time, and consumed up to eight litres of water a day. He was unconscious and in intensive care for three days. February 2, 2005: Matthew Carrington, a student at Chico State University in Chico, California, died as a direct result of a fraternity hazing ritual involving forced water intoxication. January 12, 2007: Jennifer Strange died after drinking nearly 2 gallons (7.6 liters) of water in an attempt to win a Nintendo Wii. The KDND radio stations morning show, the Morning Rave, held an on-air contest entitled "Hold Your Wee for a Wii," in which contestants were asked to drink as much water as they could without urinating. The DJs were made aware of the dangers but did not inform the contestants. KDNDs parent company, Entercom Sacramento LLC, was subsequently ordered to pay $16,577,118 in damages to Stranges family. March 11, 2020: Zachary Sabin, an 11-year-old child, died after being forced to drink almost three liters of water in just four hours by his parents. They thought his urine was too dark, so they made him drink water until he threw up. See also == References ==

Aarogya, give me a short description about Confusion

Confusion

In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion" is often used interchangeably with delirium in the International Statistical Classification of Diseases and Related Health Problems and the Medical Subject Headings publications to describe the pathology. These refer to the loss of orientation, or the ability to place oneself correctly in the world by time, location and personal identity. Mental confusion is sometimes accompanied by disordered consciousness (the loss of linear thinking) and memory loss (the inability to correctly recall previous events or learn new material). Etymology The word confusion derives from the Latin word, confundo, which means "confuse, mix, blend, pour together, disorder, embroil." Causes Confusion may result from drug side effects or from a relatively sudden brain dysfunction. Acute confusion is often called delirium (or "acute confusional state"), although delirium often includes a much broader array of disorders than simple confusion. These disorders include the inability to focus attention; various impairments in awareness, and temporal or spatial dis-orientation. Mental confusion can result from chronic organic brain pathologies, such as dementia, as well. Other Differential diagnosis The most common causes of drug induced acute confusion are dopaminergic drugs (used for the treatment of Parkinsons disease), diuretics, tricyclic, tetracyclic antidepressants and benzodiazepines or alcohol. The elderly, and especially those with pre-existing dementia, are most at risk for drug induced acute confusional states. New research is finding a link between vitamin D deficiency and cognitive impairment (which includes "foggy brain"). See also Cognitive distortion References External links National Library of Medicine - National Institutes of Health

Aarogya, give me a short description about Pulmonary fibrosis

Pulmonary fibrosis

Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failure, pneumothorax, and lung cancer.Causes include environmental pollution, certain medications, connective tissue diseases, infections, and interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease of unknown cause, is most common. Diagnosis may be based on symptoms, medical imaging, lung biopsy, and lung function tests.There is no cure and there are limited treatment options available. Treatment is directed towards efforts to improve symptoms and may include oxygen therapy and pulmonary rehabilitation. Certain medications may be used to try to slow the worsening of scarring. Lung transplantation may occasionally be an option. At least 5 million people are affected globally. Life expectancy is generally less than five years. Signs and symptoms Symptoms of pulmonary fibrosis are mainly: Shortness of breath, particularly with exertion Chronic dry, hacking coughing Fatigue and weakness Chest discomfort including chest pain Loss of appetite and rapid weight lossPulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. Sometimes fine inspiratory crackles can be heard at the lung bases on auscultation. A chest X-ray may or may not be abnormal, but high-resolution CT will frequently demonstrate abnormalities. Cause Pulmonary fibrosis may be a secondary effect of other diseases. Most of these are classified as interstitial lung diseases. Examples include autoimmune disorders, viral infections and bacterial infection like tuberculosis which may cause fibrotic changes in both lungs upper or lower lobes and other microscopic injuries to the lung. However, pulmonary fibrosis can also appear without any known cause. In this case, it is termed "idiopathic". Most idiopathic cases are diagnosed as idiopathic pulmonary fibrosis. This is a diagnosis of exclusion of a characteristic set of histologic/pathologic features known as usual interstitial pneumonia (UIP). In either case, there is a growing body of evidence which points to a genetic predisposition in a subset of patients. For example, a mutation in surfactant protein C (SP-C) has been found to exist in some families with a history of pulmonary fibrosis. Autosomal dominant mutations in the TERC or TERT genes, which encode telomerase, have been identified in about 15 percent of pulmonary fibrosis patients.Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include: Inhalation of environmental and occupational pollutants, such as metals in asbestosis, silicosis and exposure to certain gases. Coal miners, ship workers and sand blasters among others are at higher risk. Hypersensitivity pneumonitis, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products Cigarette smoking can increase the risk or make the illness worse Some typical connective tissue diseases such as rheumatoid arthritis, ankylosing spondylitis, SLE and scleroderma Other diseases that involve connective tissue, such as sarcoidosis and granulomatosis with polyangiitis Infections, including COVID-19 Certain medications, e.g. amiodarone, bleomycin (pingyangmycin), busulfan, methotrexate, apomorphine, and nitrofurantoin Radiation therapy to the chest Pathogenesis Pulmonary fibrosis involves gradual exchange of normal lung parenchyma with fibrotic tissue. The replacement of normal lung with scar tissue causes irreversible decrease in oxygen diffusion capacity, and the resulting stiffness or decreased compliance makes pulmonary fibrosis a restrictive lung disease. Pulmonary fibrosis is perpetuated by aberrant wound healing, rather than chronic inflammation. It is the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast, quadriplegia and kyphosis are examples of causes of restrictive lung disease that do not necessarily involve pulmonary fibrosis. Diagnosis The diagnosis can be confirmed by lung biopsy. A videoscopic assisted thoracoscopic wedge biopsy (VATS) under general anesthesia may be necessary to obtain enough tissue to make an accurate diagnosis. This kind of biopsy involves placement of several tubes through the chest wall, one of which is used to cut off a piece of lung to send for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and pattern of fibrosis as well as presence of other features that may indicate a specific cause e.g. specific types of mineral dust or possible response to therapy e.g. a pattern of so-called non-specific interstitial fibrosis. Misdiagnosis is common because, while overall pulmonary fibrosis is not rare, each individual type of pulmonary fibrosis is uncommon and the evaluation of patients with these diseases is complex and requires a multidisciplinary approach. Terminology has been standardized but difficulties still exist in their application. Even experts may disagree with the classification of some cases.On spirometry, as a restrictive lung disease, both the FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are reduced so the FEV1/FVC ratio is normal or even increased in contrast to obstructive lung disease where this ratio is reduced. The values for residual volume and total lung capacity are generally decreased in restrictive lung disease. Treatment Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed. Slowing the progression and prevention depends on the underlying cause: Treatment options for idiopathic pulmonary fibrosis are very limited. Though research trials are ongoing, there is no evidence that any medications can significantly help this condition. Lung transplantation is the only therapeutic option available in severe cases. Since some types of lung fibrosis can respond to corticosteroids (such as prednisone) and/or other medications that suppress the bodys immune system, these types of drugs are sometimes prescribed in an attempt to slow the processes that lead to fibrosis.The immune system is felt to play a central role in the development of many forms of pulmonary fibrosis. The goal of treatment with immune suppressive agents such as corticosteroids is to decrease lung inflammation and subsequent scarring. Responses to treatment are variable. Those whose conditions improve with immune suppressive treatment probably do not have idiopathic pulmonary fibrosis, for idiopathic pulmonary fibrosis has no significant treatment or cure.Two pharmacological agents intended to prevent scarring in mild idiopathic fibrosis are pirfenidone, which reduced reductions in the 1-year rate of decline in FVC. Pirfenidone also reduced the decline in distances on the 6-minute walk test, but had no effect on respiratory symptoms. The second agent is nintedanib, which acts as antifibrotic, mediated through the inhibition of a variety of tyrosine kinase receptors (including platelet-derived growth factor, fibroblast growth factor, and vascular endothelial growth factor). A randomized clinical trial showed it reduced lung-function decline and acute exacerbations. Anti-inflammatory agents have only limited success in reducing the fibrotic process. Some of the other types of fibrosis, such as non-specific interstitial pneumonia, may respond to immunosuppressive therapy such as corticosteroids. However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, penicillamine, and cyclosporine may be used. Colchicine has also been used with limited success. There are ongoing trials with newer drugs such as IFN-γ and mycophenolate mofetil. Hypersensitivity pneumonitis, a less severe form of pulmonary fibrosis, is prevented from becoming aggravated by avoiding contact with the causative material. Oxygen supplementation improves the quality of life and exercise capacity. Lung transplantation may be considered for some patients. Prognosis Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to heart failure of the right ventricle. Hypoxia can be prevented with oxygen supplementation.Pulmonary fibrosis may also result in an increased risk for pulmonary emboli, which can be prevented by anticoagulants. Epidemiology Five million people worldwide are affected by pulmonary fibrosis. The rates below are per 100,000 persons, and the ranges reflect narrow and broad inclusion criteria, respectively. These data do not reflect any increased rates due to the COVID-19 pandemic; pulmonary fibrosis is a known symptom of COVID-19 and is estimated (as of July 2020) to occur in roughly 1/3rd of patients hospitalized for COVID-19. Based on these rates, pulmonary fibrosis prevalence in the United States could range from more than 29,000 to almost 132,000, based on the population in 2000 that was 18 years or older. The actual numbers may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed while the incidence of idiopathic pulmonary fibrosis increases dramatically after the age of fifty. However, loss of pulmonary function is commonly ascribed to old age, heart disease or to more common lung diseases. References == External links ==

Aarogya what is Peripheral neuropathy

Peripheral neuropathy

Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent. Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation, vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessive alcohol consumption, immune system disease, celiac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause). In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of") without modifier usually means peripheral neuropathy. Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy".Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or allodynia (pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally. Classification Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy). The affected nerves are found in an EMG (electromyography) / NCS (nerve conduction study) test and the classification is applied upon completion of the exam. Mononeuropathy Mononeuropathy is a type of neuropathy that only affects a single nerve. Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia), or inflammation also may cause mononeuropathy. Polyneuropathy "Polyneuropathy" is a pattern of nerve damage that is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" sometimes is used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern is that the cell bodies of neurons remain intact, but the axons are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurons directly. This usually picks out either the motor neurons (known as motor neuron disease) or the sensory neurons (known as sensory neuronopathy or dorsal root ganglionopathy).The effect of this is to cause symptoms in more than one part of the body, often symmetrically on left and right sides. As for any neuropathy, the chief symptoms include motor symptoms such as weakness or clumsiness of movement; and sensory symptoms such as unusual or unpleasant sensations such as tingling or burning; reduced ability to feel sensations such as texture or temperature, and impaired balance when standing or walking. In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms also may occur, such as dizziness on standing up, erectile dysfunction, and difficulty controlling urination.Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Hyperglycemia-induced formation of advanced glycation end products (AGEs) is related to diabetic neuropathy. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as Lyme disease, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs). Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it was thought that many of the cases of small fiber peripheral neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in the prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes."The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain. Mononeuritis multiplex Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunks, either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves. The pattern of involvement is asymmetric, however, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to the pattern of early symptoms is important. Mononeuritis multiplex is sometimes associated with a deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex.Electrodiagnostic medicine studies will show multifocal sensory motor axonal neuropathy.It is caused by, or associated with, several medical conditions: Autonomic neuropathy Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a persons conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy.The signs and symptoms of autonomic neuropathy include the following: Urinary bladder conditions: bladder incontinence or urine retention Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhoea, constipation Cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion Respiratory system: impairments in the signals associated with regulation of breathing and gas exchange (central sleep apnea, hypopnea, bradypnea). Skin : thermal regulation, dryness through sweat disturbances Other areas: hypoglycemia unawareness, genital impotence Neuritis Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia (pins-and-needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes. Causes of neuritis include: Signs and symptoms Those with diseases or dysfunctions of their nerves may present with problems in any of the normal nerve functions. Symptoms vary depending on the types of nerve fiber involved. In terms of sensory function, symptoms commonly include loss of function ("negative") symptoms, including numbness, tremor, impairment of balance, and gait abnormality. Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins-and-needles. Motor symptoms include loss of function ("negative") symptoms of weakness, tiredness, muscle atrophy, and gait abnormalities; and gain of function ("positive") symptoms of cramps, and muscle twitch (fasciculations).In the most common form, length-dependent peripheral neuropathy, pain and parasthesia appears symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of the lower limbs, while symptoms may never appear in the upper limbs; if they do, it will be around the time that leg symptoms reach the knee. When the nerves of the autonomic nervous system are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing. CAP-PRI Scale for diagnosis A user-friendly, disease-specific, quality-of-life scale can be used to monitor how someone is doing living with the burden of chronic, sensorimotor polyneuropathy. This scale, called the Chronic, Acquired Polyneuropathy - Patient-reported Index (CAP-PRI), contains only 15 items and is completed by the person affected by polyneuropathy. The total score and individual item scores can be followed over time, with item scoring used by the patient and care-provider to estimate clinical status of some of the more common life domains and symptoms impacted by polyneuropathy. Causes The causes are grouped broadly as follows: Diagnosis Peripheral neuropathy may first be considered when an individual reports symptoms of numbness, tingling, and pain in feet. After ruling out a lesion in the central nervous system as a cause, diagnosis may be made on the basis of symptoms, laboratory and additional testing, clinical history, and a detailed examination. During physical examination, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Classically, ankle jerk reflex is absent in peripheral neuropathy. A physical examination will involve testing the deep ankle reflex as well as examining the feet for any ulceration. For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which is tested with a 128-Hz tuning fork, and decreased sensation of light touch when touched by a nylon monofilament.Diagnostic tests include electromyography (EMG) and nerve conduction studies (NCSs), which assess large myelinated nerve fibers. Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system function of small thinly- and unmyelinated fibers. These tests include a sweat test and a tilt table test. Diagnosis of small fiber involvement in peripheral neuropathy may also involve a skin biopsy in which a 3 mm-thick section of skin is removed from the calf by a punch biopsy, and is used to measure the skin intraepidermal nerve fiber density (IENFD), the density of nerves in the outer layer of the skin. Reduced density of the small nerves in the epidermis supports a diagnosis of small-fiber peripheral neuropathy. In EMG testing, demyelinating neuropathy characteristically shows a reduction in conduction velocity and prolongation of distal and F-wave latencies, whereas axonal neuropathy shows a reduction in amplitude.Laboratory tests include blood tests for vitamin B-12 levels, a complete blood count, measurement of thyroid stimulating hormone levels, a comprehensive metabolic panel screening for diabetes and pre-diabetes, and a serum immunofixation test, which tests for antibodies in the blood. Treatment The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well. Medications A range of medications that act on the central nervous system have been used to symptomatically treat neuropathic pain. Commonly used medications include tricyclic antidepressants (such as nortriptyline, amitriptyline. imapramine, and desipramine,) serotonin-norepinephrine reuptake inhibitor (SNRI) medications (duloxetine, venlafaxine, and milnacipran) and antiepileptic medications (gabapentin, pregabalin, oxcarbazepine zonisamide levetiracetam, lamotrigine, topiramate, clonazepam, phenytoin, lacosamide, sodium valproate and carbamazepine). Opioid and opiate medications (such as buprenorphine, morphine, methadone, fentanyl, hydromorphone, tramadol and oxycodone) are also often used to treat neuropathic pain. As is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess for their failings. It is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested on or for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective. The NHS for example explicitly state that amitriptyline and gabapentin can be used for treating the pain of sciatica. This is despite both the lack of high quality evidence that demonstrates efficacy of these medications for that symptom, and also the prominence of generally moderate to high quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it. Antidepressants In general, according to Cochranes systematic reviews, antidepressants have shown to either be ineffective for the treatment of neuropathic pain or the evidence available is inconclusive. Evidence also tends to be tainted by bias or issues with the methodology.Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015.A 2015 Cochrane systematic review of amitriptyline found that there was no evidence supporting the use of amitriptyline that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated. A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias."A 2017 Cochrane systematic review assessed the benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive. Antiepileptics A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly (30 - 40)% of treated patients, while placebo had a (10 - 20)% response. Three of the seven authors of the review had conflicts of interest declared. In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies.A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain and other neuropathies. The authors also call for better studies. In a 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for the treatment of pain deriving from any peripheral neuropathy. A 2014 Cochrane review found that studies of levetiracetam showed no indication for its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events.A 2013 Cochrane systematic review concluded that there was high quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages (200 - 400) mg. A 2013 Cochrane systematic review of topimirate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy. Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain."A 2012 Cochrane systematic review of lacosamide found it very likely that the drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence. For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of effect due to the inherent problems with the data and conclude that the evidence does not support its usage. In a 2014 systematic review of carbamazepine the authors believe the drug to be of benefit for some people. No trials were considered greater than level III evidence; none were longer than 4 weeks in length or were deemed as having good reporting quality.A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found the evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies. Opioids A Cochrane review of buprenorphine, fentanyl, hydromorphone and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review. A 2017 Cochrane review of methadone found very low quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to a placebo.For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect". For oxycodone the authors found very low quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of the four authors declared receiving payments from pharmaceutical companies.More generally, a 2013 review examining the overall efficacy of opioid therapy for the treatment of neuropathic pain found studies were often subject to bias and that their efficacy and safety was not deducible with the evidence available. A 2017 Cochrane review examining opioid therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents." Others A 2016 Cochrane review of paracetamol for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine is unknown.Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.There is some evidence that symptomatic relief from the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. However, the evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option.Evidence supports the use of cannabinoids for some forms of neuropathic pain. A 2018 Cochrane review of cannabis-based medicines for the treatment of chronic neuropathic pain included 16 studies. All of these studies included THC as a pharmacological component of the test group. The authors rated the quality of evidence as very low to moderate. The primary outcome was quoted as, "Cannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo" but "the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality". The authors also conclude, "The potential benefits of cannabis-based medicine... might be outweighed by their potential harms."A 2014 Cochrane review of topical lidocaine for the treatment of various peripheral neuropathies found its usage supported by a few low quality studies. The authors state that there are no high quality randomised control trials demonstrating its efficacy or safety profile.A 2015 (updated in 2022) Cochrane review of topical clonidine for the treatment of diabetic neuropathy included two studies of 8 and 12 weeks in length; both of which compared topical clonidine to placebo and both of which were funded by the same drug manufacturer. The review found that topical clonidine may provide some benefit versus placebo. However, the authors state that the included trials are potentially subject to significant bias and that the evidence is of low to moderate quality.A 2007 Cochrane review of aldose reductase inhibitors for the treatment of the pain deriving from diabetic polyneuropathy found it no better than placebo. Medical devices Transcutaneous electrical nerve stimulation (TENS) therapy is often used to treat various types of neuropathy. A 2010 review of three trials, for the treatment of diabetic neuropathy explicitly, involving a total of 78 patients found some improvement in pain scores after 4 and 6, but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks. Another 2010 review of four trials, for the treatment of diabetic neuropathy, found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of cessation of treatment.These older reviews can be balanced with a more recent 2017 review of TENS for neuropathic pain by Cochrane which concluded that, "This review is unable to state the effect of TENS versus sham TENS for pain relief due to the very low quality of the included evidence... The very low quality of evidence means we have very limited confidence in the effect estimate reported." A very low quality of evidence means, multiple sources of potential bias with a small number and size of studies. Surgery In people with diabetic peripheral neuropathy, two reviews make a case for nerve decompression surgery as an effective means of pain relief and support claims for protection from foot ulceration. There is less evidence for efficacy of surgery for non-diabetic peripheral neuropathy of the legs and feet. One uncontrolled study did before/after comparisons with a minimum of one-year follow-up and reported improvements for pain relief, impaired balance and numbness. "There was no difference in outcomes between patients with diabetic versus idiopathic neuropathy in response to nerve decompression." There are no placebo-controlled trials for idiopathic peripheral neuropathy in the published scientific literature. Diet According to a review, strict gluten-free diet is an effective treatment when neuropathy is caused by gluten sensitivity, with or without the presence of digestive symptoms or intestinal injury. Counselling A 2015 review on the treatment of neuropathic pain with psychological therapy concluded that, "There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups." Alternative medicine A 2019 Cochrane review of the treatment of herbal medicinal products for people with neuropathic pain for at least three months concluded that, "There was insufficient evidence to determine whether nutmeg or St Johns wort has any meaningful efficacy in neuropathic pain conditions.The quality of the current evidence raises serious uncertainties about the estimates of effect observed, therefore, we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect."A 2017 Cochrane review on the usage of acupuncture as a treatment for neuropathic pain concludes, "Due to the limited data available, there is insufficient evidence to support or refute the use of acupuncture for neuropathic pain in general, or for any specific neuropathic pain condition when compared with sham acupuncture or other active therapies." Also, "Most studies included a small sample size (fewer than 50 participants per treatment arm) and all studies were at high risk of bias for blinding of participants and personnel." Also, the authors state, "we did not identify any study comparing acupuncture with treatment as usual."Alpha lipoic acid (ALA) with benfotiamine is a proposed pathogenic treatment for painful diabetic neuropathy only. The results of two systematic reviews state that oral ALA produced no clinically significant benefit, intravenous ALA administered over the course of three weeks may improve symptoms and that long-term treatment has not been investigated. Research A 2008 literature review concluded that, "based on principles of evidence-based medicine and evaluations of methodology, there is only a possible association of celiac disease and peripheral neuropathy due to lower levels of evidence and conflicting evidence. There is not yet convincing evidence of causality."A 2019 review concluded that "gluten neuropathy is a slowly progressive condition. About 25% of the patients will have evidence of enteropathy on biopsy (CD [celiac disease]) but the presence or absence of an enteropathy does not influence the positive effect of a strict gluten-free diet."Stem-cell therapy is also being looked at as a possible means to repair peripheral nerve damage, however efficacy has not yet been demonstrated. See also Scrambler therapy Giant axonal neuropathy References Further reading External links Peripheral Neuropathy from the US NIH Peripheral Neuropathy at the Mayo Clinic

Aarogya, can you share information about a health condition involving Calciphylaxis

Calciphylaxis

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA) or “Grey Scale”, is a rare syndrome characterized by painful skin lesions. The pathogenesis of calciphylaxis is unclear but believed to involve calcification of the small blood vessels located within the fatty tissue and deeper layers of the skin, blood clots, and eventual death of skin cells due to lack of blood flow. It is seen mostly in people with end-stage kidney disease but can occur in the earlier stages of chronic kidney disease and rarely in people with normally functioning kidneys. Calciphylaxis is a rare but serious disease, believed to affect 1-4% of all dialysis patients. It results in chronic non-healing wounds and indicates poor prognosis, with typical life expectancy of less than one year.Calciphylaxis is one type of extraskeletal calcification. Similar extraskeletal calcifications are observed in some people with high levels of calcium in the blood, including people with milk-alkali syndrome, sarcoidosis, primary hyperparathyroidism, and hypervitaminosis D. In rare cases, certain medications such as warfarin can also result in calciphylaxis. Signs and symptoms The first skin changes in calciphylaxis lesions are mottling of the skin and induration in a livedo reticularis pattern. As tissue thrombosis and infarction occurs, a black, leathery eschar in an ulcer with adherent black slough develops. Surrounding the ulcers is usually a plate-like area of indurated skin. These lesions are always extremely painful and most often occur on the lower extremities, abdomen, buttocks, and penis. Lesions are also commonly multiple and bilateral. Because the tissue has infarcted, wound healing seldom occurs, and ulcers are more likely to become secondarily infected. Many cases of calciphylaxis lead to systemic bacterial infection and death.Calciphylaxis is characterized by the following histologic findings: systemic medial calcification of the arteries, i.e. calcification of tunica media. Unlike other forms of vascular calcifications (e.g., intimal, medial, valvular), calciphylaxis is characterized also by small vessel mural calcification with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischemia (including skin ischemia and, hence, skin necrosis). Heart of stone Severe forms of calciphylaxis may cause diastolic heart failure from cardiac calcification, called heart of stone. Widespread intravascular calcification typical of calciphylaxis lesions occur in the myocardium and prevent normal diastolic filling of the ventricles. Cause The cause of calciphylaxis is unknown. Calciphylaxis is not a hypersensitivity reaction (i.e., allergic reaction) leading to sudden local calcification. The disease is also known as calcific uremic arteriolopathy; however, the disease is not limited to patients with kidney failure. The current belief is that in end-stage kidney disease, abnormal calcium and phosphate homeostasis result in the deposition of calcium in the vessels, also known as metastatic calcification. Once the calcium has been deposited, a thrombotic event occurs within the lumen of these vessels, resulting in occlusion of the vessel and subsequent tissue infarction. Specific triggers for either thrombotic or ischemic events are unknown. Adipocytes have been shown to calcify vascular smooth muscle cells when exposed to high phosphate levels in vitro, mediated by vascular endothelial growth factor A (VEGF-A) and leptin released by adipocytes. Given that calciphylaxis tends to affect adipose tissue, this may be a contributing explanation. Another theory has been proposed that vitamin K deficiency contributes to the development of calciphylaxis. Vitamin K acts as an inhibitor of calcification in vessel walls by activating matrix Gla protein (MGP), which in turn inhibits calcification. End-stage kidney disease patients are more likely to have vitamin K deficiency due to dietary restrictions meant to limit potassium and sodium. Many end-stage kidney disease patients are also on a medication called warfarin, a vitamin K antagonist, that limits vitamin K recycling in the body.Reported risk factors include female sex, obesity, elevated calcium-phosphate product, medications such as warfarin, vitamin D derivatives (e.g. calcitriol, calcium-based binders, or systemic steroids), protein C or S deficiency, low blood albumin levels, and diabetes mellitus. Patients who require or have undergone any type of vascular procedures are also at increased risk for poor outcomes. Diagnosis There is no diagnostic test for calciphylaxis. The diagnosis is a clinical one. The characteristic lesions are the ischemic skin lesions (usually with areas of skin necrosis). The necrotic skin lesions (i.e. the dying or already dead skin areas) typically appear as violaceous (dark bluish purple) lesions and/or completely black leathery lesions. They can be extensive and found in multiples. The suspected diagnosis can be supported by a skin biopsy, usually a punch biopsy, which shows arterial calcification and occlusion in the absence of vasculitis. Excisional biopsy should not be done due to increased risk of further ulceration and necrosis. Bone scintigraphy can be performed in cases where skin biopsy is contraindicated. Results of the study show increased tracer accumulation in the soft tissues. In certain patients, an anti-nuclear antibody test may play a role in diagnosis of calciphylaxis. Plain radiography and mammography may also show calcifications but these tests are less sensitive. Laboratory studies, such as phosphate levels, calcium levels, and parathyroid levels, are nonspecific and unhelpful for diagnosis of calciphylaxis. Treatment The treatment of calciphylaxis requires a multidisciplinary approach, using the knowledge of nephrologists, plastic surgeons, dermatologists, and wound care specialists working together to manage the disease and its outcomes. The key to treating calciphylaxis is prevention via rigorous control of phosphate and calcium balance and management of risk factors in patients who have increased chances of developing calciphylaxis. There is no specific treatment. Most treatment recommendations lack significant data, and none are internationally recognized as the standard of care. It is generally accepted to apply a multi-pronged approach to each patient. Analgesia and wound management Pain management and choice of analgesia is a challenging task in managing calciphylaxis. Pain is one of the most severe and pervasive symptoms of the disease and can be unresponsive to high-dose opioids. Fentanyl and methadone are preferred analgesics over morphine, since morphine breakdown produces active metabolites that accumulate in the body of patients with kidney failure. Adjunct medications such as gabapentin and ketamine may also be used for analgesia. In refractory cases, spinal anesthetics (nerve blocks) can be used for more comprehensive pain relief. Wound care for calciphylaxis lesions involves using appropriate dressings, wound debridement (removal of dead tissue), and prevention of infection. Wound infections lead to sepsis, which is one of the leading causes of death in patients with calciphylaxis. Surgical wound debridement carries increased risk for infection, so it should only be considered as therapy if the survival benefit outweighs the chances of continued wound non-healing and pain.Hyperbaric oxygen therapy may also be considered. There are some smaller retrospective studies that show the use of hyperbaric oxygen in improving delivery of oxygen to wounds, which improves blood flow and helps with wound healing. Risk factor mitigation Most patients with calciphylaxis are already on hemodialysis, or simply dialysis, but the length or frequency of sessions may be increased. The majority of dialysis patients are on a 4-hour three times per week schedule. Indications for increasing dialysis session length or frequency include electrolyte and mineral abnormalities, such as hyperphophatemia, hypercalcemia, and hyperparathyroidism, all of which are also risk factors for development of calciphylaxis. Peritoneal dialysis patients should also transition to hemodialysis, as only hemodialysis carries the added benefit of better phosphate and calcium control. Surgical parathyroidectomy is also recommended for those who have difficulty managing phosphate and calcium level balance. However, risks include development of post-operative hungry bone syndrome (HBS), a disease state that causes low calcium and requires use of calcium supplementation and calcitriol, which should be avoided in patients with end-stage kidney disease and calciphylaxis. Pharmacotherapy Sodium thiosulfate is commonly prescribed for treatment in patients with calciphylaxis. The actual mechanism of the drug is unknown, but several theories have been proposed, including chelation of calcium, vasodilation, antioxidant properties, and restoration of endothelial function. Adverse effects of sodium thiosulfate include high anion gap metabolic acidosis and high sodium levels (hypernatremia). Bisphosphonates are a popular choice for the treatment of osteoporosis, but they have also been used to treat calciphylaxis even though the exact mechanism in calciphylaxis is unknown. They are most beneficial in patients who have a genetic ENPP1 deficiency and have been shown to slow development of calciphylaxis lesions in a small prospective study. Cinacalcet (medical parathyroidectomy) is an oral medication that can be used to suppress the parathyroid glands for patients who may not be able to undergo surgical parathyroidectomy. Vitamin K supplementation has also been shown to slow development of calcification in coronary arteries and the aortic valve in older patients. The ability for vitamin K supplementation to slow calcification of blood vessels in calciphylaxis is not well studied. Warfarin, a vitamin K antagonist discussed above, should be discontinued if possible.Other acceptable treatments may include one or more of the following: Clot-dissolving agents (tissue plasminogen activator) Maggot larval debridement Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2) Avoiding further local tissue trauma (including avoiding all subcutaneous injections, and all not-absolutely-necessary infusions and transfusions) Patients who receive kidney transplants also receive immunosuppression. Considering lowering the dose of or discontinuing the use of immunosuppressive drugs in people who have received kidney transplants and continue to have persistent or progressive calciphylactic skin lesions can contribute to an acceptable treatment of calciphylaxis. A group has reported plasma exchange effective and propose a serum marker and perhaps mediator (calciprotein particles) Prognosis Overall, the clinical prognosis for calciphylaxis is poor. The 1-year mortality rate in patients who have end-stage kidney disease is 45-80%. Median survival in patients who do not have end-stage kidney disease is 4.2 months. Response to treatment is not guaranteed. The most common cause of death in calciphylaxis patients is sepsis, severe infection originating from a non-healing ulcer. Epidemiology Calciphylaxis most commonly occurs in patients with end-stage renal disease who are on hemodialysis or who have recently received a kidney transplant. When reported in patients without end-stage renal disease (such as in earlier stages of chronic kidney disease or in normal kidney function), it is called non-uremic calciphylaxis by Nigwekar et al. Non-uremic calciphylaxis has been observed in patients with primary hyperparathyroidism, breast cancer (treated with chemotherapy), liver cirrhosis (due to hazardous alcohol use), cholangiocarcinoma, Crohns disease, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Calciphylaxis, regardless of etiology, has been reported at an incidence of 35 in 10,000 dialysis patients per year in the United States, 4 in 10,000 patients in Germany, and less than 1 in 10,000 patients in Japan. It is unknown whether the higher incidence in the United States is due to genuinely higher incidence or due to underreporting in other countries. Annual incidence in kidney transplant patients and in non-uremic calciphylaxis patients is also unknown. The median age of patients at diagnosis of calciphylaxis is 60 years and the majority of these patients are women (60-70%). The location of lesions, central (located on the trunk) or peripheral (located on the extremities), is dependent on several risk factors. Central lesions are associated with younger patients, patients with a higher body mass index, and a higher risk of death than those who have peripheral-only lesions. References Further reading Weenig RH (2008). "Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B". J. Am. Acad. Dermatol. 58 (3): 458–71. doi:10.1016/j.jaad.2007.12.006. PMID 18206262. Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR (2007). "Calciphylaxis: natural history, risk factor analysis, and outcome". J. Am. Acad. Dermatol. 56 (4): 569–79. doi:10.1016/j.jaad.2006.08.065. PMID 17141359. Li JZ, Huen W (2007). "Images in clinical medicine. Calciphylaxis with arterial calcification". N. Engl. J. Med. 357 (13): 1326. doi:10.1056/NEJMicm060859. PMID 17898102. == External links ==

Do you know what is Hair bleaching, Aarogya

Hair bleaching

Hair bleaching, is the practice of lightening the hair color mainly for cosmetic purposes using bleaching agents. Bleaching can be done alone, combined with a toner, or as a step for further hair coloring. The most common commercial bleaching agents in use are hydrogen peroxide and persulfate salts, but historically other agents such as sulfuric acid, wood ash, lye and hypochlorite bleach were used. Hair can also become bleached unintentionally, such as through sun exposure. History During the early years of the Roman Empire, blond hair was associated with prostitutes. The preference changed to bleaching the hair blond when Greek culture, which practiced bleaching, reached Rome, and was reinforced when the legions that conquered Gaul returned with blond slaves. Sherrow also states that Roman women tried to lighten their hair, but the substances often caused hair loss, so they resorted to wigs made from the captives hair. The bleaching agent used by the Roman women was composed of a solution of ashes from burnt nuts or plants.Diodorus Siculus, a 1st century BC Greek historian, described in detail how Celtic people bleached their hair: "Their aspect is terrifying... They are very tall in stature, with rippling muscles under clear white skin. Their hair is blond, but not naturally so: they bleach it, to this day, artificially, washing it in lime and combing it back from their foreheads. They look like wood-demons, their hair thick and shaggy like a horses mane. Some of them are clean-shaven, but others—especially those of high rank—shave their cheeks but leave a moustache that covers the whole mouth...".During the medieval period, Spanish women preferred to dye their hair black, yet by the time of the Renaissance in the 16th century the fashion (imported from Italy) was to bleach their hair blond or dye it red. Between the Renaissance and the Enlightenment, a number of dangerous hair bleaching methods remained widely practiced, including the use of sulfuric acid, which was an accepted form of hair coloring around the 1600s, and laying out in the sun with hair covered in lye a century later.In Sir Hugh Plats 1602 work Delightes for Ladies the use of oil of vitriol (sulfuric acid) to bleach black hair to chestnut is described as: "Take one part of lead calcined with Sulphur, and one part of quicklime: temper them somewhat thin with water: lay it upon the hair, chafing it well in, and let it dry one quarter of an hour or thereasbouts; the wash the same off with fair water divers times: and lastly with sope and water, and it will be a very natural hair-colour. The longer it lyeth upon the haire, the browner it groweth, This coloureth not the flesh at all, and yet it lasteth very long in the hair." Modern history Howard Hughes 1931 movie Platinum Blonde starring Jean Harlow is noted to have popularized platinum blonde hair color in the US. After the movies success Hughess team established a chain of "Platinum Blonde clubs" in several cities and offered a $10,000 prize that would go to any hairdresser who could copy Harlows shade. Though Harlow denied her hair was bleached, the platinum blonde color was reportedly achieved with a weekly application of ammonia, Clorox bleach, and Lux soap flakes. This process weakened and damaged Harlows naturally ash-blonde hair.During the 1930s Lawrence M. Gelb advanced the formulas of the bleaching products. In 1950 Clairol, the company Gelb founded with wife Jane Clair, introduced the first one-step hair dye product that lightened hair, which became a huge success with the masses. Bleaching process Using bleaching agents Melanin pigments, which give hair a darker color, can be broken down with oxidation. Most commercial bleaching formulas contain hydrogen peroxide and persulfate salts, which under alkaline conditions created by ammonia or monoethanolamine can bleach the hair. Persulfate salts, in combination with hydrogen peroxide or alone, is known for its ability to degrade organics, after activation with heat, transition metals, ultraviolet light, or other means that produce the sulfate radical. Without activation, the persulfate anion is known to react with some organic chemicals, although with slow kinetics. When melanin is oxidized, oxygen gas is released. Products for bleaching ones hair at home usually contain a 6% solution of hydrogen peroxide, while products for use in a hair salon can contain up to 9%. Hair bleaching products can damage hair and cause severe burns to the scalp when applied incorrectly or left on too long.Industrial bleaches that work by reduction (such as sodium hydrosulphite) react with a chromophore, the part of the molecule responsible for its color and decrease the number of carbon-oxygen bonds in it, making it uncoloured. This process might be reversed to a certain extent by oxygen in the air, such as yellowing of bleached paper if kept exposed to air. In contrast hydrogen peroxide chemically alters the chromophore so that it increases the number of carbon-oxygen bonds. Due to the relative absence of reducing agents in the environment, chromophores cannot restore themselves as seen in reduction-based bleaches.Bleaching the hair is a gradual process and different colors could be achieved dependent on the original hair color, application time, and strength of the product used. Applied on black hair, the hair will change its color to brown, red, orange, orange-yellow, yellow, and finally pale yellow. Toner Toning is a common practice after bleaching to mask the undesirable red and orange tones of "brassy" hair using a toner dye. Through toning, the yellow hue of fully bleached hair can be removed to achieve platinum blond hair. The appropriate color of the toner depends on the color of the bleached hair; e.g. to remove the yellow tones a violet toner dye will be needed, but to neutralize red and orange hues a green and blue toner would be more suitable. Tinted shampoos can also be used to tone hair. Sun exposure Excessive exposure to the sun is the most common cause of structural damage of the hair shaft. Photochemical hair damage encompasses hair protein degradation and loss, as well as hair pigment deterioration Photobleaching is common among people with European ancestry. Around 72 percent of customers who agreed to be involved in a study and have European ancestry reported in a recent 23andMe research that the sun lightens their hair. The company also have identified 48 genetic markers that may influence hair photobleaching. Medical significance Drug testing methods using hair samples are found to be disrupted by chemical hair treatments including bleaching. According to a 2019 study bleaching has caused strong chemical degradation on cannabinoids in hair, while permanent colorings in single applications had only negligible effects on cannabinoids. A 2021 study found similar results for methamphetamine concentrations in hair.Persulfate containing products may produce a variety of cutaneous and respiratory responses, such as allergic eczematous contact dermatitis, irritant dermatitis, localized edema, generalized urticaria, rhinitis, asthma, and syncope. References Further reading Robbins, Clarence R. (2006-05-26). Chemical and Physical Behavior of Human Hair. Springer Science & Business Media. ISBN 978-0-387-21695-9.

Hi Aarogya , Do you know what is Malabsorption,

Malabsorption

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.Normally the human gastrointestinal tract digests and absorbs dietary nutrients with remarkable efficiency. A typical Western diet ingested by an adult in one day includes approximately 100 g of fat, 400 g of carbohydrate, 100 g of protein, 2 L of fluid, and the required sodium, potassium, chloride, calcium, vitamins, and other elements. Salivary, gastric, intestinal, hepatic, and pancreatic secretions add an additional 7–8 L of protein-, lipid-, and electrolyte-containing fluid to intestinal contents. This massive load is reduced by the small and large intestines to less than 200 g of stool that contains less than 8 g of fat, 1–2 g of nitrogen, and less than 20 mmol each of Na+, K+, Cl–, HCO3–, Ca2+, or Mg2+. If there is impairment of any of the many steps involved in the complex process of nutrient digestion and absorption, intestinal malabsorption may ensue. If the abnormality involves a single step in the absorptive process, as in primary lactase deficiency, or if the disease process is limited to the very proximal small intestine, then selective malabsorption of only a single nutrient may occur. However, generalized malabsorption of multiple dietary nutrients develops when the disease process is extensive, thus disturbing several digestive and absorptive processes, as occurs in coeliac disease with extensive involvement of the small intestine. Signs and symptoms Gastrointestinal manifestations Depending on the nature of the disease process causing malabsorption and its extent, gastrointestinal symptoms may range from severe to subtle or may even be totally absent. Diarrhea, weight loss, flatulence, abdominal bloating, abdominal cramps, and pain may be present. Although diarrhea is a common complaint, the character and frequency of stools may vary considerably ranging from over 10 watery stools per day to less than one voluminous putty-like stool, the latter causing some patients to complain of constipation. On the other hand, stool mass is invariably increased in patients with steatorrhea and generalized malabsorption above the normal with 150–200 g/day. Not only do unabsorbed nutrients contribute to stool mass but mucosal fluid and electrolyte secretion is also increased in diseases associated with mucosal inflammation such as coeliac disease. In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both impair absorption and induce secretion of water and electrolytes by the colon adding to stool mass. Weight loss is common among patients with significant intestinal malabsorption but must be evaluated in the context of caloric intake. Some patients compensate for fecal wastage of unabsorbed nutrients by significantly increasing their oral intake. Eliciting a careful dietary history from patients with suspected malabsorption is therefore crucial. Excessive flatus and abdominal bloating may reflect excessive gas production due to fermentation of unabsorbed carbohydrate, especially among patients with a primary or secondary disaccharidase deficiency, such as lactose intolerance or sucrose intolerance. Malabsorption of dietary nutrients and excessive fluid secretion by inflamed small intestine also contribute to abdominal distention and bloating. Prevalence, severity, and character of abdominal pain vary considerably among the various disease processes associated with intestinal malabsorption. For example, pain is common in patients with chronic pancreatitis or pancreatic cancer and Crohns disease, but it is absent in many patients with coeliac disease or postgastrectomy malabsorption. Extraintestinal manifestations Substantial numbers of patients with intestinal malabsorption present initially with symptoms or laboratory abnormalities that point to other organ systems in the absence of or overshadowing symptoms referable to the gastrointestinal tract. For example, there is increasing epidemiologic evidence that more patients with coeliac disease present with anemia and osteopenia in the absence of significant classic gastrointestinal symptoms. Microcytic, macrocytic, or dimorphic anemia may reflect impaired iron, folate, or vitamin B12 absorption. Purpura, subconjunctival hemorrhage, or even frank bleeding may reflect hypoprothrombinemia secondary to vitamin K malabsorption. Osteopenia is common, especially in the presence of steatorrhea. Impaired calcium and vitamin D absorption and chelation of calcium by unabsorbed fatty acids resulting in fecal loss of calcium may all contribute. If calcium deficiency is prolonged, secondary hyperparathyroidism may develop. Prolonged malnutrition may induce amenorrhea, infertility, and impotence. Edema and even ascites may reflect hypoproteinemia associated with protein losing enteropathy caused by lymphatic obstruction or extensive mucosal inflammation. Dermatitis and peripheral neuropathy may be caused by malabsorption of specific vitamins or micronutrients and essential fatty acids. Presentation Symptoms can manifest in a variety of ways and features might give a clue to the underlying condition. Symptoms can be intestinal or extra-intestinal - the former predominates in severe malabsorption. Diarrhoea, often steatorrhoea, is the most common feature. Watery, diurnal and nocturnal, bulky, frequent stools are the clinical hallmark of overt malabsorption. It is due to impaired water, carbohydrate and electrolyte absorption or irritation from unabsorbed fatty acid. The latter also results in bloating, flatulence and abdominal discomfort. Cramping pain usually suggests obstructive intestinal segment e.g. in Crohns disease, especially if it persists after defecation. Weight loss can be significant despite increased oral intake of nutrients. Growth retardation, failure to thrive, delayed puberty in children Swelling or oedema from loss of protein Anaemias, commonly from vitamin B12, folic acid and iron deficiency presenting as fatigue and weakness. Decreased mental abilities, poor reflexes, and abnormal sensations due to vitamin B12 deficiency. Muscle cramp from decreased vitamin D, calcium absorption. Also lead to osteomalacia and osteoporosis Bleeding tendencies from vitamin K and other coagulation factor deficiencies. Causes Pathophysiology The main purpose of the gastrointestinal tract is to digest and absorb nutrients (fat, carbohydrate, protein, micronutrients (vitamins and trace minerals), water, and electrolytes. Digestion involves both mechanical and enzymatic breakdown of food. Mechanical processes include chewing, gastric churning, and the to-and-fro mixing in the small intestine. Enzymatic hydrolysis is initiated by intraluminal processes requiring gastric, pancreatic, and biliary secretions. The final products of digestion are absorbed through the intestinal epithelial cells.Malabsorption constitutes the pathological interference with the normal physiological sequence of digestion (intraluminal process), absorption (mucosal process) and transport (postmucosal events) of nutrients.Intestinal malabsorption can be due to: Congenital or acquired reduction in absorptive surface Defects of ion transport Defects of specific hydrolysis Impaired enterohepatic circulation Mucosal damage (enteropathy) Pancreatic insufficiency Diagnosis There is no single, specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centers and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Tests are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption). Classification Some prefer to classify malabsorption clinically into three basic categories: selective, as seen in lactose malabsorption. partial, as observed in abetalipoproteinaemia. total, as in exceptional cases of coeliac disease. Blood tests Routine blood tests may reveal anaemia, high CRP or low albumin; which shows a high correlation for the presence of an organic disease. In this setting, microcytic anaemia usually implies iron deficiency and macrocytosis can be caused by impaired folic acid or B12 absorption or both. Low cholesterol or triglyceride may give a clue toward fat malabsorption. Low calcium and phosphate may give a clue toward osteomalacia from low vitamin D. Specific vitamins like vitamin D or micronutrient like zinc levels can be checked. Fat soluble vitamins (A, D, E and K) are affected in fat malabsorption. Prolonged prothrombin time can be caused by vitamin K deficiency. Serological studies. Specific tests are carried out to determine the underlying cause.IgA Anti-transglutaminase antibodies or IgA Anti-endomysial antibodies for Coeliac disease (gluten sensitive enteropathy). Stool studies Microscopy is particularly useful in diarrhoea, may show protozoa like Giardia, ova, cyst and other infective agents. Fecal fat study to diagnose steatorrhoea is rarely performed nowadays. Low fecal pancreatic elastase is indicative of pancreatic insufficiency. Chymotrypsin and pancreolauryl can be assessed as well Radiological studies Barium follow through is useful in delineating small intestinal anatomy. Barium enema may be undertaken to see colonic or ileal lesions. CT abdomen is useful in ruling out structural abnormality, done in pancreatic protocol when visualising pancreas. Magnetic resonance cholangiopancreatography (MRCP) to complement or as an alternative to ERCP. Interventional studies OGD to detect duodenal pathology and obtain D2 biopsy (for coeliac disease, tropical sprue, Whipples disease, abetalipoproteinaemia etc.) Enteroscopy for enteropathy and jejunal aspirate and culture for bacterial overgrowth Capsule Endoscopy is able to visualise the whole small intestine and is occasionally useful. Colonoscopy is necessary in colonic and ileal disease. ERCP will show pancreatic and biliary structural abnormalities. Other investigations 75SeHCAT test to diagnose bile acid malabsorption in ileal disease or primary bile acid diarrhea. Glucose hydrogen breath test for bacterial overgrowth Lactose hydrogen breath test for lactose intolerance Sugar probes or 51Cr-EDTA to determine intestinal permeability. Obsolete tests no longer used clinically D-xylose absorption test for mucosal disease or bacterial overgrowth. Normal in pancreatic insufficiency. Bile salt breath test (14C-glycocholate) to determine bile salt malabsorption. Schilling test to establish cause of B12 deficiency. Management Treatment is directed largely towards management of underlying cause: Replacement of nutrients, electrolytes and fluid may be necessary. In severe deficiency, hospital admission may be required for nutritional support and detailed advice from dietitians. Use of enteral nutrition by naso-gastric or other feeding tubes may be able to provide sufficient nutritional supplementation. Tube placement may also be done by percutaneous endoscopic gastrostomy, or surgical jejunostomy. In patients whose intestinal absorptive surface is severely limited from disease or surgery, long term total parenteral nutrition may be needed. Pancreatic enzymes are supplemented orally in pancreatic insufficiency. Dietary modification is important in some conditions: Gluten-free diet in coeliac disease. Lactose avoidance in lactose intolerance. Antibiotic therapy to treat Small Bowel Bacterial overgrowth. Cholestyramine or other bile acid sequestrants will help reducing diarrhoea in bile acid malabsorption. See also Fructose malabsorption Protein losing enteropathy References == External links ==

Hi Aarogya, explain a situation where Urinary cast occurs

Urinary cast

Urinary casts are microscopic cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy. They form via precipitation of Tamm–Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH). Tamm–Horsfall protein is particularly susceptible to precipitation in these conditions. Casts were first described by Henry Bence Jones (1813–1873).As reflected in their cylindrical form, casts are generated in the small distal convoluted tubules and collecting ducts of the kidney, and generally maintain their shape and composition as they pass through the urinary system. Although the most common forms are benign, others indicate disease. All rely on the inclusion or adhesion of various elements on a mucoprotein base—the hyaline cast. "Cast" itself merely describes the shape, so an adjective is added to describe the composition of the cast. Various casts found in urine sediment may be classified as follows. Overview table Main types of urinary casts: Acellular casts Hyaline casts The most common type of cast, hyaline casts are solidified Tamm–Horsfall mucoprotein secreted from the tubular epithelial cells of individual nephrons. Low urine flow, concentrated urine, or an acidic environment can contribute to the formation of hyaline casts, and as such, they may be seen in normal individuals in dehydration or vigorous exercise. Hyaline casts are cylindrical and clear, with a low refractive index, so they can easily be missed on cursory review under brightfield microscopy, or in an aged sample where dissolution has occurred whereas, on the other hand, phase contrast microscopy leads to easier identification. Given the ubiquitous presence of Tamm–Horsfall protein, other cast types are formed via the inclusion or adhesion of other elements to the hyaline base. Granular casts The second-most common type of cast, granular casts can result either from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g., albumin) or immunoglobulin light chains. Depending on the size of inclusions, they can be classified as fine or coarse, though the distinction has no diagnostic significance. Their appearance is generally more cigar-shaped and of a higher refractive index than hyaline casts. While most often indicative of chronic renal disease, these casts, as with hyaline casts, can also be seen for a short time following strenuous exercise. The "muddy brown cast" seen in acute tubular necrosis is a type of granular cast. Waxy casts Thought to represent the end product of cast evolution, waxy casts suggest the very low urine flow associated with severe, longstanding kidney disease such as kidney failure. Additionally, due to urine stasis and their formation in diseased, dilated ducts, these casts are significantly larger than hyaline casts. They are cylindrical. They possess a higher refractive index. They are more rigid, demonstrating sharp edges, fractures, and broken-off ends.Waxy casts are broad casts, which is a more general term to describe the wider cast product of a dilated duct. It is seen in chronic kidney failure. In nephrotic syndrome many additional types of cast exist including broad and waxy casts if the condition is chronic (this is referred to as a telescopic urine with the presence of many casts). Fatty casts Formed by the breakdown of lipid-rich epithelial cells, these are hyaline casts with fat globule inclusions, yellowish-tan in color. If cholesterol or cholesterol esters are present, they are associated with the "Maltese cross" sign under polarized light. They are pathognomonic for high urinary protein nephrotic syndrome. Pigment casts Formed by the adhesion of metabolic breakdown products or drug pigments, these casts are so named due to their discoloration. Pigments include those produced endogenously, such as hemoglobin in hemolytic anemia, myoglobin in rhabdomyolysis, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration. Crystal casts Though crystallized urinary solutes, such as oxalates, urates, or sulfonamides, may become enmeshed within a ketanaline cast during its formation, the clinical significance of this occurrence is not felt to be great. Cellular casts Red blood cell casts The presence of red blood cells within the cast is always pathological and is strongly indicative of granulomatosis with polyangiitis, systemic lupus erythematosus, post-streptococcal glomerulonephritis, or Goodpastures syndrome. They can also be associated with renal infarction and subacute bacterial endocarditis. They are a yellowish-brown color and are generally cylindrical with sometimes ragged edges; their fragility makes inspection of a fresh sample necessary. They are usually associated with nephritic syndromes or urinary tract injury. White blood cell casts Indicative of inflammation or infection, the presence of white blood cells within or upon casts strongly suggests pyelonephritis, a direct infection of the kidney. They may also be seen in inflammatory states, such as acute allergic interstitial nephritis, nephrotic syndrome, or post-streptococcal acute glomerulonephritis. White cells sometimes can be difficult to discern from epithelial cells and may require special staining. Differentiation from simple clumps of white cells can be made by the presence of hyaline matrix. Bacterial casts Given their appearance in pyelonephritis, these should be seen in association with loose bacteria, white blood cells, and white blood cell casts. Their discovery is likely rare, due to the infection-fighting efficiency of neutrophils and the possibility of misidentification as a fine granular cast. Epithelial cell casts This cast is formed by inclusion or adhesion of desquamated epithelial cells of the tubule lining. Cells can adhere in random order or in sheets and are distinguished by large, round nuclei and a lower amount of cytoplasm. These can be seen in acute tubular necrosis and toxic ingestion, such as from mercury, diethylene glycol, or salicylate. In each case, clumps or sheets of cells may slough off simultaneously, depending on the focality of injury. Cytomegalovirus and viral hepatitis are organisms that can cause epithelial cell death as well. Eosinophilic cast This type of cast contains eosinophils. It is seen in Tubulo Interstitial Nephritis and occurs in allergy, commonly to drugs like Methicillin & NSAIDs. References Haber, Meryl H. Urinary Sediment: A Textbook Atlas. American Society of Clinical Pathologists. Chicago, 1981. Lillian Mundt, Kirsty Shanahan, Graffs Textbook of Routine of Urinanalysis and Body Fluids, 2nd edition, Lippincott Williams & Wilkins, Philadelphia, 2011. External links Urine Casts – different types and what they mean. [1] – Good description of various cast forms.

Hi Aarogya, explain a situation where Stupor occurs

Stupor

Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin stupor ("numbness, insensibility"). Signs and symptoms Stupor is characterised by impaired reaction to external stimuli. Those in a stuporous state are rigid, mute and only appear to be conscious, as the eyes are open and follow surrounding objects. If not stimulated externally, a patient with stupor will appear to be in a sleepy state most of the time. In some extreme cases of severe depressive disorders the patient can become motionless, lose their appetite and become mute. Short periods of restricted responsivity can be achieved by intense stimulation (e.g. pain, bright light, loud noise, shock). Causes Stupor is associated with infectious diseases, complicated toxic states (e.g. heavy metals), severe hypothermia, mental illnesses (e.g. schizophrenia, major depressive disorder), epilepsy, vascular illnesses (e.g. hypertensive encephalopathy), acute stress reaction, neoplasms (e.g. brain tumors), brain disorders (e.g. alzheimers, dementia, fatal insomnia), B12 deficiency affects mental abilities, major trauma, alcohol poisoning, vitamin D excess and other maladies.Lesions of the ascending reticular activation system on height of the pons and metencephalon have been shown to cause stupor. The incidence is higher after left-sided lesions. Management Because stupors are caused by another health condition, treatment focuses on uncovering and treating the cause. Doctors may administer IV antibiotics or fluids to treat infections and nutritional deficits, or conduct an MRI to check for lesions on the brain. See also Torpor Notes References C. Lafosse, Zakboek Neuropsychologische Symptomatologie, p. 37, ISBN 90-334-3995-6. == External links ==

Hello Aarogya, could you help me understand about Catatonia

Catatonia

Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. There are several subtypes of catatonia: akinetic catatonia, excited catatonia, malignant catatonia, delirious mania, and self-injurious behaviors in autism.Although catatonia has historically been related to schizophrenia (catatonic schizophrenia), catatonia is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions. Catatonia is not a stand-alone diagnosis (although some experts disagree), and the term is used to describe a feature of the underlying disorder.Recognizing and treating catatonia is very important as failure to do so can lead to poor outcomes and can be potentially fatal. Treatment with benzodiazepines or ECT can lead to remission of catatonia. There is growing evidence of the effectiveness of the NMDA receptor antagonists amantadine and memantine for benzodiazepine-resistant catatonia. Antipsychotics are sometimes employed, but they can worsen symptoms and have serious adverse effects. Signs and symptoms The presentation of a patient with catatonia varies greatly depending on the subtype, underlying cause and it can be acute or subtle.Because most patients with catatonia have an underlying psychiatric illness, the majority will present with worsening depression, mania, or psychosis followed by catatonia symptoms. Catatonia presents as a motor disturbance in which patients will display marked reduction in movement, marked agitation, or a mixture of both despite having the physical capacity to move normally. These patients may be unable to start an action or stop one. Movements and mannerisms may be repetitive, or purposeless.The most common signs of catatonia are immobility, mutism, withdrawal and refusal to eat, staring, negativism, posturing (rigidity), rigidity, waxy flexibility/catalepsy, stereotypy (purposeless, repetitive movements), echolalia or echopraxia, verbigeration (repeat meaningless phrases). It should not be assumed that patients presenting with catatonia are unaware of their surroundings as some patients can recall in detail their catatonic state and their actions.There are several subtypes of catatonia and they are characterized by the specific movement disturbance and associated features. Although catatonia can be divided into various subtypes, the natural history of catatonia is often fluctuant and different states can exist within the same individual. Subtypes Withdrawn Catatonia: This form of catatonia is characterized by decreased response to external stimuli, immobility or inhibited movement, mutism, staring, posturing, and negativism. Patients may sit or stand in the same position for hours, may hold odd positions, and may resist movement of their extremities.Excited Catatonia: Excited catatonia is characterized by odd mannerisms/gestures, performing purposeless or inappropriate actions, excessive motor activity restlessness, stereotypy, impulsivity, agitation, combativeness. Speech and actions may be repetitive or mimic another persons. People in this state are extremely hyperactive and may have delusions and hallucinations. Catatonic excitement is commonly cited as one of the most dangerous mental states in psychiatry. Malignant Catatonia: Malignant catatonia is a life-threatening condition that may progress rapidly within a few days. It is characterized by fever, abnormalities in blood pressure, heart rate, respiratory rate, diaphoresis (sweating), and delirium. Certain lab findings are common with this presentation; however, they are nonspecific, which means that they are also present in other conditions and do not diagnose catatonia. These lab findings include: leukocytosis, elevated creatine kinase, low serum iron. The signs and symptoms of malignant catatonia overlap significantly with neuroleptic malignant syndrome (NMS) and so a careful history, review of medications, and physical exam are critical to properly differentiate these conditions. For example, if the patient has waxy flexibility and holds a position against gravity when passively moved into that position, then it is likely catatonia. If the patient has a "lead-pipe rigidity" then NMS should be the prime suspect.Other forms: Periodic catatonia is an inconsistently defined entity. In the Wernicke-Kleist-Leonhard school, it is a distinct form of "non-system schizophrenia" characterized by recurrent acute phases with hyperkinetic and akinetic features and often psychotic symptoms, and the build-up of a residual state in between these acute phases, which is characterized by low-level catatonic features and aboulia of varying severity. The condition has a strong hereditary component. According to modern classifications, this may be diagnosed as a form of bipolar disorder, schizoaffective disorder or schizophrenia. Independently, the term periodic catatonia is sometimes used in modern literature to describe a syndrome of recurrent phases of acute catatonia (excited or inhibited type) with full remission between episodes, which resembles the description of "motility psychosis" in the Wernicke-Kleist-Leonhard school. System catatonias or systematic catatonias are only defined in the Wernicke-Kleist-Leonhard school. These are chronic-progressive conditions characterized by specific disturbances of volition and psychomotricity, leading to a dramatic decline of executive and adaptive functioning and ability to communicate. They are considered forms of schizophrenia but distinct from other schizophrenic conditions. Affective flattening and apparent loss of interests are common but may be related to reduced emotional expression rather than lack of emotion. Heredity is low. Of the 21 different forms (6 "simple" and 15 "combined" forms) that have been described, most overlap only partially - if at all - with current definitions of either catatonia or schizophrenia, and thus are difficult to classify according to modern diagnostic manuals. Early childhood catatonias are also a diagnosis exclusive to the Wernicke-Kleist-Leonhard school, and refers to system catatonias that manifest in young children. Clinically, these conditions resemble severe regressive forms of autism. Chronic catatonia-like breakdown or Autistic catatonia refers to a functional decline seen in some patients with pre-existing autism spectrum disorder and/or intellectual disability which usually runs a chronic-progressive course and encompasses attenuated catatonic symptoms as well as mood and anxiety symptoms that increasingly interfere with adaptive functioning. Onset is typically insidious and often mistaken for background autistic symptoms. Slowing of voluntary movement, reduced speech, aboulia, increased prompt dependency and obsessive-compulsive symptoms are frequently seen; negativism, (auto-)aggressive behaviors and ill-defined hallucinations have also been reported. Both the causes of this disorder as well as its prognosis appear to be heterogenous, with most patients showing partial recovery upon treatment. It seems to be related to chronic stress as a result of life transitions, loss of external time structuring, sensory sensitivities and/or traumatic experiences, co-morbid mental disorders, or other unknown causes. Since clinical catatonia can not always be diagnosed, this condition has also been renamed to the more general term "late regression". Complications Patients may experience several complications from being in a catatonic state. The nature of these complications will depend on the type of catatonia being experienced by the patient. For example, patients presenting with retarded catatonia may have refusal to eat which will in turn lead to malnutrition and dehydration. Furthermore, if immobility is a symptom the patient is presenting with, then they may develop pressure ulcers, muscle contractions, and are at risk of developing deep vein thrombosis (DVT) and pulmonary embolus (PE). Patients with excited catatonia may be aggressive and violent, and physical trauma may result from this. Catatonia may progress to the malignant type which will present with autonomic instability and may be life-threatening. Other complications also include the development of pneumonia and neuroleptic malignant syndrome. Causes Catatonia is almost always secondary to another underlying illness, often a psychiatric disorder. Mood disorders such as a bipolar disorder and depression are the most common etiologies to progress to catatonia. Other psychiatric associations include schizophrenia and other primary psychotic disorders. It also is related to autism spectrum disorders.Catatonia is also seen in many medical disorders, including infections (such as encephalitis), autoimmune disorders, meningitis, focal neurological lesions (including strokes), alcohol withdrawal, abrupt or overly rapid benzodiazepine withdrawal, cerebrovascular disease, neoplasms, head injury, and some metabolic conditions (homocystinuria, diabetic ketoacidosis, hepatic encephalopathy, and hypercalcaemia). Pathogenesis The pathophysiology that leads to catatonia is still poorly understood and a definite mechanism remains unknown. Neurologic studies have implicated several pathways; however, it remains unclear whether these findings are the cause or the consequence of the disorder.Abnormalities in GABA, glutamate signaling, serotonin, and dopamine transmission are believed to be implicated in catatonia.Furthermore, it has also been hypothesized that pathways that connect the basal ganglia with the cortex and thalamus is involved in the development of catatonia. Diagnosis There is not yet a definitive consensus regarding diagnostic criteria of catatonia. In the American Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the World Health Organizations eleventh edition of the International Classification of Disease (ICD-11) the classification is more homogeneous than in earlier editions. Prominent researchers in the field have other suggesions for diagnostic criteria.DSM-5 classification The DSM-5 does not classify catatonia as an independent disorder, but rather it classifies it as catatonia associated with another mental disorder, due to another medical condition, or as unspecified catatonia. Catatonia is diagnosed by the presence of three or more of the following 12 psychomotor symptoms in association with a mental disorder, medical condition, or unspecified: stupor: no psycho-motor activity; not actively relating to the environment catalepsy: passive induction of a posture held against gravity waxy flexibility: allowing positioning by an examiner and maintaining that position mutism: no, or very little, verbal response (exclude if known aphasia) negativism: opposition or no response to instructions or external stimuli posturing: spontaneous and active maintenance of a posture against gravity mannerisms that are odd, circumstantial caricatures of normal actions stereotypy: repetitive, abnormally frequent, non-goal-directed movements agitation, not influenced by external stimuli grimacing: keeping a fixed facial expression echolalia: mimicking anothers speech echopraxia: mimicking anothers movements.Other disorders (additional code 293.89 [F06.1] to indicate the presence of the co-morbid catatonia): Catatonia associated with autism spectrum disorder Catatonia associated with schizophrenia spectrum and other psychotic disorders Catatonia associated with brief psychotic disorder Catatonia associated with schizophreniform disorder Catatonia associated with schizoaffective disorder Catatonia associated with a substance-induced psychotic disorder Catatonia associated with bipolar and related disorders Catatonia associated with major depressive disorder Catatonic disorder due to another medical conditionIf catatonic symptoms are present but do not form the catatonic syndrome, a medication- or substance-induced aetiology should first be considered.ICD-11 classification In ICD-11 catatonia is defined as a syndrome of primarily psychomotor disturbances that is characterized by the simultaneous occurrence of several symptoms such as stupor; catalepsy; waxy flexibility; mutism; negativism; posturing; mannerisms; stereotypies; psychomotor agitation; grimacing; echolalia and echopraxia. Catatonia may occur in the context of specific mental disorders, including mood disorders, schizophrenia or other primary psychotic disorders, and Neurodevelopmental disorders, and may be induced by psychoactive substances, including medications. Catatonia may also be caused by a medical condition not classified under mental, behavioral, or neurodevelopmental disorders. Assessment/Physical Catatonia is often overlooked and under-diagnosed. Patients with catatonia most commonly have an underlying psychiatric disorder, for this reason, physicians may overlook signs of catatonia due to the severity of the psychosis the patient is presenting with. Furthermore, the patient may not be presenting with the common signs of catatonia such as mutism and posturing. Additionally, the motor abnormalities seen in catatonia are also present in psychiatric disorders. For example, a patient with mania will show increased motor activity that may progress to exciting catatonia. One way in which physicians can differentiate between the two is to observe the motor abnormality. Patients with mania present with increased goal-directed activity. On the other hand, the increased activity in catatonia is not goal-directed and often repetitive.Catatonia is a clinical diagnosis and there is no specific laboratory test to diagnose it. However, certain testing can help determine what is causing the catatonia. An EEG will likely show diffuse slowing. If seizure activity is driving the syndrome, then an EEG would also be helpful in detecting this. CT or MRI will not show catatonia; however, they might reveal abnormalities that might be leading to the syndrome. Metabolic screens, inflammatory markers, or autoantibodies may reveal reversible medical causes of catatonia.Vital signs should be frequently monitored as catatonia can progress to malignant catatonia which is life-threatening. Malignant catatonia is characterized by fever, hypertension, tachycardia, and tachypnea. Rating scale Various rating scales for catatonia have been developed, however, their utility for clinical care has not been well established. The most commonly used scale is the Bush-Francis Catatonia Rating Scale (BFCRS) (external link is provided below). The scale is composed of 23 items with the first 14 items being used as the screening tool. If 2 of the 14 are positive, this prompts for further evaluation and completion of the remaining 9 items. A diagnosis can be supported by the lorazepam challenge or the zolpidem challenge. While proven useful in the past, barbiturates are no longer commonly used in psychiatry; thus the option of either benzodiazepines or ECT. Differential diagnosis The differential diagnosis of catatonia is extensive as signs and symptoms of catatonia may overlap significantly with those of other conditions. Therefore, a careful and detailed history, medication review, and physical exam are key to diagnosing catatonia and differentiating it from other conditions. Furthermore, some of these conditions can themselves lead to catatonia. The differential diagnosis is as follows: Neuroleptic malignant syndrome (NMS) and catatonia are both life-threatening conditions that share many of the same characteristics including fever, autonomic instability, rigidity, and delirium. Lab values of low serum iron, elevated creatine kinase, and white blood cell count are also shared by the two disorders further complicating the diagnosis. There are features of malignant catatonia (posturing, impulsivity, etc.) that are absent from NSM and the lab results are not as consistent in malignant catatonia as they are in NMS. Some experts consider NMS to be a drug-induced condition associated with antipsychotics, particularly, first generation antipsychotics, but it has not been established as a subtype. Therefore, discontinuing antipsychotics and starting benzodiazepines is a treatment for this condition, and similarly it is helpful in catatonia as well. Anti-NMDA receptor encephalitis is an autoimmune disorder characterized by neuropsychiatric features and the presence of IgG antibodies. The presentation of anti-NMDAR encephalitis has been categorized into 5 phases: prodromal phase, psychotic phase, unresponsive phase, hyperkinetic phase, and recovery phase. The psychotic phase progresses into the unresponsive phase characterized by mutism, decreased motor activity, and catatonia. Both Serotonin syndrome and malignant catatonia may present with signs and symptoms of delirium, autonomic instability, hyperthermia, and rigidity. Again, similar to the presentation in NSM. However, patients with Serotonin syndrome have a history of ingestion of serotonergic drugs (Ex: SSRI). These patients will also present with hyperreflexia, myoclonus, nausea, vomiting, and diarrhea. Malignant hyperthermia and malignant catatonia share features of autonomic instability, hyperthermia, and rigidity. However, malignant hyperthermia is a hereditary disorder of skeletal muscle that makes these patients susceptible to exposure to halogenated anesthetics and/or depolarizing muscle relaxants like succinylcholine. Malignant hyperthermia most commonly occurs in the intraoperative or postoperative periods. Other signs and symptoms of malignant hyperthermia include metabolic and respiratory acidosis, hyperkalemia, and cardiac arrhythmias. Akinetic mutism is a neurological disorder characterized by a decrease in goal-directed behavior and motivation; however, the patient has an intact level of consciousness. Patients may present with apathy, and may seem indifferent to pain, hunger, or thirst. Akinetic mutism has been associated with structural damage in a variety of brain areas. Akinetic mutism and catatonia may both manifest with immobility, mutism, and waxy flexibility. Differentiating both disorders is the fact that akinetic mutism does not present with echolalia, echopraxia, or posturing. Furthermore, it is not responsive to benzodiazepines as is the case for catatonia. Elective mutism has an anxious etiology but has also been associated with personality disorders. Patients with this disorder fail to speak with some individuals but will speak with others. Likewise, they may refuse to speak in certain situations; for example, a child who refuses to speak at school but is conversational at home. This disorder is distinguished from catatonia by the absence of any other signs/symptoms. Nonconvulsive status epilepticus is seizure activity with no accompanying tonic-clonic movements. It can present with stupor, similar to catatonia, and they both respond to benzodiazepines. Nonconvulsive status epilepticus is diagnosed by the presence of seizure activity seen on electroencephalogram (EEG). Catatonia on the other hand, is associated with normal EEG or diffuse slowing. Delirium is characterized by fluctuating disturbed perception and consciousness in the ill individual. It has hypoactive and hyperactive or mixed forms. People with hyperactive delirium present similarly to those with excited catatonia and have symptoms of restlessness, agitation, and aggression. Those with hypoactive delirium present with similarly to retarded catatonia, withdrawn and quiet. However, catatonia also includes other distinguishing features including posturing and rigidity as well as a positive response to benzodiazepines. Patients with locked-in syndrome present with immobility and mutism; however, unlike patients with catatonia who are unmotivated to communicate, patients with locked-in syndrome try to communicate with eye movements and blinking. Furthermore, locked-in syndrome is caused by damage to the brainstem. Stiff-person syndrome and catatonia are similar in that they may both present with rigidity, autonomic instability and a positive response to benzodiazepines. However, stiff-person syndrome may be associated with anti-glutamic acid decarboxylase (anti-GAD) antibodies and other catatonic signs such as mutism and posturing are not part of the syndrome. Untreated late-stage Parkinsons disease may present similarly to retarded catatonia with symptoms of immobility, rigidity, and difficulty speaking. Further complicating the diagnosis is the fact that many patients with Parkinsons disease will have major depressive disorder, which may be the underlying cause of catatonia. Parkinsons disease can be distinguished from catatonia by a positive response to levodopa. Catatonia on the other hand will show a positive response to benzodiazepines. Extrapyramidal side effects of antipsychotic medication, especially dystonia and akathisia, can be difficult to distinguish from catatonic symptoms, or may confound them in the psychiatric setting. Extrapyramidal motor disorders usually do not involve social symptoms like negativism, while individuals with catatonic excitement typically do not have the physically painful compulsion to move that is seen in akathisia. Certain stimming behaviors and stress responses in individuals with autism spectrum disorders can present similarly to catatonia. In autism spectrum disorders, chronic catatonia is distinguished by a lasting deterioration of adaptive skills from the background of pre-existing autistic symptomatology that cannot be easily explained. Acute catatonia is usually clearly distinguishable from autistic symptoms. The diagnostic entities of obsessional slowness and psychogenic parkinsonism show overlapping features with catatonia, such as motor slowness, gegenhalten (oppositional paratonia), mannerisms, and reduced or absent speech. However, psychogenic parkinsonism involves tremor which is unusual in catatonia. Obsessional slowness is a controversial diagnosis, with presentations ranging from severe but common manifestations of obsessive compulsive disorder to catatonia. Treatment The initial treatment of catatonia is to stop medication that could be potentially leading to the syndrome. These may include steroids, stimulants, anticonvulsants, neuroleptics, dopamine blockers, etc. The next step is to provide a "lorazepam challenge," in which patients are given 2 mg of IV lorazepam (or another benzodiazepine). Most patients with catatonia will respond significantly to this within the first 15–30 minutes. If no change is observed during the first dose, then a second dose is given and the patient is re-examined. If the patient responds to the lorazepam challenge, then lorazepam can be scheduled at interval doses until the catatonia resolves. The lorazepam must be tapered slowly, otherwise, the catatonia symptoms may return. The underlying cause of the catatonia should also be treated during this time. If within a week the catatonia is not resolved, then ECT can be used to reverse the symptoms. ECT in combination with benzodiazepines is used to treat malignant catatonia. In France, zolpidem has also been used in diagnosis, and response may occur within the same time period. Ultimately the underlying cause needs to be treated.Electroconvulsive therapy (ECT) is an effective treatment for catatonia that is well acknowledged. ECT has also shown favorable outcomes in patients with chronic catatonia. However, it has been pointed out that further high quality randomized controlled trials are needed to evaluate the efficacy, tolerance, and protocols of ECT in catatonia.Antipsychotics should be used with care as they can worsen catatonia and are the cause of neuroleptic malignant syndrome, a dangerous condition that can mimic catatonia and requires immediate discontinuation of the antipsychotic.There is evidence clozapine works better than other antipsychotics to treat catatonia, following a recent systematic review.Excessive glutamate activity is believed to be involved in catatonia; when first-line treatment options fail, NMDA antagonists such as amantadine or memantine may be used. Amantadine may have an increased incidence of tolerance with prolonged use and can cause psychosis, due to its additional effects on the dopamine system. Memantine has a more targeted pharmacological profile for the glutamate system, reduced incidence of psychosis and may therefore be preferred for individuals who cannot tolerate amantadine. Topiramate is another treatment option for resistant catatonia; it produces its therapeutic effects by producing glutamate antagonism via modulation of AMPA receptors. Prognosis Patients who experience an episode of catatonia are more likely to recur. Treatment response for patients with catatonia is 50–70% and these patients have a good prognosis. However, failure to respond to medication is a very poor prognosis. Many of these patients will require long-term and continuous mental health care. For patients with catatonia with underlying schizophrenia, the prognosis is much poorer. Epidemiology Catatonia has been mostly studied in acutely ill psychiatric patients. Catatonia frequently goes unrecognized, leading to the belief that the syndrome is rare; however, this is not true and prevalence has been reported to be as high as 10% in patients with acute psychiatric illnesses. One large population estimate has suggested that the incidence of catatonia is 10.6 episodes per 100 000 person-years. It occurs in males and females in approximately equal numbers. 21-46% of all catatonia cases can be attributed to a general medical condition. History It was first described in 1874 by Karl Ludwig Kahlbaum as Die Katatonie oder das Spannungsirresein (Catatonia or Tension Insanity). See also References External links Catatonia in DSM-5 Encyclopedia of Mental Disorders – Catatonic Disorders "Schizophrenia: Catatonic Type" video by Heinz Edgar Lehmann, 1952 Bush-Francis Catatonia Rating Scale

Would you describe Ischemic colitis, to me Aarogya

Ischemic colitis

Ischemic colitis (also spelled ischaemic colitis) is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater frequency in the elderly, and is the most common form of bowel ischemia. Causes of the reduced blood flow can include changes in the systemic circulation (e.g. low blood pressure) or local factors such as constriction of blood vessels or a blood clot. In most cases, no specific cause can be identified.Ischemic colitis is usually suspected on the basis of the clinical setting, physical examination, and laboratory test results; the diagnosis can be confirmed by endoscopy or by using sigmoid or endoscopic placement of a visible light spectroscopic catheter (see Diagnosis). Ischemic colitis can span a wide spectrum of severity; most patients are treated supportively and recover fully, while a minority with very severe ischemia may develop sepsis and become critically, sometimes fatally, ill.Patients with mild to moderate ischemic colitis are usually treated with IV fluids, analgesia, and bowel rest (that is, no food or water by mouth) until the symptoms resolve. Those with severe ischemia who develop complications such as sepsis, intestinal gangrene, or bowel perforation may require more aggressive interventions such as surgery and intensive care. Most patients make a full recovery; occasionally, after severe ischemia, patients may develop long-term complications such as a stricture or chronic colitis. Signs and symptoms Three progressive phases of ischemic colitis have been described: A hyperactive phase occurs first, in which the primary symptoms are severe abdominal pain and the passage of bloody stools. Many patients get better and do not progress beyond this phase. A paralytic phase can follow if ischemia continues; in this phase, the abdominal pain becomes more widespread, the belly becomes more tender to the touch, and bowel motility decreases, resulting in abdominal bloating, no further bloody stools, and absent bowel sounds on exam. Finally, a shock phase can develop as fluids start to leak through the damaged colon lining. This can result in shock and metabolic acidosis with dehydration, low blood pressure, rapid heart rate, and confusion. Patients who progress to this phase are often critically ill and require intensive care.Symptoms of ischemic colitis vary depending on the severity of the ischemia. The most common early signs of ischemic colitis include abdominal pain (often left-sided), with mild to moderate amounts of rectal bleeding. The sensitivity of findings among 73 patients were: abdominal pain (78%) lower gastrointestinal tract bleeding (62%) diarrhea (38%) Fever higher than 38 °C (100.4 °F) (34%)Physical examination abdominal pain (77%) abdominal tenderness (21%) Causes Ischemic colitis is often classified according to the underlying cause. Non-occlusive ischemia develops because of low blood pressure or constriction of the vessels feeding the colon; occlusive ischemia indicates that a blood clot or other blockage has cut off blood flow to the colon. Non-occlusive ischemia In hemodynamically unstable patients (i.e. shock) the mesenteric perfusion may be compromised. This condition is commonly asymptomatic, and usually only apparent through a systemic inflammatory response. Occlusive ischemia Mostly the result of a thromboembolism. Commonly the embolism is caused by atrial fibrillation, valvular disease, myocardial infarction, or cardiomyopathy.In addition, ischemic colitis is a well-recognized complication of abdominal aortic aneurysm repair, when the origin of the inferior mesenteric artery is covered by the aortic graft. In a 1991 review concerning 2137 patients the accidental inferior mesenteric artery ligation was the most common cause (74%) of ischemic colitis. Thus, patients without adequate collateralization are at risk for ischemia of the descending and sigmoid colon. Bloody diarrhea and leukocytosis in the postoperative period are essentially diagnostic of ischemic colitis. The complication can be prevented through careful selection of subjects that may require replanting inferior mesenteric artery (IMA) and completing the pre surgical procedure information with an instrumental evaluation during surgical treatment. Pathophysiology Colonic blood supply The colon receives blood from both the superior and inferior mesenteric arteries. The blood supply from these two major arteries overlaps, with abundant collateral circulation via the marginal artery of the colon. However, there are weak points, or "watershed" areas, at the borders of the territory supplied by each of these arteries, such as the splenic flexure and the rectosigmoid junction. These watershed areas are most vulnerable to ischemia when blood flow decreases, as they have the fewest vascular collaterals.The rectum receives blood from both the inferior mesenteric artery and the internal iliac artery; the rectum is rarely involved by colonic ischemia due to this dual blood supply. Development of ischemia Under ordinary conditions, the colon receives between 10% and 35% of the total cardiac output. If blood flow to the colon drops by more than about 50%, ischemia will develop. The arteries feeding the colon are very sensitive to vasoconstrictors; presumably this is an evolutionary adaptation to shunt blood away from the bowel and to the heart and brain in times of stress. As a result, during periods of low blood pressure, the arteries feeding the colon clamp down vigorously; a similar process can result from vasoconstricting drugs such as ergotamine, cocaine, or vasopressors. This vasoconstriction can result in non-occlusive ischemic colitis. Pathologic findings A range of pathologic findings are seen in ischemic colitis, corresponding to the spectrum of clinical severity. In its mildest form, mucosal and submucosal hemorrhage and edema are seen, possibly with mild necrosis or ulceration. With more severe ischemia, a pathologic picture resembling inflammatory bowel disease (i.e. chronic ulcerations, crypt abscesses and pseudopolyps) may be seen. In the most severe cases, transmural infarction with resulting perforation may be seen; after recovery, the muscularis propria may be replaced by fibrous tissue, resulting in a stricture. Following restoration of normal blood flow, reperfusion injury may also contribute to the damage to the colon. Diagnosis Ischemic colitis must be differentiated from the many other causes of abdominal pain and rectal bleeding (for example, infection, inflammatory bowel disease, diverticulosis, or colon cancer). It is also important to differentiate ischemic colitis, which often resolves on its own, from the more immediately life-threatening condition of acute mesenteric ischemia of the small bowel.There are devices which test the sufficiency of oxygen delivery to the colon. The first device approved by the U.S. FDA in 2004 uses visible light spectroscopy to analyze capillary oxygen levels. Use during Aortic Aneurysm repair detected when colon oxygen levels fell below sustainable levels, allowing real-time repair. In several studies, Specificity has been 90% or higher for acute colonic ischemia, and 83% for chronic mesenteric ischemia, with a sensitivity of 71%-92%. This device must be placed using endoscopy, however. Diagnostic tests There is a recent optical test, but it requires endoscopy (see Diagnosis). There are no specific blood tests for ischemic colitis. The sensitivity of tests among 73 patients were: The white blood cell count was more than 15,000/mm3 in 20 patients (27%) The serum bicarbonate level was less than 24 mmol/L in 26 patients (36%)Plain X-rays are often normal or show non-specific findings. In a series of 73 patients, plain abdominal radiography (56%) showing colic distension in 53% or a pneumoperitoneum in 3%.CT scans are often used in the evaluation of abdominal pain and rectal bleeding, and may suggest the diagnosis of ischemic colitis, pick up complications, or suggest an alternate diagnosis.Endoscopic evaluation, via colonoscopy or flexible sigmoidoscopy, is the procedure of choice if the diagnosis remains unclear. Ischemic colitis has a distinctive endoscopic appearance; endoscopy can also facilitate alternate diagnoses such as infection or inflammatory bowel disease. Biopsies can be taken via endoscopy to provide more information. Visible light spectroscopy, performed using catheters placed through the 5 mm channel of the endoscope, is diagnostic (see Diagnosis). Treatment Except in the most severe cases, ischemic colitis is treated with supportive care. IV fluids are given to treat dehydration, and the patient is placed on bowel rest (meaning nothing to eat or drink) until the symptoms resolve. If possible, cardiac function and oxygenation should be optimized to improve oxygen delivery to the ischemic bowel. A nasogastric tube may be inserted if an ileus is present.Antibiotics are sometimes given in moderate to severe cases; the data supporting this practice date to the 1950s, although there is more recent animal data suggesting that antibiotics may increase survival and prevent bacteria from crossing the damaged lining of the colon into the bloodstream. The use of prophylactic antibiotics in ischemic colitis has not been prospectively evaluated in humans, but many authorities recommend their use based on the animal data.Patients being treated supportively are carefully monitored. If they develop worsening symptoms and signs such as high white blood cell count, fever, worsened abdominal pain, or increased bleeding, then they may require surgical intervention; this usually consists of laparotomy and bowel resection. Prognosis Most patients with ischemic colitis recover fully, although the prognosis depends on the severity of the ischemia. Patients with pre-existing peripheral vascular disease or ischemia of the ascending (right) colon may be at increased risk for complications or death.Non-gangrenous ischemic colitis, which comprises the vast majority of cases, is associated with a mortality rate of approximately 6%. However, the minority of patients who develop gangrene as a result of colonic ischemia have a mortality rate of 50–75% with surgical treatment; the mortality rate is almost 100% without surgical intervention. Long-term complications About 20% of patients with acute ischemic colitis may develop a long-term complication known as chronic ischemic colitis. Symptoms can include recurrent infections, bloody diarrhea, weight loss, and chronic abdominal pain. Chronic ischemic colitis is often treated with surgical removal of the chronically diseased portion of the bowel.A colonic stricture is a band of scar tissue which forms as a result of the ischemic injury and narrows the lumen of the colon. Strictures are often treated observantly; they may heal spontaneously over 12–24 months. If a bowel obstruction develops as a result of the stricture, surgical resection is the usual treatment, although endoscopic dilatation and stenting have also been employed. Epidemiology The exact incidence of ischemic colitis is difficult to estimate, as many patients with mild ischemia may not seek medical attention. Ischemic colitis is responsible for about 1 in 2000 hospital admissions and is seen on about 1 in 100 endoscopies. Men and women are affected equally; ischemic colitis is a disease of the elderly, with more than 90% of cases occurring in people over the age of 60. References == External links ==

Aarogya, can you share information about a health condition involving Leukocytosis

Leukocytosis

Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections or bone tumors as well as leukemia. It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, as a side effect of medication (e.g., lithium), and epinephrine administration. There are five principal types of leukocytosis: Neutrophilia (the most common form) Lymphocytosis Monocytosis Eosinophilia BasophiliaThis increase in leukocyte (primarily neutrophils) is usually accompanied by a "left upper shift" in the ratio of immature to mature neutrophils and macrophages. The proportion of immature leukocytes increases due to proliferation and inhibition of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF. Although it may indicate illness, leukocytosis is considered a laboratory finding instead of a separate disease. This classification is similar to that of fever, which is also a test result instead of a disease."Right shift" in the ratio of immature to mature neutrophils is considered with reduced count or lack of "young neutrophils" (metamyelocytes, and band neutrophils) in blood smear, associated with the presence of "giant neutrophils". This fact shows suppression of bone marrow activity, as a hematological sign specific for pernicious anemia and radiation sickness.A leukocyte count above 25 to 30 × 109/L is termed a leukemoid reaction, which is the reaction of a healthy bone marrow to extreme stress, trauma, or infection. It is different from leukemia and from leukoerythroblastosis, in which either immature white blood cells (acute leukemia) or mature, yet non-functional, white blood cells (chronic leukemia) are present in peripheral blood. Classification Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which neutrophils are elevated is neutrophilia; leukocytosis in which lymphocyte count is elevated is lymphocytosis; leukocytosis in which monocyte count is elevated is monocytosis; and leukocytosis in which eosinophil count is elevated is eosinophilia.An extreme form of leukocytosis, in which the WBC count exceeds 100,000/µL, is leukostasis. In this form there are so many WBCs that clumps of them block blood flow. This leads to ischemic problems including transient ischemic attack and stroke. Causes Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids. For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present.The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from bone marrow storage pools, decreased margination of leukocytes onto vessel walls, decreased extravasation of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.Certain medications, including corticosteroids, lithium and beta agonists, may cause leukocytosis.Leukocytosis is an expected finding in healthy women during the post-partum period and is not a cause for alarm unless accompanied by clinical manifestations of infection. Diagnosis Leukocyte counts Below are blood reference ranges for various types of leukocytes/WBCs. The 97.5 percentile (right limits in intervals in image, showing 95% prediction intervals) is a common limit for defining leukocytosis. Treatment While treatment is usually not necessary in the majority of cases, hyperleukocytosis (WBC count > 50 or 100 × 109/L), which can be seen in some leukemic patients, is treated to prevent leukostasis. See also Bacterial infection Complete blood count Leukocytosis in head trauma White blood cell References == External links ==

Aarogya, share information about a health condition involving Rhinitis medicamentosa

Rhinitis medicamentosa

Rhinitis medicamentosa (or RM) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) and certain oral medications (e.g., sympathomimetic amines and various 2-imidazolines) that constrict blood vessels in the lining of the nose, although evidence has been contradictory. Presentation The characteristic presentation of RM involves nasal congestion without rhinorrhea, postnasal drip, or sneezing following several days of decongestant use. This condition typically occurs after 5–7 days of use of topical decongestants. Patients often try increasing both the dose and the frequency of nasal sprays upon the onset of RM, worsening the condition. The swelling of the nasal passages caused by rebound congestion may eventually result in permanent turbinate hypertrophy, which may block nasal breathing until surgically removed. Causes Common issues that lead to overuse of topical decongestants: Deviated septum Upper respiratory tract infection Vasomotor rhinitis Cocaine use and other stimulant abuse Pregnancy (these products are not considered safe for pregnancy) Chronic rhinosinusitis Hypertrophy of the inferior turbinates Pathophysiology The pathophysiology of RM is unclear, although several mechanisms involving norepinephrine signaling have been proposed. RM is associated with histological changes that include: an increase in the number of lymphocytes and fibroblasts, epithelial cell denudation, epithelial edema, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, increased mucus production, nasociliary loss, inflammatory cell infiltration, and squamous cell metaplasia.Direct acting sympathomimetic amines, such as phenylephrine stimulate alpha adrenergic receptors, while mixed-acting agents, such as pseudoephedrine can stimulate both alpha and beta adrenergic receptors directly and indirectly by releasing norepinephrine from sympathetic nerve terminals. At first, the vasoconstrictive effect of alpha-receptors dominates, but with continued use of an alpha agonist, this effect fades first, allowing the vasodilation due to beta-receptor stimulation to emerge.2-Imidazoline derivatives, such as oxymetazoline, may participate in negative feedback on endogenous norepinephrine production. Therefore, after cessation of prolonged use, there will be inadequate sympathetic vasoconstriction in the nasal mucosa, and domination of parasympathetic activity can result in increased secretions and nasal edema. Evidence suggests that if oxymetazoline is used only nightly for allergic rhinitis (instead of more frequent dosage as may be directed on product label), it may be used longer than one week without high risk of rhinitis medicamentosa especially with use of intranasal steroid like fluticasone furoate. Treatment The treatment of RM involves withdrawal of the offending nasal spray or oral medication. Both a "cold turkey" and a "weaning" approach can be used. Cold turkey is the most effective treatment method, as it directly removes the cause of the condition, yet the time period between the discontinuation of the drug and the relief of symptoms may be too long and uncomfortable for some individuals (particularly when trying to go to sleep when they are unable to breathe through their nose). The use of over-the-counter (OTC) saline nasal sprays may help open the nose without causing RM if the spray does not contain a decongestant. Symptoms of congestion and runny nose can often be treated with corticosteroid nasal sprays under the supervision of a physician. For very severe cases, oral steroids or nasal surgery may be necessary. For RM caused by topical decongestants, there are anecdotal reports of persons having success by withdrawing treatment from one nostril at a time.A study has shown that the anti-infective agent benzalkonium chloride, which is frequently added to topical nasal sprays as a preservative, aggravates the condition by further increasing the rebound swelling. See also Topical decongestant References Further reading Bernstein, I.Leonard (January 2000). "Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport". Journal of Allergy and Clinical Immunology. 105 (1): 39–44. doi:10.1016/S0091-6749(00)90175-1. PMID 10629450. Remsen, K. A.; Black, M. J. (19 April 1980). "Rhinitis medicamentosa". CMAJ. 122 (8): 881–884. PMC 1801634. PMID 6154514. Adams, H. Richard (2013). "Adrenergic Agonists and Antagonists". In Riviere, Jim E.; Papich, Mark G. (eds.). Veterinary Pharmacology and Therapeutics. pp. 125–56. ISBN 978-1-118-68590-7. Elwany, Samy S.; Stephanos, Wahid M. (1983). "Rhinitis medicamentosa: An experimental histopathological and histochemical study". ORL. 45 (4): 187–194. doi:10.1159/000275642. PMID 6192384. Baldwin, R. L.; Jolly, P. A.; Mizes, J. S.; Fleece, L. (1984). "Rhinitis medicamentosa. Conceptualization, incidence, and treatment". The Alabama Journal of Medical Sciences. 21 (2): 205–208. PMID 6375416. Graf, Peter (October 1999). "Adverse Effects of benzalkonium chloride on the nasal mucosa: Allergic rhinitis and rhinitis medicamentosa". Clinical Therapeutics. 21 (10): 1749–1755. doi:10.1016/S0149-2918(99)80053-8. PMID 10566570. Graf, P.; Hallen, H.; Juto, J.-E. (May 1995). "Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers". Clinical & Experimental Allergy. 25 (5): 395–400. doi:10.1111/j.1365-2222.1995.tb01069.x. PMID 7553241. S2CID 19989791. Lin, Chun-Yu; Cheng, Po-Hsu; Fang, Sheen-Yie (28 June 2016). "Mucosal Changes in Rhinitis Medicamentosa". Annals of Otology, Rhinology & Laryngology. 113 (2): 147–151. doi:10.1177/000348940411300213. PMID 14994772. S2CID 850948. Mabry, R. L. (1982). "Rhinitis medicamentosa: the forgotten factor in nasal obstruction". Southern Medical Journal. 75 (7): 817–819. doi:10.1097/00007611-198207000-00013. PMID 6178170. Bu, G. X.; Wang, J. Q. (1991). "Studies of rhinitis medicamentosa". Chinese Medical Journal. 104 (1): 60–63. PMID 1879198. == External links ==

Do you know what is Primary sclerosing cholangitis, Aarogya

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain. The bile duct scarring that occurs in PSC narrows the ducts of the biliary tree and impedes the flow of bile to the intestines. Eventually, it can lead to cirrhosis of the liver and liver failure. PSC increases the risk of various cancers, including liver cancer, gallbladder carcinoma, colorectal cancer, and cholangiocarcinoma. The underlying cause of PSC is unknown. Genetic susceptibility, immune system dysfunction, and abnormal composition of the gut flora may play a role. This is further suggested by the observation that around 75% of individuals with PSC also have inflammatory bowel disease (IBD), most often ulcerative colitis.No effective medical treatment for primary sclerosing cholangitis is known. Its most definitive treatment is a liver transplant, but it can recur after transplantation. Many people affected by PSC require a liver transplant. PSC is a rare disease and most commonly affects people with IBD. About 3.0 to 7.5% of people with ulcerative colitis have PSC, and 80% of people with PSC have some form of IBD. Diagnosis usually occurs in people in their 30s or 40s. Individuals of Northern European ancestry are affected more often than people of Southern European or Asian descent. Men are affected more often than women. The disease was initially described in the mid-1800s, but was not fully characterized until the 1970s with the advent of improved medical-imaging techniques such as endoscopic retrograde cholangiopancreatography. Signs and symptoms Nearly half of people with PSC do not have symptoms, and are often incidentally discovered to have PSC due to abnormal liver function tests; however, a substantial proportion have debilitating signs and symptoms of the disease. Signs and symptoms of PSC may include severe itching and nonspecific fatigue. Yellowing of the skin and white portion of the eyes may also be seen. Enlargement of the liver and spleen are seen in roughly 40% of affected individuals. Abdominal pain affects about 20% of people with PSC.Multiple episodes of life-threatening acute cholangitis (infection within the bile ducts) can be seen due to impaired drainage of the bile ducts, which increases the risk of infection. Dark urine due to excess conjugated bilirubin, which is water-soluble and excreted by the kidneys (i.e. choluria) Malabsorption, especially of fat, and steatorrhea (fatty stool), due to an inadequate amount of bile reaching the small intestine, leading to decreased levels of the fat-soluble vitamins, A, D, E, and K. Portal hypertension, a complication of cirrhosis, which can manifest with esophageal and parastomal varices as well as hepatic encephalopathy (mental status alteration/disturbance caused by liver dysfunction and shunting of blood away from the scarred liver; such that ammonia detoxification is reduced with concomitant encephalopathy) or ascites. Cause The exact cause of primary sclerosing cholangitis is unknown, and its pathogenesis is improperly understood. Although PSC is thought to be caused by autoimmune disease, it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases.Data have provided novel insights suggesting: an important association between the intestinal microbiota and PSC and a process referred to as cellular senescence and the senescence-associated secretory phenotype in the pathogenesis of PSC.In addition, longstanding, well-recognized associations are seen between PSC and human leukocyte antigen alleles (A1, B8, and DR3). Pathophysiology PSC is characterized by inflammation of the bile ducts (cholangitis) with consequent stricturing (i.e., narrowing) and hardening (sclerosis) of these ducts due to scar formation, be it inside and/or outside the liver. The resulting scarring of the bile ducts obstructs the flow of bile, which further perpetuates bile duct and liver injury. Chronic impairment of bile flow due to blockage and dysfunctional bile transport (cholestasis) causes progressive biliary fibrosis and ultimately biliary cirrhosis and liver failure.The primary physiological function of bile is to assist in the breakdown and absorption of fat in the intestinal tract; a relative deficiency of bile can lead to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).Liver enlargement is seen due to portal hypertension caused by compression of portal veins by the proximate sclerosed intrahepatic bile ducts, and leads to right upper quadrant abdominal pain. Diagnosis PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out: serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months cholangiography demonstrating biliary strictures or irregularity consistent with PSC liver biopsy consistent with PSC (if available)Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its noninvasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear antineutrophil cytoplasmic antibodies (P-ANCA); however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20-50% of PSC patients, and likewise are not specific for the disease,but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation nonanastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with IBD, which includes ulcerative colitis and Crohns disease, response to treatment, and risks of disease progression. Classification Primary sclerosing cholangitis is typically classified into three subgroups based on whether the small and/or large bile ducts are affected. The subgroups of PSC include: Classic PSC Small-duct PSC PSC associated with autoimmune hepatitis Management No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as cholestyramine); antibiotics to treat episodes of ascending cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (A, D, E, and K).ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile-duct cancer (cholangiocarcinoma).Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial ascending cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some experience disease recurrence afterward. The reasons why some patients develop recurrent PSC remains largely obscure, but surprisingly, those without recurrence of disease (hence protected from recurrence) are characterized by an increased presence of the potentially pathogenic Shigella species. Prognosis Estimated median survival from diagnosis until liver transplant or PSC-related death is 21.3 years. Various models have been developed to help predict survival, but their use is generally best suited for research and not clinical purposes. A serum alkaline phosphatase less than 1.5 times the upper limit of normal has been associated with better outcomes, but its use in predicting long-term outcomes is unclear. An IgA isotype autoantibody to the pancreatic GP2 protein (anti-GP2 IgA antibody) is the first verified prognostic biomarker in PSC. The role of anti-GP2 IgA in PSC was simultaneously investigated and reported by two research groups, and later confirmed by others. Association was demonstrated between anti-GP2 IgA and progressive liver fibrosis, cholangiocarcinoma development and shorter transplantation free survival in PSC patients.Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent. Related diseases The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.PSC is strongly associated with IBD, in particular ulcerative colitis (UC) and to a lesser extent Crohns disease. As many as 5% of patients with IBD are co-diagnosed with PSC, and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital. Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis (hepatic osteodystrophy) and hypothyroidism are also associated with PSC.A 2–3:1 male-to-female predilection occurs in primary sclerosing cholangitis. PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of IBD. PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. Relatively few data are available on the prevalence and incidence of PSC, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, the risk is likely higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC. Research Although no curative treatment is known, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody against the profibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC. Notable cases Chris Klug – professional snowboarder with PSC who had liver transplant Chris LeDoux – professional rodeo rider and country musician with PSC who died of cholangiocarcinoma Elena Baltacha – British professional tennis player, diagnosed with PSC at age 19 and died five months after being diagnosed with PSC-associated liver cancer (specifically cholangiocarcinoma) at the age of 30 Walter Payton – died of complications of PSC Kieron Dyer – professional footballer James Redford – director and son of Robert Redford who underwent two liver transplants due to PSC References External links Patient support organizations: www.pscpartners.org—based in the US www.pscpartners.ca—based in Canada www.pscsupport.org.au—based in Australia www.pscsupport.org.uk—based in the UK

Aarogya what is Lipoma

Lipoma

A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than 5 cm (2.0 in) in size. Common locations include upper back, shoulders, and abdomen. It is possible to have a number of lipomas.The cause is generally unclear. Risk factors include family history, obesity, and lack of exercise. Diagnosis is typically based on a physical exam. Occasionally medical imaging or tissue biopsy is used to confirm the diagnosis.Treatment is typically by observation or surgical removal. Rarely, the condition may recur following removal, but this can generally be managed with repeat surgery. They are not generally associated with a future risk of cancer.Lipomas have a prevalence of roughly 2 out of every 100 people. Lipomas typically occur in adults between 40 and 60 years of age. Males are more often affected than females. They are the most common noncancerous soft-tissue tumor. The first use of the term "lipoma" to describe these tumors was in 1709. Types The many subtypes of lipomas include:: 624–5  Adenolipomas are lipomas associated with eccrine sweat glands.: 627  Angiolipoleiomyomas are acquired, solitary, asymptomatic acral nodules, characterized histologically by well-circumscribed subcutaneous tumors composed of smooth muscle cells, blood vessels, connective tissue, and fat.: 627  Angiolipomas are painful subcutaneous nodules having all other features of a typical lipoma.: 624  Cerebellar pontine angle and internal auditory canal lipomas Chondroid lipomas are deep-seated, firm, yellow tumors that characteristically occur on the legs of women.: 625  Corpus callosum lipoma is a rare congenital brain condition that may or may not present with symptoms. This occurs in the corpus callosum, also known as the calossal commissure, which is a wide, flat bundle of neural fibers beneath the cortex in the human brain. Hibernomas are lipomas of brown fat. Intradermal spindle cell lipomas are distinct in that they most commonly affect women and have a wide distribution, occurring with relatively equal frequency on the head and neck, trunk, and upper and lower extremities.: 625  A fibrolipoma is a lipoma with focal areas of large amounts of fibrous tissue. A sclerotic lipoma is a predominantly fibrous lesion with focal areas of fat.Neural fibrolipomas are overgrowths of fibro-fatty tissue along a nerve trunk, which often leads to nerve compression.: 625 Pleomorphic lipomas, like spindle-cell lipomas, occur for the most part on the backs and necks of elderly men and are characterized by floret giant cells with overlapping nuclei.: 625  Spindle-cell lipomas are asymptomatic, slow-growing, subcutaneous tumors that have a predilection for the posterior back, neck, and shoulders of older men.: 625  Superficial subcutaneous lipomas, the most common type of lipoma, lie just below the surface of the skin. Most occur on the trunk, thigh, and forearm, although they may be found anywhere in the body where fat is located. Causes The tendency to develop a lipoma is not necessarily hereditary, although hereditary conditions such as familial multiple lipomatosis might include lipoma development. Genetic studies in mice have shown a correlation between the HMG I-C gene (previously identified as a gene related to obesity) and lipoma development. These studies support prior epidemiologic data in humans showing a correlation between HMG I-C and mesenchymal tumors.Cases have been reported where minor injuries are alleged to have triggered the growth of a lipoma, called a "post-traumatic lipoma". However, the link between trauma and the development of lipomas is controversial. Other conditions Lipomatosis is believed to be a hereditary condition in which multiple lipomas are present on the body.Adiposis dolorosa (Dercum disease) is a rare condition involving multiple painful lipomas, swelling, and fatigue. Early studies mentioned prevalence in obese postmenopausal women. However, current literature demonstrates that Dercum disease is present in more women than men of all body types; the average age for diagnosis is 35 years.Benign symmetric lipomatosis (Madelung disease) is another condition involving lipomatosis. It nearly always appears in middle-aged males after many years of alcoholism, but nonalcoholic males and females can also be affected. Diagnosis A physical exam is typically the easiest way to diagnose it. Rarely, a tissue biopsy or imaging may be required. The imaging modality of choice is magnetic resonance imaging (MRI) because it has superior sensitivity of distinguishing it from liposarcoma as well as mapping the surrounding anatomy. Treatment Usually, treatment of lipomas is not necessary, unless they become painful or restrict movement. They are usually removed for cosmetic reasons if they grow very large or for histopathology to verify that they are not a more dangerous type of tumor such as a liposarcoma. This last point can be important, as the characteristics of a tumor are not known until after it is removed and medically examined.Lipomas are normally removed by simple excision. The removal can often be done under local anesthetic and takes less than 30 minutes. This cures the great majority of cases, with about 1–2% of lipomas recurring after excision. Liposuction is another option if the lipoma is soft and has a small connective tissue component. Liposuction typically results in less scarring; however, with large lipomas, it may fail to remove the entire tumor, which can lead to regrowth.New methods under development are supposed to remove the lipomas without scarring. One is removal by injecting compounds that trigger lipolysis, such as steroids or phosphatidylcholine. Other potential methods based on tissue-targeted heating include cauterization, electrosurgery, and harmonic scalpel. Post surgery Patients who have a lipoma removed are usually able to return home the same day, without any need for hospitalization. Some patients may have pain, swelling, or bruising where the lipoma was removed. These symptoms usually subside after a few days. Resection of an intermuscular lipoma in the elbow region Other lipomas Prognosis Lipomas are rarely life-threatening, and the common subcutaneous lipomas are not a serious condition. Lipomas growing in internal organs can be more dangerous; for example, lipomas in the gastrointestinal tract can cause bleeding, ulceration, and painful obstructions (so-called "malignant by location", despite being a benign growth histologically). Malignant transformation of lipomas into liposarcomas is very rare, and most liposarcomas are not produced from pre-existing benign lesions. A few cases of malignant transformation have been described for bone and kidney lipomas, but it is possible that these few reported cases were well-differentiated liposarcomas in which the subtle malignant characteristics were missed when the tumor was first examined. Deep lipomas have a greater tendency to recur than superficial lipomas because complete surgical removal of deep lipomas is not always possible.The presence of multiple lipomas, lipomatosis, is more commonly encountered in men. Some superficial lipomas can extend into deep fascia and may complicate excision. Liposarcoma is found in 1% of lipomas and is more likely to occur in lesions of the lower extremities, shoulders, and retroperitoneal areas. Other risk factors for liposarcoma include large size (>5 cm), associated with calcification, rapid growth, and/or invasion into nearby structures or through fascia into muscle tissue. Epidemiology Around 2% of the general population has a lipoma. These tumors can occur at any age, but are most common in middle age, often appearing in people from 40 to 60 years old. Cutaneous lipomas are rare in children, but these tumors can occur as part of the inherited disease Bannayan-Zonana syndrome.Lipomas are usually relatively small with diameters of about 1–3 cm, but in rare cases they can grow over several years into "giant lipomas" that are 10–20 cm across and weigh up to 4–5 kg. Other animals Lipomas occur in many animals, but are most common in older dogs, particularly older Labrador Retrievers, Doberman Pinschers, and Miniature Schnauzers. Overweight female dogs are especially prone to developing these tumors, and most older or overweight dogs have at least one lipoma. In dogs, lipomas usually occur in the trunk or upper limbs. They are also found less commonly in cattle and horses, and rarely in cats and pigs. However, a pedunculated lipoma can cause entrapment and torsion of the intestine in horses, causing necrosis, colic, and possibly death. The intestine becomes twisted around the stalk of the lipoma and loses blood supply. References == External links ==

Aarogya, can you share information about a health condition involving Cholinergic crisis

Cholinergic crisis

A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine. Symptoms and diagnosis As a result of cholinergic crisis, the muscles stop responding to the high synaptic levels of ACh, leading to flaccid paralysis, respiratory failure, and other signs and symptoms reminiscent of organophosphate poisoning. Other symptoms include increased sweating, salivation, bronchial secretions along with miosis (constricted pupils). This crisis may be masked by the concomitant use of atropine along with cholinesterase inhibitor medication in order to prevent side effects. Flaccid paralysis resulting from cholinergic crisis can be distinguished from myasthenia gravis by the use of the drug edrophonium (Tensilon), as it only worsens the paralysis caused by cholinergic crisis but strengthens the muscle response in the case of myasthenia gravis. (Edrophonium is a cholinesterase inhibitor, hence increases the concentration of acetylcholine present). Some of the symptoms of increased cholinergic stimulation include: Salivation: stimulation of the salivary glands Lacrimation: stimulation of the lacrimal glands (tearing) Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles Defecation Gastrointestinal distress: Smooth muscle tone changes causing gastrointestinal problems, including cramping Emesis: Vomiting Miosis constriction of the pupils of the eye via stimulation of the pupillary constrictor muscles Muscle spasm: stimulation of skeletal muscle (due to nicotinic acetylcholine receptor stimulation) Cause Cholinergic crisis, sometimes known by the mnemonic "SLUDGE syndrome" ( Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress and Emesis), can be a consequence of: Contamination with - or excessive exposure to - certain chemicals including: nerve agents, (e.g. sarin, VX, Novichok agents). organophosphorus insecticides (e.g. parathion, aldicarb) nicotine poisoning can be thought of as a subset of cholinergic crisis, as it also involves excessive parasympathetic stimulation. Ingestion of certain poisonous fungi (particularly the muscarine-containing members of the genera Amanita, Inocybe and Clitocybe). In medicine, this is seen in patients with myasthenia gravis who take too high a dose of medications such as cholinesterase inhibitors, or seen following general anaesthesia, when too high a dose of a cholinesterase inhibitor drug is given to reverse surgical muscle paralysis. Treatment Some elements of the cholinergic crisis can be reversed with antimuscarinic drugs like atropine or diphenhydramine, but the most dangerous effect - respiratory depression, cannot. The neuromuscular junction, where the brain communicates with muscles (like the diaphragm, the main breathing muscle), works by acetylcholine activating nicotinic acetylcholine receptors and leading to muscle contraction. Atropine only blocks muscarinic acetylcholine receptors (a different receptor class than the nicotinic receptors at the neuromuscular junction), so atropine will not improve the muscle strength and ability to breathe in someone with cholinergic crisis. Such a patient will require neuromuscular blocking drugs and mechanical ventilation until the crisis resolves on its own. See also Physostigmine == References ==

Can you describe Renal tubular acidosis, to me Aarogya

Renal tubular acidosis

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by insufficient secretion of hydrogen ions (which are acidic) into the latter portions of the nephron (the distal tubule) or by failure to reabsorb sufficient bicarbonate ions (which are alkaline) from the filtrate in the early portion of the nephron (the proximal tubule). Although a metabolic acidosis also occurs in those with chronic kidney disease, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.The word acidosis refers to the tendency for RTA to cause an excess of acid, which lowers the bloods pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis. Types An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications): Type 1: distal Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated cells of the medullary collecting duct of the distal nephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating H+ from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while K+ cannot be reclaimed by the cell, leading to acidemia (as H+ builds up in the body) and hypokalemia (as K+ cannot be reabsorbed by the alpha cell).This leads to the clinical features of dRTA; In other words, the intercalated cells apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types. Normal anion gap metabolic acidosis/acidemia Hypokalemia, Hypocalcemia, Hyperchloremia Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate). Nephrocalcinosis (deposition of calcium in the substance of the kidney) Bone demineralisation (causing rickets in children and osteomalacia in adults) Growth deficiency Medullary cysts Sensorineural hearing loss Hereditary hemolytic anemiaDistal RTA has also been linked to specific genetic mutations that will alter when the disease will present in the patients life. Patients with mutations in ATP6V1B1 and ATP6V0A4 will present with symptoms within the first year of life, while those with mutation of the SLC4A1 have delayed onset around 10 years of age. Electrolyte imbalances remain the same, while in severe cases symptoms can advance to amino aciduria and hyperammonemia. In a large Asian series of Distal renal Tubular Acidosis in Sjogrens Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of themdRTA is the most common form of RTA diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary RTA generally results from systemic and autoimmune diseases or drug and toxin exposure in adults, whereas pediatric RTA results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite. Type 2: proximal Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and metabolic acidosis. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal tubular cells called Fanconi syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.The principal feature of Fanconi syndrome is bone demineralization (osteomalacia or rickets) due to phosphate wasting. Type 3: combined proximal and distal In some patients, RTA shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA (possibly in relation with some exogenous factor such as high salt intake) and is no longer observed. This form of RTA has also been referred to as juvenile RTA.Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, cerebral calcification, and mental retardation. It is very rare and cases from all over the world have been reported, of which about 70% are from the Maghreb region of North Africa, possibly due to the high prevalence of consanguinity there. The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification. Type 3 is rarely discussed. Most comparisons of RTA are limited to a comparison of types 1, 2, and 4. Type 4: absolute hypoaldosteronism or aldosterone insensitivity Type 4 RTA is not actually a tubular disorder at all nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in proximal tubular ammonium excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia.Causes include: Aldosterone deficiency (hypoaldosteronism): Primary vs. hyporeninemic (including diabetic nephropathy) Aldosterone resistanceDrugs: NSAIDs, ACE inhibitors and ARBs, Eplerenone, Spironolactone, Trimethoprim, Pentamidine Pseudohypoaldosteronism History Renal tubular acidosis was first described in 1935 by Lightwood and 1936 by Butler et al. in children. Baines et al. first described it in adults in 1945.Donald L. Lewis postulated the character Tiny Tim, of A Christmas Carol, was suffering from renal tubular acidosis.Researchers published in PLOS ONE in 2009 speculated that the infamously afflicted Charles II of Spain may have suffered from renal tubular acidosis in tandem with combined pituitary hormone deficiency. See also Charles II of Spain, who is speculated to have suffered with dRTA Hyperchloremic acidosis Hypokalemic acidosis Lightwood–Albright syndrome References == External links ==

Would you describe Biliary colic, to me Aarogya

Biliary colic

Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct. Typically, the pain is in the right upper part of the abdomen, and can be severe. Pain usually lasts from 15 minutes to a few hours. Often, it occurs after eating a heavy meal, or during the night. Repeated attacks are common.Gallstone formation occurs from the precipitation of crystals that aggregate to form stones. The most common form is cholesterol gallstones. Other forms include calcium, bilirubin, pigment, and mixed gallstones. Other conditions that produce similar symptoms include appendicitis, stomach ulcers, pancreatitis, and gastroesophageal reflux disease.Treatment for gallbladder attacks is typically surgery to remove the gallbladder. This can be either done through small incisions or through a single larger incision. Open surgery through a larger incision is associated with more complications than surgery through small incisions. Surgery is typically done under general anesthesia. In those who are unable to have surgery, medication to try to dissolve the stones or shock wave lithotripsy may be tried. As of 2017, it is not clear whether surgery is indicated for everyone with biliary colic.In the developed world, 10 to 15% of adults have gallstones. Of those with gallstones, biliary colic occurs in 1 to 4% each year. Nearly 30% of people have further problems related to gallstones in the year following an attack. About 15% of people with biliary colic eventually develop inflammation of the gallbladder if not treated. Other complications include inflammation of the pancreas. Signs and symptoms Pain is the most common presenting symptom. It is usually described as sharp, crampy, dull or severe right upper quadrant pain, which may radiate to the right shoulder, or less commonly, behind the breastbone. Nausea and vomiting can be associated with biliary colic. Individuals may also present with pain that is induced following a fatty meal and the symptom of indigestion. The pain often lasts longer than 30 minutes, up to a few hours. Patients usually have normal vital signs with biliary colic, whereas patients with cholecystitis are usually febrile and more ill appearing. Lab studies that should be ordered include a complete blood count, liver function tests and lipase. In biliary colic, lab findings are usually within normal limits. Alanine aminotransferase and aspartate transaminase are usually suggestive of liver disease whereas elevation of bilirubin and alkaline phosphatase suggests common bile duct obstruction. Pancreatitis should be considered if the lipase value is elevated; gallstone disease is the major cause of pancreatitis. Complications The presence of gallstones can lead to inflammation of the gallbladder (cholecystitis) or the biliary tree (cholangitis) or acute inflammation of the pancreas (pancreatitis). Rarely, a gallstone can become impacted in the ileocecal valve that joins the caecum and the ileum, causing gallstone ileus (mechanical ileus).Complications from delayed surgery include pancreatitis, empyema, and perforation of the gallbladder, cholecystitis, cholangitis, and obstructive jaundice.Biliary pain in the absence of gallstones, known as postcholecystectomy syndrome, may severely affect the patients quality of life, even in the absence of disease progression. Causes Biliary pain is most frequently caused by obstruction of the common bile duct or the cystic duct by a gallstone. However, the presence of gallstones is a frequent incidental finding and does not always necessitate treatment, in the absence of identifiable disease. Furthermore, biliary pain may be associated with functional disorders of the biliary tract, so-called acalculous biliary pain (pain without stones), and can even be found in patients post-cholecystectomy (removal of the gallbladder), possibly as a consequence of dysfunction of the biliary tree and the sphincter of Oddi. Acute episodes of biliary pain may be induced or exacerbated by certain foods, most commonly those high in fat. Risk factors Cholesterol gallstone formation risk factors include age, female sex, family history, race, pregnancy, parity, obesity, hormonal birth control, diabetes mellitus, cirrhosis, prolonged fasting, rapid weight loss, total parenteral nutrition, ileal disease and impaired gallbladder emptying.Patients that have gallstones and biliary colic are at increased risk for complications, including cholecystitis. Complications from gallstone disease is 0.3% per year and therefore prophylactic cholecystectomy are rarely indicated unless part of a special population that includes porcelain gallbladder, individuals eligible for organ transplant, diabetics and those with sickle cell anemia. Diagnosis Diagnosis is guided by the persons presenting symptoms and laboratory findings. The gold standard imaging modality for the presence of gallstones is ultrasound of the right upper quadrant. There are many reasons for this choice, including no exposure to radiation, low cost, and availability in city, urban, and rural hospitals. Gallstones are detected with a specificity and sensitivity of greater than 95% with ultrasound. Further signs on ultrasound may suggest cholecystitis or choledocholithiasis. Computed Tomography (CT) is not indicated when investigating for gallbladder disease as 60% of stones are not radiopaque. CT should only be utilized if other intra-abdominal pathology exists or the diagnosis is uncertain. Endoscopic retrograde cholangiopancreatography (ERCP) should be used only if lab tests suggest the existence of a gallstone in the bile duct. ERCP is then both diagnostic and therapeutic. Management Medications Initial management includes the relief of symptoms and correcting electrolyte and fluid imbalance that may occur with vomiting. Antiemetics, such as dimenhydrinate, are used to treat the nausea. Pain may be treated with anti-inflammatories, NSAIDs such as ketorolac or diclofenac. Opioids, such as morphine, less commonly may be used. NSAIDs are more or less equivalent to opioids. Hyoscine butylbromide, an antispasmodic, is also indicated in biliary colic.In biliary colic, the risk of infection is minimal and therefore antibiotics are not required. Presence of infection indicates cholecystitis. Surgery It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not. The scientific basis to assess whether surgery outperformed other treatment was insufficient and better studies were needed as of a SBU report in 2017. Treatment of biliary colic is dictated by the underlying cause. The presence of gallstones, usually visualized by ultrasound, generally necessitates a surgical treatment (removal of the gall bladder, typically via laparoscopy). Removal of the gallbladder with surgery, known as a cholecystectomy, is the definitive surgical treatment for biliary colic. A 2013 Cochrane review found tentative evidence to suggest that early gallbladder removal may be better than delayed removal. Early laparoscopic cholecystectomy happens within 72 hours of diagnosis. In a Cochrane review that evaluated receiving early versus delayed surgery, they found that 23% of those who waited on average 4 months ended up in hospital for complications, compared to none with early intervention with surgery. Early intervention has other advantages including a reduced number of visits to the emergency department, fewer conversions to open surgery, less operating time required, and reduced time in hospital postoperatively. The Swedish agency SBU estimated in 2017 that increasing acute phase surgeries could free multiple in-hospital days per patient and would additionally spare pain and suffering in wait of receiving an operation. The report found that those with acute inflammation of the gallbladder can be surgically treated in the acute phase, within a few days of symptom debut, without increasing the risk for complications (compared to when the surgery is done later in an asymptomatic stage). Epidemiology The annual risk of developing biliary colic is 2 to 3%. References External links Diagram of pain radiation

Hey Aarogya!, what is Splenic infarction

Splenic infarction

Splenic infarction is a condition in which blood flow supply to the spleen is compromised, leading to partial or complete infarction (tissue death due to oxygen shortage) in the organ. Splenic infarction occurs when the splenic artery or one of its branches are occluded, for example by a blood clot.In one series of 59 patients, mortality amounted to 5%. Complications include a ruptured spleen, bleeding, an abscess of the spleen (for example, if the underlying cause is infective endocarditis) or pseudocyst formation. Splenectomy may be warranted for persistent pseudocysts due to the high risk of subsequent rupture. Diagnosis Although it can occur asymptomatically, the typical symptom is severe pain in the left upper quadrant of the abdomen, sometimes radiating to the left shoulder. Fever and chills develop in some cases. It has to be differentiated from other causes of acute abdomen. An abdominal CT scan is the most commonly used modality to confirm the diagnosis, although abdominal ultrasound can also contribute. Treatment There is no specific treatment, except treating the underlying disorder and providing adequate pain relief. Surgical removal of the spleen (splenectomy) is only required if complications ensue; surgical removal predisposes to overwhelming post-splenectomy infections. Causes Several factors may increase the tendency for clot formation, such as specific infections (such as infectious mononucleosis, cytomegalovirus infection, malaria, or babesiosis), inherited clotting disorders (thrombophilia, such as Factor V Leiden, antiphospholipid syndrome), malignancy (such as pancreatic cancer) or metastasis, or a combination of these factors. In some conditions, blood clots form in one part of the circulatory system and then dislodge and travel to another part of the body, which could include the spleen. These emboligenic disorders include atrial fibrillation, patent foramen ovale, endocarditis or cholesterol embolism. Splenic infarction is also more common in hematological disorders with associated splenomegaly, such as the myeloproliferative disorders. Other causes of splenomegaly (for example, Gaucher disease or hemoglobinopathies) can also predispose to infarction. Splenic infarction can also result from a sickle cell crisis in patients with sickle cell anemia. Both splenomegaly and a tendency towards clot formation feature in this condition. In sickle cell disease, repeated splenic infarctions lead to a non-functional spleen (autosplenectomy). Any factor that directly compromises the splenic artery can cause infarction. Examples include abdominal traumas, aortic dissection, torsion of the splenic artery (for example, in wandering spleen) or external compression on the artery by a tumor. It can also be a complication of vascular procedures.Splenic infarction can be due to vasculitis or disseminated intravascular coagulation. Various other conditions have been associated with splenic infarction in case reports, for example granulomatosis with polyangiitis or treatment with medications that predispose to vasospasm or blood clot formation, such as vasoconstrictors used to treat esophageal varices, sumatriptan or bevacizumab.In a single-center retrospective cases review, people who were admitted to the hospital with a confirmed diagnosis of acute splenic infarction, cardiogenic emboli was the dominant etiology followed by atrial fibrillation, autoimmune disease, associated infection, and hematological malignancy. In spite of those already had risk factors of developing splenic infarction, there were nine beforehand healthy people. And among them, 5 of 9 hitherto silent antiphospholipid syndrome or mitral valve disease had been identified. Two remained cryptogenic. Therapeutic infarction Splenic infarction can be induced for the treatment of such conditions as portal hypertension or splenic injury. It can also be used prior to splenectomy for the prevention of blood loss. References == External links ==

Aarogya , Do you know what is Abdominal compartment syndrome,

Abdominal compartment syndrome

Abdominal compartment syndrome (ACS) occurs when the abdomen becomes subject to increased pressure reaching past the point of intra-abdominal hypertension (IAH). ACS is present when intra-abdominal pressure rises and is sustained at > 20 mmHg and there is new organ dysfunction or failure. ACS is classified into three groups: Primary, secondary and recurrent ACS. It is not a disease and as such it occurs in conjunction with many disease processes, either due to the primary illness or in association with treatment interventions. Specific cause of abdominal compartment syndrome is not known, although some causes can be sepsis and severe abdominal trauma. Increasing pressure reduces blood flow to abdominal organs and impairs pulmonary, cardiovascular, renal, and gastro-intestinal (GI) function, causing obstructive shock, multiple organ dysfunction syndrome and death. Causes Peritoneal tissue edema secondary to diffuse peritonitis, abdominal trauma Fluid therapy due to massive volume resuscitation Retroperitoneal hematoma secondary to trauma and aortic rupture Peritoneal trauma secondary to emergency abdominal operations Reperfusion injury following bowel ischemia due to any cause Retroperitoneal and mesenteric inflammatory edema secondary to acute pancreatitis Ileus and bowel obstruction Intra-abdominal masses of any cause Abdominal packing for control of bleeding Closure of the abdomen under undue tension Ascites (intra-abdominal fluid accumulation) Acute pancreatitis with abscesses formation Pathophysiology Abdominal compartment syndrome occurs when tissue fluid within the peritoneal and retroperitoneal space (either edema, retroperitoneal blood or free fluid in the abdomen) accumulates in such large volumes that the abdominal wall compliance threshold is crossed and the abdomen can no longer stretch. Once the abdominal wall can no longer expand, any further fluid leaking into the tissue results in fairly rapid rises in the pressure within the closed space. Initially this increase in pressure does not cause organ failure but does prevent organs from working properly – this is called intra-abdominal hypertension and is defined as a pressure over 12 mmHg in adults. ACS is defined by a sustained IAP(intra-abdominal pressure) above 20 mmHg with new-onset or progressive organ failure. Severe organ dysfunctionent syndrome. These pressure measurements are relative. Small children get into trouble and develop compartment syndromes at much lower pressures while young previously healthy athletic individuals may tolerate an abdominal pressure of 20 mmHg very well. The underlying cause of the disease process is capillary permeability caused by the systemic inflammatory response syndrome (SIRS) that occurs in every critically ill patient. SIRS leads to leakage of fluid out of the capillary beds into the interstitial space in the entire body with a profound amount of this fluid leaking into the gut wall, mesentery and retroperitoneal tissue. Abdominal compartment syndrome follows a destructive pathway similar to compartment syndrome of the extremities. When increased compression occurs in such a hollow space, organs will begin to collapse under the pressure. As the pressure increases and reaches a point where the abdomen can no longer be distended it starts to affect the cardiovascular and pulmonary systems. When abdominal compartment syndrome reaches this point without surgery and help of a silo the patient will most likely die. There is a high mortality rate associated with abdominal compartment syndrome. Diagnosis Abdominal compartment syndrome is defined as an intra-abdominal pressure above 20 mmHg with evidence of organ failure. Abdominal compartment syndrome develops when the intra-abdominal pressure rapidly reaches certain pathological values, within several hours (intra-abdominal hypertension is observed), and lasts for 6 or more hours. The key to recognizing abdominal compartment syndrome is the demonstration of elevated intra-abdominal pressure which is performed most often via the urinary bladder, and it is considered to be the "gold standard". Multiorgan failure includes damage to the cardiac, pulmonary, renal, neurological, gastrointestinal, abdominal wall, and ophthalmic systems. The gut is the most sensitive to intra-abdominal hypertension, and it develops evidence of end-organ damage before alterations are observed in other systems. In a recent systematic review, Holodinsky et al. described 25 risk factors associated with IAH (intra-abdominal hypertension) and 16 with ACS (abdominal compartment syndrome). These can be roughly categorized in three categories, which may be more helpful at the bedside to identify patients at risk (Table 1). Especially noteworthy is the potential role of fluid resuscitation in the development of IAH and ACS. Recognizing the pivotal role of fluid resuscitation in the pathogenesis of IAH and ACS supplies the clinician with a target for preventive measures. Large volume resuscitation with crystalloids should be avoided in patients with or at risk of ACS. Treatment Operative decompression The mortality rate associated with abdominal compartment syndrome is significant, ranging between 60% and 70%. The poor outcome relates not only to abdominal compartment syndrome itself but also to concomitant injury and hemorrhagic shock. The surgical decompression of the abdomen remains the treatment of choice of abdominal compartment syndrome; this usually improves the organ changes and is followed by one of the temporary abdominal closure techniques in order to prevent secondary intra-abdominal hypertension. Surgical decompression can be achieved by opening the abdominal wall and abdominal fascia anterior in order to physically create more space for the abdominal viscera. Once opened, the fascia can be bridged for support and to prevent loss of domain by a variety of medical devices (Bogota bag, artificial bur, and vacuum devices using negative pressure wound therapy). References External links openabdomen.org wsacs.org

Aarogya, share information about a health condition involving Hemolytic–uremic syndrome

Hemolytic–uremic syndrome

Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7. Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications. The underlying mechanism typically involves the production of Shiga toxin by the bacteria. Atypical hemolytic uremic syndrome (aHUS) is often due to a genetic mutation and presents differently. However, both can lead to widespread inflammation and multiple blood clots in small blood vessels, a condition known as thrombotic microangiopathy.Treatment involves supportive care and may include dialysis, steroids, blood transfusions, or plasmapheresis. About 1.5 per 100,000 people are affected per year. Less than 5% of those with the condition die. Of the remainder, up to 25% have ongoing kidney problems. HUS was first defined as a syndrome in 1955. Signs and symptoms After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days. These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, or vomiting that results in dehydration and reduced urine. HUS typically develops about 5–10 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. Related symptoms and signs include lethargy, decreased urine output, blood in the urine, kidney failure, low platelets, (which are needed for blood clotting), and destruction of red blood cells (microangiopathic hemolytic anemia). High blood pressure, jaundice (a yellow tinge in skin and the whites of the eyes), seizures, and bleeding into the skin can also occur. In some cases, there are prominent neurologic changes.People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), proteinuria (indicative of kidney injury), confusion, fatigue, swelling, nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. Cause Typical HUS STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype. Atypical HUS Atypical HUS (aHUS) represents 5–10% of HUS cases and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of the complement system, which is a group of immune signaling factors that promote inflammation, enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body, and directly attack the pathogens cell membrane. This results in platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and ultimately death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. Despite the use of supportive care, an estimated 33–40% of patients will die or have end-stage renal disease (ESRD) with the first clinical manifestation of aHUS, and 65% of patients will die, require dialysis, or have permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI) therapy. Patients who survive the presenting signs and symptoms of aHUS endure a chronic thrombotic and inflammatory state, which puts them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.Historically, treatment options for aHUS were limited to plasma exchange or plasma infusion (PE/PI) therapy, which carries significant risks and has not been proven effective in any controlled trials. People with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5-year survival rate of 34–38%. Pathogenesis HUS is one of the thrombotic microangiopathies, a category of disorders that includes STEC-HUS, aHUS, and thrombotic thrombocytopenic purpura (TTP). STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin(s), usually types of E. coli, that expresses verotoxin (also called Shiga-like toxin). E. coli can produce stx1 and/or stx2 Shiga toxins, the latter being more dangerous. A combination of both toxins in certain ratios is usually associated with HUS. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue. Children have more GB3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin-producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. STEC-HUS is usually preceded by a prodrome of diarrhea, which is often bloody, and is caused by Shiga-like toxin-producing bacteria such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype. Other serotypes also cause disease and can emerge as new causes of STEC-HUS, as occurred with E. coli O104:H4, which triggered a 2011 epidemic of STEC-HUS in Germany.The typical pathophysiology of HUS involves the binding of Shiga-toxin to the globotriaosylceramide (Gb3; also called ceramide trihexoside which accumulates in Fabry disease) receptor on the surface of the glomerular endothelium. This action includes a cascade of signaling events leading to apoptosis and binding of leukocytes to endothelial cells. The Shiga-toxin-activated endothelial cells then become thrombogenic (clot-producing) by a mechanism that is not fully understood, though they have been shown to induce the release of cytokines and chemokines that are implicated in platelet activation. Additionally, the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes the closely related TTP. Once ADAMTS13 is disabled, multimers of von Willebrand Factor (vWF) form and initiate platelet activation, causing microthrombus formation. The activation of platelets resulting from inhibition of ADAMTS13 is due to the hyperactivity of large multimers of uncleaved vWF. The arterioles and capillaries of the body become obstructed by the resulting complexes of activated platelets, which have adhered to the endothelium via large multimeric vWF. Through a mechanism known as microangiopathic hemolysis, the growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. The presence of schistocytes is a key finding that helps to diagnose HUS. Typically, this hemolysis results in a hemoglobin level of less than 80 g/L.Shiga-toxin directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement factor H, an inhibitor of the complement cascade. Shiga-toxin causes complement-mediated platelet, leukocyte, and endothelial cell activation, resulting in systemic hemolysis, inflammation and thrombosis. Severe clinical complications of TMA have been reported in patients from 2 weeks to more than 44 days after presentation with STEC-HUS, with improvements in clinical condition extending beyond this time frame, suggesting that complement activation persists beyond the acute clinical presentation and for at least 4 months.The consumption of platelets as they adhere to the thrombi lodged in the small vessels typically leads to mild or moderate thrombocytopenia with a platelet count of less than 60,000 per microliter. As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature leads to reduced blood flow to vital organs, and ischemia may develop. The kidneys and the central nervous system (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, and are thus the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected.In contrast with typical disseminated intravascular coagulation seen with other causes of sepsis and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen, fibrinogen level, and assays for fibrin degradation products such as "D-Dimers", are generally normal despite the low platelet count (thrombocytopenia).HUS occurs after 3–7% of all sporadic E. coli O157:H7 infections and up to approximately 20% or more of epidemic infections. Children and adolescents are commonly affected. Grossly, the kidneys may show patchy or diffuse renal cortical necrosis. Histologically, the glomeruli show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin-related materials in the capillary lumens, subendothelially, and in the mesangium are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi.STEC-HUS most often affects infants and young children, but also occurs in adults. The most common form of transmission is ingestion of undercooked meat, unpasteurized fruits and juices, contaminated produce, contact with unchlorinated water, and person-to-person transmission in daycare or long-term care facilities.Unlike typical HUS, aHUS does not follow STEC infection and is thought to result from one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. This leads to platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis, damage to multiple organs, and ultimately, death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin, and/or the presence of schistocytes. Diagnosis The similarities between HUS, aHUS, and TTP make differential diagnosis essential. All three of these systemic TMA-causing diseases are characterized by thrombocytopenia and microangiopathic hemolysis, plus one or more of the following: neurological symptoms (e.g., confusion, cerebral convulsions, seizures); renal impairment (e.g., elevated creatinine, decreased estimated glomerular filtration rate [eGFR], abnormal urinalysis); and gastrointestinal (GI) symptoms (e.g., diarrhea, nausea/vomiting, abdominal pain, gastroenteritis).The presence of diarrhea does not exclude aHUS as the cause of TMA, as 28% of patients with aHUS present with diarrhea and/or gastroenteritis. First diagnosis of aHUS is often made in the context of an initial, complement-triggering infection, and Shiga-toxin has also been implicated as a trigger that identifies patients with aHUS. Additionally, in one study, mutations of genes encoding several complement regulatory proteins were detected in 8 of 36 (22%) patients diagnosed with STEC-HUS. However, the absence of an identified complement regulatory gene mutation does not preclude aHUS as the cause of the TMA, as approximately 50% of patients with aHUS lack an identifiable mutation in complement regulatory genes.Diagnostic work-up supports the differential diagnosis of TMA-causing diseases. A positive Shiga-toxin/EHEC test confirms a cause for STEC-HUS, and severe ADAMTS13 deficiency (i.e., ≤5% of normal ADAMTS13 levels) confirms a diagnosis of TTP. Prevention The effect of antibiotics in shiga toxin producing E. coli is unclear. While some early studies raised concerns more recent studies show either no effect or a benefit. Treatment Treatment involves supportive care and may include dialysis, steroids, blood transfusions, and plasmapheresis.While eculizumab is being used to treat atypical hemolytic uremic syndrome, no evidence as of 2018 supports its use in the main forms of HUS. Scientists are trying to understand how useful it would be to immunize humans or cattle. Prognosis Acute renal failure occurs in 55–70% of people with STEC-HUS, although up to 70–85% recover renal function. With aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. The overall mortality rate from HUS is 5–15%. Children and the elderly have a worse prognosis.Patients with aHUS generally have poor outcomes, with up to 50% progressing to end-stage renal disease (ESRD) or irreversible brain damage; as many as 25% die during the acute phase. Epidemiology The country with the highest incidence of HUS is Argentina and it performs a key role in the research of this condition. In the United States, the overall incidence of HUS is estimated at 2.1 cases per 100,000 persons/year, with a peak incidence between six months and four years of age.HUS and the E. coli infections that cause it have been the source of much negative publicity for the FDA, meat industries, and fast-food restaurants since the 1990s, especially in the contaminations linked to Jack in the Box restaurants. In 2006, an epidemic of harmful E. coli emerged in the United States due to contaminated spinach. In June, 2009, Nestlé Toll House cookie dough was linked to an outbreak of E. coli O157:H7 in the United States, which sickened 70 people in 30 states.In May, 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4-contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 3,800 cases, with HUS developing in more than 800 of the cases, including 36 fatal cases. Nearly 90% of the HUS cases were in adults. References External links GeneReviews/NCBI/NIH/UW entry on Atypical hemolytic–uremic syndrome

Hi Aarogya , Do you know what is Atelectasis,

Atelectasis

Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct from pulmonary consolidation, in which they are filled with liquid. It is often called a collapsed lung, although that term may also refer to pneumothorax.It is a very common finding in chest X-rays and other radiological studies, and may be caused by normal exhalation or by various medical conditions. Although frequently described as a collapse of lung tissue, atelectasis is not synonymous with a pneumothorax, which is a more specific condition that can cause atelectasis. Acute atelectasis may occur as a post-operative complication or as a result of surfactant deficiency. In premature babies, this leads to infant respiratory distress syndrome. The term uses combining forms of atel- + ectasis, from Greek: ἀτελής, "incomplete" + ἔκτασις, "extension". Signs and symptoms May have no signs and symptoms or they may include: cough, but not prominent; chest pain (not common); breathing difficulty (fast and shallow); low oxygen saturation; pleural effusion (transudate type); cyanosis (late sign); increased heart rate.It is a common misconception and pure speculation that atelectasis causes fever. A study of 100 post-op patients followed with serial chest X-rays and temperature measurements showed that the incidence of fever decreased as the incidence of atelectasis increased. A recent review article summarizing the available published evidence on the association between atelectasis and post-op fever concluded that there is no clinical evidence supporting this speculation. Causes The most common cause is post-surgical atelectasis, characterized by splinting, i.e. restricted breathing after abdominal surgery. Atelectasis develops in 75–90% of people undergoing general anesthesia for a surgical procedure.Another common cause is pulmonary tuberculosis. Smokers and the elderly are also at an increased risk. Outside of this context, atelectasis implies some blockage of a bronchiole or bronchus, which can be within the airway (foreign body, mucus plug), from the wall (tumor, usually squamous cell carcinoma) or compressing from the outside (tumor, lymph node, tubercle). Another cause is poor surfactant spreading during inspiration, causing the surface tension to be at its highest which tends to collapse smaller alveoli. Atelectasis may also occur during suction, as along with sputum, air is withdrawn from the lungs. There are several types of atelectasis according to their underlying mechanisms or the distribution of alveolar collapse; resorption, compression, microatelectasis and contraction atelectasis. Relaxation atelectasis (also called passive atelectasis) is when a pleural effusion or a pneumothorax disrupts the contact between the parietal and visceral pleurae.Risk factors associated with increased likelihood of the development of atelectasis include: type of surgery (thoracic, cardiopulmonary surgeries), use of muscle relaxation, obesity, high oxygen, the lower lung segments. Factors also associated with the development of atelectasis include: age, presence of chronic obstructive pulmonary disease or asthma, and type of anesthetic. In the early 1950s, in UK aviation medicine, the condition "acceleration atelectasis" was given the name "Hunter Lung" due to its prevalence in pilots of the transonic fighter jet, the Hawker Hunter, which used a 100% oxygen supply. Diagnosis Clinically significant atelectasis is generally visible on chest X-ray; findings can include lung opacification and/or loss of lung volume. Post-surgical atelectasis will be bibasal in pattern. Chest CT or bronchoscopy may be necessary if the cause of atelectasis is not clinically apparent. Direct signs of atelectasis include displacement of interlobar fissures and mobile structures within the thorax, overinflation of the unaffected ipsilateral lobe or contralateral lung, and opacification of the collapsed lobe. In addition to clinically significant findings on chest X-rays, patients may present with indirect signs and symptoms such as elevation of the diaphragm, shifting of the trachea, heart and mediastinum; displacement of the hilus and shifting granulomas. Classification Atelectasis may be an acute or chronic condition. In acute atelectasis, the lung has recently collapsed and is primarily notable only for airlessness. In chronic atelectasis, the affected area is often characterized by a complex mixture of airlessness, infection, widening of the bronchi (bronchiectasis), destruction, and scarring (fibrosis). Absorption (resorption) atelectasis The Earths atmosphere is mainly composed of 78 vol. % nitrogen and 21 vol. % oxygen (+ 1 vol. % argon and traces of other gases). Since oxygen is exchanged at the alveoli-capillary membrane, nitrogen is a major component for the alveolis state of inflation. If a large volume of nitrogen in the lungs is replaced with oxygen, the oxygen may subsequently be absorbed into the blood, reducing the volume of the alveoli, resulting in a form of alveolar collapse known as absorption atelectasis. Compression (relaxation) atelectasis It is usually associated with accumulation of blood, fluid, or air within the pleural cavity, which mechanically collapses the lung. This is a frequent occurrence with pleural effusion, caused by congestive heart failure (CHF). Leakage of air into the pleural cavity (pneumothorax) also leads to compression atelectasis. Cicatrization (contraction) atelectasis It occurs when either local or generalized fibrotic changes in the lung or pleura hamper expansion and increase elastic recoil during expiration. Causes include granulomatous disease, necrotising pneumonia and radiation fibrosis. Chronic atelectasis Chronic atelectasis may take one of two forms—middle lobe syndrome or rounded atelectasis. Right middle lobe syndrome In right middle lobe syndrome, the middle lobe of the right lung contracts, usually because of pressure on the bronchus from enlarged lymph glands and occasionally a tumor. The blocked, contracted lung may develop pneumonia that fails to resolve completely and leads to chronic inflammation, scarring, and bronchiectasis. Patchy atelectasis Is due to lack of surfactant, as occurs in hyaline membrane disease of newborn or acute (adult) respiratory distress syndrome (ARDS). Rounded atelectasis In rounded atelectasis (folded lung or Blesovsky syndrome), an outer portion of the lung slowly collapses as a result of scarring and shrinkage of the membrane layers covering the lungs (pleura), which would show as visceral pleural thickening and entrapment of lung tissue. This produces a rounded appearance on X-ray that doctors may mistake for a tumor. Rounded atelectasis is usually a complication of asbestos-induced disease of the pleura, but it may also result from other types of chronic scarring and thickening of the pleura. Treatment Treatment is directed at correcting the underlying cause. In atelectasis manifestations that result from the mucus plugging of the airways as seen in patients with cystic fibrosis and pneumonia, mucolytic agents such as acetylcysteine (NAC) is used. This nebulized treatment works by reducing mucous viscosity and elasticity by breaking disulfide bonds in mucoproteins within the mucus complex, thus facilitating mucus clearance. Post-surgical atelectasis is treated by physiotherapy, focusing on deep breathing and encouraging coughing. An incentive spirometer is often used as part of the breathing exercises. Walking is also highly encouraged to improve lung inflation. People with chest deformities or neurologic conditions that cause shallow breathing for long periods may benefit from mechanical devices that assist their breathing. One method is continuous positive airway pressure, which delivers pressurized air or oxygen through a nose or face mask to help ensure that the alveoli do not collapse, even at the end of a breath. This is helpful, as partially inflated alveoli can be expanded more easily than collapsed alveoli. Sometimes additional respiratory support is needed with a mechanical ventilator. The primary treatment for acute massive atelectasis is correction of the underlying cause. A blockage that cannot be removed by coughing or by suctioning the airways often can be removed by bronchoscopy. Antibiotics are given for an infection. Chronic atelectasis is often treated with antibiotics because infection is almost inevitable. In certain cases, the affected part of the lung may be surgically removed when recurring or chronic infections become disabling or bleeding is significant. If a tumor is blocking the airway, relieving the obstruction by surgery, radiation therapy, chemotherapy, or laser therapy may prevent atelectasis from progressing and recurrent obstructive pneumonia from developing. See also Alveolar capillary dysplasia, a very rare type of diffuse congenital disorder of the lung Flat-chested kitten syndrome or FCKS: atelectasis in neo-natal kittens Tympanic membrane atelectasis: Retraction of the ear drum into the middle ear can also be referred to as atelectasis. William Pasteur, pioneer pulmonologist References External links 04-048a. at Merck Manual of Diagnosis and Therapy Home Edition Atelectasis at Merck Manual of Diagnosis and Therapy Professional Edition

Hello Aarogya, what is Parosmia

Parosmia

Parosmia (from the Greek παρά pará and ὀσμή osmḗ "smell") is a dysfunctional smell detection characterized by the inability of the brain to correctly identify an odors "natural" smell. Instead, the natural odor is usually transformed into an unpleasant aroma, typically a "burned", "rotting", "fecal", or "chemical" smell. There can also be rare instances of a pleasant odor called euosmia. The condition was rare and little-researched until it became relatively more widespread since 2020 as a side effect of COVID-19. Causes There are numerous diseases with which parosmia is associated. In a case study, Frasnelli et al. examined five patients that endured parosmia or phantosmia, most as a result of upper respiratory tract infections (URTIs). It is hypothesized that URTIs can result in parosmia because of damage to olfactory receptor neurons (ORNs). The condition has been linked to coronavirus disease 2019 as a rare side effect. Common triggers in COVID-19 related parosmia include coffee, chocolate, meat, onion and toothpaste. Exposure to harmful solvents has also been linked to parosmia, specifically by damaging ORNs. Damage to these neurons could render them unable to correctly encode a signal representing a particular odor, which would send an erroneous signal to the odor processing center, the olfactory bulb. This, in turn, leads to the signal triggering a different smell than the stimulating odor, and thus the patient cannot sync the input and output odors. Damage to ORNs describes a peripheral defect in the pathway, but there are also instances where damage to the processing center in the brain can lead to distorted odors. Different types of head trauma could also lead to dysfunctions that relate to what the afflicted brain area controls. In humans, the olfactory bulb is located on the inferior side of the brain. Physical damage to this area would alter how the area processes information in a variety of ways, but there are also diseases that can alter how this area works. If the part of the brain that interprets these input signals is damaged, then a distorted output is possible. This would also lead to parosmia. Temporal lobe epilepsy has led to cases of parosmia, but these were only temporary; the onset of parosmia was a seizure and it typically lasted a week or two after. Parosmia is sometimes associated with Parkinsons disease. Although the specific pathway is undetermined, the lack of dopamine has resulted in documented cases of parosmia and phantosmia. Diagnosing One method used to diagnose parosmia is the University of Pennsylvania Smell Identification Test (UPSIT). "Sniffin Sticks" are another diagnostic method. These techniques can help deduce whether a specific case of parosmia can be attributed to just one stimulating odor or if there is a group of odors that will elicit the displaced smell. In one case studied by Frasnelli et al. certain smells, specifically coffees, cigarettes, onions, and perfumes, induced a "nauseating" odor for the patient, which was artificial and unrelated to a known smell. In another case study cited in the same paper, a woman had parosmia in one nostril but not the other. Medical examination including MRI did not reveal any abnormalities; however the parosmia in this case was degenerative, getting worse in time. The authors report that cases of parosmia can predict regeneration of olfactory senses. Treatment Symptoms of most patients afflicted with parosmia decrease over time. Although there are instances of parosmia affecting patients for years, this is certainly not the majority of cases. There have been experimental treatments of parosmia with L-Dopa, but there are no other current treatments except inducing anosmia or hyposmia to the point that the odors are negligible. See also Phantosmia, perceiving smells not objectively present References External links ECU "Signs and symptoms, etiologies and clinical course of parosmia + in a series of 84 patients" WebMD

Hey Aarogya, explain a situation where Autosensitization dermatitis occurs

Autosensitization dermatitis

Autosensitization dermatitis presents with the development of widespread dermatitis or dermatitis distant from a local inflammatory focus, a process referred to as autoeczematization.: 81 See also Id reaction List of cutaneous conditions References == External links ==

Could you describe Hematospermia, to me Aarogya

Hematospermia

Hematospermia (also known as haematospermia, hemospermia, or haemospermia) is the presence of blood in ejaculation. It is most often a benign symptom. Among men age 40 or older, hematospermia is a slight predictor of cancer, typically prostate cancer. No specific cause is found in up to 70% of cases. Cause Though haematospermia may cause considerable distress to patients, it is often a benign and self-limiting condition caused by infections, particularly in younger patients. An isolated episode is usually considered benign and not likely to be associated with malignancy. Recurrent haematospermia may indicate a more serious underlying pathology particularly in patients over 40 years of age. Infection and inflammation Infection or inflammation is considered the most common cause of the condition. Implicated pathogens include; Gram-negative bacteria (often E. coli), gonococci, T. pallidum, C. trachomatis, N. gonorrhoeae, echinococcus (rarely), HSV type 1 or 2, and HPV. The condition may also rarely be caused by some chronic systemic infections like tuberculosis or schistosomiasis. Additionally, testicular, prostate, and epididymal inflammation in general may present with haematospermia as feature. Neoplasm Some neoplasms of the genitourinary system may present with haematospermia. Malignant causes of haematospermia include; prostate cancer, testicular or epididymal tumours, seminal vesicle carcinoma (rarely), and urethral tumour. Lymphomas and leukaemias may also feature haematospermia as symptom. Prostate Various prostate pathologies (including prostatitis, calculi (stones), cysts, benign prostatic hyperplasia, bacterial infection, etc.) may result in blood occurring in the ejaculate. Other Systemic conditions like malignant hypertension, liver dysfunction, or bleeding disorders, and amyloidosis may sometimes present with haematospermia as symptom. Trauma to the region may also cause the condition. Additionally, structural anomalies of genitourinary anatomy (e.g. vascular anomalies, polyps, urethral malformations, etc.) may result in haematospermia as symptom.Excessive sex or masturbation, prolonged sexual abstinence, interrupted sex, and certain sexual behaviours may also result in (mostly isolated events of) haematospermia. Unknown The exact cause cannot be determined in up to 70% of patients. Diagnosis The main focus of an evaluation should be to determine its cause (if possible) and rule out infection and malignancy. It is important to rule out pseudo-haematospermia where blood originates from the partner during intercourse. Epidemiology Though the exact incidence is unknown, haematospermia has been reported in one per 5,000 patients in initial examinations at urological out-patient clinics. Most patients are between 30–40 years of age. It is thought to make up ~1% of all urological symptoms. History Traditionally, the condition was thought to be a clinically insignificant consequence of prolonged sexual abstinence or intense sexual experiences. References == External links ==

Can you describe Preterm birth, to me Aarogya

Preterm birth

Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 36 weeks, late preterm birth is between 34 and 36 weeks gestation. These babies are also known as premature babies or colloquially preemies (American English) or premmies (Australian English). Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be.The cause of spontaneous preterm birth is often not known. Risk factors include diabetes, high blood pressure, multiple gestation (being pregnant with more than one baby), being either obese or underweight, vaginal infections, air pollution exposure, tobacco smoking, and psychological stress. For a healthy pregnancy, medical induction of labor or cesarean section are not recommended before 39 weeks unless required for other medical reasons. There may be certain medical reasons for early delivery such as preeclampsia.Preterm birth may be prevented in those at risk if the hormone progesterone is taken during pregnancy. Evidence does not support the usefulness of bed rest. It is estimated that at least 75% of preterm infants would survive with appropriate treatment, and the survival rate is highest among the infants born the latest in gestation. In women who might deliver between 24 and 37 weeks, corticosteroid treatment may improve outcomes. A number of medications, including nifedipine, may delay delivery so that a mother can be moved to where more medical care is available and the corticosteroids have a greater chance to work. Once the baby is born, care includes keeping the baby warm through skin-to-skin contact or incubation, supporting breastfeeding and/or formula feeding, treating infections, and supporting breathing. Preterm babies sometimes require intubation.Preterm birth is the most common cause of death among infants worldwide. About 15 million babies are preterm each year (5% to 18% of all deliveries). Late preterm birth accounts for 75% of all preterm births. This rate is inconsistent across countries. In the United Kingdom 7.9% of babies are born pre-term and in the United States 12.3% of all births are before 37 weeks gestation. Approximately 0.5% of births are extremely early periviable births (20–25 weeks of gestation), and these account for most of the deaths. In many countries, rates of premature births have increased between the 1990s and 2010s. Complications from preterm births resulted in 0.81 million deaths in 2015, down from 1.57 million in 1990. The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72%. The chances of survival without any long-term difficulties are lower. Signs and symptoms Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labour, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process. Causes The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. Risk factors The exact cause of spontaneous preterm birth is difficult to determine and it may be caused by many different factors at the same time as labor is a complex process. Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension (placental abruption), decidual bleeding, and intrauterine inflammation or infection.Identifying women at high risk of giving birth early would enable the health services to provide specialized care for these women and their babies, for example a hospital with a special care baby unit such as a neonatal intensive care unit (NICU). In some instances, it may be possible to delay the birth. Risk scoring systems have been suggested as an approach to identify those at higher risk, however, there is no strong research in this area so it is unclear whether the use of risk scoring systems for identifying mothers would prolong pregnancy and reduce the numbers of preterm births or not. Maternal factors Risk factors in the mother have been identified that are linked to a higher risk of a preterm birth. These include age (either very young or older), high or low body mass index (BMI), length of time between pregnancies, previous spontaneous (i.e., miscarriage) or surgical abortions, unintended pregnancies, untreated or undiagnosed celiac disease, fertility difficulties, heat exposure, and genetic variables.Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth. Obesity does not directly lead to preterm birth; however, it is associated with diabetes and hypertension which are risk factors by themselves. To some degree those individuals may have underlying conditions (i.e., uterine malformation, hypertension, diabetes) that persist. Couples who have tried more than 1 year versus those who have tried less than 1 year before achieving a spontaneous conception have an adjusted odds ratio of 1.35 (95% confidence interval 1.22-1.50) of preterm birth. Pregnancies after IVF confers a greater risk of preterm birth than spontaneous conceptions after more than 1 year of trying, with an adjusted odds ratio of 1.55 (95% CI 1.30-1.85).Certain ethnicities may have a higher risk as well. For example, in the U.S. and the UK, Black women have preterm birth rates of 15–18%, more than double than that of the white population. Many Black women have higher preterm birth rates due to multiple factors but the most common is high amounts of chronic stress, which can eventually lead to premature birth. Adult chronic disease isnt always the case with premature birth in Black women, which makes the main factor of premature birth challenging to identify. Filipinos are also at high risk of premature birth, and it is believed that nearly 11–15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature. Filipinos being a big risk factor is evidenced with the Philippines being the eighth-highest ranking in the world for preterm births, the only non-African country in the top 10. This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained. Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births. An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated. No single gene has been identified. Marital status is associated with risk for preterm birth. A study of 25,373 pregnancies in Finland revealed that unmarried mothers had more preterm deliveries than married mothers (P=0.001). Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents. Factors during pregnancy Medications during pregnancy, living conditions, air pollution, smoking, illicit drugs or alcohol, infection, or physical trauma may also cause a preterm birth. Air pollution: Living in an area with a high concentration of air pollution is a major risk factor for preterm labor, including living near major roadways or highways where vehicle emissions are high from traffic congestion or are a route for diesel trucks that tend to emit more pollution.The use of fertility medication that stimulates the ovary to release multiple eggs and of IVF with embryo transfer of multiple embryos has been implicated as a risk factor for preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure, pre-eclampsia, maternal diabetes, asthma, thyroid disease, and heart disease. Certain medical conditions in the pregnant mother may also increase the risk of preterm birth. Some women have anatomical problems that prevent the baby from being carried to term. These include a weak or short cervix (the strongest predictor of premature birth). Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption—conditions that occur frequently preterm—even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate. Women with abnormal amounts of amniotic fluid, whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk. Anxiety and depression have been linked as risk factors for preterm birth.The use of tobacco, cocaine, and excessive alcohol during pregnancy increases the chance of preterm delivery. Tobacco is the most commonly used drug during pregnancy and contributes significantly to low birth weight delivery. Babies with birth defects are at higher risk of being born preterm.Passive smoking and/or smoking before the pregnancy influences the probability of a preterm birth. The World Health Organization published an international study in March 2014.Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.9 and 95% confidence interval of 1.1–3.5.Intimate violence against the mother is another risk factor for preterm birth.Physical trauma may case a preterm birth. The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby. This ought not be confused with massage therapy conducted by a fully trained and certified/licensed massage therapist or by significant others trained to provide massage during pregnancy, which—in a study involving pregnant females with prenatal depression—has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety. In healthy women, however, no effects have been demonstrated in a controlled study. Infection The frequency of infection in preterm birth is inversely related to the gestational age. Mycoplasma genitalium infection is associated with increased risk of preterm birth, and spontaneous abortion.Infectious microorganisms can be ascending, hematogeneous, iatrogenic by a procedure, or retrograde through the Fallopian tubes. From the deciduas they may reach the space between the amnion and chorion, the amniotic fluid, and the fetus. A chorioamnionitis also may lead to sepsis of the mother. Fetal infection is linked to preterm birth and to significant long-term disability including cerebral palsy.It has been reported that asymptomatic colonization of the decidua occurs in up to 70% of women at term using a DNA probe suggesting that the presence of micro-organism alone may be insufficient to initiate the infectious response. As the condition is more prevalent in black women in the U.S. and the UK, it has been suggested to be an explanation for the higher rate of preterm birth in these populations. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth. The condition known as aerobic vaginitis can be a serious risk factor for preterm labor; several previous studies failed to acknowledge the difference between aerobic vaginitis and bacterial vaginosis, which may explain some of the contradiction in the results.Untreated yeast infections are associated with preterm birth.A review into prophylactic antibiotics (given to prevent infection) in the second and third trimester of pregnancy (13–42 weeks of pregnancy) found a reduction in the number of preterm births in women with bacterial vaginosis. These antibiotics also reduced the number of waters breaking before labor in full-term pregnancies, reduced the risk of infection of the lining of the womb after delivery (endometritis), and rates of gonococcal infection. However, the women without bacterial vaginosis did not have any reduction in preterm births or pre-labor preterm waters breaking. Much of the research included in this review lost participants during follow-up so did not report the long-term effects of the antibiotics on mothers or babies. More research in this area is needed to find the full effects of giving antibiotics throughout the second and third trimesters of pregnancy.A number of maternal bacterial infections are associated with preterm birth including pyelonephritis, asymptomatic bacteriuria, pneumonia, and appendicitis. A review into giving antibiotics in pregnancy for asymptomatic bacteriuria (urine infection with no symptoms) found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight. Another review found that one dose of antibiotics did not seem as effective as a course of antibiotics but fewer women reported side effects from one dose. This review recommended that more research is needed to discover the best way of treating asymptomatic bacteriuria.A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections. The women being routinely tested also gave birth to fewer babies with a low birth weight. Even though these results look promising, the review was only based on one study so more research is needed into routine screening for low genital tract infections.Also periodontal disease has been shown repeatedly to be linked to preterm birth. In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth. Genetics There is believed to be a maternal genetic component in preterm birth. Estimated heritability of timing-of-birth in women was 34%. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature. Prenatal Care The absence of prenatal care has been associated with higher rates of preterm births. Analysis of 15,627,407 live births in the United States in 1995–1998 concluded that the absence of prenatal care carried a 2.9 (95%CI 2.8, 3.0) times higher risk of preterm births. This same study found statistically significant relative risks of maternal anemia, intrapartum fever, unknown bleeding, renal disease, placental previa, hydramnios, placenta abruption, and pregnancy-induced hypertension with the absence of prenatal care. All these prenatal risks were controlled for other high-risk conditions, maternal age, gravidity, marital status, and maternal education. The absence of prenatal care prior to and during the pregnancy is primarily a function of socioeconomic factors (low family income and education), access to medical consultations (large distance from the place of residence to the healthcare unit and transportation costs), quality of healthcare, and social support. Efforts to decrease rates of preterm birth should aim to increase the deficits posed by the aforementioned barriers and to increase access to prenatal care. Diagnosis Placental alpha microglobulin-1 Placental alpha microglobulin-1 (PAMG-1) has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor. In one investigation comparing this test to fetal fibronectin testing and cervical length measurement via transvaginal ultrasound, the test for PAMG-1 (commercially known as the PartoSure test) has been reported to be the single best predictor of imminent spontaneous delivery within 7 days of a patient presenting with signs, symptoms, or complaints of preterm labor. Specifically, the PPV, or positive predictive value, of the tests were 76%, 29%, and 30% for PAMG-1, fFN and CL, respectively (P < 0.01). Fetal fibronectin Fetal fibronectin (fFN) has become an important biomarker—the presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and deciduas has been disrupted. A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value. It has been shown that only 1% of women in questionable cases of preterm labor delivered within the next week when the test was negative. Ultrasound Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. A short cervix preterm is undesirable: A cervical length of less than 25 mm at or before 24 weeks of gestational age is the most common definition of cervical incompetence. Classification In humans, the usual definition of preterm birth is birth before a gestational age of 37 complete weeks. In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to mature in the womb; because of this, many premature babies spend the first days and weeks of their lives on ventilators. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate surfactant, which allows the lungs to remain expanded between breaths. Sequelae of prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth. Prevention Historically efforts have been primarily aimed to improve survival and health of preterm infants (tertiary intervention). Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children. Smoking bans are effective in decreasing preterm births. Different strategies are used in the administration of prenatal care, and future studies need to determine if the focus can be on screening for high-risk women, or widened support for low-risk women, or to what degree these approaches can be merged. Before pregnancy Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer was limited. Many countries have established specific programs to protect pregnant women from hazardous or night-shift work and to provide them with time for prenatal visits and paid pregnancy-leave. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work (over 42 hours per week) or prolonged standing (over 6 hours per day). Also, night work has been linked to preterm birth. Health policies that take these findings into account can be expected to reduce the rate of preterm birth. Preconceptional intake of folic acid is recommended to reduce birth defects. There is also some evidence that folic acid supplement preconceptionally (before becoming pregnant) may reduce premature birth. Reducing smoking is expected to benefit pregnant women and their offspring. During pregnancy Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Reducing physical activity during pregnancy has not been shown to reduce the risk of a preterm birth. Healthy eating can be instituted at any stage of the pregnancy including nutritional adjustments and consuming suggested vitamin supplements. Calcium supplementation in women who have low dietary calcium may reduce the number of negative outcomes including preterm birth, pre-eclampsia, and maternal death. The World Health Organization (WHO) suggests 1.5–2 g of calcium supplements daily, for pregnant women who have low levels of calcium in their diet. Supplemental intake of C and E vitamins have not been found to reduce preterm birth rates.While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates. Smoking cessation has also been shown to reduce the risk. The use of personal at home uterine monitoring devices to detect contractions and possible preterm births in women at higher risk of having a preterm baby have been suggested. These home monitors may not reduce the number of preterm births, however, using these devices may increase the number of unplanned antenatal visits and may reduce the number of babies admitted to special care when compared with women receiving normal antenatal care. Support from medical professionals, friends, and family during pregnancy may be beneficial at reducing caesarean birth and may reduce prenatal hospital admissions, however, these social supports alone may not prevent preterm birth. Screening during pregnancy Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth. Extensive studies have been carried out to determine if other forms of screening in low-risk women followed by appropriate intervention are beneficial, including screening for and treatment of Ureaplasma urealyticum, group B streptococcus, Trichomonas vaginalis, and bacterial vaginosis did not reduce the rate of preterm birth. Routine ultrasound examination of the length of the cervix may identify women at risk of preterm labour and tentative evidence suggests ultrasound measurement of the length of the cervix in those with preterm labor can help adjust management and results in the extension of pregnancy by about 4 days. Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk of preterm birth. Reducing existing risks Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors. Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction (i.e. removal of a uterine septum), and those with certain medical problems can be helped by optimizing medical therapies prior to conception, be it for asthma, diabetes, hypertension, and others. Multiple pregnancies In multiple pregnancies, which often result from use of assisted reproductive technology, there is a high risk of preterm birth. Selective reduction is used to reduce the number of fetuses to two or three. Reducing indicated preterm birth A number of agents have been studied for the secondary prevention of indicated preterm birth. Trials using low-dose aspirin, fish oil, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-dose aspirin was used. Even if agents such as calcium or antioxidants were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed. Reducing spontaneous preterm birth Reduction in activity by the mother—pelvic rest, limited work, bed rest—may be recommended although there is no evidence it is useful with some concerns it is harmful. Increasing medical care by more frequent visits and more education has not been shown to reduce preterm birth rates. Use of nutritional supplements such as omega-3 polyunsaturated fatty acids is based on the observation that populations who have a high intake of such agents are at low risk for preterm birth, presumably as these agents inhibit production of proinflammatory cytokines. A randomized trial showed a significant decline in preterm birth rates, and further studies are in the making. Antibiotics While antibiotics can get rid of bacterial vaginosis in pregnancy, this does not appear to change the risk of preterm birth. It has been suggested that chronic chorioamnionitis is not sufficiently treated by antibiotics alone (and therefore they cannot ameliorate the need for preterm delivery in this condition). Progestogens Progestogens—often given in the form of vaginal progesterone or hydroxyprogesterone caproate—relax the uterine musculature, maintain cervical length, and possess anti-inflammatory properties; all of which invoke physiological and anatomical changes considered to be beneficial in reducing preterm birth. Two meta-analyses demonstrated a reduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.Progestogen supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix. A short cervix is one that is less than 25mm, as detected during a transvaginal cervical length assessment in the midtrimester. However, progestogens are not effective in all populations, as a study involving twin gestations failed to see any benefit. Despite extensive research related to progestogen effectiveness, uncertainties remain concerning types of progesterone and routes of administration. Cervical cerclage In preparation for childbirth, the womans cervix shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage is a surgical intervention that places a suture around the cervix to prevent its shortening and widening. Numerous studies have been performed to assess the value of cervical cerclage and the procedure appears helpful primarily for women with a short cervix and a history of preterm birth. Instead of a prophylactic cerclage, women at risk can be monitored during pregnancy by sonography, and when shortening of the cervix is observed, the cerclage can be performed. Management (Treatment) Tertiary interventions are aimed at women who are about to go into preterm labor, or rupture the membranes or bleed preterm. The use of the fibronectin test and ultrasonography improves the diagnostic accuracy and reduces false-positive diagnosis. While treatments to arrest early labor where there is progressive cervical dilatation and effacement will not be effective to gain sufficient time to allow the fetus to grow and mature further, it may defer delivery sufficiently to allow the mother to be brought to a specialized center that is equipped and staffed to handle preterm deliveries. In a hospital setting women are hydrated via intravenous infusion (as dehydration can lead to premature uterine contractions).If a baby has cardiac arrest at birth and is before 23 weeks or less than 400 g attempts at resuscitation are not indicated. Steroids Severely premature infants may have underdeveloped lungs because they are not yet producing their own surfactant. This can lead directly to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, an antenatal steroid that crosses the placental barrier and stimulates the production of surfactant in the lungs of the baby. Steroid use up to 37 weeks is also recommended by the American Congress of Obstetricians and Gynecologists. Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the pregnancy has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There are still some concerns about the efficacy and side effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. A 2015 Cochrane review (updated in 2022) supports the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course.A Cochrane review from 2020 recommends the use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and respiratory distress syndrome and probably reduces the risk of IVH.Concerns about adverse effects of prenatal corticosteroids include increased risk for maternal infection, difficulty with diabetic control, and possible long-term effects on neurodevelopmental outcomes for the infants. There is ongoing discussion about when steroids should be given (i.e. only antenatally or postnatally too) and for how long (i.e. single course or repeated administration). Despite these unknowns, there is a consensus that the benefits of a single course of prenatal glucocorticosteroids vastly outweigh the potential risks. Antibiotics The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby to get infected with group B streptococcus and has been shown to reduce related mortality rates.When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks. Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav). Tocolysis A number of medications may be useful to delay delivery including: nonsteroidal anti-inflammatory drugs, calcium channel blockers, beta mimetics, and atosiban. Tocolysis rarely delays delivery beyond 24–48 hours. This delay, however, may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects. Magnesium sulfate does not appear to be useful to prevent preterm birth. Its use before delivery, however, does appear to decrease the risk of cerebral palsy. Mode of delivery The routine use of caesarean section for early delivery of infants expected to have very low birth weight is controversial, and a decision concerning the route and time of delivery probably needs to be made on a case-by-case basis. Neonatal care In developed countries premature infants are usually cared for in a NICU. The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. After delivery, plastic wraps or warm mattresses are useful to keep the infant warm on their way to the neonatal intensive care unit (NICU). Treatments may include fluids and nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care (skin to skin warming), encouraging breastfeeding, and basic infection control measures can significantly reduce preterm morbidity and mortality. Kangaroo mother care (KMC) can decrease the risk of neonatal sepsis, hypothermia, hypoglycemia and increase exclusive breastfeeding Bili lights may also be used to treat newborn jaundice (hyperbilirubinemia). Water can be carefully provided to prevent dehydration but not so much to increase risks of side effects. Breathing support In terms of respiratory support, there may be little or no difference in the risk of death or chronic lung disease between high flow nasal cannulae (HFNC) and continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NPPV). For extremely preterm babies (born before 28 weeks gestation), targeting a higher versus a lower oxygen saturation range makes little or no difference overall to the risk of death or major disability. Babies born before 32 weeks probably have a lower risk of death from bronchopulmonary dysplasia if they have CPAP immediately after being born, compared to receiving either supportive care or assisted ventilation.There is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding). Nutrition Meeting the appropriate nutritional needs of preterm infants is important for long-term health. Optimal care may require a balance of meeting nutritional needs and preventing complications related to feeding. The ideal growth rate is not known, however, preterm infants usually require a higher energy intake compared to babies who are born at term. The recommended amount of milk is often prescribed based on approximated nutritional requirements of a similar aged fetus who is not compromised. An immature gastrointestinal tract (GI tract), medical conditions (or co-morbidities), risk of aspirating milk, and necrotizing enterocolitis may lead to difficulties in meeting this high nutritional demand and many preterm infants have nutritional deficits that may result in growth restrictions. In addition, very small preterm infants cannot coordinate sucking, swallowing, and breathing. Tolerating a full enteral feeding (the prescribed volume of milk or formula) is a priority in neonatal care as this reduces the risks associated with venous catheters including infection, and may reduce the length of time the infant requires specialized care in the hospital. Different strategies can be used to optimize feeding for preterm infants. The type of milk/formula and fortifiers, route of administration (by mouth, tube feeding, venous catheter), timing of feeding, quantity of milk, continuous or intermittent feeding, and managing gastric residuals are all considered by the neonatal care team when optimizing care. The evidence in the form of high quality randomized trials is generally fairly weak in this area, and for this reason different neonatal intensive care units may have different practices and this results in a fairly large variation in practice. The care of preterm infants also varies in different countries and depends on resources that are available. Human breast milk and formula The American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including lower rates of necrotizing enterocolitis (NEC). In the absence of evidence from randomised controlled trials about the effects of feeding preterm infants with formula compared with mothers own breast milk, data collected from other types of studies suggest that mothers own breast milk is likely to have advantages over formula in terms of the babys growth and development. When a mothers breast milk is not available, formula is probably better than donor breast milk for preterm babies in terms of weight gain, linear growth and head growth but there may be little or no difference in terms of neuro-developmental disability, death or necrotising enterocolitis. Fortified human breast milk and preterm/term formula Breast milk or formula alone may not be sufficient to meet the nutritional needs of some preterm infants. Fortification of breast milk or formula by adding extra nutrients is an approach often taken for feeding preterm infants, with the goal of meeting the high nutritional demand. High quality randomized controlled trials are needed in this field to determine the effectiveness of fortification. It is unclear if fortification of breast milk improves outcomes in preterm babies, though it may speed growth. Supplementing human milk with extra protein may increase short-term growth but the longer-term effects on body composition, growth and brain development are uncertain. Higher protein formula (between 3 and 4 grams of protein per kilo of body weight) may be more effective than low protein formula (less than 3 grams per kilo per day) for weight gain in formula-fed low-birth-weight infants. There is insufficient evidence about the effect on preterm babies growth of supplementing human milk with carbohydrate, fat, and branched-chain amino acids. Conversely, there is some indication that preterm babies who cannot breastfeed may do better if they are fed only with diluted formula compared to full strength formula but the clinical trial evidence remains uncertain.Individualizing the nutrients and quantities used to fortify enteral milk feeds in infants born with very low birth weight may lead to better short-term weight gain and growth but the evidence is uncertain for longer term outcomes and for the risk of serious illness and death. This includes targeted fortification (adjusting the level of nutrients in response to the results of a test on the breast milk) and adjustable fortification (adding nutrients based on testing the infant).Multi-nutrient fortifier used to fortify human milk and formula has traditionally been derived from bovine milk. Fortifier derived from humans is available, however, the evidence from clinical trials is uncertain and it is not clear if there are any differences between human-derived fortifier and bovine-derived fortifier in terms of neonatal weight gain, feeding intolerance, infections, or the risk of death. Timing of feeds For very preterm infants, most neonatal care centres start milk feeds gradually, rather than starting with a full enteral feeding right away, however, is not clear if starting full enteral feeding early effects the risk of necrotising enterocolitis. In these cases, the preterm infant would be receiving the majority of their nutrition and fluids intravenously. The milk volume is usually gradually increased over the following weeks. Research into the ideal timing of enteral feeding and whether delaying enteral feeding or gradually introducing enteral feeds is beneficial at improving growth for preterm infants or low birth weight infants is needed. In addition, the ideal timing of enteral feeds to prevent side effects such as necrotising enterocolitis or mortality in preterm infants who require a packed red blood cell transfusion is not clear. Potential disadvantages of a more gradual approach to feeding preterm infants associated with less milk in the gut and include slower GI tract secretion of hormones and gut motility and slower microbial colonization of the gut.Regarding the timing of starting fortified milk, preterm infants are often started on fortified milk/formula once they are fed 100 mL/kg of their body weight. Other some neonatal specialists feel that starting to feed a preterm infant fortified milk earlier is beneficial to improve intake of nutrients. The risks of feeding intolerance and necrotising enterocolitis related to early versus later fortification of human milk are not clear. Once the infant is able to go home from the hospital there is limited evidence to support prescribing a preterm (fortified) formula. Intermittent feeding versus continuous feeding For infants who weigh less than 1500 grams, tube feeding is usually necessary. Most often, neonatal specialists feed preterm babies intermittently with a prescribed amount of milk over a short period of time. For example, a feed could last 10–20 minutes and be given every 3 hours. This intermittent approach is meant to mimic conditions of normal bodily functions involved with feeding and allow for a cyclic pattern in the release of gastrointestinal tract hormones to promote development of the gastrointestinal system. In certain cases, continuous nasogastric feeding is sometimes preferred. There is low to very low certainty evidence to suggest that low birth weight babies who receive continuous nasogastic feeding may reach the benchmark of tolerating full enteral feeding later than babies fed intermittently and it is not clear if continuous feeding has any effect on weight gain or the number of interruptions in feedings. Continuous feeding may have little to no effect on length of body growth or head circumference and the effects of continuous feeding on the risk of developing necrotising enterocolitis is not clear.Since preterm infants with gastro-oesophageal reflux disease do not have a fully developed antireflux mechanism, deciding on the most effective approach for nutrition is important. It is not clear if continuous bolus intragastric tube feeding is more effective compared to intermittent bolus intragastric tube feeding for feeding preterm infants with gastro-oesophageal reflux disease.For infants who would benefit from intermittent bolus feeding, some infants may be fed using the "push feed" method using a syringe to gently push the milk or formula into the stomach of the infant. Others may be fed using a gravity feeding system where the syringe is attached directly to a tube and the milk or formula drips into the infants stomach. It is not clear from medical studies which approach to intermittent bolus feeding is more effective or reduces adverse effects such as apnoea, bradycardia, or oxygen desaturation episodes. High volume feeds High-volume (more than 180 mL per kilogram per day) enteral feeds of fortified or non-fortified human breast milk or formula may improve weight gain while the pre-term infant is hospitalized, however, there is insufficient evidence to determine if this approach improves growth of the neonate and other clinical outcomes including length of hospital stay. The risks or adverse effects associated with high-volume enteral feeding of preterm infants including aspiration pneumonia, reflux, apnoea, and sudden oxygen desaturation episodes have not been reported in the trials considered in a 2021 systematic review. Parenteral (intraveneous) nutrition For preterm infants who are born after 34 weeks of gestation ("late preterm infants") who are critically ill and cannot tolerate milk, there is some weak evidence that the infant may benefit from including amino acids and fats in the intravenous nutrition at a later time point (72 hours or longer from hospital admission) versus early (less than 72 hours from admission to hospital), however further research is required to understand the ideal timing of starting intravenous nutrition. Gastric residuals For preterm infants in neonatal intensive care on gavage feeds, monitoring the volume and colour of gastric residuals, the milk and gastrointestinal secretions that remain in the stomach after a set amount of time, is common standard of care practice. Gastric residual often contains gastric acid, hormones, enzymes, and other substances that may help improve digestion and mobility of the gastrointestinal tract. Analysis of gastric residuals may help guide timing of feeds. Increased gastric residual may indicate feeding intolerance or it may be an early sign of necrotizing enterocolitis. Increased gastric residual may be caused by an underdeveloped gastrointestinal system that leads to slower gastric emptying or movement of the milk in the intestinal tract, reduced hormone or enzyme secretions from the gastrointestinal tract, duodenogastric reflux, formula, medications, and/or illness. The clinical decision to discard the gastric residuals (versus re-feeding) is often individualized based on the quantity and quality of the residual. Some experts also suggest replacing the fresh milk or curded milk and bile-stained aspirates, but not replacing haemorrhagic residual. Evidence to support or refute the practice of re-feeding preterm infants with gastric residuals is lacking. Hearing assessment The Joint Committee on Infant Hearing (JCIH) state that for preterm infants who are in the neonatal intensive care unit (NICU) for a prolonged time should have a diagnostic audiologic evaluation before they are discharged from the hospital. Well babies follow a 1-2-3-month benchmark timeline where they are screened, diagnosed, and receiving intervention for a hearing loss. However, very premature babies it might not be possible to complete a hearing screen at one month of age due to several factors. Once the baby is stable an audiologic evaluation should be performed. For premature babies in the NICU, auditory brainstem response (ABR) testing is recommended. If the infant doesnt pass the screen, they should be referred for an audiologic evaluation by an audiologist. If the infant is on aminoglycosides such as gentamicin for less than five days they should be monitored and have a follow up 6–7 months of being discharged from the hospital to ensure there is no late onset hearing loss due to the medication. Outcomes and prognosis Preterm births can result in a range of problems including mortality and physical and mental delays. Mortality and morbidity In the U.S. where many neonatal infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%. Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below. The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks. Most newborns who die, and 40% of older infants who die, were born between 20 and 25.9 weeks (gestational age), during the second trimester.As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate. Specific risks for the preterm neonate Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems. Neurological problems include apnea of prematurity, hypoxic-ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), developmental disability, transient hyperammonemia of the newborn, cerebral palsy and intraventricular hemorrhage, the latter affecting 25% of babies born preterm, usually before 32 weeks of pregnancy. Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death. Neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet postnatal needs. Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA). Respiratory problems are common, specifically the respiratory distress syndrome (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be chronic lung disease (previously called bronchopulmonary dysplasia or BPD). Gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, rickets of prematurity, hypocalcemia, inguinal hernia, and necrotizing enterocolitis (NEC). Hematologic complications include anemia of prematurity, thrombocytopenia, and hyperbilirubinemia (jaundice) that can lead to kernicterus. Infection, including sepsis, pneumonia, and urinary tract infection [1] Survival The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72% as of 2016. With extensive treatment up to 30% of those who survive birth at 22 weeks survive longer term as of 2019. The chances of survival without long-term difficulties is less. Of those who survive following birth at 22 weeks 33% have severe disabilities. In the developed world overall survival is about 90% while in low-income countries survival rates are about 10%.Some children will adjust well during childhood and adolescence, although disability is more likely nearer the limits of viability. A large study followed children born between 22 and 25 weeks until the age of 6 years old. Of these children, 46 percent had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34 percent had mild disabilities, and 20 percent had no disabilities. 12 percent had disabling cerebral palsy. Up to 15 out of 100 premature infants have significant hearing loss.As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury. Some of the complications related to prematurity may not be apparent until years after the birth. A long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include cerebral palsy, intellectual disability, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy. Standard intelligence tests showed that 41 percent of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full term. It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth. People born prematurely may be more susceptible to developing depression as teenagers. Some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes. Studies of people born premature and investigated later with MRI brain imaging, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.Despite the neurosensory, mental and educational problems studied in school age and adolescent children born extremely preterm, the majority of preterm survivors born during the early years of neonatal intensive care are found to do well and to live fairly normal lives in young adulthood. Young adults born preterm seem to acknowledge that they have more health problems than their peers, yet feel the same degree of satisfaction with their quality of life.Beyond the neurodevelopmental consequences of prematurity, infants born preterm have a greater risk for many other health problems. For instance, children born prematurely have an increased risk for developing chronic kidney disease. Epidemiology Preterm birth complicates the births of infants worldwide affecting 5% to 18% of births. In Europe and many developed countries the preterm birth rate is generally 5–9%, and in the U.S. it has even risen to 12–13% in the last decades.As weight is easier to determine than gestational age, the World Health Organization tracks rates of low birth weight (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000. It is estimated that one third of these low birth weight deliveries are due to preterm delivery. Weight generally correlates to gestational age; however, infants may be underweight for other reasons than a preterm delivery. Neonates of low birth weight (LBW) have a birth weight of less than 2,500 g (5 lb 8 oz) and are mostly but not exclusively preterm babies as they also include small for gestational age (SGA) babies. Weight-based classification further recognizes Very Low Birth Weight (VLBW) which is less than 1,500 g, and Extremely Low Birth Weight (ELBW) which is less than 1,000 g. Almost all neonates in these latter two groups are born preterm. About 75% of nearly a million deaths due to preterm deliver would survive if provided warmth, breastfeeding, treatments for infection, and breathing support. Complications from preterm births resulted in 740,000 deaths in 2013, down from 1.57 million in 1990. Society and culture Economics Preterm birth is a significant cost factor in healthcare, not even considering the expenses of long-term care for individuals with disabilities due to preterm birth. A 2003 study in the U.S. determined neonatal costs to be $224,400 for a newborn at 500–700 g versus $1,000 at over 3,000 g. The costs increase exponentially with decreasing gestational age and weight. The 2007 Institute of Medicine report Preterm Birth found that the 550,000 premature babies born each year in the U.S. run up about $26 billion in annual costs, mostly related to care in neonatal intensive care units, but the real tab may top $50 billion. Notable cases James Elgin Gill (born on 20 May 1987 in Ottawa, Ontario, Canada) was the earliest premature baby in the world, until that record was broken in 2004. He was 128 days premature (21 weeks 5 days gestation) and weighed 624 g (1 lb 6 oz). He survived.In 2014, Lyla Stensrud, born in San Antonio, Texas, U.S. became the youngest premature baby in the world. She was born at 21 weeks 4 days and weighed 410 grams (less than a pound). Kaashif Ahmad resuscitated the baby after she was born. As of November 2018, Lyla was attending preschool. She had a slight delay in speech, but no other known medical issues or disabilities.Amillia Taylor is also often cited as the most premature baby. She was born on 24 October 2006 in Miami, Florida, U.S. at 21 weeks and 6 days gestation. This report has created some confusion as her gestation was measured from the date of conception (through in vitro fertilization) rather than the date of her mothers last menstrual period, making her appear 2 weeks younger than if gestation was calculated by the more common method. At birth, she was 23 cm (9 in) long and weighed 280 g (10 oz). She had digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Childrens Hospital on 20 February 2007.The record for the smallest premature baby to survive was held for a considerable amount of time by Madeline Mann, who was born in 1989 at 26 weeks, weighing 280 g (9+7⁄8 oz) and measuring 24 cm (9+1⁄2 in) long. This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital, Loyola University Medical Center in Maywood, Illinois. at 25 weeks gestation. At birth, she was 20 cm (8 in) long and weighed 261 g (9+1⁄4 oz). Her twin sister was also a small baby, weighing 563 g (1 lb 3+7⁄8 oz) at birth. During pregnancy their mother had pre-eclampsia, requiring birth by caesarean section. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February 2005 by which time her weight had increased to 1.18 kg (2 lb 9+5⁄8 oz). Generally healthy, the twins had to undergo laser eye surgery to correct vision problems, a common occurrence among premature babies. In May 2019, Sharp Mary Birch Hospital for Women & Newborns in San Diego announced that a baby nicknamed "Saybie" had been discharged almost five months after being born at 23 weeks gestation and weighing 244 g (8+5⁄8 oz). Saybie was confirmed by Dr. Edward Bell of the University of Iowa, which keeps the Tiniest Babies Registry, to be the new smallest surviving premature baby in that registry.The worlds smallest premature boy to survive was born in February 2009 at Childrens Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, U.S. Jonathon Whitehill was born at 25 weeks gestation with a weight of 310 g (10+7⁄8 oz). He was hospitalized in a neonatal intensive care unit for five months, and then discharged.In 2020, at the height of the COVID-19 pandemic, the worlds most premature baby was born. The baby, named Richard Hutchinson, was born at Childrens Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, on June 5, 2020, at 21 weeks 2 days gestation. At birth he weighed 340 g (12 oz). He remained hospitalized until November 2020, when he was then discharged.Historical figures who were born prematurely include Johannes Kepler (born in 1571 at seven months gestation), Isaac Newton (born in 1642, small enough to fit into a quart mug, according to his mother), Winston Churchill (born in 1874 at seven months gestation), and Anna Pavlova (born in 1885 at seven months gestation). Effect of the coronavirus pandemic During the COVID-19 pandemic, a drastic drop in the rate of premature births has been reported in many countries, ranging from a 20% reduction to a 90% drop in the starkest cases. Studies in Ireland and Denmark first noticed the phenomenon, and it has been confirmed elsewhere. There is no universally accepted explanation for this drop as of August 2020. Hypotheses include additional rest and support for expectant mothers staying at home, less air pollution due to shutdowns and reduced car fumes, and reduced likelihood of catching other diseases and viruses in general due to the lockdowns. Research Brain injury is common among preterms, ranging from white matter injury to intraventricular and cerebellar haemorrhages. The characteristic neuropathology of preterms has been described as the "encephalopathy of prematurity". The number of preterms that receive special education is doubled compared to the general population. School marks are lower and so are verbal learning, executive function, language skills, and memory performance scores, as well as IQ scores. Behaviourally, adolescents who were born very preterm and/or very low birth weight have similar self-reports of quality of life, health status and self-esteem as term controls.Various structural magnetic resonance studies found consistent reductions in whole brain volume. The extensive list of particular regions with smaller volumes compared to controls includes many cortical areas (temporal, frontal, parietal, occipital and cingulate), the hippocampal regions, thalamus, basal ganglia, amygdala, brain stem, internal capsule, corpus callosum and cerebellum. Brain volume reduction seems to be present throughout the whole brain. In contrast, larger volumes were found in some of the same areas including medial/anterior frontal, parietal and temporal cortex, cerebellum, middle temporal gyrus, parahippocampal gyrus, and fusiform gyrus, as well as larger lateral ventricles on average. The cause of these inconsistencies are unknown. Additionally, reductions in cortical surface area/cortical thickness were found in the temporal lobes bilaterally and in left frontal and parietal areas. Thicker cortex was found bilaterally in the medial inferior and anterior parts of the frontal lobes and in the occipital lobes. Gestational age was positively correlated with volumes of the temporal and fusiform gyri and sensorimotor cortex bilaterally, left inferior parietal lobule, brain stem, and various white matter tracts, as well as specific positive associations with the cerebellum and thalamus. Several structural brain alterations have been linked back to cognitive and behavioural outcome measures. For example, total brain tissue volume explained between 20 and 40% of the IQ and educational outcome differences between extremely preterm born adolescents and control adolescents. In another study, a 25% quartile decrease in white matter values in middle temporal gyrus was associated with a 60% increase in the risk of cognitive impairment. Nosarti and colleagues previously hypothesised that maturational patterns in preterm brains were consistent with the age-related stages typically observed in younger subjects. Their most recent study suggests, however, that their trajectory may not only be delayed but also fundamentally distinctive. Since both smaller and larger regional volumes were found in very preterm individuals compared to controls.The evidence to support the use of osteopathic manipulations to provide benefit in neonatal care is weak. See also Canadian Perinatal Network Preemie Parents: 26 Little Ways to Grow With Your Premature Baby (2011), by Tami Gaines World Prematurity Day References == External links ==

Aarogya, What does Takotsubo cardiomyopathy mean

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy or Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart. It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome. Examples of physical stressors that can cause TTS are sepsis, shock, and pheochromocytoma, and emotional stressors include bereavement, divorce, or the loss of a job. Reviews suggest that of patients diagnosed with the condition, about 70–80% recently experienced a major stressor, including 41–50% with a physical stressor and 26–30% with an emotional stressor. TTS can also appear in patients who have not experienced major stressors.The pathophysiology is not well understood, but a sudden massive surge of catecholamines such as adrenaline and norepinephrine from extreme stress or a tumor secreting these chemicals is thought to play a central role. Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or "stunning". Further, this adrenaline surge triggers the arteries to tighten, thereby raising blood pressure and placing more stress on the heart, and may lead to spasm of the coronary arteries that supply blood to the heart muscle. This impairs the arteries from delivering adequate blood flow and oxygen to the heart muscle. Together, these events can lead to congestive heart failure and decrease the hearts output of blood with each squeeze.Takotsubo cardiomyopathy occurs worldwide. The condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals. Although TTS has generally been considered a self-limiting disease, spontaneously resolving over the course of days to weeks, contemporary observations show that "a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure, pulmonary oedema, stroke, cardiogenic shock, or cardiac arrest". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome (ACS), but that patients with acute complications may co-occur with TTS. These cases of shock and death have been associated with the occurrence of TTS secondary to an enciting physical stressor such as hemorrhage, brain injury sepsis, pulmonary embolism or severe COPD.It occurs more commonly in postmenopausal women. The name "takotsubo" comes from the Japanese word takotsubo "octopus trap", because the left ventricle of the heart takes on a shape resembling an octopus trap when affected by this condition.A study published in the Journal of the American Heart Association in October 2021 found a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older. Signs and symptoms The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking a myocardial infarction of the anterior wall. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome its name takotsubo "octopus trap", in Japan, where it was first described.Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms. Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems. Acute asthma, surgery, chemotherapy, and stroke are examples of physical stressors. In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday. Risk factors Stress trigger Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful event. Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury, asthma attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers. Roughly one-third of patients have no preceding stressful event. A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter. Sex Women, specifically postmenopausal women, are at greatest risk of developing TTS. This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS. Genetic risk factors It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS. There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process. Hormonal dysregulation Certain endocrine diseases including pheochromocytoma and thyrotoxicosis have been identified as potential risk factors for TTS. The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena. A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS. Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality. Pathophysiology The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed. It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals and the effects these chemicals have on areas of the heart. More specifically, adrenal stimulation by the sympathetic nervous system has been noted in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one. How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood. Research supports the widely-held understanding that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes results in apical stunning and transient cardiomyopathy. Microvascular dysfunction/Transient vasospasm: Some of the original researchers of takotsubo suggested that multiple simultaneous spasms of coronary arteries could cause enough loss of blood flow to cause transient stunning of the myocardium. Other researchers have shown that vasospasm is much less common than initially thought. It has been noted that when there are vasospasms, even in multiple arteries, that they do not correlate with the areas of myocardium that are not contracting. However, the idea of coronary artery vasospasm is still believed to contribute to the TTS disease process. The theory of vasospasm is not easily separated from that of microvascular dysfunction and in fact, microvascular dysfunction could explain vasospasticity. Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is currently one of the most supported theories. Most of the dysfunction occurs as a result of abnormalities within the endothelial linings of blood vessels supplying the heart. In TTS, these highly sensitive interior linings of the vessels have reduced functionality which create dysregulation of vascular tone and predispose the individual to vasoconstriction. When the increased vasoconstrictor effects of catecholamines are introduced, the result is acute cardiac ischemia. Catecholamine-induced myocyte injury: It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy. The effects of this toxicity can be greater in those with a predisposition to anxiety or panic disorders. Delivery of catecholamines (epinephrine, norepinephrine) via circulating blood and through direct delivery from cardiac nerves is increased by the stimulation of stress control centers of the brain. During an emotionally or physically stressful event, brain centers initiate the sympathetic nervous pathways and increase myocardial activity. Excessive catecholamine stimulation has a toxic effect on cardiac muscle cells which creates necrosis of the contractile units of cells similarly seen during acute myocardial infarction. The increased workload of cardiac muscle created by the stimulation of catecholamines, increases the need for more blood and oxygen to these muscles to sustain function. When these demands are unable to be met, the heart is starved of blood and oxygen and begins to die. Included in the cytotoxic sequela of catecholamine toxicity is the molecular transformation of the cardiac myocyte to produce apical stunning. Mid-ventricular obstruction, apical stunning: It has been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology. This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell. Overstimulation of catecholamine receptors create physiological changes in the receptor which has an inverse effect on cardiac cellular function. Termed cellular-trafficking, this property of the cardiac muscle cell is actually a molecular transformation of the cell to produce a down-regulation of catecolaminergic sensitivity. This means that in the presence of excess epinephrine, a normal cardiac contraction is inhibited in an effort to reduce energy demands, prevent hyperactivity and spare the integrity of the cell. Further bolstering this idea is the concentration of these kinds of receptors in the heart. Higher concentrations of the receptor effected to produce cardiac stunning are found closer to the apex of the ventricle. This is what creates the classic ballooning effect of the ventricle.It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality. For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia. An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction. Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS.A 2019 case involved a 60-year-old woman presenting with Takotsubo cardiomyopathy due to over-consumption of wasabi, mistaking it for avocado. Diagnosis Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, Gothenburg University, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology. All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin.Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome. While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram to rule out occlusion of the left anterior descending artery, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months.The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings often are confused with those found during an acute anterior wall myocardial infarction. It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease.The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments.The ballooning patterns were classified by Shimizu et al. as takotsubo type for apical akinesia and basal hyperkinesia, reverse takotsubo for basal akinesia and apical hyperkinesia, mid-ventricular type for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and localised type for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction.In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patients ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time. Treatment The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder. Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months. Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases. After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of supporting the patient. There is currently no internationally agreed protocol for treatment of this condition.While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations.Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated. These most commonly include congestive heart failure and very low blood pressure, and less commonly include blood clotting in the apex of the left ventricle, irregular heart beat, and tearing of the heart wall. Heart failure For patients in acute heart failure, ACE inhibitors, angiotensin receptor blockers, and beta blockers, are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit. Low blood pressure For people with cardiogenic shock, medical treatment is based on whether a left ventricular outflow tract (LVOT) obstruction is present. Therefore, early echocardiography is necessary to determine proper management. For those with obstructed LVOTs inotropic agents should not be used, but instead should be managed like patients with hypertrophic cardiomyopathy, (e.g. phenylephrine and fluid resuscitation). For cases in which the LVOT is not obstructed, inotropic therapy (e.g. dobutamine and dopamine) may be used, but with the consideration that takotsubo is caused by excess catecholamines.Furthermore, mechanical circulatory support (MCS) with an intra-aortic balloon pump (IABP) is well-established as supportive treatment. Prognosis Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most. Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months. Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger. Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall. Epidemiology Takotsubo cardiomyopathy is common, affecting between 1.2% and 2.2% of people in Japan and 2% to 3% in Western countries who experience a myocardial infarction. It also affects far more women than men with 90% of cases being women, most postmenopausal. Scientists believe one reason is that estrogen causes the release of catecholamine and glucocorticoid in response to mental stress. It is not likely for the same recovered patient to experience the syndrome twice, although it has happened in rare cases. The average ages at onset are between 58 and 75 years. Less than 3% of cases occurred in patients under age 50. History Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven.Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: (1) on the impact of the collapse or death of a close person; (2) during acute grief; (3) on threat of loss of a close person; (4) during mourning or on an anniversary; (5) on loss of status or self-esteem; (6) personal danger or threat of injury; (7) after the danger is over; (8) reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease.Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in Cuyahoga County, Ohio, the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had myofibrillar degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart".The first studied case of takotsubo cardiomyopathy was in Japan in 1991 by Sato et al. More cases of the syndrome appeared in Japan within the next decade, although western medicine had still not acknowledged it. The syndrome finally occurred in 1997 when Pavin, et al., wrote about two cases of "reversible LV dysfunction precipitated by acute emotional stress". The western world had not heard of such a thing at the time, as it was incredibly rare and often misdiagnosed. The Japanese at last reported about the syndrome to the west in 2001 under the name "transient LV apical ballooning" though at this point the west had already heard of numerous cases. The syndrome reached international audiences through the media in 2005 when the New England Journal of Medicine wrote about the syndrome.In the bible, when Jacob was told his long lost son, Joseph, is still alive, "his heart faltered, because he did not believe them". The medieval commentator, Nachmanides, further explains: "This condition is known when joy suddenly comes upon one, and it is mentioned in the books of medicines that old or feeble persons cannot withstand the shock, for many of them faint when joy comes to them very suddenly. The heart widens and opens suddenly, and its natural heat goes out and scatters throughout the outer parts of the body, and the heart thus ceases to function because of its coolness." In popular culture The name and title track of the 2021 album Tako Tsubo by French band LImpératrice refers to the intense emotional stress which may provoke this syndrome. See also Widowhood effect References External links Krishnan, Lakshmi; Marchalik, Daniel (8 September 2018). "Understanding Heartbreak: From Takotsubo to Wuthering Heights". The Lancet. 392 (10150): 812. doi:10.1016/S0140-6736(18)32061-0. S2CID 54271789. Retrieved 25 September 2019. Wagner, Judith N. (Fall 2014). "Death by voodoo: truth or tale?". Hektoen International Journal. 6 (4). ISSN 2155-3017. Takotsubo Network - website for professionals and people who have experienced Takotsubo

Hello Aarogya, could you help me understand about Trismus

Trismus

Trismus, commonly called lockjaw as associated with tetanus, is a condition of limited jaw mobility. It may be caused by spasm of the muscles of mastication or a variety of other causes. Temporary trismus occurs much more frequently than permanent trismus. It is known to interfere with eating, speaking, and maintaining proper oral hygiene. This interference, specifically with an inability to swallow properly, results in an increased risk of aspiration. In some instances, trismus presents with altered facial appearance. The condition may be distressing and painful. Examination and treatments requiring access to the oral cavity can be limited, or in some cases impossible, due to the nature of the condition itself. Definition Trismus is defined as painful restriction in opening the mouth due to a muscle spasm, however it can also refer to limited mouth opening of any cause. Another definition of trismus is simply a limitation of movement. Historically and commonly, the term lockjaw was sometimes used as a synonym for both trismus and tetanus.Normal mouth-opening ranges from 35 to 45 mm. Males usually have slightly greater mouth opening than females. (40–60 mm, average of 50 mm). The normal lateral movement is 8–12 mm, and normal protrusive movement is approximately 10 mm. Some have distinguished mild trismus as 20–30 mm interincisal opening, moderate as 10–20 mm and severe as less than 10 mm.Trismus is derived from the Greek word trigmos/trismos meaning "a scream; a grinding, rasping or gnashing". Differential diagnosis Traditionally causes of trismus are divided into intra-articular (factors within the temporomandibular joint [TMJ]) and extra-articular (factors outside the joint, see table). Joint problems Ankylosis True bony ankylosis: can result from trauma to chin, infections and from prolonged immobilization following condylar fracture Treatment – several surgical procedures are used to treat bony ankylosis, e.g.: Gap arthroplasty using interpositional materials between the cut segments. Fibrous ankylosis: usually results due to trauma and infection Treatment – trismus appliances in conjunction with physical therapy. Arthritis synovitis Meniscus pathology Extra-articular causes Infection Odontogenic- Pulpal Periodontal Pericoronal Non-odontogenic- Peritonsillar abscess Tetanus Meningitis Brain abscess Parotid abscess The hallmark of a masticatory space infection is trismus or infection in anterior compartment of lateral pharyngeal space results in trismus. If these infections are unchecked, can spread to various facial spaces of the head and neck and lead to serious complications such as cervical cellulitis or mediastinitis. Treatment: Elimination of etiologic agent along with antibiotic coverage Trismus or lock jaw due to masseter muscle spasm, can be a primary presenting symptom in tetanus, Caused by Clostridium tetani, where tetanospasmin (toxin) is responsible for muscle spasms. Prevention: primary immunization (DPT) Dental treatment Dental trismus is characterized by a difficulty in opening the jaw. It is a temporary condition with a duration usually not longer than two weeks. Dental trismus results from some sort of insult to the muscles of mastication, such as opening the jaw for a period of time or having a needle pass through a muscle. Typical dental anesthesia to the lower jaw often involves the needle passing into or through a muscle. In these cases it is usually the medial pterygoid or the buccinator muscles. Oral surgery procedures, as in the extraction of lower molar teeth, may cause trismus as a result either of inflammation to the muscles of mastication or direct trauma to the TMJ. Barbing of needles at the time of injection followed by tissue damage on withdrawal of the barbed needle causes post-injection persistent paresthesia, trismus and paresis. Treatment: in acute phase: Heat therapy Analgesics A soft diet Muscle relaxants (if necessary) Note: When acute phase is over the patient should be advised to initiate physiotherapy for opening and closing mouth. Trauma Fractures, particularly those of the mandible and fractures of zygomatic arch and zygomatic arch complex, accidental incorporation of foreign bodies due to external traumatic injury. Treatment: fracture reduction, removal of foreign bodies with antibiotic coverage TMJ disorders Extra-capsular disorders – Myofascial pain dysfunction syndrome Intra-capsular problems – Disc displacement, arthritis, fibrosis, etc. Acute closed locked conditions – displaced meniscus Tumors and oral care Rarely, trismus is a symptom of nasopharyngeal or infratemporal tumors/ fibrosis of temporalis tendon, when patient has limited mouth opening, always premalignant conditions like oral submucous fibrosis (OSMF) should also be considered in differential diagnosis. Drug therapy Succinyl choline, phenothiazines and tricyclic antidepressants causes trismus as a secondary effect. Trismus can be seen as an extra-pyramidal side-effect of metoclopromide, phenothiazines and other medications. Radiotherapy and chemotherapy Complications of radiotherapy: Osteoradionecrosis may result in pain, trismus, suppuration and occasionally a foul smelling wound. When muscles of mastication are within the field of radiation, it leads to fibrosis and result in decreased mouth opening. Complications of Chemotherapy: Oral mucosal cells have high growth rate and are susceptible to the toxic effects of chemotherapy, which lead to stomatitis. Congenital and developmental causes Hypertrophy of coronoid process causes interference of coronoid against the anteromedial margin of the zygomatic arch. Treatment: Coronoidectomy Trismus-pseudo-camtodactyly syndrome is a rare combination of hand, foot and mouth abnormalities and trismus. Miscellaneous disorders Hysteric patients: Through the mechanisms of conversion, the emotional conflict are converted into a physical symptom. E.g.: trismus Scleroderma: A condition marked by edema and induration of the skin involving facial region can cause trismus Common causes Pericoronitis (inflammation of soft tissue around impacted third molar) is the most common cause of trismus. Inflammation of muscles of mastication. It is a frequent sequel to surgical removal of mandibular third molars (lower wisdom teeth). The condition is usually resolved on its own in 10–14 days, during which time eating and oral hygiene are compromised. The application of heat (e.g. heat bag extraorally, and warm salt water intraorally) may help, reducing the severity and duration of the condition. Peritonsillar abscess, a complication of tonsillitis which usually presents with sore throat, dysphagia, fever, and change in voice. Temporomandibular joint dysfunction (TMD). Trismus is often mistaken as a common temporary side effect of many stimulants of the sympathetic nervous system. Users of amphetamines as well as many other pharmacological agents commonly report bruxism as a side-effect; however, it is sometimes mis-referred to as trismus. Users jaws do not lock, but rather the muscles become tight and the jaw clenched. It is still perfectly possible to open the mouth. Submucous fibrosis. Fracture of the zygomatic arch. Other causes Acute osteomyelitis Ankylosis of the TMJ (fibrous or bony) Condylar fracture or other trauma. Gaucher disease which is caused by deficiency of the enzyme glucocerebrosidase. Giant cell arteritis Sympathomimetic drugs, such as amphetamine, methamphetamine, MDA, MDMA, MDEA, methylphenidate, ethylphenidate, and related substances. Infection Local anesthesia (dental injections into the infratemporal fossa) Needle prick to the medial pterygoid muscle Oral submucous fibrosis. Radiation therapy to the head and neck. Tetanus, also called lockjaw for this reason Malignant hyperthermia Malaria severa Secondary to neuroleptic drug use Malignant otitis externa Mumps Peritonsillar abscess Retropharyngeal or parapharyngeal abscess Seizure Stroke Toothache Diagnostic approach X-ray/CT scan taken from the TMJ to see if there is any damage to the TMJ and surrounding structures. Treatment Treatment requires treating the underlying condition with dental treatments, speech therapy for swallowing difficulty and mouth opening restrictions, physical therapy, and passive range of motion devices. Additionally, control of symptoms with pain medications (NSAIDs), muscle relaxants, and warm compresses may be used. Splints have been used. History Historically, the term trismus was used to describe the early effects of tetany, also called "lockjaw". References == External links ==

Aarogya, What does Acute intermittent porphyria mean

Acute intermittent porphyria

Acute intermittent porphyria (AIP) is a rare metabolic disorder affecting the production of heme resulting from a deficiency of the porphobilinogen deaminase. It is the most common of the acute porphyrias. Signs and symptoms The clinical presentation of AIP is highly variable and non-specific. The patients are typically asymptomatic, with most gene carriers having no family history because the condition had remained latent for several generations. The syndrome marked by acute attacks affects only 10% of gene carriers. The mean age at diagnosis is 33 years old. Like other porphyrias, AIP is more likely to present in women. A distinguishing feature of AIP that separates it from other porphyrias is the absence of photosensitive cutaneous symptoms that occur in addition to acute attacks. Acute attacks AIP is one of the four porphyrias that presents as an acute attack. 90% of affected individuals never experience an acute attack and are asymptomatic, while an estimated 5% of affected individuals experience repeat attacks. Attacks are most common in young adult women and are rare before puberty or after menopause. Severe acute attacks may require hospitalization. Patients usually experience symptoms in attacks that last from several hours to a few days. Between attacks, patients are asymptomatic.The most frequent presenting symptoms are abdominal pain and tachycardia. The abdominal pain is typically severe, colicky, poorly localized, and often associated with pain in back and legs. Patients may also present with vomiting and constipation, but diarrhea is unusual. The onset of back and leg pain is characterized by severe pain and stiffness in back and thighs followed by loss of tendon reflexes and paralysis. Psychiatric symptoms are present, such as paranoid schizophrenia-like features but rarely psychosis and hallucinations. The acute attacks classically present with dark-red photosensitive urine (often called port-wine urine), but this is a nonspecific symptom. Physical examination often shows no abnormalities.Hyponatremia is the most common electrolyte abnormality during acute attacks, occurring in 40% of patients and presenting as SIADH. Hypomagnesemia is also common. There are no pathognomonic signs or symptoms.The most common identified triggers for acute attacks are medications, weight loss diets, and surgery. Many medications have been associated with AIP including antibiotics, hormonal contraceptives, seizure medications, anesthetics, and HIV treatment drugs. Cause Porphyrias are caused by mutations in genes that encode enzymes in heme synthesis. In normal physiology, heme synthesis begins in the mitochondrion, proceeds into the cytoplasm, and finishes back in the mitochondrion. Heme is produced in all cells, but 80% of all heme is produced in erythropoietic cells in bone marrow and 15% in parenchymal cells in the liver, where turnover of hemoproteins is high. In AIP, over 100 mutations have been identified on the long arm of chromosome 11 at the HMBS gene, which codes for the cytoplasmic enzyme porphobilinogen deaminase. This deficiency prevents heme synthesis, which can not be completed and the metabolite porphobilinogen accumulates in the cytoplasm.AIP is an autosomal dominant porphyria resulting in about 50% normal activity of the affected enzyme. The penetrance of AIP is incomplete with only 10% of gene carriers experiencing acute attacks suggesting role for other modifying genes or environment.The exact mechanism of acute attacks is not clear. The most favored hypothesis is that porpholobilinogen buildup causes a toxic effects on neurons. The autonomic and peripheral nervous system are more vulnerable than the central nervous system because they are not protected by the blood-brain barrier. This explains findings such as abdominal pain and tachycardia. Some individuals may be more likely to develop paresis based on increased susceptibility of neurons to toxins. Genetics Inheritance AIP has an autosomal dominant pattern of inheritance. The dominance pattern is a result of partial deficiencies from the heme biosynthesis enzymes, hydroxymethylbilane synthase (HMBS; EC 2.5.1.61). Due to the rarity of this disease it is difficult to estimate the prevalence of AIP and the inclusion criteria differs widely among studies causing varying statistics. AIP has a low penetrance when considering the general population, but within families the penetrance increases. This is indicative of another interaction affecting the inheritance pattern. It is speculated that this pattern is due to AIP propensity caused by the inheritance of an additional gene mutation, HMBS, in addition to other genetic and environmental influences. There have been 421 HMBS mutations that have been linked to AIP. This suggests that AIP inheritance instead follows an oligogenic or polygenic inheritance pattern. Research shows that HMBS mutations are estimated to occur in approximately 1 in 1700 caucasians (there is not enough data in other populations) while AIP symptoms are shown to be present in approximately 1 in 200,000 caucasians. It can be inferred that the penetrance of AIP is approximately 1% of the HMBS heterozygous community, concluding that there are other factors needed to induce AIP symptoms. Variants of AIP There have been more than 400 mutations in the heme biosynthesis identified to cause AIP. In the erythroid variant, mutations in the exon 1 sequence of the housekeeping gene, splicing of exon 1, and splicing of exon 3 causes an alternative form of AIP wherein there is decreased activity of the liver enzyme but erythroid cells have regular activity. HMBS has two isoforms, housekeeping and erythroid. Additionally, there is also the non-erythroid variant of AIP in which there are mutations in exons 3-15 and there is decreased activity in both isozymes. Most individuals with AIP have mutations in exons 3–15. Loss of function mutations of HMBS cause decreased activity of the enzymes normally present. Diagnosis The initial diagnosis of acute porphyria is confirmed by urinalysis, including the common method, the Watson-Schwartz test. Elevated urine porphobilinogen confirms diagnosis of AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP). A positive test should be indicated with an increase of five times normal, not just a slight increase which can occur with dehydration. To distinguish between AIP from HCP and VP, fecal porphyrin levels are normal in AIP but elevated in HCP and VP.Rapid, accurate diagnosis is important. Delays in diagnosis may result in permanent neurological damage or death. Diagnosis with Genetic Testing With advancement and increased accessibility to genetic testing and follow up counseling, the morbidity of AIP has decreased because of early diagnosis. The combination of targeted mutation analysis and biochemical activity tracking have provided positive results for identifying the risk of AIP development. Mutation analysis has a 95% sensitivity and a 100% specificity for confirmation of pathogenicity of a mutation. Genetic testing can detect AIP in patients with symptoms that would have otherwise gone undiagnosed or misdiagnosed. The biochemical analysis route of detection is slightly less accurate compared to genetic testing, which has 84% sensitivity and 71% specificity, but is still chosen over other alternatives and can provide some of the predictive information that genetic testing does. Patients diagnosed with genetic testing at the asymptomatic stage were less likely to develop symptoms throughout their life. Additionally, individuals who were diagnosed at the symptomatic stage encountered more mild attacks after diagnosis, although they still had symptoms. Genetic testing availability has decreased the rate of patients seeking treatment by medical staff, as patients experiencing less severe symptoms instead opt to self treat at home. Treatment If drugs have caused the attack, discontinuing the offending substances is essential. A high-carbohydrate (10% glucose) infusion is recommended, which may aid in recovery. Hematin and heme arginate is the treatment of choice during an acute attack. Heme is not a curative treatment, but can shorten attacks and reduce the intensity of an attack. Side-effects are rare but can be serious. Pain is extremely severe and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible due to its severity. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths or showers may lessen nausea temporarily, but can present a risk of burns or falls.Seizures often accompany this disease. Most seizure medications exacerbate this condition due to their induction of cytochrome P450. Treatment can be problematic: Barbiturates and primidone must be avoided as they commonly precipitate symptoms. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control. Society One of the many hypothesized diagnoses of the artist Vincent van Gogh is that he and his siblings, in particular his brother Theo, had AIP and syphilis. Another theorized case was King George III of the United Kingdom who even had a medallion struck to commemorate his "curing". His descendant Prince William of Gloucester was reliably diagnosed with variegate porphyria in 1968. It is probable that the philosopher Jean-Jacques Rousseau had porphyria. It has even been suggested that Vlad III, Prince of Wallachia, more commonly known by his surname Dracula, had porphyria. References == External links ==

Aarogya what is Melanosis coli

Melanosis coli

Melanosis coli, also pseudomelanosis coli, is a disorder of pigmentation of the wall of the colon, often identified at the time of colonoscopy. It is benign and may have no significant correlation with disease. The brown pigment is lipofuscin in macrophages, not melanin. Cause The most common cause of melanosis coli is the extended use of laxatives, and commonly anthraquinone containing laxatives such as senna, aloe vera, and other plant glycosides. The anthranoid laxatives pass through the gastrointestinal tract unabsorbed until they reach the large intestine, where they are changed into their active forms. The resulting active compounds cause damage to the cells in the lining of the intestine and leads to apoptosis (a form of cell death). The damaged (apoptotic) cells appear as darkly pigmented bodies that may be taken up by scavenger cells known as macrophages. When enough cells have been damaged, the characteristic pigmentation of the bowel wall develops. The condition can develop after just a few months of laxative use.However, other causes are identified, including an increase in colonic epithelial apoptosis. Endoscopically, the mucosa may show a brownish discoloration in a moiré pattern. Histologic appearance On biopsy, melanosis coli shows characteristic pigment-laden macrophages within the mucosa on PAS staining.The histologic differential diagnosis of mucosal pigmentation is: lipofuscin (melanosis coli), hemosiderin-laden macrophages, and melanin (rare). Prognosis No adverse effects or consequences of melanosis coli have been identified. Relation to true melanoses The condition is unrelated to true melanoses, such as Peutz–Jeghers syndrome and smokers melanosis.Peutz–Jeghers syndrome causes pigmentation of the skin and mucous surfaces with melanin, and polyps in the digestive tract. Non-colonic pseudomelanoses Pseudomelanoses of other parts of the gastrointestinal tract have also been reported, and are of unclear relevance.Patients with colostomies can have melanosis involving the stoma, which is also of no significance. References == External links ==

Please give me a short description about Dissociation , Aarogya

Dissociation

Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts) split into smaller particles, usually in a reversible manner Dissociation (neuropsychology), identification of the neural substrate of a particular brain function through various methods Dissociation (psychology), an experience of having ones attention and emotions detached from the environment Dissociation (rhetoric), a rhetorical device in which the speaker separates a notion considered to form a unitary concept into two new notions to affect an audience in some way Dissociation (album), by the Dillinger Escape Plan, 2016 See also Dissociation: Progress in the Dissociative Disorders (1988-1997) published by International Society for the Study of Trauma and Dissociation "Disassociation", a 2021 song by the Rions Dissociative, a class of hallucinogen All pages with titles beginning with Dissociation All pages with titles containing Dissociation

Aarogya what is Heart murmur

Heart murmur

Heart murmurs are unique heart sounds produced when blood flows across a heart valve or blood vessel. This occurs when turbulent blood flow creates a sound loud enough to hear with a stethoscope. Turbulent blood flow is not smooth. The sound differs from normal heart sounds by their characteristics. For example, heart murmurs may have a distinct pitch, duration and timing. The major way health care providers examine the heart on physical exam is heart auscultation; another clinical technique is palpation, which can detect by touch when such turbulence causes the vibrations called cardiac thrill. A murmur is a sign found during the cardiovascular exam. Murmurs are of various types and are important in the detection of cardiac and valvular pathologies (i.e. can be a sign of heart diseases or defects). There are two types of murmur. A functional murmur is a benign heart murmur that is primarily due to physiologic conditions outside the heart. The other type of heart murmur is due to a structural defect in the heart itself. Defects may be due to narrowing of one or more valves (stenosis), backflow of blood, through a leaky valve, (regurgitation), or the presence of abnormal passages through which blood flows in or near the heart.Most murmurs are normal variants that can present at various ages which relate to changes of the body with age such as chest size, blood pressure, and pliability or rigidity of structures.Heart murmurs are frequently categorized by timing. These include systolic heart murmurs, diastolic heart murmurs, or continuous murmurs. These differ in the part of the heartbeat they make sound, during systole, or diastole. Yet, continuous murmurs create sound throughout both parts of the heartbeat. Continuous murmurs are not placed into the categories of diastolic or systolic murmurs. Diagnostic approach and diagnosis Classification Murmurs have seven main characteristics. These include timing, shape, location, radiation, intensity, pitch and quality. Timing refers to whether the murmur is a systolic, diastolic, or continuous murmur. Shape refers to the intensity over time. Murmurs can be crescendo, decrescendo or crescendo-decrescendo. Crescendo murmurs increase in intensity over time. Decrescendo murmurs decrease in intensity over time. Crescendo-decrescendo murmurs have both shapes over time. These have progressive increase in intensity, peak, and progressive decrease in intensity. Crescendo–decrescendo murmurs resemble a diamond or kite shape. Location refers to where the heart murmur is usually heard best. There are four places on the anterior chest wall to listen for heart murmurs. Each location roughly corresponds to a specific part of the heart. Health care providers listen to these areas with a stethoscope.Position for auscultation: The patient is most often lying on their back (supine) with the head of bed at slight upward angle. The head of the bed is usually at a 30 degree upward angle. Usually the health care provider is standing to the right of the person they are examining. Below are positional changes that one may use: Left lateral decubitus (lying on the left side). This will decrease the distance from wall of the chest to the apex of the heart. This will help to examine the point of maximal impulse. Also, this will help to hear extra heart sounds (S3 or S4). With the patient sitting upright. With the patient seated, leaning forward and holding breath after exhalation. This will decrease the distance of the chest wall to the left ventricular outflow tract. By doing so this will help find the presence of an aortic regurgitation murmur. Radiation refers to where the sound of the murmur travels. The rule of thumb is that the sound radiates in the direction of the blood flow. Intensity refers to the loudness of the murmur with grades according to the Levine scale, from 1 to 6:Pitch may be low, medium or high. This depends on whether auscultation is best with the bell or diaphragm of a stethoscope. Quality refers to unusual characteristics of a murmur. For example, blowing, harsh, rumbling or musical. Mnemonics A mnemonic to remember what characteristics to look for when listening to murmurs is SCRIPT: Site, Configuration (shape), Radiation, Intensity, Pitch and quality, and Timing in the cardiac cycle. The use of two simple mnemonics may help differentiate systolic and diastolic murmurs; PASS and PAID. Pulmonary and aortic stenoses are systolic while pulmonary and aortic insufficiency (regurgitation) are diastolic. Mitral and tricuspid defects are opposite. Interventions that change murmur sounds Inhalation leads to an increase in intrathoracic negative pressure. This increases the capacity of pulmonary circulation, thereby prolonging ejection time. This will affect the closure of the pulmonary valve. This finding is also called Carvallos maneuver. This maneuver in studies had a sensitivity of 100% and a specificity of 80% to 88% in detecting murmurs originating in the right heart. Positive Carvallos sign describes the increase in intensity of a tricuspid regurgitation murmur heard with inspiration. Abrupt standing Squatting, by increasing afterload and increasing preload. Squatting leads to an increase in systemic vascular resistance. An increase in systemic vascular resistance results in an increase in afterload. With HOCM, an increase in afterload will hold the obstruction in a more open configuration. This will decrease the loudness of the murmur with HOCM. Handgrip maneuver, by increasing afterload. Like squatting, this will decrease the loudness of the HOCM murmur. Valsalva maneuver. Valsalva maneuver has utility in detecting hypertrophic obstructive cardiomyopathy (HOCM). According to one study, it has a sensitivity of 65% and specificity of 96% in HOCM. Valsalva maneuver, as well as standing, decrease venous return to the heart. As a result, this decreases left ventricular filling. With HOCM, the outflow obstruction increases with a decrease in preload. This will increase the loudness of the murmur with HOCM. Post ectopic potentiation Inhaled amyl nitrite. This is a vasodilator that diminishes systolic murmurs in left-to-right shunts in ventricular septal defects. It also reveals right-to left shunts in the setting of pulmonic stenosis and a ventricular septal defect. Methoxamine Positioning of the patient. In the lateral decubitus position or lying on the left side. This will make murmurs in the mitral valve area more pronounced. Anatomic sources Systolic Aortic valve stenosis is a crescendo/decrescendo systolic murmur. It is best heard at the right upper sternal border (aortic area). It sometimes radiates to the carotid arteries. In mild aortic stenosis, the crescendo-decrescendo is early peaking. Whereas in severe aortic stenosis, the crescendo is late-peaking. In severe cases, obliteration of the S2 heart sound may occur. Stenosis of Bicuspid aortic valve is like the aortic valve stenosis heart murmur. But, one may hear a systolic ejection click after S1 in calcified bicuspid aortic valves. Symptoms tend to present between 40 and 70 years of age. Mitral regurgitation is a holosystolic murmur. One can best hear it at the apex location and it may radiate to the axilla or precordium. When associated with mitral valve prolapse, one may hear a systolic click. In this scenario, valsalva maneuver will decrease left ventricular preload. This will move the murmur onset closer to S1. Isometric handgrip will increase left ventricular afterload. This will increase murmur intensity. In acute severe mitral regurgitation, one may not hear a holosystolic murmur. Pulmonary valve stenosis is a crescendo-decrescendo systolic murmur. One can hear it best at the left upper sternal border. It has association with a systolic ejection click that increases with inspiration. This finding results from an increased venous return to the right side of the heart. Pulmonary stenosis sometimes radiates to the left clavicle. Tricuspid valve regurgitation is a holosystolic murmur. It presents at the left lower sternal border with radiation to the left upper sternal border. One may see prominent v and c waves in the JVP (jugular venous pressure). The murmur will increase with inspiration. Hypertrophic obstructive cardiomyopathy (or hypertrophic subaortic stenosis) will be a systolic crescendo-decrescendo murmur. One can best hear it at the left lower sternal border. Valsalva maneuver will increase the intensity of the murmur. Going from squatting to standing will also increase the intensity of the murmur. Atrial septal defect will present with a systolic crescendo-decrescendo murmur. It is best heard at the left upper sternal border. This is the result of an increased volume going through the pulmonary valve. It has association with a fixed, split S2 and a right ventricular heave. Ventricular septal defect (VSD) will present as a holosystolic murmur. One can hear it at the left lower sternal border. It has association with a palpable thrill, and increases with isometric handgrip. A right to left shunt (Eisenmenger syndrome) may develop with uncorrected VSDs. This is due to worsening pulmonary hypertension. Pulmonary hypertension will increase the murmur intensity and may present with cyanosis. Flow murmur presents at the right upper sternal border. It may present in certain conditions, such as anemia, hyperthyroidism, fever, and pregnancy. Diastolic Aortic valve regurgitation will present as a diastolic decrescendo murmur. One can hear it at the left lower sternal border. One may also hear it at the right lower sternal border (when associated with a dilated aorta). Other possible exam findings are bounding carotid and peripheral pulses. These are also known as Corrigans pulse or Watsons water hammer pulse. Another possible finding is a widened pulse pressure. Mitral stenosis presents as a diastolic low-pitched decrescendo murmur. It is best heard at the cardiac apex in the left lateral decubitus position. Mitral stenosis may have an opening snap. Increasing severity will shorten the time between S2 (A2) and the opening snap. For example, in severe MS the opening snap will occur earlier after A2. Tricuspid valve stenosis presents as a diastolic decrescendo murmur. One can hear it at the left lower sternal border. One may see signs of right heart failure on exam. Pulmonary valve regurgitation presents as a diastolic decrescendo murmur. One may hear it at the left lower sternal border. A palpable S2 in the second left intercostal space correlates with pulmonary hypertension due to mitral stenosis. The cooing dove murmur is a cardiac murmur with a musical quality (high pitched). Associated with aortic valve regurgitation (or mitral regurgitation before rupture of chordae). It is a diastolic murmur heard over the mid-precordium.Continuous and Combined Systolic/Diastolic Patent ductus arteriosus may present as a continuous murmur radiating to the back. Severe coarctation of the aorta can present with a continuous murmur. One may hear the systolic component at the left infraclavicular region and the back. This is due to the stenosis. One may hear the diastolic component over the chest wall. This is due to blood flow through collateral vessels. Acute severe aortic regurgitation may present with a three phase murmur. First, a midsystolic murmur followed by S2. Following this is a parasternal early diastolic and mid-diastolic murmur (Austin Flint murmur). The exact cause of an Austin Flint murmur is unknown. Hypothesis is that the mechanism of murmur is from the severe aortic regurgitation. In severe aortic regurgitation the jet vibrates the anterior mitral valve leaflet. This causes collision with the mitral inflow during diastole. As such, the mitral valve orifice narrows. This results in increased mitral inflow velocity. This leads to the jet impinging on the myocardial wall.Ruptured aortic sinus (sinus of Valsalva) may present as a continuous murmur. This is an uncommon cause of continuous murmur One may hear it at the aortic area and along the left sternal border. Types and disease associations Continuous machinery murmur, at the left upper sternal border Classic for a patent ductus arteriosus (PDA). Signs of infants associated with serious cases of PDA are poor feeding, failure to thrive and respiratory distress. Other examination findings may include widened pulse pressures and bounding pulses. Systolic murmur loudest below the left scapula Classic for a coarctation of the aorta. Coarctation of the aorta is narrowing of the aorta. This can occur in Turners Syndrome, (gonadal dysgenesis). Turners Syndrome is an X-linked disorder with absence of one X-chromosome. Other exam findings of coarctation of the aorta include radio-femoral delay. This is when the femoral pulse is later than the radial pulse. The pulses in the lower extremity may be weaker than those of the upper extremity. Another exam finding is of varying blood pressure in the upper and lower extremities. This presents as higher blood pressure in the arms and lower blood pressure in the legs. Harsh holosystolic (pansystolic) murmur at the left lower sternal border Classic for a ventricular septal defect (VSD). This may lead to the development of the delayed-onset cyanotic heart disease known as Eisenmenger syndrome. Eisenmenger syndrome is a reversal of the left-to-right heart shunt. This is the result of hypertrophy of the right ventricle over time. This causes a right-to-left heart shunt. The VSD allows deoxygenated blood to flow from the right to left side of the heart. This blood bypasses the lungs. The lack of oxygenation in the pulmonary circulation results in cyanosis. Widely split fixed S2 and systolic ejection murmur at the left upper sternal border Classic for a patent foramen ovale (PFO) or atrial septal defect (ASD). A PFO is lack of closure of the foramen ovale. At first, this produces a left-to-right heart shunt. This does not produce cyanosis, but causes pulmonary hypertension. Longstanding uncorrected atrial septal defects can also result in Eisenmenger syndrome. Eisenmenger syndrome can result in cyanosis. Management A medical provider (e.g. doctor) may order tests for further evaluation of a heart murmur. The echocardiogram is a common test used. This is also known as an "echo" or ultrasound of the heart. It shows the heart structures and blood flow through the heart. Further testing is usually done when symptoms that may be of concern are present. The need for treatment depends on the diagnosis and severity. In some cases, the condition causing the heart murmur may prompt monitoring. Sometimes, heart murmurs disappear on their own. This happens when the cause of the heart murmur is no longer present. Monitoring will help determine how the condition changes. It may stay the same, worsen, or improve. In other cases, the condition causing the heart murmur may not prompt any further tests. Treatment ranges from medication to surgeries. See also Benign paediatric heart murmur George Alexander Gibson discoverer of the Gibson murmur. Precordial examination References == External links ==

Please give me a short description about Amyloid-related imaging abnormalities , Aarogya

Amyloid-related imaging abnormalities

Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in magnetic resonance imaging of the brain in patients with Alzheimers disease. ARIA is associated with amyloid-modifying therapies, particularly human monoclonal antibodies such as aducanumab. There are two types of ARIA: ARIA-E and ARIA-H. The phenomenon was first seen in trials of bapineuzumab. ARIA-E ARIA-E refers to cerebral edema, involving the breakdown of the tight endothelial junctions of the blood-brain barrier and subsequent accumulation of fluid. In a double-blind trial of the humanised monoclonal antibody solanezumab (n = 2042), sixteen patients (11 taking the drug, 5 taking a placebo), or 0.78% developed ARIA-E. A further 7 patients developed ARIA-E during an open-label extension of the trial.The effect of ARIA-E depends on the severity and location of the edema. Symptoms may include headache, changes in mental state, confusion, vomiting, nausea, tremor and gait disturbances. ARIA-H ARIA-H refers to cerebral microhaemorrhages (mH), small haemorrhages on the brain, often accompanied by hemosiderosis. mH are usually seen as small, round and low intensity lesions and are small haemosiderin deposits. Some studies define mH as being less than or equal to 10mm, while others define the cut-off as ≤ 5mm. The prevalence of mH in healthy elderly people is approximately 6%, but this value increases to between 50% and 80% in elderly people with cerebrovascular disease. ARIA MRI Classification Criteria References == External links ==

Aarogya, could you share information about a health condition involving Parotitis

Parotitis

Parotitis is an inflammation of one or both parotid glands, the major salivary glands located on either side of the face, in humans. The parotid gland is the salivary gland most commonly affected by inflammation. Etymology From Greek παρωτῖτις (νόσος), parōtĩtis (nósos) : (disease of the) parotid gland < παρωτίς (stem παρωτιδ-) : (gland) behind the ear < παρά - pará : behind, and οὖς - ous (stem ὠτ-, ōt-) : ear. Causes Dehydration Dehydration: This is a common, non-infectious cause of parotitis. It may occur in elderly or after surgery. Infectious parotitis Acute bacterial parotitis: is most often caused by a bacterial infection of Staphylococcus aureus but may be caused by any commensal bacteria. Parotitis presents as swelling at the angle of the jaw. Bacterial parotitis presents as a unilateral swelling, where the gland is swollen and tender and usually produces pus at the Stensens duct. This pus is usually sampled and the bacteria within are identified. Common causative bacteria are Staphylococcus aureus, Streptococcus pyogenes and E coli. It is associated with poor oral hygiene; oral infections and decreased saliva production. Symptoms include fever, dehydration, chills, fast heartbeat and breathing if the infection is causing sepsis. Medications such as antihistamines and diuretics can be predisposing factors. Treatment is usually antibiotics.Parotitis as extrapulmonary tuberculosis: The mycobacterium that cause tuberculosis can also cause parotid infection. Parotid swelling can be an uncommon symptom of extrapulmonary tuberculosis (TB outside of the lungs). The usual symptoms are a cough, fever, weight loss, shortness of breath, chest pain, tiredness and chills. This is caused by the bacteria Mycobacterium tuberculosis. TB can also affect the heart, thyroid and adrenal glands but the main site of infection is the lungs. Risk factors are chronic alcohol consumption, diabetes, long term steroid use, HIV infection and kidney failure. Those infected tend to have enlarged, nontender, but moderately painful glands. The diagnosis is made by typical chest radiograph findings, cultures, or histologic diagnosis after the gland has been removed. When diagnosed and treated with antitubercular medications, the gland may return to normal in 1–3 months.Acute viral parotitis (mumps): The most common viral cause of parotitis is mumps. Routine vaccinations have dropped the incidence of mumps to a very low level. Mumps resolves on its own in about ten days. A viral infection caused by Paramyxovirus, a single-stranded RNA virus. Common symptoms include fever, headache and bilateral or unilateral parotitis (swelling of the parotid gland on one or both sides of the face). The parotid gland is usually swollen and tender. Parotid swelling usually occurs 16–18 days after exposure to the virus. Treatment includes isolation and therefore prevention of spread of the disease and supportive measures such as hot or cold packs. Mumps usually resolves itself and can be prevented by vaccination.HIV parotitis: Generalized lymphadenopathy has long been associated with HIV, but the localized enlargement of the parotid gland is less well known. HIV-associated salivary gland disease can involve many diseases but often presents as enlargement of the parotid gland and a dry mouth. Causes have not been specifically identified but the most likely are viral opportunists and autoimmune responses. Viruses linked to this can include; hepatitis C, cytomegalovirus, paramyxovirus, influenza A, and adenovirus. Treatment is anti-retroviral therapy.Disseminated histoplasmosis: During a large urban disseminated histoplasmosis outbreak (est. 100,000 victims) in Indianapolis from 1978 to 1979, manifestations included parotitis. Autoimmune causes These are also collectively known as chronic punctate parotitis or chronic autoimmune parotitis.Sjögrens syndrome: Chronic inflammation of the salivary glands may also be an autoimmune disease known as Sjögrens syndrome. The disease most commonly appears in people aged 40–60 years, but it may affect small children. In Sjögren syndrome, the prevalence of parotitis in women versus men is approximately 9:1. The involved parotid gland is enlarged and tender at times. The cause is unknown. The syndrome is often characterized by excessive dryness in the eyes, mouth, nose, vagina, and skin.Lymphoepithelial lesion of Godwin: Most frequently associated with a circumscribed tumor with the histologic features of Sjögren syndrome. This designation has also fallen out of favour. Blockage Blockage of the main parotid duct, or one of its branches, is often a primary cause of acute parotitis, with further inflammation secondary to bacterial superinfection. The blockage may be from a salivary stone, a mucous plug, or, more rarely, by a tumor, usually benign. Salivary stones (also called sialolithiasis, or salivary duct calculus) are mainly made of calcium, but do not indicate any kind of calcium disorder. Other causes can be duct stricture (narrowing of the duct), infection or injury. Symptoms may include recurrent swelling, pain and aggravation during eating as this is when saliva production is stimulated. Ductal obstruction may cause less saliva flow, which can result in recurrent gland infections.Stones may be diagnosed via X-ray (with a success rate of about 80%), a computed tomography (CT) scan or medical ultrasonography. Stones may be removed by manipulation in the doctors office, or, in the worst cases, by surgery. Lithotripsy, also known as "shock wave" treatment, is best known for its use breaking up kidney stones. Lithotripsy can now be used on salivary stones as well. Ultrasound waves break up the stones, and the fragments flush out of the salivary duct. Diseases of uncertain cause Chronic nonspecific parotitis: This term is generally used for patients in whom no definite cause is found. Episodes may last for several days, paralleling the time course of a bacterial or viral illness. Others may experience episodes that last only a few hours from onset to resolution. Some episodes may last for several weeks. Quiescent periods between episodes last for hours, days, or even years.Recurrent parotitis of childhood: An uncommon syndrome in which recurring episodes clinically resembling mumps. Generally, episodes begin by age 5 years, and virtually all patients become asymptomatic by age 10–15 years. The duration of attacks averages 3–7 days but may last 2–3 weeks in some individuals. The spectrum varies from mild and infrequent attacks to episodes so frequent that they prevent regular school attendance. Local heat applied to the gland, massaging the gland from back to front, and taking penicillin usually cure individual episodes. Treatment of individual infections may prevent injury to the gland parenchyma. Severe disease may be treated by parotidectomy.Sialadenosis (sialosis): In this disorder, both parotid glands may be diffusely enlarged with only modest symptoms. Patients are aged 20–60 years at onset, and the sexes are equally involved. The glands are soft and non-tender. Approximately half of the patients have endocrine disorders such as diabetes, nutritional disorders such as pellagra or kwashiorkor, or have taken drugs such as guanethidine, thioridazine, or isoprenaline.Sarcoidosis: The lungs, skin, and lymph nodes are most often affected, but the salivary glands are involved in approximately 10% of cases. Bilateral firm, smooth, and non-tender parotid enlargement is classic. Xerostomia occasionally occurs. The Heerfordt-Waldenstrom syndrome consists of sarcoidosis with parotid enlargement, fever, anterior uveitis, and facial nerve palsy.IgG4-related sialadenitis: This term refers to IgG4-related disease (IgG4-RD) involving any of the major salivary glands, i.e. parotid or submandibular glands. This is often symmetrical and is usually associated with manifestations of IgG4-RD elsewhere in the body. IgG4-related sialadenitis is particularly associated with involvement of one or both of the lacrimal glands (referred to as IgG4-related dacryo-sialadenitis). Mikuliczs disease, now considered to be a subtype of IgG4-related disease, was a term used when (i) any two of the parotid, submandibular and lacrimal glands were persistently and symmetrically enlarged and (ii) other diseases that may mimic this presentation were excluded. Pneumoparotitis: Air within the ducts of the parotid gland with or without inflammation. The duct orifice normally functions as a valve to prevent air from entering the gland from a pressurized oral cavity. Rarely, an incompetent valve allows insufflation of air into the duct system. Pneumoparotitis most commonly occurs in wind instrument players, glass blowers, and scuba divers.Several lymph nodes reside within the parotid gland as a superficial and deep group of nodes. These nodes may be involved with any process that affects lymph nodes, including bacterial, fungal, viral, and neoplastic processes. Rarely, drugs such as iodides, phenylbutazone, thiouracil, isoproterenol, heavy metals, sulfisoxazole, and phenothiazines cause parotid swelling.Associated with Bulimia: Parotid gland swelling is a common feature of self-induced vomiting. This swelling usually develops 3–4 days after the stopping of chronic excessive self-induced vomiting. The swelling is bilateral, with little tenderness. Causes are not well understood. Ideal treatment should be preventative and can involve medication that increases saliva production (sialagogues), anti-inflammatory medication and the application of hot packs. Occasionally pilocarpine can be used to help resolve the swelling. Masseteric hypertrophy Masseteric hypertrophy (enlargement of the masseter muscles volume) can present as facial swelling in the parotid gland area and may be confused with true parotid gland swelling. The specific cause of masseteric hypertrophy is still unclear, but it may be related to tooth grinding or malocclusion. Treatment options can include surgical removal of some of the muscle and botulinum toxin type A injections. Diagnosis Serum and urinary amylase rise during the first week of parotitis. Treatment Treatment is based on lab investigation report. Notes References Brook I. Acute bacterial suppurative parotitis: microbiology and management. [Journal Article] Journal of Craniofacial Surgery. 14(1):37–40, 2003. Mandel L. Surattanont F. Bilateral parotid swelling: a review. [Review] [160 refs] [Journal Article. Review] Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics. 93(3):221–37, 2002. External links eMedicine

Aarogya, share information about a health condition involving Bladder sphincter dyssynergia

Bladder sphincter dyssynergia

Bladder sphincter dyssynergia (also known as detrusor sphincter dyssynergia (DSD) (the ICS standard terminology agreed 1998) and neurogenic detrusor overactivity (NDO)) is a consequence of a neurological pathology such as spinal injury or multiple sclerosis which disrupts central nervous system regulation of the micturition (urination) reflex resulting in dyscoordination of the detrusor muscles of the bladder and the male or female external urethral sphincter muscles. In normal lower urinary tract function, these two separate muscle structures act in synergistic coordination. But in this neurogenic disorder, the urethral sphincter muscle, instead of relaxing completely during voiding, dyssynergically contracts causing the flow to be interrupted and the bladder pressure to rise. Presentation People with this condition generally experience daytime and night time wetting, urinary retention, and often have a history of urinary tract and bladder infections. Constipation and encopresis are often associated with this condition. Pseudodyssynergia has different causes but presents similarly. Pathology The pathophysiology of the condition results from neuronal plasticity associated with bladder afferents and motor neurons innervating the external urethral sphincter. Treatment Botulinum A toxin is a valuable alternative for patients who do not want surgical methods. References Further reading == External links ==

Aarogya, give me a short description about Emergence delirium

Emergence delirium

Emergence delirium is a condition in which emergence from general anesthesia is accompanied by psychomotor agitation. Some see a relation to pavor nocturnus while others see a relation to the excitement stage of anesthesia. Children The pediatric anesthesia emergence delirium scale may be used to measure the severity of this condition in children. Elderly Elderly people are more likely to experience confusion or problems with thinking following surgery, which can occur up to several days postoperatively. These cognitive problems can last for weeks or months, and can affect the patients’ ability to plan, focus, remember, or undertake activities of daily living. A review of intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery showed little or no difference in postoperative delirium according to the type of anaesthetic maintenance agents from five studies (321 participants). The authors of this review were uncertain whether maintenance of anaesthesia with propofol-based total intravenous anaesthesia (TIVA) or with inhalational agents can affect incidences of postoperative delirium. Epidemiology The overall incidence of emergence delirium is 5.3%, with a significantly greater incidence (12–13%) in children. The incidence of emergence delirium after halothane, isoflurane, sevoflurane or desflurane ranges from 2–55%. Most emergence delirium in the literature describes agitated emergence. Unless a delirium detection tool is used, it is difficult to distinguish if the agitated emergence from anesthesia was from delirium or pain or fear, etc. A research study of 400 adult patients emerging from general anesthesia in the PACU were assessed for delirium using the Confusion Assessment Method for the ICU (CAM-ICU) found rates of emergence delirium of 31% at PACU admission with rates declining to 8% by 1 hour. References Further reading Vlajkovic GP, Sindjelic RP (Jan 2007). "Emergence delirium in children: many questions, few answers". Anesth. Analg. 104 (1): 84–91. doi:10.1213/01.ane.0000250914.91881.a8. PMID 17179249. S2CID 7315961. Lepouse C, Lautner CA, Liu L, Gomis P, Leon A (Jun 2006). "Emergence delirium in adults in the post-anaesthesia care unit". Br. J. Anaesth. 96 (6): 747–53. doi:10.1093/bja/ael094. PMID 16670111. == External links ==

Hello Aarogya, what is Cauda equina syndrome

Cauda equina syndrome

Cauda equina syndrome (CES) is a condition that occurs when the bundle of nerves below the end of the spinal cord known as the cauda equina is damaged. Signs and symptoms include low back pain, pain that radiates down the leg, numbness around the anus, and loss of bowel or bladder control. Onset may be rapid or gradual.The cause is usually a disc herniation in the lower region of the back. Other causes include spinal stenosis, cancer, trauma, epidural abscess, and epidural hematoma. The diagnosis is suspected based on symptoms and confirmed by medical imaging such as MRI or CT scan.CES is generally treated surgically via laminectomy. Sudden onset is regarded as a medical emergency requiring prompt surgical decompression, with delay causing permanent loss of function. Permanent bladder problems, sexual dysfunction or numbness may occur despite surgery. A poor outcome occurs in about 20% of people despite treatment. About 1 in 70,000 people is affected every year. It was first described in 1934. Signs and symptoms Signs and symptoms of cauda equina syndrome include: Severe back pain Saddle anesthesia (see diagram), i.e., anesthesia or paraesthesia involving S3 to S5 dermatomes,: 26  including the perineum, external genitalia and anus; or more descriptively, numbness or "pins-and-needles" sensations of the groin and inner thighs which would contact a saddle when riding a horse. Bladder and bowel dysfunction,: 216  caused by decreased tone of the urinary and anal sphincters. Detrusor weaknesses causing urinary retention and post-void residual incontinence as assessed by bladder scanning the patient after the patient has urinated. Sciatica-type pain on one side or both sides, although pain may be wholly absent Weakness of the muscles of the lower legs (often paraplegia) Achilles (ankle) reflex absent on both sides.: 216  Sexual dysfunction Absent anal reflex and bulbocavernosus reflex Gait disturbanceSevere back pain, saddle anesthesia, urinary or fecal incontinence and sexual dysfunction are considered "red flags", i.e. features which require urgent investigation. Causes After the conus medullaris (near lumbar vertebral levels 1 (L1) and 2 (L2), occasionally lower), the spinal canal contains a bundle of nerve fibers (the cauda equina or "horse-tail") that branches off the lower end of the spinal cord and contains the nerve roots from L1–L5 and S1–S5. The nerve roots from L4–S4 join in the sacral plexus which affects the sciatic nerve, which travels caudally (toward the feet). Compression, trauma or other damage to this region of the spinal canal can result in cauda equina syndrome.The symptoms may also appear as a temporary side-effect of a sacral extra-dural injection. Trauma Direct trauma can also cause cauda equina syndrome. Most common causes include as a complication of lumbar punctures, burst fractures resulting in posterior migration of fragments of the vertebral body, severe disc herniations, spinal anaesthesia involving trauma from catheters and high local anaesthetic concentrations around the cauda equina, penetrating trauma such as knife wounds or ballistic trauma. Spinal stenosis CES can be caused by lumbar spinal stenosis, which is when the diameter of the spinal canal narrows. This could be the result of a degenerative process of the spine (such as osteoarthritis) or a developmental defect which is present at birth. In the most severe cases of spondylolisthesis cauda equina syndrome can result. Inflammatory conditions Chronic spinal inflammatory conditions such as Paget disease, neurosarcoidosis, chronic inflammatory demyelinating polyneuropathy, ankylosing spondylitis, rheumatoid disease of the spine, and chronic tuberculosis can cause it. This is due to the spinal canal narrowing that these kinds of syndromes can produce. Risk factors Individuals most at risk for disc herniation are the most likely to develop CES. Race has little influence with the notable exception that African Americans appear slightly less likely to develop CES than other groups. Middle age also appears to be a notable risk factor, as those populations are more likely to develop a herniated disc; heavy lifting can also be inferred as a risk factor for CES.Other risk factors include obesity and being female. Diagnosis Diagnosis is first suspected clinically based on history and physical exam and usually confirmed by an MRI scan or CT scan, depending on availability. Bladder scanning and loss of catheter sensation can also be used to evaluate bladder dysfunction in suspected cases of cauda equina syndrome and can aid diagnosis before MRI scanning. Early surgery in acute onset of severe cases has been reported to be important. Prevention Early diagnosis of cauda equina syndrome can allow for preventive treatment. Signs that allow early diagnosis include changes in bowel and bladder function and loss of feeling in groin. Changes in sensation can start as pins and needles leading to numbness. Changes in bladder function may be changes to stream or inability to fully empty the bladder. If a person progresses to full retention intervention is less likely to be successful. Management The management of true cauda equina syndrome frequently involves surgical decompression. When cauda equina syndrome is caused by a herniated disk early surgical decompression is recommended.Sudden onset cauda equina syndrome is regarded as a medical/surgical emergency. Surgical decompression by means of laminectomy or other approaches may be undertaken within 6, 24 or 48 hours of symptoms developing if a compressive lesion (e.g., ruptured disc, epidural abscess, tumor or hematoma) is demonstrated. Early treatment may significantly improve the chance that long-term neurological damage will be avoided.Surgery may be required to remove blood, bone fragments, a tumor or tumors, a herniated disc or an abnormal bone growth. If the tumor cannot be removed surgically and is malignant then radiotherapy may be used as an alternative to relieve pressure. Chemotherapy can also be used for spinal neoplasms. If the syndrome is due to an inflammatory condition e.g., ankylosing spondylitis, anti-inflammatory, including steroids can be used as an effective treatment. If a bacterial infection is the cause then an appropriate course of antibiotics can be used to treat it.Cauda equina syndrome can occur during pregnancy due to lumbar disc herniation. The risk of cauda equina syndrome during pregnancy increases with age of the mother. Surgery can still be performed and pregnancy does not adversely affect treatment. Treatment for those with cauda equina can and should be carried out at any time during pregnancy.Lifestyle issues may need to be addressed post-treatment. Issues could include the persons need for physiotherapy and occupational therapy due to lower limb dysfunction. Obesity might also need to be tackled. Bowel and bladder control Rehabilitation of CES depends on the severity of the injury. If permanent damage occurs, then impairment in bladder and bowel control may result. Once surgery is performed, resting is required until the bladder and bowel dysfunction can be assessed. Urinary catheterization may help with bladder control. Gravity and exercise can help control bowel movement (Hodges, 2004). Pelvic floor exercises assist in controlling bowel movements (Pelvic Floor Exercises, 2010). These exercises can be done standing, lying, or on all fours with the knees slightly separated. Full recovery of bowel and bladder control can take as long as two years. Prognosis The prognosis for complete recovery is dependent upon many factors. The most important of these is the severity and duration of compression upon the damaged nerve(s). Generally, the longer the time before intervention to remove the compression causing nerve damage, the greater the damage caused to the nerve(s).Damage can be so severe that nerve regrowth is impossible, and the nerve damage will be permanent. In cases where the nerve has been damaged but is still capable of regrowth, recovery time is widely variable. Surgical intervention with decompression of the cauda equina can assist recovery. Delayed or severe nerve damage can mean up to several years recovery time because nerve growth is exceptionally slow.Review of the literature indicates that around 50–70% of patients have urinary retention (CES-R) on presentation with 30–50% having an incomplete syndrome (CES-I). The latter group, especially if the history is less than a few days, usually requires emergency MRI to confirm the diagnosis followed by prompt decompression. CES-I with its more favourable prognosis may become CES-R at a later stage. Epidemiology Various etiologies of CES include fractures, abscesses, hematomas, and any compression of the relevant nerve roots. Injuries to the thoracolumbar spine will not necessarily result in a clinical diagnosis of CES, but in all such cases it is necessary to consider. Few epidemiological studies of CES have been done in the United States, owing to difficulties such as amassing sufficient cases as well as defining the affected population, therefore this is an area deserving of additional scrutiny.Traumatic spinal cord injuries occur in approximately 40 people per million annually in the United States, resulting from traumas due to motor vehicle accidents, sporting injuries, falls, and other factors. An estimated 10 to 25% of vertebral fractures will result in injury to the spinal cord. Thorough physical examinations are required, as 5 to 15% of trauma patients have fractures that initially go undiagnosed. The most frequent injuries of the thoracolumbar region are to the conus medullaris and the cauda equina, particularly between T12 and L2. Of these two syndromes, CES is the more common. CES mainly affects middle-aged individuals, particularly those in their forties and fifties, and presents more often in men. It is not a typical diagnosis, developing in only 4 to 7 out of every 10,000 to 100,000 patients, and is more likely to occur proximally. Disc herniation is reportedly the most common cause of CES, and it is thought that 1 to 2% of all surgical disc herniation cases result in CES. CES is often concurrent with congenital or degenerative diseases and represents a high cost of care to those admitted to the hospital for surgery. Hospital stays generally last 4 to 5 days, and cost an average of $100,000 to $150,000. Delays in care for cauda equina results in the English NHS paying about £23 million a year in compensation. In animals Degenerative lumbosacral stenosis (DLSS), also known as cauda equina syndrome, is a pathologic degeneration in the lumbosacral disk in dogs. DLSS affects the articulation, nerve progression, and tissue and joint connections of the disk. This degeneration causes compressions in soft tissues and nerve root locations in the caudal area of the medulla, causing neuropathic pain in the lumbar vertebrae. References External links 06-093c. at Merck Manual of Diagnosis and Therapy Home Edition

Aarogya what is Emotional disturbance

Emotional disturbance

Emotional disturbance may refer to: Emotional and behavioral disorders, most frequently used in an educational context Mental disorders, especially those involving emotions or emotional disorders Emotional trauma Emotional distress Mania and depression Anxiety, fear, extreme sadness or anger, and other emotions that may disturb the mental state of an individual

Aarogya, could you share information about a health condition involving Freckle

Freckle

Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that overproduce melanin granules (melanosomes) changing the coloration of the outer skin cells (keratinocytes). As such, freckles are different from lentigines and moles, which are caused by accumulation of melanocytes in a small area. Freckles can appear on all types of skin tones. Of the six Fitzpatrick skin types, they are most common on skin tones 1 and 2, which usually belong to North Europeans. However, it can also be found on people all over the world. Biology The formation of freckles is caused by exposure to sunlight. The exposure to UV-B radiation activates melanocytes to increase melanin production, which can cause freckles to become darker and more visible. This means that one who has never developed freckles may develop them suddenly following extended exposure to sunlight. Freckles are predominantly found on the face, although they may appear on any skin exposed to the sun, such as arms or shoulders. Heavily distributed concentrations of melanin may cause freckles to multiply and cover an entire area of skin, such as the face. Freckles are rare on infants, and more commonly found on children before puberty. Upon exposure to the sun, freckles will reappear if they have been altered with creams or lasers and not protected from the sun, but do fade with age in some cases. Freckles are not a skin disorder, but people with freckles generally have a lower concentration of photo-protective melanin, and are therefore more susceptible to the harmful effects of UV radiation. It is suggested that people whose skin tends to freckle should avoid overexposure to sun and use sunscreen. Genetics The presence of freckles is related to rare alleles of the MC1R gene, though it does not differentiate whether an individual will have freckles if they have one or even two copies of this gene. Also, individuals with no copies of the MC1R do sometimes display freckles. Even so, individuals with a high number of freckling sites have one or more of variants of the MC1R gene. Of the variants of the MC1R gene Arg151Cys, Arg160Trp, and Asp294His are the most common in the freckled subjects. The MC1R gene is also associated with red hair more strongly than with freckles. Most red-haired individuals have two variants of the MC1R gene and almost all have one. The variants that cause red hair are the same that cause freckling. Freckling can also be found in areas, such as Japan, where red hair is not seen. These individuals have the variant Val92Met which is also found in Europeans, although it has minimal effects on their pigmentation. The R162Q allele has a disputed involvement in freckling.The variants of the MC1R gene that are linked with freckles started to emerge in the human genotype when humans started to leave Africa. The variant Val92Met arose somewhere between 250,000 and 100,000 years ago, long enough for this gene to be carried by humans into central Asia. Arg160Trp is estimated to have arisen around 80,000 years ago while Arg151Cys and Asp294His have been estimated to arise around 30,000 years ago. The wide variation of the MC1R gene exists in people of European descent because of the lack of strong environmental pressures on the gene. The original allele of MC1R is coded for dark skin with a high melanin content in the cells. The high melanin content is protective in areas of high UV light exposure. The need was less as humans moved into higher latitudes where incoming sunlight has lower UV light content. The adaptation of lighter skin is needed so that individuals in higher latitudes can still absorb enough UV for the production of vitamin D. Freckled individuals tend to tan less and have very light skin, an adaptation to allow individuals that expressed these genes to synthesise sufficient vitamin D. Types Ephelides describes a freckle that is flat and light brown or red and fades with a reduction of sun exposure. Ephelides are more common in those with light complexions, although they are found on people with a variety of skin tones. The regular use of sunblock can inhibit their development. Liver spots (also known as sunspots and lentigines) look like large freckles, but they form after years of exposure to the sun. Liver spots are more common in older people. See also Beauty mark List of Mendelian traits in humans Melanocortin 1 receptor Mole References External links MedicineNet.com: Freckles Ephelides (Freckles) at eMedicine

Hi Aarogya, explain a situation where Facial nerve paralysis occurs

Facial nerve paralysis

Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial nerve paralysis. The most common is Bells palsy, a disease of unknown cause that may only be diagnosed by exclusion of identifiable serious causes. Signs and symptoms Facial nerve paralysis is characterised by facial weakness, usually only in one side of the face, with other symptoms possibly including loss of taste, hyperacusis and decreased salivation and tear secretion. Other signs may be linked to the cause of the paralysis, such as vesicles in the ear, which may occur if the facial palsy is due to shingles. Symptoms may develop over several hours. : 1228  Acute facial pain radiating from the ear may precede the onset of other symptoms. : 2585 Causes Bells palsy Bells palsy is the most common cause of acute facial nerve paralysis. There is no known cause of Bells palsy, although it has been associated with herpes simplex infection. Bells palsy may develop over several days, and may last several months, in the majority of cases recovering spontaneously. It is typically diagnosed clinically, in patients with no risk factors for other causes, without vesicles in the ear, and with no other neurological signs. Recovery may be delayed in the elderly, or those with a complete paralysis. Bells palsy is often treated with corticosteroids. Infection Lyme disease, an infection caused by Borrelia burgdorferi bacteria and spread by ticks, can account for about 25% of cases of facial palsy in areas where Lyme disease is common. In the U.S., Lyme is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota, but it is expanding into other areas. The first sign of about 80% of Lyme infections, typically one or two weeks after a tick bite, is usually an expanding rash that may be accompanied by headaches, body aches, fatigue, or fever. In up to 10-15% of Lyme infections, facial palsy appears several weeks later, and may be the first sign of infection that is noticed, as the Lyme rash typically does not itch and is not painful. Lyme disease is treated with antibiotics.Reactivation of herpes zoster virus, as well as being associated with Bells palsy, may also be a direct cause of facial nerve palsy. Reactivation of latent virus within the geniculate ganglion is associated with vesicles affecting the ear canal, and termed Ramsay Hunt syndrome type II. In addition to facial paralysis, symptoms may include ear pain and vesicles, sensorineural hearing loss, and vertigo. Management includes antiviral drugs and oral steroids. Otitis media is an infection in the middle ear, which can spread to the facial nerve and inflame it, causing compression of the nerve in its canal. Antibiotics are used to control the otitis media, and other options include a wide myringotomy (an incision in the tympanic membrane) or decompression if the patient does not improve. Chronic otitis media usually presents in an ear with chronic discharge (otorrhea), or hearing loss, with or without ear pain (otalgia). Once suspected, there should be immediate surgical exploration to determine if a cholesteatoma has formed as this must be removed if present. Inflammation from the middle ear can spread to the canalis facialis of the temporal bone - through this canal travels the facial nerve together with the statoacoustisus nerve. In the case of inflammation the nerve is exposed to edema and subsequent high pressure, resulting in a periferic type palsy. Trauma In blunt trauma, the facial nerve is the most commonly injured cranial nerve. Physical trauma, especially fractures of the temporal bone, may also cause acute facial nerve paralysis. Understandably, the likelihood of facial paralysis after trauma depends on the location of the trauma. Most commonly, facial paralysis follows temporal bone fractures, though the likelihood depends on the type of fracture. Transverse fractures in the horizontal plane present the highest likelihood of facial paralysis (40-50%). Patients may also present with blood behind the tympanic membrane, sensory deafness, and vertigo; the latter two symptoms due to damage to vestibulocochlear nerve and the inner ear. Longitudinal fracture in the vertical plane present a lower likelihood of paralysis (20%). Patients may present with blood coming out of the external auditory meatus), tympanic membrane tear, fracture of external auditory canal, and conductive hearing loss. In patients with mild injuries, management is the same as with Bells palsy – protect the eyes and wait. In patients with severe injury, progress is followed with nerve conduction studies. If nerve conduction studies show a large (>90%) change in nerve conduction, the nerve should be decompressed. The facial paralysis can follow immediately the trauma due to direct damage to the facial nerve, in such cases a surgical treatment may be attempted. In other cases the facial paralysis can occur a long time after the trauma due to oedema and inflammation. In those cases steroids can be a good help. Tumors A tumor compressing the facial nerve anywhere along its complex pathway can result in facial paralysis. Common culprits are facial neuromas, congenital cholesteatomas, hemangiomas, acoustic neuromas, parotid gland neoplasms, or metastases of other tumours.Often, since facial neoplasms have such an intimate relationship with the facial nerve, removing tumors in this region becomes perplexing as the physician is unsure how to manage the tumor without causing even more palsy. Typically, benign tumors should be removed in a fashion that preserves the facial nerve, while malignant tumors should always be resected along with large areas of tissue around them, including the facial nerve. While this will inevitably lead to heightened paralysis, safe removal of a malignant neoplasm is worth the often treatable palsy that follows. In the best case scenario, paralysis can be corrected with techniques including hypoglossal-facial nerve anastomosis, end-to-end nerve repair, cross facial nerve grafting, or muscle transfer/transposition techniques, such as the gracilis free muscle transfer. Patients with facial nerve paralysis resulting from tumours usually present with a progressive, twitching paralysis, other neurological signs, or a recurrent Bells palsy-type presentation. The latter should always be suspicious, as Bells palsy should not recur. A chronically discharging ear must be treated as a cholesteatoma until proven otherwise; hence, there must be immediate surgical exploration. Computed tomography (CT) or magnetic resonance (MR) imaging should be used to identify the location of the tumour, and it should be managed accordingly. Other neoplastic causes include leptomeningeal carcinomatosis. Stroke Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. Unlike peripheral facial palsy, central facial palsy does not affect the forehead, because the forehead is served by nerves coming from both motor cortexes. Other Other causes may include: Diabetes mellitus Facial nerve paralysis, sometimes bilateral, is a common manifestation of sarcoidosis of the nervous system, neurosarcoidosis. Bilateral facial nerve paralysis may occur in Guillain–Barré syndrome, an autoimmune condition of the peripheral nervous system. Moebius syndrome is a bilateral facial paralysis resulting from the underdevelopment of the VII cranial nerve (facial nerve), which is present at birth. The VI cranial nerve, which controls lateral eye movement, is also affected, so people with Moebius syndrome cannot form facial expression or move their eyes from side to side. Moebius syndrome is extremely rare, and its cause or causes are not known. Facial piercings, namely eyebrow piercings or tongue piercings, can in very rare cases cause damage to the facial nerve. Diagnosis A medical history and physical examination, including a neurological examination, are needed for diagnosis. The first step is to observe what parts of the face do not move normally when the person tries to smile, blink, or raise the eyebrows. If the forehead wrinkles normally, a diagnosis of central facial palsy is made, and the person should be evaluated for stroke. Otherwise, the diagnosis is peripheral facial palsy, and its cause needs to be identified, if possible. Ramsey Hunts syndrome causes pain and small blisters in the ear on the same side as the palsy. Otitis media, trauma, or post-surgical complications may alternatively become apparent from history and physical examination. If there is a history of trauma, or a tumour is suspected, a CT scan or MRI may be used to clarify its impact. Blood tests or x-rays may be ordered depending on suspected causes. The likelihood that the facial palsy is caused by Lyme disease should be estimated, based on recent history of outdoor activities in likely tick habitats during warmer months, recent history of rash or symptoms such as headache and fever, and whether the palsy affects both sides of the face (much more common in Lyme than in Bells palsy). If that likelihood is more than negligible, a serological test for Lyme disease should be performed. If the test is positive, the diagnosis is Lyme disease. If no cause is found, the diagnosis is Bells Palsy. Classification Facial nerve paralysis may be divided into supranuclear and infranuclear lesions. In a clinical setting, other commonly used classifications include: intra-cranial and extra-cranial; acute, subacute and chronic duration. Supranuclear and nuclear lesions Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. These are corticobulbar fibers travelling in internal capsule. Infranuclear lesions Infranuclear lesions refer to the majority of causes of facial palsy. Treatment If an underlying cause has been found for the facial palsy, it should be treated. If it is estimated that the likelihood that the facial palsy is caused by Lyme disease exceeds 10%, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease. All other patients should be treated with corticosteroids and, if the palsy is severe, antivirals. Facial palsy is considered severe if the person is unable to close the affected eye completely or the face is asymmetric even at rest. Corticosteroids initiated within three days of Bells palsy onset have been found to increase chances of recovery, reduce time to recovery, and reduce residual symptoms in case of incomplete recovery. However, for facial palsy caused by Lyme disease, corticosteroids have been found in some studies to harm outcomes. Other studies have found antivirals to possibly improve outcomes relative to corticosteroids alone for severe Bells palsy. In those whose blinking is disrupted by the facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping. References == External links ==

Do you know what is Seminoma, Aarogya

Seminoma

A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in early stages.Testicular seminoma originates in the germinal epithelium of the seminiferous tubules. About half of germ cell tumors of the testicles are seminomas. Treatment usually requires removal of one testicle. However, fertility usually isnt affected. All other sexual functions will remain intact. Signs and symptoms The average age of diagnosis is between 35 and 50 years. This is about 5 to 10 years older than men with other germ cell tumors of the testes. In most cases, they produce masses that are readily felt on testicular self-examination; however, in up to 11 percent of cases, there may be no mass able to be felt, or there may be testicular atrophy. Testicular pain is reported in up to one fifth of cases. Low back pain may occur after metastasis to the retroperitoneum.Some cases of seminoma can present as a primary tumour outside the testis, most commonly in the mediastinum. In the ovary, the tumor is called a dysgerminoma, and in non-gonadal sites, particularly the central nervous system, it is called a germinoma. Diagnosis Blood tests may detect the presence of placental alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos) in fifty percent of cases. However, Alk Phos cannot usefully stand alone as a marker for seminoma and contributes little to follow-up, due to its rise with smoking. Human chorionic gonadotropin (hCG) may be elevated in some cases, but this correlates more to the presence of trophoblast cells within the tumour than to the stage of the tumour. A classical or pure seminoma by definition does not cause an elevated serum alpha fetoprotein. Lactate dehydrogenase (LDH) may be the only marker that is elevated in some seminomas. The degree of elevation in the serum LDH has prognostic value in advanced seminoma.The cut surface of the tumour is fleshy and lobulated, and varies in colour from cream to tan to pink. The tumour tends to bulge from the cut surface, and small areas of hemorrhage may be seen. These areas of hemorrhage usually correspond to trophoblastic cell clusters within the tumour.Microscopic examination shows that seminomas are usually composed of either a sheet-like or lobular pattern of cells with a fibrous stromal network. The fibrous septa almost always contain focal lymphocyte inclusions, and granulomas are sometimes seen. The tumour cells themselves typically have abundant clear to pale pink cytoplasm containing abundant glycogen, which is demonstrable with a periodic acid-Schiff (PAS) stain. The nuclei are prominent and usually contain one or two large nucleoli, and have prominent nuclear membranes. Foci of syncytiotrophoblastic cells may be present in varied amounts. The adjacent testicular tissue commonly shows intratubular germ cell neoplasia, and may also show variable spermatocytic maturation arrest. Relation to spermatocytic tumor Spermatocytic tumors are not considered a subtype of seminoma and unlike other germ cell tumours do not arise from intratubular germ cell neoplasia. Treatment Intratesticular masses that appear suspicious on an ultrasound should be treated with an inguinal orchiectomy. The pathology of the removed testicle and spermatic cord indicate the presence of the seminoma and assist in the staging. Tumors with both seminoma and nonseminoma elements or that occur with the presence of AFP should be treated as nonseminomas. Abdominal CT or MRI scans as well as chest imaging are done to detect for metastasis. The analysis of tumor markers also helps in staging.The preferred treatment for most forms of stage 1 seminoma is active surveillance. Stage 1 seminoma is characterized by the absence of clinical evidence of metastasis. Active surveillance consists of periodic history and physical examinations, tumor marker analysis, and radiographic imaging. Around 85-95% of these cases will require no further treatment. Modern radiotherapy techniques as well as one or two cycles of single-agent carboplatin have been shown to reduce the risk of relapse, but carry the potential of causing delayed side effects. Regardless of treatment strategy, stage 1 seminoma has nearly a 100% cure rate.Stage 2 seminoma is indicated by the presence of retroperitoneal metastasis. Cases require radiotherapy or, in advanced cases, combination chemotherapy. Large residual masses found after chemotherapy may require surgical resection. Second-line treatment is the same as for nonseminomas.Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols. References == External links ==

Aarogya, What does Acute hemorrhagic edema of infancy mean

Acute hemorrhagic edema of infancy

Acute hemorrhagic edema of infancy is a skin condition that affects children under the age of two with a recent history of upper respiratory illness, a course of antibiotics, or both.: 833  The disease was first described in 1938 by Finkelstein and later by Seidlmayer as "Seidlmayer cockade purpura". See also Cutaneous small-vessel vasculitis List of cutaneous conditions Henoch–Schönlein purpura References == External links ==

Hey Aarogya , Do you know what is Livedo reticularis,

Livedo reticularis

Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by reduction in blood flow through the arterioles that supply the cutaneous capillaries, resulting in deoxygenated blood showing as blue discoloration. This can be a secondary effect of a condition that increases a persons risk of forming blood clots, including a wide array of pathological and nonpathological conditions. Examples include hyperlipidemia, microvascular hematological or anemia states, nutritional deficiencies, hyper- and autoimmune diseases, and drugs/toxins. The condition may be normal or related to more severe underlying pathology. Its differential diagnosis is broadly divided into possible blood diseases, autoimmune (rheumatologic) diseases, cardiovascular diseases, cancers, and endocrine disorders. It can usually (in 80% of cases) be diagnosed by biopsy.It may be aggravated by exposure to cold, and occurs most often in the lower extremities.The conditions name derives from the Latin livere which means bluish, and reticular which refers to the net-like pattern. Causes A number of conditions may cause the appearance of livedo reticularis: Cutis marmorata telangiectatica congenita, a rare congenital condition Sneddon syndrome – association of livedoid vasculitis and systemic vascular disorders, such as strokes, due to underlying genetic cause Idiopathic livedo reticularis – the most common form of livedo reticularis, completely benign condition of unknown cause affecting mostly young women during the winter: It is a lacy purple appearance of skin in extremities due to sluggish venous blood flow. It may be mild, but ulceration may occur later in the summer. Secondary livedo reticularis: Vasculitis autoimmune conditions: Livedoid vasculitis – with painful ulceration occurring in the lower legs Polyarteritis nodosa Systemic lupus erythematosus Dermatomyositis Rheumatoid arthritis Lymphoma Pancreatitis Chronic pancreatitis Tuberculosis Drug-related: Adderall (side effect) Amantadine (side effect) Bromocriptine (side effect) Beta interferon treatment, e.g. in multiple sclerosis Livedo reticularis associated with rasagiline Methylphenidate and dextroamphetamine-induced peripheral vasculopathy Gefitinib Obstruction of capillaries: Cryoglobulinaemia – proteins in the blood that clump together in cold conditions Antiphospholipid syndrome due to small blood clots Hypercalcaemia (raised blood calcium levels which may be deposited in the capillaries) Haematological disorders of polycythaemia rubra vera or thrombocytosis (excessive red cells or platelets) Infections (infective endocarditis, syphilis, tuberculosis, Lyme disease) Associated with acute kidney injury due to cholesterol emboli status after cardiac catheterization Arteriosclerosis (cholesterol emboli) and homocystinuria (due to Chromosome 21 autosomal recessive Cystathionine beta synthase deficiency) Intra-arterial injection (especially in drug addicts) Ehlers-Danlos syndrome – connective tissue disorder, often with many secondary conditions, may be present in all types Pheochromocytoma Livedoid vasculopathy and its association with factor V Leiden mutation FILS syndrome (polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature) Primary hyperoxaluria, oxalosis (oxalate vasculopathy) Cytomegalovirus infection (very rare clinical form, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes) Generalized livedo reticularis induced by silicone implants for soft tissue augmentation As a rare skin finding in children with Down syndrome Idiopathic livedo reticularis with polyclonal IgM hypergammopathy CO2 angiography (rare, reported case) A less common skin lesion of Churg–Strauss syndrome Erythema nodosum-like cutaneous lesions of sarcoidosis showing livedoid changes in a patient with sarcoidosis and Sjögrens syndrome Livedo vasculopathy associated with IgM antiphosphatidylserine-prothrombin complex antibody Livedo vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity and prothrombin G20210A heterozygosity As a first sign of metastatic breast carcinoma (very rare) Livedo reticularis associated with renal cell carcinoma (rare) Buergers disease (as an initial symptom) As a rare manifestation of Graves hyperthyroidism Associated with pernicious anaemia Moyamoya disease (a rare, chronic cerebrovascular occlusive disease of unknown cause, characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages) Associated with the use of a midline catheter Familial primary cryofibrinogenemia. Diagnosis Livedo reticularis is diagnosed by its clinical appearance and history. No further test or examination confirms idiopathic livedo reticularis, however, further investigations may be undertaken where an underlying cause is suspected such as skin biopsies, or blood tests for antibodies associated with antiphospholipid syndrome or systemic lupus erythematosus. Treatment Other than identifying and treating any underlying conditions in secondary livedo, idiopathic livedo reticularis may improve with warming the area. See also Livedoid dermatitis Livedo racemosa Perinatal gangrene of the buttock erythema ab igne (AKA livedo recticularis e calore) - a rash caused by prolonged heat exposure (e.g. hot water bottle or heat pad) List of cutaneous conditions References External links DermNet

Hello Aarogya, what is Cardiac arrest

Cardiac arrest

Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that without immediate medical intervention will result within minutes in sudden cardiac death. Cardiopulmonary resuscitation (CPR), and possibly defibrillation are needed until further treatment can be provided. Cardiac arrest results in a rapid loss of consciousness, and breathing may be abnormal or absent.While cardiac arrest may be caused by heart attack or heart failure, these are not the same, and in 15 to 25% of cases there is a non-cardiac cause. Some individuals may experience chest pain, shortness of breath, nausea, an elevated heart rate and feeling light-headed immediately before entering cardiac arrest.The most common cause of cardiac arrest is an underlying heart problem like coronary artery disease which decreases the amount of oxygenated blood supplying the heart muscle. This, in turn, damages the structure of the muscle, which can alter its function. These changes can over time cause ventricular fibrillation (V-fib) which most commonly precedes cardiac arrest. Less common causes include major blood loss, lack of oxygen, very low potassium, electrical injury, heart failure, inherited heart arrhythmias and intense physical exercise. Cardiac arrest is diagnosed by the inability to find a pulse.CPR and defibrillation can reverse a cardiac arrest, leading to return of spontaneous circulation, but without such intervention it will prove fatal. In some cases, cardiac arrest is an anticipated outcome of serious illnesses where death is expected. Treatment for cardiac arrest includes immediate CPR and, if a shockable rhythm is present, defibrillation. Two protocols have been established for CPR: basic life support (BLS) and advanced cardiac life support (ACLS). Among those whose pulses are reestablished, targeted temperature management may improve outcomes. In addition, the care team may initiate measures to protect the patient from brain injury and preserve brain function. In post-resuscitation care, an implantable cardiac defibrillator may be considered to reduce the chance of death from recurrence.In the United States, approximately 535,000 cases occur a year (about 13 per 10,000 people). Of these, 326,000 (61%) experience cardiac arrest outside of a hospital setting, while 209,000 (39%) occur within a hospital. Cardiac arrest becomes more common with age and affects males more often than females.The percentage of people who survive out-of-hospital cardiac arrest with treatment by emergency medical services is about 8%. However, fictional media in the U.S. has often portrayed the immediate survival rate of cardiac arrest to be unreasonably high. This may contribute to misinformed expectations of the resuscitative efforts from the general public with many studies showing the expected survival rate of resuscitative efforts after cardiac arrest exceeding 40–50%. These portrayals may also contribute to a patients or medical decision makers desire to pursue aggressive measures. However, it has been shown that many of the critically ill are less likely to choose resuscitation when given accurate information about its limitations.In the event that cardiopulmonary resuscitation is successful, complete recovery is not guaranteed as many survivors experience an array of disability including partial paralysis, seizures, difficulty with walking, speaking, or memory, limited consciousness, or persistent vegetative state and brain death. Signs and symptoms Cardiac arrest is not preceded by any warning symptoms in approximately 50 percent of people. For individuals who do experience symptoms, the symptoms are usually nonspecific to the cardiac arrest. This can present in the form of new or worsening: chest pain fatigue blackouts dizziness shortness of breath weakness vomitingWhen cardiac arrest is suspected due to signs of unconsciousness or abnormal breathing, a bystander should attempt to feel a pulse for 10 seconds; if no pulse is felt, it should be assumed the victim is in cardiac arrest. As a result of loss of cerebral perfusion (blood flow to the brain), the person will rapidly lose consciousness and can stop breathing. Near-death experiences are reported by 10 to 20 percent of people who survived cardiac arrest, which demonstrates a certain level of cognitive processes that are still active during resuscitation. Risk factors The risk factors for sudden cardiac arrest (SCA) are similar to those of coronary artery disease and include age, cigarette smoking, high blood pressure, high cholesterol, lack of physical exercise, obesity, diabetes, and family history of cardiac disease. A prior episode of sudden cardiac arrest also increases the likelihood of future episodes. A statistical analysis of many of these risk factors determined that approximately 50% of all cardiac arrests occur in 10% of the population perceived to be at greatest risk due to aggregate harm of multiple risk factors demonstrating that cumulative risk of multiple comorbidities exceeds the sum of each risk individually.Previous adverse cardiac events, non-sustained ventricular tachycardia (NSVT), syncope, and left ventricular hypertrophy (LVT) have been shown to predict sudden cardiac death in children. Current cigarette smokers with coronary artery disease were found to have a two to threefold increase in the risk of sudden death between ages 30 and 59. Furthermore, it was found that former smokers risk was closer to that of those who had never smoked.Functional changes in the heart such as reduced ejection fraction or cardiac arrhythmia have been shown to increase the risk of cardiac arrest and act independently from the risk factors previously mentioned. Conditions that produce these functional changes can be acquired following previous cardiac injury, or inherited through familial history of arrhythmogenic disorders.: 828 Causes and mechanisms Sudden cardiac arrest (SCA), or sudden cardiac death (SCD), occur when the heart abruptly begins to beat in an abnormal or irregular rhythm (arrhythmia). Without organized electrical activity in the heart muscle, there is no consistent contraction of the ventricles, which results in the hearts inability to generate an adequate cardiac output (forward pumping of blood from heart to rest of the body). There are many different types of arrhythmias, but the ones most frequently recorded in sudden cardiac arrest are ventricular tachycardia and ventricular fibrillation. Less common causes of dysrhythmias in cardiac arrest include pulseless electrical activity (PEA), bradyarrhythmias or asystole. Such rhythms are seen when there is prolonged cardiac arrest, progression of ventricular fibrillation, or efforts such as defibrillation executed to resuscitate the person. The rhythm changes also appear to have a correlation to the underlying cause of cardiac injury when present (ischemic vs. nonischemic causes).: 831 Sudden cardiac arrest can result from cardiac and non-cardiac causes including the following: Cardiac causes Coronary artery disease Coronary artery disease (CAD), also known as ischemic heart disease, is responsible for 62 to 70 percent of all sudden cardiac deaths. CAD is a much less frequent cause of sudden cardiac death in people under the age of 40. Cases have shown that the most common finding at postmortem examination of sudden cardiac death is chronic high-grade stenosis of at least one segment of a major coronary artery, the arteries that supply the heart muscle with its blood supply. This stenosis is often the result of narrowing and hardening of the arteries following deposition of cholesterol plaques and inflammation over several years. This accumulation and remodeling of the coronary vessels along with other systemic blood vessels characterizes the progression of Atherosclerotic Cardiovascular Disease. When a stable plaque ruptures, it can block the flow of blood and oxygen through small arteries resulting in ischemic injury as a result. The injury to tissue following ischemia can lead to structural and functional changes preventing the heart from continuing normal conduction cycles and altering heart rate.: 829 : 829 Non-atherosclerotic coronary artery abnormalities Abnormalities of the coronary arteries not related to atherosclerosis include congenital coronary artery anomalies (most commonly anomalous origin of left coronary artery from the pulmonary artery), inflammation known as coronary arteritis, embolism, vasospasm, and mechanical abnormalities related to connective tissue diseases or trauma. These conditions account for 10-15% of cardiac arrest and sudden cardiac death.: 829  Coronary arteritis commonly results from a pediatric febrile inflammatory condition known as Kawasaki disease. Other vasculitides can also contribute to increased risk of sudden cardiac death. Embolism, or clotting, of the coronary arteries most commonly occurs from septic emboli secondary to endocarditis with involvement of the aortic valve, tricuspid valve, or prosthetic valves. Coronary vasospasm may result in cardiac arrhythmias, altering the electrical conduction of the heart with a risk of complete cardiac arrest from severe or prolonged rhythm changes. Mechanical abnormalities with associated risk of cardiac arrest may arise from coronary artery dissection which can be attributed to Marfan Syndrome or trauma.: 829 Structural heart disease Structural heart diseases not related to coronary artery disease account for 10% of all sudden cardiac deaths. Examples of these include: cardiomyopathies (hypertrophic, dilated, or arrythmogenic), cardiac rhythm disturbances, myocarditis, hypertensive heart disease, and congestive heart failure. Left ventricular hypertrophy is thought to be a leading cause of sudden cardiac deaths in the adult population. This is most commonly the result of longstanding high blood pressure, or hypertension, which has caused a maladaptive change to the wall of the main pumping chamber of the heart, the left ventricle. Increased blood pressure means that the heart must pump even harder to adequately circulate blood throughout the body. If the heart does this for a prolonged period of time due to uncontrolled hypertension, the left ventricle can hypertrophy (grow larger) in a way that decreases the effectiveness of the heart. Left ventricular hypertrophy can be demonstrated on echocardiogram and electrocardiogram (EKG).A 1999 review of sudden cardiac deaths in the United States found that structural heart diseases accounted for over 30% of sudden cardiac arrests for those under 30 years. A study of military recruits age 18-35 found that this accounted for over 40% of sudden cardiac deaths.Congestive heart failure increases the risk of sudden cardiac death fivefold.Structural abnormalities of the cardiac conduction system (notably the Atrioventricular Node and His-Purkinje system) may predispose an individual to arrhythmias with risk of progressing to sudden cardiac arrest, albeit this risk remains low. Many of these conduction blocks can be treated with internal cardiac defibrillators for those determined to be at high risk due to severity of fibrosis or severe electrophysiologic disturbances.: 833 Inherited arrhythmia syndromes Arrhythmias that are not due to structural heart disease account for 5 to 10% of sudden cardiac arrests. These are frequently caused by genetic disorders that lead to abnormal heart rhythms. The genetic mutations often affect specialized proteins known as ion channels that conduct electrically charged particles across the cell membrane, and this group of conditions are therefore often referred to as channelopathies. Examples of these inherited arrhythmia syndromes include Long QT syndrome (LQTS), Brugada Syndrome, Catecholaminergic polymorphic ventricular tachycardia, and Short QT syndrome. Many are also associated with environmental or neurogenic triggers such as response to loud sounds that can initiate lethal arrhythmias.: 833  Other conditions that promote arrhythmias but are not caused by genetic mutations include Wolff-Parkinson-White syndrome.Long QT syndrome, a condition often mentioned in young peoples deaths, occurs in one of every 5000 to 7000 newborns and is estimated to be responsible for 3000 deaths each year compared to the approximately 300,000 cardiac arrests seen by emergency services. These conditions are a fraction of the overall deaths related to cardiac arrest but represent conditions which may be detected prior to arrest and may be treatable. The symptomatic expression of Long-QT syndrome is quite broad and more often presents with syncope rather than cardiac arrest. However, the risk of cardiac arrest is still present and individuals with family history of sudden cardiac arrests should be screened for LQTS and other treatable causes of lethal arrhythmia. Higher levels of risk for cardiac arrest are associated with female sex, more significant QT prolongation, history of unexplained syncope (fainting spells) or premature sudden cardiac death.: 833  Additionally, individuals with LQTS should avoid certain medications that carry the risk of increasing the severity of this conduction abnormality such as certain anti-arrhythmic, anti-depressant, and quinolone or macrolide antibiotics. Non-cardiac causes Non-cardiac causes accounts for 15 to 25% of cardiac arrests. The most common non-cardiac causes are trauma, major bleeding (gastrointestinal bleeding, aortic rupture, or intracranial hemorrhage), hypovolemic shock, overdose, drowning, and pulmonary embolism. Cardiac arrest can also be caused by poisoning like the stings of certain jellyfish, or through electrocution, like lightning. Reversible causes Other non-cardiac causes of cardiac arrest may result from temporary disturbances in the bodies homeostasis. This may be the result from changes in electrolyte ratios, oxygen saturation, or alterations of other ions influencing the bodys pH. Mnemonic for reversible causes "Hs and Ts" is the name for a mnemonic used to remember the treatable or reversible causes of cardiac arrest. Note: This mnemonic includes causes of cardiac and non-cardiac origin, but all are reversible with appropriate and time-sensitive treatment. HsHypovolemia – A lack of blood volume Hypoxia – A lack of oxygen Hydrogen ions (acidosis) – An abnormal pH in the body Hyperkalemia or hypokalemia – Both increased and decreased potassium can be life-threatening Hypothermia – A low core body temperature Hypoglycemia or hyperglycemia – A low or high blood glucoseTsTablets or toxins such as drug overdose Cardiac tamponade – Fluid building up around the heart Tension pneumothorax – A collapsed lung Thrombosis (myocardial infarction) – A heart attack Thromboembolism (pulmonary embolism) – A blood clot in the lung Traumatic cardiac arrest Children In children, the most common cause of cardiopulmonary arrest is shock or respiratory failure that has not been treated. Heart arrhythmia is not the most common cause in children. When there is a cardiac arrhythmia, it is most often asystole or bradycardia, in contrast to ventricular fibrillation or tachycardia as seen in adults. Other causes can include drugs such as cocaine, methamphetamine, or overdose of medications such as antidepressants in a child who was previously healthy but is now presenting with a dysrhythmia that has progressed to cardiac arrest. Common causes of sudden unexplained cardiac arrest in children include hypertrophic cardiomyopathy, coronary artery abnormalities, and arrhythmias. Mechanism The definitive electrical mechanisms of cardiac arrest, which may arise from any of the functional, structural or physiologic abnormalities mentioned above are characterized by tachyarrhythmic or bradyarrhythmic events that do not result in systole.: 837–838  The tachyarrhythmias can be further classified as Ventricular fibrillation (V-fib) and pulseless or sustained Ventricular tachycardia (V-tach), both of which are rapid and erratic arrhythmias that alter the circulatory pathway such that adequate blood flow cannot be sustained and is inadequate to meet the bodys needs.: 837–838 The mechanism responsible for the majority of sudden cardiac deaths is ventricular fibrillation. Ventricular fibrillation is a tachyarrhythmia characterized by turbulent electrical activity in the ventricular myocardium leading to a heart rate too disorganized and rapid to produce any meaningful cardiac output, thus resulting in insufficient perfusion of the brain and essential organs. In ventricular tacycardia, the heart also beats faster than normal, which may prevent the heart chambers from properly filling with blood. Some of the electrophysiologic mechanisms underpinning ventricular fibrillations include ectopic automaticity, re- entry, and triggered activity. Structural changes in the diseased heart as a result of inherited factors (mutations in ion-channel coding genes for example) cannot explain the suddenness of sudden cardiac death.Both ventricular fibrillation and ventricular tachycardia can result in the heart ineffectively pumping blood to the body. Ventricular tachycardia is characterized by an altered QRS complex and a heart rate greater than 100 beats per minute. When V-tach is sustained (lasts for at least 30 seconds), inadequate blood flow to heart tissue can lead to cardiac arrest.Bradyarrhthmias occur following dissociation of spontaneous electrical conduction and the mechanical function of the heart resulting in pulseless electrical activity (PEA) or through complete absence of electrical activity of the heart resulting in asystole. Similar to the result of tachyarrhthmias, these conditions lead to an inability to sustain adequate blood flow as well, though in the case of bradyarrhthmias, the underlying cause is absence mechanical activity and not rapid beats leading to disorganization.: 837–838 Diagnosis Cardiac arrest is synonymous with clinical death. Historical information and a physical exam can diagnose cardiac arrest and provide information regarding the potential cause and the prognosis. The provider taking the persons clinical history should aim to determine if the episode was observed by anyone else, what time the episode took place, what the person was doing (in particular if there was any trauma), and if there were involvement of drugs. The physical examination portion of diagnosing cardiac arrest focuses on the absence of a pulse. In many cases, lack of a carotid pulse is the gold standard for diagnosing cardiac arrest. Lack of a pulse in the periphery (radial/pedal) may also result from other conditions (e.g. shock), or simply an error on the part of the rescuer. Studies have shown that rescuers may often make a mistake when checking the carotid pulse in an emergency, whether they are healthcare professionals or lay persons.Point-of-care ultrasound (POCUS) is a tool that can be used to examine the movement of the heart and its force of contraction at the person experiencing cardiac arrests bedside. POCUS can accurately diagnose cardiac arrest in hospital settings, overcoming some of the shortcomings of diagnosis through checking the central pulse (carotid arteries or subclavian arteries), as well as detecting movement and contractions of the heart.Using POCUS, clinicians can have limited, two-dimensional views of different parts of the heart during arrest. These images can help clinicians determine whether electrical activity within the heart is pulseless or pseudo-pulseless, as well as help them diagnose the potentially reversible causes of an arrest. Published guidelines from the American Society of Echocardiography, American College of Emergency Physicians, European Resuscitation Council, and the American Heart Association, as well as the 2018 preoperative Advanced Cardiac Life Support guidelines, have recognized the potential benefits of using POCUS in diagnosing and managing cardiac arrest.Owing to the inaccuracy in this method of diagnosis, some bodies such as the European Resuscitation Council (ERC) have de-emphasised its importance. Instead, the current guidelines prompt individuals to begin CPR on any unconscious person who has absent or abnormal breathing. The Resuscitation Council in the United Kingdom stand in line with the ERCs recommendations and those of the American Heart Association. They have suggested that the technique to check carotid pulses should be used only by healthcare professionals with specific training and expertise, and even then that it should be viewed in conjunction with other indicators such as agonal respiration.Various other methods for detecting circulation, and therefore diagnosing cardiac arrest have been proposed. Guidelines following the 2000 International Liaison Committee on Resuscitation (ILCOR) recommendations were for rescuers to look for "signs of circulation", but not specifically the pulse. These signs included coughing, gasping, colour, twitching, and movement. However, in face of evidence that these guidelines were ineffective, the current recommendation of ILCOR is that cardiac arrest should be diagnosed in all casualties who are unconscious and not breathing normally, a similar protocol that of which the European Resuscitation Council has adopted. In a non-acute setting where the patient is expired, diagnosis of cardiac arrest can be done via molecular autopsy or postmortem molecular testing which uses a set of molecular techniques to find the ion channels that are cardiac defective. This could help elucidate the cause of death in the patient. Other physical signs or symptoms can help determine the potential cause of the cardiac arrest. Below is a chart of the clinical findings and signs/symptoms a person may have and a potential cause associated with it. Classifications Clinicians classify cardiac arrest into "shockable" versus "non-shockable", as determined by the EKG rhythm. This refers to whether a particular class of cardiac dysrhythmia is treatable using defibrillation. The two "shockable" rhythms are ventricular fibrillation and pulseless ventricular tachycardia, while the two "non-shockable" rhythms are asystole and pulseless electrical activity. Prevention With the lack of positive outcomes following cardiac arrest, efforts have been spent finding effective strategies to prevent cardiac arrest. With the prime causes of cardiac arrest being ischemic heart disease, efforts to promote a healthy diet, exercise, and smoking cessation are important. For people at risk of heart disease, measures such as blood pressure control, cholesterol lowering, and other medico-therapeutic interventions are used.[1] Of note, however, a Cochrane review published in 2016 found moderate-quality evidence to show that blood pressure-lowering drugs do not actually reduce the risk of sudden cardiac death. Exercise is an effective preventative measure for cardiac arrest in the general population but may be risky for those with pre-existing conditions. The risk of a transient catastrophic cardiac event increases in individuals with heart disease during and immediately after exercise. However, both the lifetime and acute risk of cardiac arrest are decreased in individuals with heart disease that perform regular exercise, suggesting the risks of exercise are outweighed by the benefits. Diet According to a study published in the Journal of the American Heart Association in 2021, diet may be a modifiable risk factor that leads to a lower incidence of sudden cardiac death. The study found that those who fell under the category of having "Southern diets" representing those of "added fats, fried food, eggs, organ and processed meats, and sugar‐sweetened beverages" had a positive association with an increased risk of cardiac arrest, while those deemed following the "Mediterranean diets" of had an inverse relationship regarding the risk of cardiac arrest. The American Heart Association also has diet recommendations here that is aimed to prevent cardiovascular disease. Here, the readers may find broad information regarding healthy eating and some tips on what to look for and what to avoid from grocery stores to restaurant dining.Additionally, marine-derived omega-3 polyunsaturated fatty acids (PUFAs) have been promoted for the prevention of sudden cardiac death due to their postulated ability to lower triglyceride levels, prevent arrhythmias, decrease platelet aggregation, and lower blood pressure. However, according to a systematic review published in 2012, omega-3 PUFA supplementation are not being associated with a lower risk of sudden cardiac death. Code teams In medical parlance, cardiac arrest is referred to as a "code" or a "crash". This typically refers to "code blue" on the hospital emergency codes. A dramatic drop in vital sign measurements is referred to as "coding" or "crashing", though coding is usually used when it results in cardiac arrest, while crashing might not. Treatment for cardiac arrest is sometimes referred to as "calling a code". People in general wards often deteriorate for several hours or even days before a cardiac arrest occurs. This has been attributed to a lack of knowledge and skill amongst ward-based staff, in particular, a failure to carry out measurement of the respiratory rate, which is often the major predictor of a deterioration and can often change up to 48 hours prior to a cardiac arrest. In response to this, many hospitals now have increased training for ward-based staff. A number of "early warning" systems also exist which aim to quantify the persons risk of deterioration based on their vital signs and thus provide a guide to staff. In addition, specialist staff are being used more effectively in order to augment the work already being done at ward level. These include: Crash teams (or code teams) – These are designated staff members with particular expertise in resuscitation who are called to the scene of all arrests within the hospital. This usually involves a specialized cart of equipment (including defibrillator) and drugs called a "crash cart" or "crash trolley". Medical emergency teams – These teams respond to all emergencies, with the aim of treating the people in the acute phase of their illness in order to prevent a cardiac arrest. These teams have been found to decrease the rates of in-hospital cardiac arrest and improve survival. Critical care outreach – As well as providing the services of the other two types of team, these teams are also responsible for educating non-specialist staff. In addition, they help to facilitate transfers between intensive care/high dependency units and the general hospital wards. This is particularly important, as many studies have shown that a significant percentage of patients discharged from critical care environments quickly deteriorate and are re-admitted; the outreach team offers support to ward staff to prevent this from happening. Implantable cardioverter defibrillator An implantable cardioverter defibrillator (ICD) is a battery-powered device that monitors electrical activity in the heart and when an arrhythmia is detected is able to deliver an electrical shock to terminate the abnormal rhythm. ICDs are used to prevent sudden cardiac death (SCD) in those that have survived a prior episode of sudden cardiac arrest (SCA) due to ventricular fibrillation or ventricular tachycardia (secondary prevention). ICDs are also used prophylactically to prevent sudden cardiac death in certain high risk patient populations (primary prevention).Numerous studies have been conducted on the use of ICDs for the secondary prevention of SCD. These studies have shown improved survival with ICDs compared to the use of anti-arrhythmic drugs. ICD therapy is associated with a 50% relative risk reduction in death caused by an arrhythmia and a 25% relative risk reduction in all cause mortality.Primary prevention of SCD with ICD therapy for high-risk patient populations has similarly shown improved survival rates in a number of large studies. The high-risk patient populations in these studies were defined as those with severe ischemic cardiomyopathy (determined by a reduced left ventricular ejection fraction (LVEF)). The LVEF criteria used in these trials ranged from less than or equal to 30% in MADIT-II to less than or equal to 40% in MUSTT. Management Sudden cardiac arrest may be treated via attempts at resuscitation. This is usually carried out based upon basic life support, advanced cardiac life support (ACLS), pediatric advanced life support (PALS), or neonatal resuscitation program (NRP) guidelines. Cardiopulmonary resuscitation Early cardiopulmonary resuscitation (CPR) is essential to surviving cardiac arrest with good neurological function. It is recommended that it be started as soon as possible with minimal interruptions once begun. The components of CPR that make the greatest difference in survival are chest compressions and defibrillating shockable rhythms. After defibrillation, chest compressions should be continued for two minutes before a rhythm check is again done. This is based on a compression rate of 100-120 compressions per minute, a compression depth of 5–6 centimeters into the chest, full chest recoil, and a ventilation rate of 10 breath ventilations per minute. Correctly performed bystander CPR has been shown to increase survival; however, it is performed in less than 30% of out of hospital arrests as of 2007. If high-quality CPR has not resulted in return of spontaneous circulation and the persons heart rhythm is in asystole, discontinuing CPR and pronouncing the persons death is reasonable after 20 minutes. Exceptions to this include certain cases with hypothermia or who have drowned. Some of these cases should have longer and more sustained CPR until they are nearly normothermic. Longer durations of CPR may be reasonable in those who have cardiac arrest while in hospital. Bystander CPR, by the lay public, before the arrival of EMS also improves outcomes.Either a bag valve mask or an advanced airway may be used to help with breathing particularly since vomiting and regurgitation are common, particularly in out-of-hospital cardiac arrest (OHCA). If this occurs, then modification to existing oropharyngeal suction may be required, such as the use of Suction Assisted Laryngoscopy Airway Decontamination. High levels of oxygen are generally given during CPR. Tracheal intubation has not been found to improve survival rates or neurological outcome in cardiac arrest and in the prehospital environment may worsen it. Endotracheal tube and supraglottic airways appear equally useful. When done by EMS 30 compressions followed by two breaths appear better than continuous chest compressions and breaths being given while compressions are ongoing.For bystanders, CPR which involves only chest compressions results in better outcomes as compared to standard CPR for those who have gone into cardiac arrest due to heart issues. Mouth-to-mouth as a means of providing respirations to the patient has been phased out due to the risk of contracting infectious diseases from the patient. Mechanical chest compressions (as performed by a machine) are no better than chest compressions performed by hand. It is unclear if a few minutes of CPR before defibrillation results in different outcomes than immediate defibrillation. If cardiac arrest occurs after 20 weeks of pregnancy someone should pull or push the uterus to the left during CPR. If a pulse has not returned by four minutes emergency Cesarean section is recommended. Defibrillation Defibrillation is indicated if an electric-shockable heart rhythm is present. The two shockable rhythms are ventricular fibrillation and pulseless ventricular tachycardia. In children 2 to 4 J/Kg is recommended.The defibrillation is made by an automated external defibrillator (AED), a portable machine that can be used even by any user because it produces voice instructions that guide the process, automatically checks the victims condition, and applies the correct electric shocks. Some defibrillators even provide feedback on the quality of CPR compressions, encouraging the lay rescuer to press the persons chest hard enough to circulate blood.In addition, there is increasing use of public access defibrillation. This involves placing an automated external defibrillator in public places, and training staff in these areas how to use them. This allows defibrillation to take place prior to the arrival of emergency services and has been shown to lead to increased chances of survival. It has been shown that those who have arrests in remote locations have worse outcomes following cardiac arrest. Medications As of 2016, medications other than epinephrine (adrenaline), while included in guidelines, have not been shown to improve survival to hospital discharge following out-of-hospital cardiac arrest. This includes the use of atropine, lidocaine, and amiodarone. Epinephrine in adults, as of 2019, appears to improve survival but does not appear to improve neurologically normal survival. It is generally recommended every five minutes. Epinephrine acts on the alpha-1 receptor, which in turn increases the blood flow that supplies the heart. This would assist with providing more oxygen to the heart. Based on 2019 guidelines, 1 mg of epinephrine may be administered to patients every 3–5 minutes, but doses higher than 1 mg epinephrine are not recommended for routine use in cardiac arrest. If the patient has a non-shockable rhythm, the epinephrine should be administered as soon as possible. For a shockable rhythm, epinephrine should only be administered after initial defibrillation attempts have failed. Vasopressin overall does not improve or worsen outcomes compared to epinephrine. The combination of epinephrine, vasopressin, and methylprednisolone appears to improve outcomes. Some of the lack of long-term benefit may be related to delays in epinephrine use. While evidence does not support its use in children, guidelines state its use is reasonable. Lidocaine and amiodarone are also deemed reasonable in children with cardiac arrest who have a shockable rhythm. The general use of sodium bicarbonate or calcium is not recommended. The use of calcium in children has been associated with poor neurological function as well as decreased survival. Correct dosing of medications in children is dependent on weight. To minimize time spent calculating medication doses, the use of a Broselow tape is recommended.The 2010 guidelines from the American Heart Association no longer contain the recommendation for using atropine in pulseless electrical activity and asystole for want of evidence for its use. Neither lidocaine nor amiodarone, in those who continue in ventricular tachycardia or ventricular fibrillation despite defibrillation, improves survival to hospital discharge but both equally improve survival to hospital admission.Thrombolytics when used generally may cause harm but may be of benefit in those with a confirmed pulmonary embolism as the cause of arrest. Evidence for use of naloxone in those with cardiac arrest due to opioids is unclear but it may still be used. In those with cardiac arrest due to local anesthetic, lipid emulsion may be used. Targeted temperature management Current international guidelines suggest cooling adults after cardiac arrest using targeted temperature management (TTM), which was previously known as therapeutic hypothermia. People are typically cooled for a 24-hour period, with a target temperature of 32–36 °C (90–97 °F). There are a number of methods used to lower the body temperature, such as applying ice packs or cold-water circulating pads directly to the body, or infusing cold saline. This is followed by gradual rewarming over the next 12 to 24 hrs.Effectiveness of TTM after out-of-hospital cardiac arrest is an area of ongoing study. Pre-hospital TTM after out-of-hospital cardiac arrest has been shown to increase the risk of adverse outcomes. The rates of re-arrest may be higher in people who were treated with pre-hospital TTM, however, more research is needed on the effectiveness and risks of TTM. TTM in post-arrest care has not been found to improve mortality or neurological outcomes. Moreover, TTM may have adverse neurological effects in people who survive post cardiac arrest. Do not resuscitate Some people choose to avoid aggressive measures at the end of life. A do not resuscitate order (DNR) in the form of an advance health care directive makes it clear that in the event of cardiac arrest, the person does not wish to receive cardiopulmonary resuscitation. Other directives may be made to stipulate the desire for intubation in the event of respiratory failure or, if comfort measures are all that are desired, by stipulating that healthcare providers should "allow natural death". Chain of survival Several organizations promote the idea of a chain of survival. The chain consists of the following "links": Early recognition If possible, recognition of illness before the person develops a cardiac arrest will allow the rescuer to prevent its occurrence. Early recognition that a cardiac arrest has occurred is key to survival for every minute a patient stays in cardiac arrest, their chances of survival drop by roughly 10%. Early CPR improves the flow of blood and of oxygen to vital organs, an essential component of treating a cardiac arrest. In particular, by keeping the brain supplied with oxygenated blood, chances of neurological damage are decreased. Early defibrillation is effective for the management of ventricular fibrillation and pulseless ventricular tachycardia Early advanced care Early post-resuscitation care which may include percutaneous coronary interventionIf one or more links in the chain are missing or delayed, then the chances of survival drop significantly. These protocols are often initiated by a code blue, which usually denotes impending or acute onset of cardiac arrest or respiratory failure, although in practice, code blue is often called in less life-threatening situations that require immediate attention from a physician. Other Resuscitation with extracorporeal membrane oxygenation devices has been attempted with better results for in-hospital cardiac arrest (29% survival) than out-of-hospital cardiac arrest (4% survival) in populations selected to benefit most. Cardiac catheterization in those who have survived an out-of-hospital cardiac arrest appears to improve outcomes although high quality evidence is lacking. It is recommended that it is done as soon as possible in those who have had a cardiac arrest with ST elevation due to underlying heart problems.The precordial thump may be considered in those with witnessed, monitored, unstable ventricular tachycardia (including pulseless VT) if a defibrillator is not immediately ready for use, but it should not delay CPR and shock delivery or be used in those with unwitnessed out of hospital arrest. Prognosis The overall chance of survival among those who have cardiac arrest outside hospital is poor, at 10%. Among those who have an out-of-hospital cardiac arrest, 70% occur at home and their survival rate is 6%. For those who have an in-hospital cardiac arrest, the survival rate one year from at least the occurrence of cardiac arrest is estimated to be 13%. One year survival is estimated to be higher in people with cardiac admission diagnoses (39%), when compared to those with non-cardiac admission diagnoses (11%). Among children rates of survival are 3 to 16% in North America. For in hospital cardiac arrest survival to discharge is around 22%. Those who survive to Return-of-Spontaneous-Circulation (ROSC) and hospital admission frequently present with Post-Cardiac Arrest Syndrome which usually presents with neurological injury that can range from mild memory problems to coma.Hypoxic ischemic brain injury is the most detrimental outcome for people suffering a cardiac arrest. Poor neurological outcomes following cardiac arrest are much more prevalent in countries that do not use withdrawal of life support (~50%) as compared to those that do (less than 10%). Most improvements in cognition occur during the first three months following cardiac arrest, with some individuals reporting improvement up to one-year post cardiac arrest. 50 – 70% of cardiac arrest survivors report fatigue as a symptom, making fatigue the most prevalent patient-reported symptom.Prognosis is typically assessed 72 hours or more after cardiac arrest. Rates of survival are better in those who someone saw collapse, got bystander CPR, or had either ventricular tachycardia or ventricular fibrillation when assessed. Survival among those with Vfib or Vtach is 15 to 23%. Women are more likely to survive cardiac arrest and leave hospital than men.A 1997 review found rates of survival to discharge of 14% although different studies varied from 0 to 28%. In those over the age of 70 who have a cardiac arrest while in hospital, survival to hospital discharge is less than 20%. How well these individuals are able to manage after leaving hospital is not clear.The global rate of people who were able to recover from out-of-hospital cardiac arrest after receiving CPR has been found to be approximately 30%, and the rate of survival to discharge from the hospital has been estimated at 9%. Survival to discharge from the hospital is more likely among people whose cardiac arrest was witnessed by a bystander or emergency medical services, who received bystander CPR and among those living in Europe and North America. Relatively lower survival to hospital discharge rates have been observed in Asian countries. Epidemiology The risk of cardiac arrest varies with geographical region, age, and gender. The lifetime risk is three times greater in men (12.3%) than women (4.2%) based on analysis of the Framingham Heart Study. However this gender difference disappeared beyond 85 years of age. Around half of these individuals are younger than 65 years of age. North America Based on death certificates, sudden cardiac death accounts for about 20% of all deaths in the United States. In the United States, approximately 326,000 cases of out-of-hospital and 209,000 cases of in-hospital cardiac arrest occur among adults a year, which works out to be an incidence of approximately 110.8 per 100,000 adults a year. In the United States, during-pregnancy cardiac arrest occurs in about one in twelve-thousand deliveries or 1.8 per 10,000 live births. Rates are lower in Canada. Other regions Non-Western regions of the world have differing incidences. The incidence of sudden cardiac death in China is 41.8 per 100,000 and South India is 39.7 per 100,000. Society and culture Names In many publications the stated or implicit meaning of "sudden cardiac death" is sudden death from cardiac causes. However, sometimes physicians call cardiac arrest "sudden cardiac death" even if the person survives. Thus one can hear mentions of "prior episodes of sudden cardiac death" in a living person.In 2021, the American Heart Association clarified that "heart attack" is often mistakenly used to describe cardiac arrest. While a heart attack refers to death of heart muscle tissue as a result of blood supply loss, cardiac arrest is caused when the hearts electrical system malfunctions. Furthermore, the American Heart Association explains that "if corrective measures are not taken rapidly, this condition progresses to sudden death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing. Sudden cardiac death should not be used to describe events that are not fatal". Slow code A "slow code" is a slang term for the practice of deceptively delivering sub-optimal CPR to a person in cardiac arrest, when CPR is considered to have no medical benefit. A "show code" is the practice of faking the response altogether for the sake of the persons family.Such practices are ethically controversial, and are banned in some jurisdictions. The European Resuscitation Council Guidelines released a statement in 2021 that clinicians are not suggested to participate/take part in "slow codes". According to the American College of Physicians, half-hearted resuscitation efforts are deceptive and should not be performed by physicians or nurses. See also Chain of survival Sudden cardiac death of athletes Post-cardiac arrest syndrome References External links The Center for Resuscitation Science at the Hospital of the University of Pennsylvania

Aarogya, could you share information about a health condition involving Bone marrow failure

Bone marrow failure

Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the bodys tissue. White blood cells fight off infections that enter the body. Bone marrow also contains platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs. Signs and symptoms The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and tend to last longer than normal. Children have a bigger chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent colds can also be symptoms of bone marrow failure. Causes Bone marrow failure in both children and adults can be either inherited or acquired. Inherited bone marrow failure is often the cause in young children, while older children and adults may acquire the disease later in life. A maturation defect in genes is a common cause of inherited bone marrow failure. The most common cause of acquired bone marrow failure is aplastic anemia. Working with chemicals such as benzene could be a factor in causing the illness. Other factors include radiation or chemotherapy treatments, and immune system problems. Diagnosis Treatment The type of treatment depends on the severity of the patients bone marrow failure disease. Blood transfusion is one treatment. Blood is collected from volunteer donors who agree to let doctors draw blood stem cells from their blood or bone marrow for transplantation. Blood that is taken straight from collected blood stem cells is known as peripheral blood stem cell donation. A peripheral stem cell donor must have the same blood type as the patient receiving the blood cells. Once the stem cells are in the patients body through an IV, the cells mature and become blood cells. Before donation, a drug is injected into the donor, which increases the number of stem cells into their body. Feeling cold and lightheaded, having numbness around the mouth and cramping in the hands are common symptoms during the donation process. After the donation, the amount of time for recovery varies for every donor, "But most stem cell donors are able to return to their usual activities within a few days to a week after donation". Epidemiology For those with severe bone marrow failure, the cumulative incidence of resulting stem cell transplantation or death was greater than 70% by individuals 60 years of age. The incidence of bone marrow failure is triphasic: one peak at two to five years during childhood (due to inherited causes), and two peaks in adulthood, between 20 and 25 years old and after 60 years old (from acquired causes).One in ten individuals with bone marrow failure have unsuspected Fanconi anemia (FA). FA is the most common inherited bone marrow failure with an incidence of one to five episodes per million individuals. The carrier frequency for FA is 1 in 200 to 300, however this differs by ethnicity. In Europe and North America, the incidence of acquired aplastic anemia is rare with two episodes per million people each year, yet in Asia rises with 3.9 to 7.4 episodes per million people each year. While acquired aplastic anemia with an unknown cause is rare, it is commonly permanent and life-threatening as half of those with this condition die within the first six months.The prevalence of bone marrow failure is over three times higher in Japan and East Asia than in the United States and Europe. When ones body fails to produce blood cell lines, the morbidity and mortality rate increases. Myelodysplastic syndromes (MDS) is a form of blood cancer found within the bone marrow in which the body no longer produces enough healthy, normal blood cells. MDS are a frequently unrecognized and rare group of bone marrow failure disorders, yet the incidence rate has rose from 143 reported cases in 1973 to approximately 15,000 cases in the United States each year. Although MDS is often under-diagnosed, leading the believed actual incidence rate to be estimated at 35,000 to 55,000 new cases annually. One in three people with MDS progress to acute myeloid leukemia. For lower risk patients, those who do not undergo a bone marrow transplant have an average survival rate of up to six years. However, high-risk patients have a survival rate of approximately five months. History Bone marrow failure is associated with three types of diseases, Fanconi anemia (FA), dyskeratosis congenita, and aplastic anemia. Fanconi anemia is an inherited blood disorder due to abnormal breakages in DNA genes. It is linked to hyperpigmentation, which is the darkening of an area of skin or nails caused by increased melanin. According to Histopathology, "However, in about 30% of FA patients no physical abnormalities are found". Dyskeratosis congenita often affects multiple parts of the body. Individuals with this disorder usually show changes in skin pigmentations, unusual fingernail growth, and mucosa leukoplakia; the inner part of the mouth is encased with white patches that may never resolve. Aplastic anemia happens when bone marrow doesnt produce enough new blood cells throughout the body. Aplastic anemia is an acquired autoimmune disease, which occurs when the immune system mistakenly attacks and destroys healthy body tissue. == References ==

Aarogya, could you share information about a health condition involving Mental disorder

Mental disorder

A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitting, or occur as single episodes. Many disorders have been described, with signs and symptoms that vary widely between specific disorders. Such disorders may be diagnosed by a mental health professional, usually a clinical psychologist or psychiatrist. The causes of mental disorders are often unclear. Theories may incorporate findings from a range of fields. Mental disorders are usually defined by a combination of how a person behaves, feels, perceives, or thinks. This may be associated with particular regions or functions of the brain, often in a social context. A mental disorder is one aspect of mental health. Cultural and religious beliefs, as well as social norms, should be taken into account when making a diagnosis.Services are based in psychiatric hospitals or in the community, and assessments are carried out by mental health professionals such as psychiatrists, psychologists, psychiatric nurses and clinical social workers, using various methods such as psychometric tests but often relying on observation and questioning. Treatments are provided by various mental health professionals. Psychotherapy and psychiatric medication are two major treatment options. Other treatments include lifestyle changes, social interventions, peer support, and self-help. In a minority of cases, there might be involuntary detention or treatment. Prevention programs have been shown to reduce depression.In 2019, common mental disorders around the globe include depression, which affects about 264 million, bipolar disorder, which affects about 45 million, dementia, which affects about 50 million, and schizophrenia and other psychoses, which affects about 20 million people. Neurodevelopmental disorders include intellectual disability and autism spectrum disorders which usually arise in infancy or childhood. Stigma and discrimination can add to the suffering and disability associated with mental disorders, leading to various social movements attempting to increase understanding and challenge social exclusion. Definition The definition and classification of mental disorders are key issues for researchers as well as service providers and those who may be diagnosed. For a mental state to classify as a disorder, it generally needs to cause dysfunction. Most international clinical documents use the term mental "disorder", while "illness" is also common. It has been noted that using the term "mental" (i.e., of the mind) is not necessarily meant to imply separateness from the brain or body. According to DSM-IV, a mental disorder is a psychological syndrome or pattern which is associated with distress (e.g. via a painful symptom), disability (impairment in one or more important areas of functioning), increased risk of death, or causes a significant loss of autonomy; however it excludes normal responses such as grief from loss of a loved one and also excludes deviant behavior for political, religious, or societal reasons not arising from a dysfunction in the individual.DSM-IV predicates the definition with caveats, stating that, as in the case with many medical terms, mental disorder "lacks a consistent operational definition that covers all situations", noting that different levels of abstraction can be used for medical definitions, including pathology, symptomology, deviance from a normal range, or etiology, and that the same is true for mental disorders so that sometimes one type of definition is appropriate, and sometimes another, depending on the situation.In 2013, the American Psychiatric Association (APA) redefined mental disorders in the DSM-5 as "a syndrome characterized by clinically significant disturbance in an individuals cognition, emotion regulation, or behavior that reflects a dysfunction in the psychological, biological, or developmental processes underlying mental functioning." The final draft of ICD-11 contains a very similar definition.The terms "mental breakdown" or "nervous breakdown" may be used by the general population to mean a mental disorder. The terms "nervous breakdown" and "mental breakdown" have not been formally defined through a medical diagnostic system such as the DSM-5 or ICD-10, and are nearly absent from scientific literature regarding mental illness. Although "nervous breakdown" is not rigorously defined, surveys of laypersons suggest that the term refers to a specific acute time-limited reactive disorder, involving symptoms such as anxiety or depression, usually precipitated by external stressors. Many health experts today refer to a nervous breakdown as a mental health crisis. Nervous illness Additionally to the concept of mental disorder, some people have argued for a return to the old-fashioned concept of nervous illness. In How Everyone Became Depressed: The Rise and Fall of the Nervous Breakdown (2013), Edward Shorter, a professor of psychiatry and the history of medicine, says: About half of them are depressed. Or at least that is the diagnosis that they got when they were put on antidepressants. ... They go to work but they are unhappy and uncomfortable; they are somewhat anxious; they are tired; they have various physical pains—and they tend to obsess about the whole business. There is a term for what they have, and it is a good old-fashioned term that has gone out of use. They have nerves or a nervous illness. It is an illness not just of mind or brain, but a disorder of the entire body. ... We have a package here of five symptoms—mild depression, some anxiety, fatigue, somatic pains, and obsessive thinking. ... We have had nervous illness for centuries. When you are too nervous to function ... it is a nervous breakdown. But that term has vanished from medicine, although not from the way we speak.... The nervous patients of yesteryear are the depressives of today. That is the bad news.... There is a deeper illness that drives depression and the symptoms of mood. We can call this deeper illness something else, or invent a neologism, but we need to get the discussion off depression and onto this deeper disorder in the brain and body. That is the point. In eliminating the nervous breakdown, psychiatry has come close to having its own nervous breakdown. Nerves stand at the core of common mental illness, no matter how much we try to forget them. "Nervous breakdown" is a pseudo-medical term to describe a wealth of stress-related feelings and they are often made worse by the belief that there is a real phenomenon called "nervous breakdown". Classifications There are currently two widely established systems that classify mental disorders: ICD-11 Chapter 06: Mental, behavioural or neurodevelopmental disorders, part of the International Classification of Diseases produced by the WHO (in effect since 1 January 2022). Diagnostic and Statistical Manual of Mental Disorders (DSM-5) produced by the APA since 1952.Both of these list categories of disorder and provide standardized criteria for diagnosis. They have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be used in non-western cultures, for example, the Chinese Classification of Mental Disorders, and other manuals may be used by those of alternative theoretical persuasions, such as the Psychodynamic Diagnostic Manual. In general, mental disorders are classified separately from neurological disorders, learning disabilities or intellectual disability. Unlike the DSM and ICD, some approaches are not based on identifying distinct categories of disorder using dichotomous symptom profiles intended to separate the abnormal from the normal. There is significant scientific debate about the relative merits of categorical versus such non-categorical (or hybrid) schemes, also known as continuum or dimensional models. A spectrum approach may incorporate elements of both. In the scientific and academic literature on the definition or classification of mental disorder, one extreme argues that it is entirely a matter of value judgements (including of what is normal) while another proposes that it is or could be entirely objective and scientific (including by reference to statistical norms). Common hybrid views argue that the concept of mental disorder is objective even if only a "fuzzy prototype" that can never be precisely defined, or conversely that the concept always involves a mixture of scientific facts and subjective value judgments. Although the diagnostic categories are referred to as disorders, they are presented as medical diseases, but are not validated in the same way as most medical diagnoses. Some neurologists argue that classification will only be reliable and valid when based on neurobiological features rather than clinical interview, while others suggest that the differing ideological and practical perspectives need to be better integrated.The DSM and ICD approach remains under attack both because of the implied causality model and because some researchers believe it better to aim at underlying brain differences which can precede symptoms by many years. Dimensional models The high degree of comorbidity between disorders in categorical models such as the DSM and ICD have led some to propose dimensional models. Studying comorbidity between disorders have demonstrated two latent (unobserved) factors or dimensions in the structure of mental disorders that are thought to possibly reflect etiological processes. These two dimensions reflect a distinction between internalizing disorders, such as mood or anxiety symptoms, and externalizing disorders such as behavioral or substance use symptoms. A single general factor of psychopathology, similar to the g factor for intelligence, has been empirically supported. The p factor model supports the internalizing-externalizing distinction, but also supports the formation of a third dimension of thought disorders such as schizophrenia. Biological evidence also supports the validity of the internalizing-externalizing structure of mental disorders, with twin and adoption studies supporting heritable factors for externalizing and internalizing disorders. A leading dimensional model is the Hierarchical Taxonomy of Psychopathology. Disorders There are many different categories of mental disorder, and many different facets of human behavior and personality that can become disordered. Anxiety disorder An anxiety disorder is anxiety or fear that interferes with normal functioning may be classified as an anxiety disorder. Commonly recognized categories include specific phobias, generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder and post-traumatic stress disorder. Mood disorder Other affective (emotion/mood) processes can also become disordered. Mood disorder involving unusually intense and sustained sadness, melancholia, or despair is known as major depression (also known as unipolar or clinical depression). Milder, but still prolonged depression, can be diagnosed as dysthymia. Bipolar disorder (also known as manic depression) involves abnormally "high" or pressured mood states, known as mania or hypomania, alternating with normal or depressed moods. The extent to which unipolar and bipolar mood phenomena represent distinct categories of disorder, or mix and merge along a dimension or spectrum of mood, is subject to some scientific debate. Psychotic disorder Patterns of belief, language use and perception of reality can become dysregulated (e.g., delusions, thought disorder, hallucinations). Psychotic disorders in this domain include schizophrenia, and delusional disorder. Schizoaffective disorder is a category used for individuals showing aspects of both schizophrenia and affective disorders. Schizotypy is a category used for individuals showing some of the characteristics associated with schizophrenia, but without meeting cutoff criteria. Personality disorder Personality—the fundamental characteristics of a person that influence thoughts and behaviors across situations and time—may be considered disordered if judged to be abnormally rigid and maladaptive. Although treated separately by some, the commonly used categorical schemes include them as mental disorders, albeit on a separate axis II in the case of the DSM-IV. A number of different personality disorders are listed, including those sometimes classed as eccentric, such as paranoid, schizoid and schizotypal personality disorders; types that have described as dramatic or emotional, such as antisocial, borderline, histrionic or narcissistic personality disorders; and those sometimes classed as fear-related, such as anxious-avoidant, dependent, or obsessive-compulsive personality disorders. Personality disorders, in general, are defined as emerging in childhood, or at least by adolescence or early adulthood. The ICD also has a category for enduring personality change after a catastrophic experience or psychiatric illness. If an inability to sufficiently adjust to life circumstances begins within three months of a particular event or situation, and ends within six months after the stressor stops or is eliminated, it may instead be classed as an adjustment disorder. There is an emerging consensus that personality disorders, similar to personality traits in general, incorporate a mixture of acute dysfunctional behaviors that may resolve in short periods, and maladaptive temperamental traits that are more enduring. Furthermore, there are also non-categorical schemes that rate all individuals via a profile of different dimensions of personality without a symptom-based cutoff from normal personality variation, for example through schemes based on dimensional models. Eating disorder Eating disorders involve disproportionate concern in matters of food and weight. Categories of disorder in this area include anorexia nervosa, bulimia nervosa, exercise bulimia or binge eating disorder. Sleep disorder Sleep disorders are associated with disruption to normal sleep patterns. A common sleep disorder is insomnia, which is described as difficulty falling and/or staying asleep. Other sleep disorders include narcolepsy, sleep apnea, REM sleep behavior disorder, chronic sleep deprivation, and restless leg syndrome. Narcolepsy is a condition of extreme tendencies to fall asleep whenever and wherever. People with narcolepsy feel refreshed after their random sleep, but eventually get sleepy again. Narcolepsy diagnosis requires an overnight stay at a sleep center for analysis, during which doctors ask for a detailed sleep history and sleep records. Doctors also use actigraphs and polysomnography. Doctors will do a multiple sleep latency test, which measures how long it takes a person to fall asleep.Sleep apnea, when breathing repeatedly stops and starts during sleep, can be a serious sleep disorder. Three types of sleep apnea include obstructive sleep apnea, central sleep apnea, and complex sleep apnea. Sleep apnea can be diagnosed at home or with polysomnography at a sleep center. An ear, nose, and throat doctor may further help with the sleeping habits. Sexuality related Sexual disorders include dyspareunia and various kinds of paraphilia (sexual arousal to objects, situations, or individuals that are considered abnormal or harmful to the person or others). Other Impulse control disorder: People who are abnormally unable to resist certain urges or impulses that could be harmful to themselves or others, may be classified as having an impulse control disorder, and disorders such as kleptomania (stealing) or pyromania (fire-setting). Various behavioral addictions, such as gambling addiction, may be classed as a disorder. Obsessive-compulsive disorder can sometimes involve an inability to resist certain acts but is classed separately as being primarily an anxiety disorder. Substance use disorder: This disorder refers to the use of drugs (legal or illegal, including alcohol) that persists despite significant problems or harm related to its use. Substance dependence and substance abuse fall under this umbrella category in the DSM. Substance use disorder may be due to a pattern of compulsive and repetitive use of a drug that results in tolerance to its effects and withdrawal symptoms when use is reduced or stopped. Dissociative disorder: People with severe disturbances of their self-identity, memory, and general awareness of themselves and their surroundings may be classified as having these types of disorders, including depersonalization disorder or dissociative identity disorder (which was previously referred to as multiple personality disorder or "split personality"). Cognitive disorder: These affect cognitive abilities, including learning and memory. This category includes delirium and mild and major neurocognitive disorder (previously termed dementia). Developmental disorder: These disorders initially occur in childhood. Some examples include autism spectrum disorder, oppositional defiant disorder and conduct disorder, and attention deficit hyperactivity disorder (ADHD), which may continue into adulthood. Conduct disorder, if continuing into adulthood, may be diagnosed as antisocial personality disorder (dissocial personality disorder in the ICD). Popular labels such as psychopath (or sociopath) do not appear in the DSM or ICD but are linked by some to these diagnoses. Somatoform disorders may be diagnosed when there are problems that appear to originate in the body that are thought to be manifestations of a mental disorder. This includes somatization disorder and conversion disorder. There are also disorders of how a person perceives their body, such as body dysmorphic disorder. Neurasthenia is an old diagnosis involving somatic complaints as well as fatigue and low spirits/depression, which is officially recognized by the ICD-10 but no longer by the DSM-IV.Factitious disorders are diagnosed where symptoms are thought to be reported for personal gain. Symptoms are often deliberately produced or feigned, and may relate to either symptoms in the individual or in someone close to them, particularly people they care for. There are attempts to introduce a category of relational disorder, where the diagnosis is of a relationship rather than on any one individual in that relationship. The relationship may be between children and their parents, between couples, or others. There already exists, under the category of psychosis, a diagnosis of shared psychotic disorder where two or more individuals share a particular delusion because of their close relationship with each other. There are a number of uncommon psychiatric syndromes, which are often named after the person who first described them, such as Capgras syndrome, De Clerambault syndrome, Othello syndrome, Ganser syndrome, Cotard delusion, and Ekbom syndrome, and additional disorders such as the Couvade syndrome and Geschwind syndrome. Signs and symptoms Course The onset of psychiatric disorders usually occurs from childhood to early adulthood. Impulse-control disorders and a few anxiety disorders tend to appear in childhood. Some other anxiety disorders, substance disorders, and mood disorders emerge later in the mid-teens. Symptoms of schizophrenia typically manifest from late adolescence to early twenties.The likely course and outcome of mental disorders vary and are dependent on numerous factors related to the disorder itself, the individual as a whole, and the social environment. Some disorders may last a brief period of time, while others may be long-term in nature. All disorders can have a varied course. Long-term international studies of schizophrenia have found that over a half of individuals recover in terms of symptoms, and around a fifth to a third in terms of symptoms and functioning, with many requiring no medication. While some have serious difficulties and support needs for many years, "late" recovery is still plausible. The World Health Organization (WHO) concluded that the long-term studies findings converged with others in "relieving patients, carers and clinicians of the chronicity paradigm which dominated thinking throughout much of the 20th century."A follow-up study by Tohen and coworkers revealed that around half of people initially diagnosed with bipolar disorder achieve symptomatic recovery (no longer meeting criteria for the diagnosis) within six weeks, and nearly all achieve it within two years, with nearly half regaining their prior occupational and residential status in that period. Less than half go on to experience a new episode of mania or major depression within the next two years. Disability Some disorders may be very limited in their functional effects, while others may involve substantial disability and support needs. The degree of ability or disability may vary over time and across different life domains. Furthermore, continued disability has been linked to institutionalization, discrimination and social exclusion as well as to the inherent effects of disorders. Alternatively, functioning may be affected by the stress of having to hide a condition in work or school, etc., by adverse effects of medications or other substances, or by mismatches between illness-related variations and demands for regularity.It is also the case that, while often being characterized in purely negative terms, some mental traits or states labeled as disorders can also involve above-average creativity, non-conformity, goal-striving, meticulousness, or empathy. In addition, the public perception of the level of disability associated with mental disorders can change.Nevertheless, internationally, people report equal or greater disability from commonly occurring mental conditions than from commonly occurring physical conditions, particularly in their social roles and personal relationships. The proportion with access to professional help for mental disorders is far lower, however, even among those assessed as having a severely disabling condition. Disability in this context may or may not involve such things as: Basic activities of daily living. Including looking after the self (health care, grooming, dressing, shopping, cooking etc.) or looking after accommodation (chores, DIY tasks, etc.) Interpersonal relationships. Including communication skills, ability to form relationships and sustain them, ability to leave the home or mix in crowds or particular settings Occupational functioning. Ability to acquire an employment and hold it, cognitive and social skills required for the job, dealing with workplace culture, or studying as a student.In terms of total disability-adjusted life years (DALYs), which is an estimate of how many years of life are lost due to premature death or to being in a state of poor health and disability, mental disorders rank amongst the most disabling conditions. Unipolar (also known as Major) depressive disorder is the third leading cause of disability worldwide, of any condition mental or physical, accounting for 65.5 million years lost. The first systematic description of global disability arising in youth, in 2011, found that among 10- to 24-year-olds nearly half of all disability (current and as estimated to continue) was due to mental and neurological conditions, including substance use disorders and conditions involving self-harm. Second to this were accidental injuries (mainly traffic collisions) accounting for 12 percent of disability, followed by communicable diseases at 10 percent. The disorders associated with most disabilities in high-income countries were unipolar major depression (20%) and alcohol use disorder (11%). In the eastern Mediterranean region, it was unipolar major depression (12%) and schizophrenia (7%), and in Africa it was unipolar major depression (7%) and bipolar disorder (5%).Suicide, which is often attributed to some underlying mental disorder, is a leading cause of death among teenagers and adults under 35. There are an estimated 10 to 20 million non-fatal attempted suicides every year worldwide. Risk factors The predominant view as of 2018 is that genetic, psychological, and environmental factors all contribute to the development or progression of mental disorders. Different risk factors may be present at different ages, with risk occurring as early as during prenatal period. Genetics A number of psychiatric disorders are linked to a family history (including depression, narcissistic personality disorder and anxiety). Twin studies have also revealed a very high heritability for many mental disorders (especially autism and schizophrenia). Although researchers have been looking for decades for clear linkages between genetics and mental disorders, that work has not yielded specific genetic biomarkers yet that might lead to better diagnosis and better treatments.Statistical research looking at eleven disorders found widespread assortative mating between people with mental illness. That means that individuals with one of these disorders were two to three times more likely than the general population to have a partner with a mental disorder. Sometimes people seemed to have preferred partners with the same mental illness. Thus, people with schizophrenia or ADHD are seven times more likely to have affected partners with the same disorder. This is even more pronounced for people with Autism spectrum disorders who are 10 times more likely to have a spouse with the same disorder. Environment During the prenatal stage, factors like unwanted pregnancy, lack of adaptation to pregnancy or substance use during pregnancy increases the risk of developing a mental disorder. Maternal stress and birth complications including prematurity and infections have also been implicated in increasing susceptibility for mental illness. Infants neglected or not provided optimal nutrition have a higher risk of developing cognitive impairment.Social influences have also been found to be important, including abuse, neglect, bullying, social stress, traumatic events, and other negative or overwhelming life experiences. Aspects of the wider community have also been implicated, including employment problems, socioeconomic inequality, lack of social cohesion, problems linked to migration, and features of particular societies and cultures. The specific risks and pathways to particular disorders are less clear, however. Nutrition also plays a role in mental disorders.In schizophrenia and psychosis, risk factors include migration and discrimination, childhood trauma, bereavement or separation in families, recreational use of drugs, and urbanicity.In anxiety, risk factors may include parenting factors including parental rejection, lack of parental warmth, high hostility, harsh discipline, high maternal negative affect, anxious childrearing, modelling of dysfunctional and drug-abusing behaviour, and child abuse (emotional, physical and sexual). Adults with imbalance work to life are at higher risk for developing anxiety.For bipolar disorder, stress (such as childhood adversity) is not a specific cause, but does place genetically and biologically vulnerable individuals at risk for a more severe course of illness. Drug use Mental disorders are associated with drug use including: cannabis, alcohol and caffeine, use of which appears to promote anxiety. For psychosis and schizophrenia, usage of a number of drugs has been associated with development of the disorder, including cannabis, cocaine, and amphetamines. There has been debate regarding the relationship between usage of cannabis and bipolar disorder. Cannabis has also been associated with depression. Adolescents are at increased risk for tobacco, alcohol and drug use; Peer pressure is the main reason why adolescents start using substances. At this age, the use of substances could be detrimental to the development of the brain and place them at higher risk of developing a mental disorder. Chronic disease People living with chronic conditions like HIV and diabetes are at higher risk of developing a mental disorder. People living with diabetes experience significant stress from biological impact of the disease, which places them at risk for developing anxiety and depression. Diabetic patients also have to deal with emotional stress trying to manage the disease. Conditions like heart disease, stroke, respiratory conditions, cancer, and arthritis increase the risk of developing a mental disorder when compared to the general population. Personality traits Risk factors for mental illness include a propensity for high neuroticism or "emotional instability". In anxiety, risk factors may include temperament and attitudes (e.g. pessimism). Causal models Mental disorders can arise from multiple sources, and in many cases there is no single accepted or consistent cause currently established. An eclectic or pluralistic mix of models may be used to explain particular disorders. The primary paradigm of contemporary mainstream Western psychiatry is said to be the biopsychosocial model which incorporates biological, psychological and social factors, although this may not always be applied in practice. Biological psychiatry follows a biomedical model where many mental disorders are conceptualized as disorders of brain circuits likely caused by developmental processes shaped by a complex interplay of genetics and experience. A common assumption is that disorders may have resulted from genetic and developmental vulnerabilities, exposed by stress in life (for example in a diathesis–stress model), although there are various views on what causes differences between individuals. Some types of mental disorders may be viewed as primarily neurodevelopmental disorders. Evolutionary psychology may be used as an overall explanatory theory, while attachment theory is another kind of evolutionary-psychological approach sometimes applied in the context of mental disorders. Psychoanalytic theories have continued to evolve alongside and cognitive-behavioral and systemic-family approaches. A distinction is sometimes made between a "medical model" or a "social model" of disorder and disability. Diagnosis Psychiatrists seek to provide a medical diagnosis of individuals by an assessment of symptoms, signs and impairment associated with particular types of mental disorder. Other mental health professionals, such as clinical psychologists, may or may not apply the same diagnostic categories to their clinical formulation of a clients difficulties and circumstances. The majority of mental health problems are, at least initially, assessed and treated by family physicians (in the UK general practitioners) during consultations, who may refer a patient on for more specialist diagnosis in acute or chronic cases. Routine diagnostic practice in mental health services typically involves an interview known as a mental status examination, where evaluations are made of appearance and behavior, self-reported symptoms, mental health history, and current life circumstances. The views of other professionals, relatives, or other third parties may be taken into account. A physical examination to check for ill health or the effects of medications or other drugs may be conducted. Psychological testing is sometimes used via paper-and-pen or computerized questionnaires, which may include algorithms based on ticking off standardized diagnostic criteria, and in rare specialist cases neuroimaging tests may be requested, but such methods are more commonly found in research studies than routine clinical practice.Time and budgetary constraints often limit practicing psychiatrists from conducting more thorough diagnostic evaluations. It has been found that most clinicians evaluate patients using an unstructured, open-ended approach, with limited training in evidence-based assessment methods, and that inaccurate diagnosis may be common in routine practice. In addition, comorbidity is very common in psychiatric diagnosis, where the same person meets the criteria for more than one disorder. On the other hand, a person may have several different difficulties only some of which meet the criteria for being diagnosed. There may be specific problems with accurate diagnosis in developing countries. More structured approaches are being increasingly used to measure levels of mental illness. HoNOS is the most widely used measure in English mental health services, being used by at least 61 trusts. In HoNOS a score of 0–4 is given for each of 12 factors, based on functional living capacity. Research has been supportive of HoNOS, although some questions have been asked about whether it provides adequate coverage of the range and complexity of mental illness problems, and whether the fact that often only 3 of the 12 scales vary over time gives enough subtlety to accurately measure outcomes of treatment. Criticism Since the 1980s, Paula Caplan has been concerned about the subjectivity of psychiatric diagnosis, and people being arbitrarily "slapped with a psychiatric label." Caplan says because psychiatric diagnosis is unregulated, doctors are not required to spend much time interviewing patients or to seek a second opinion. The Diagnostic and Statistical Manual of Mental Disorders can lead a psychiatrist to focus on narrow checklists of symptoms, with little consideration of what is actually causing the persons problems. So, according to Caplan, getting a psychiatric diagnosis and label often stands in the way of recovery.In 2013, psychiatrist Allen Frances wrote a paper entitled "The New Crisis of Confidence in Psychiatric Diagnosis", which said that "psychiatric diagnosis... still relies exclusively on fallible subjective judgments rather than objective biological tests." Frances was also concerned about "unpredictable overdiagnosis." For many years, marginalized psychiatrists (such as Peter Breggin, Thomas Szasz) and outside critics (such as Stuart A. Kirk) have "been accusing psychiatry of engaging in the systematic medicalization of normality." More recently these concerns have come from insiders who have worked for and promoted the American Psychiatric Association (e.g., Robert Spitzer, Allen Frances). A 2002 editorial in the British Medical Journal warned of inappropriate medicalization leading to disease mongering, where the boundaries of the definition of illnesses are expanded to include personal problems as medical problems or risks of diseases are emphasized to broaden the market for medications.Gary Greenberg, a psychoanalyst, in his book "the Book of Woe", argues that mental illness is really about suffering and how the DSM creates diagnostic labels to categorize peoples suffering. Indeed, the psychiatrist Thomas Szasz, in his book "the Medicalization of Everyday Life", also argues that what is psychiatric illness, is not always biological in nature (i.e. social problems, poverty, etc.), and may even be a part of the human condition. Potential routine use of MRI/fMRI in diagnosis in 2018 the American Psychological Association commissioned a review to reach a consensus on whether modern clinical MRI/fMRI will be able to be used in the diagnosis of mental health disorders. the criteria presented by the APA stated that the Biomarkers used in diagnosis should: "have a sensitivity of at least 80% for detecting a particular psychiatric disorder" should "have a specificity of at least 80% for distinguishing this disorder from other psychiatric or medical disorders" "should be reliable, reproducible, and ideally be noninvasive, simple to perform, and inexpensive" proposed biomarkers should be verified by 2 independent studies each by a different investigator and different population samples and published in a peer-reviewed journal.the review concluded that although neuroimaging diagnosis may technically be feasible, very large studies are needed to evaluate specific biomarkers which were not available. Prevention The 2004 WHO report "Prevention of Mental Disorders" stated that "Prevention of these disorders is obviously one of the most effective ways to reduce the [disease] burden." The 2011 European Psychiatric Association (EPA) guidance on prevention of mental disorders states "There is considerable evidence that various psychiatric conditions can be prevented through the implementation of effective evidence-based interventions." A 2011 UK Department of Health report on the economic case for mental health promotion and mental illness prevention found that "many interventions are outstandingly good value for money, low in cost and often become self-financing over time, saving public expenditure". In 2016, the National Institute of Mental Health re-affirmed prevention as a research priority area.Parenting may affect the childs mental health, and evidence suggests that helping parents to be more effective with their children can address mental health needs.Universal prevention (aimed at a population that has no increased risk for developing a mental disorder, such as school programs or mass media campaigns) need very high numbers of people to show effect (sometimes known as the "power" problem). Approaches to overcome this are (1) focus on high-incidence groups (e.g. by targeting groups with high risk factors), (2) use multiple interventions to achieve greater, and thus more statistically valid, effects, (3) use cumulative meta-analyses of many trials, and (4) run very large trials. Management Treatment and support for mental disorders are provided in psychiatric hospitals, clinics or a range of community mental health services. In some countries services are increasingly based on a recovery approach, intended to support individuals personal journey to gain the kind of life they want. There is a range of different types of treatment and what is most suitable depends on the disorder and the individual. Many things have been found to help at least some people, and a placebo effect may play a role in any intervention or medication. In a minority of cases, individuals may be treated against their will, which can cause particular difficulties depending on how it is carried out and perceived. Compulsory treatment while in the community versus non-compulsory treatment does not appear to make much of a difference except by maybe decreasing victimization. Lifestyle Lifestyle strategies, including dietary changes, exercise and quitting smoking may be of benefit. Therapy There is also a wide range of psychotherapists (including family therapy), counselors, and public health professionals. In addition, there are peer support roles where personal experience of similar issues is the primary source of expertise.A major option for many mental disorders is psychotherapy. There are several main types. Cognitive behavioral therapy (CBT) is widely used and is based on modifying the patterns of thought and behavior associated with a particular disorder. Other psychotherapies include dialectic behavioral therapy (DBT) and interpersonal psychotherapy (IPT). Psychoanalysis, addressing underlying psychic conflicts and defenses, has been a dominant school of psychotherapy and is still in use. Systemic therapy or family therapy is sometimes used, addressing a network of significant others as well as an individual. Some psychotherapies are based on a humanistic approach. There are many specific therapies used for particular disorders, which may be offshoots or hybrids of the above types. Mental health professionals often employ an eclectic or integrative approach. Much may depend on the therapeutic relationship, and there may be problems with trust, confidentiality and engagement. Medication A major option for many mental disorders is psychiatric medication and there are several main groups. Antidepressants are used for the treatment of clinical depression, as well as often for anxiety and a range of other disorders. Anxiolytics (including sedatives) are used for anxiety disorders and related problems such as insomnia. Mood stabilizers are used primarily in bipolar disorder. Antipsychotics are used for psychotic disorders, notably for positive symptoms in schizophrenia, and also increasingly for a range of other disorders. Stimulants are commonly used, notably for ADHD.Despite the different conventional names of the drug groups, there may be considerable overlap in the disorders for which they are actually indicated, and there may also be off-label use of medications. There can be problems with adverse effects of medication and adherence to them, and there is also criticism of pharmaceutical marketing and professional conflicts of interest. However, these medications in combination with non-pharmacological methods, such as cognitive-behavioral therapy (CBT) are seen to be most effective in treating mental disorders. Other Electroconvulsive therapy (ECT) is sometimes used in severe cases when other interventions for severe intractable depression have failed. ECT is usually indicated for treatment resistant depression, severe vegetative symptoms, psychotic depression, intense suicidal ideation, depression during pregnancy, and catatonia. Psychosurgery is considered experimental but is advocated by some neurologists in certain rare cases.Counseling (professional) and co-counseling (between peers) may be used. Psychoeducation programs may provide people with the information to understand and manage their problems. Creative therapies are sometimes used, including music therapy, art therapy or drama therapy. Lifestyle adjustments and supportive measures are often used, including peer support, self-help groups for mental health and supported housing or supported employment (including social firms). Some advocate dietary supplements.Reasonable accommodations (adjustments and supports) might be put in place to help an individual cope and succeed in environments despite potential disability related to mental health problems. This could include an emotional support animal or specifically trained psychiatric service dog. As of 2019 cannabis is specifically not recommended as a treatment. Epidemiology Mental disorders are common. Worldwide, more than one in three people in most countries report sufficient criteria for at least one at some point in their life. In the United States, 46% qualify for a mental illness at some point. An ongoing survey indicates that anxiety disorders are the most common in all but one country, followed by mood disorders in all but two countries, while substance disorders and impulse-control disorders were consistently less prevalent. Rates varied by region.A review of anxiety disorder surveys in different countries found average lifetime prevalence estimates of 16.6%, with women having higher rates on average. A review of mood disorder surveys in different countries found lifetime rates of 6.7% for major depressive disorder (higher in some studies, and in women) and 0.8% for Bipolar I disorder.In the United States the frequency of disorder is: anxiety disorder (28.8%), mood disorder (20.8%), impulse-control disorder (24.8%) or substance use disorder (14.6%).A 2004 cross-Europe study found that approximately one in four people reported meeting criteria at some point in their life for at least one of the DSM-IV disorders assessed, which included mood disorders (13.9%), anxiety disorders (13.6%), or alcohol disorder (5.2%). Approximately one in ten met the criteria within a 12-month period. Women and younger people of either gender showed more cases of the disorder. A 2005 review of surveys in 16 European countries found that 27% of adult Europeans are affected by at least one mental disorder in a 12-month period.An international review of studies on the prevalence of schizophrenia found an average (median) figure of 0.4% for lifetime prevalence; it was consistently lower in poorer countries.Studies of the prevalence of personality disorders (PDs) have been fewer and smaller-scale, but one broad Norwegian survey found a five-year prevalence of almost 1 in 7 (13.4%). Rates for specific disorders ranged from 0.8% to 2.8%, differing across countries, and by gender, educational level and other factors. A US survey that incidentally screened for personality disorder found a rate of 14.79%.Approximately 7% of a preschool pediatric sample were given a psychiatric diagnosis in one clinical study, and approximately 10% of 1- and 2-year-olds receiving developmental screening have been assessed as having significant emotional/behavioral problems based on parent and pediatrician reports.While rates of psychological disorders are often the same for men and women, women tend to have a higher rate of depression. Each year 73 million women are affected by major depression, and suicide is ranked 7th as the cause of death for women between the ages of 20–59. Depressive disorders account for close to 41.9% of the disability from neuropsychiatric disorders among women compared to 29.3% among men. History Ancient civilizations Ancient civilizations described and treated a number of mental disorders. Mental illnesses were well known in ancient Mesopotamia, where diseases and mental disorders were believed to be caused by specific deities. Because hands symbolized control over a person, mental illnesses were known as "hands" of certain deities. One psychological illness was known as Qāt Ištar, meaning "Hand of Ishtar". Others were known as "Hand of Shamash", "Hand of the Ghost", and "Hand of the God". Descriptions of these illnesses, however, are so vague that it is usually impossible to determine which illnesses they correspond to in modern terminology. Mesopotamian doctors kept detailed record of their patients hallucinations and assigned spiritual meanings to them. The royal family of Elam was notorious for its members often being insane. The Greeks coined terms for melancholy, hysteria and phobia and developed the humorism theory. Mental disorders were described, and treatments developed, in Persia, Arabia and in the medieval Islamic world. Europe Middle Ages Conceptions of madness in the Middle Ages in Christian Europe were a mixture of the divine, diabolical, magical and humoral, and transcendental. In the early modern period, some people with mental disorders may have been victims of the witch-hunts. While not every witch and sorcerer accused were mentally ill, all mentally ill were considered to be witches or sorcerers. Many terms for mental disorders that found their way into everyday use first became popular in the 16th and 17th centuries. Eighteenth century By the end of the 17th century and into the Enlightenment, madness was increasingly seen as an organic physical phenomenon with no connection to the soul or moral responsibility. Asylum care was often harsh and treated people like wild animals, but towards the end of the 18th century a moral treatment movement gradually developed. Clear descriptions of some syndromes may be rare before the 19th century. Nineteenth century Industrialization and population growth led to a massive expansion of the number and size of insane asylums in every Western country in the 19th century. Numerous different classification schemes and diagnostic terms were developed by different authorities, and the term psychiatry was coined (1808), though medical superintendents were still known as alienists. Twentieth century The turn of the 20th century saw the development of psychoanalysis, which would later come to the fore, along with Kraepelins classification scheme. Asylum "inmates" were increasingly referred to as "patients", and asylums were renamed as hospitals. Europe and the United States Early in the 20th century in the United States, a mental hygiene movement developed, aiming to prevent mental disorders. Clinical psychology and social work developed as professions. World War I saw a massive increase of conditions that came to be termed "shell shock". World War II saw the development in the U.S. of a new psychiatric manual for categorizing mental disorders, which along with existing systems for collecting census and hospital statistics led to the first Diagnostic and Statistical Manual of Mental Disorders. The International Classification of Diseases (ICD) also developed a section on mental disorders. The term stress, having emerged from endocrinology work in the 1930s, was increasingly applied to mental disorders. Electroconvulsive therapy, insulin shock therapy, lobotomies and the neuroleptic chlorpromazine came to be used by mid-century. In the 1960s there were many challenges to the concept of mental illness itself. These challenges came from psychiatrists like Thomas Szasz who argued that mental illness was a myth used to disguise moral conflicts; from sociologists such as Erving Goffman who said that mental illness was merely another example of how society labels and controls non-conformists; from behavioral psychologists who challenged psychiatrys fundamental reliance on unobservable phenomena; and from gay rights activists who criticised the APAs listing of homosexuality as a mental disorder. A study published in Science by Rosenhan received much publicity and was viewed as an attack on the efficacy of psychiatric diagnosis.Deinstitutionalization gradually occurred in the West, with isolated psychiatric hospitals being closed down in favor of community mental health services. A consumer/survivor movement gained momentum. Other kinds of psychiatric medication gradually came into use, such as "psychic energizers" (later antidepressants) and lithium. Benzodiazepines gained widespread use in the 1970s for anxiety and depression, until dependency problems curtailed their popularity. Advances in neuroscience, genetics, and psychology led to new research agendas. Cognitive behavioral therapy and other psychotherapies developed. The DSM and then ICD adopted new criteria-based classifications, and the number of "official" diagnoses saw a large expansion. Through the 1990s, new SSRI-type antidepressants became some of the most widely prescribed drugs in the world, as later did antipsychotics. Also during the 1990s, a recovery approach developed. Africa and Nigeria Most Africans view mental disturbances as external spiritual attack on the person. Those who have a mental illness are thought to be under a spell or bewitched. Often than usual, People view mentally ill person as possession of evil spirit, and seen as more of sociological perspective than a psychological order.The WHO estimated that fewer than 10% of mentally ill Nigerians have access to a psychiatrist or health worker, because they are low ration of psychiatrist available for the country of 200 million people. WHO estimates that the number of mentally ill Nigerians ranges from 40 million to 60 million. Disorders like depression, anxiety and schizophrenia, personality disorder, old age-related disorder, substance abuse disorder are common in Nigeria, as in other countries in Africa.Nigeria is still nowhere near being equipped to solve prevailing mental health challenges. With little scientific research been carried out, coupled with insufficient mental health hospitals in the country, traditional healers provide specialised psychotherapy care to those that require their services.and pharmacotherapy Society and culture Different societies or cultures, even different individuals in a subculture, can disagree as to what constitutes optimal versus pathological biological and psychological functioning. Research has demonstrated that cultures vary in the relative importance placed on, for example, happiness, autonomy, or social relationships for pleasure. Likewise, the fact that a behavior pattern is valued, accepted, encouraged, or even statistically normative in a culture does not necessarily mean that it is conducive to optimal psychological functioning. People in all cultures find some behaviors bizarre or even incomprehensible. But just what they feel is bizarre or incomprehensible is ambiguous and subjective. These differences in determination can become highly contentious. The process by which conditions and difficulties come to be defined and treated as medical conditions and problems, and thus come under the authority of doctors and other health professionals, is known as medicalization or pathologization. Mental illness in the Latin American community There is a perception in Latin American communities, especially among older people, that discussing problems with mental health can create embarrassment and shame for the family. This results in fewer people seeking treatment.Latin Americans from the USA, are slightly more likely to have a mental health disorder than first-generation Latin American immigrants, although differences between ethnic groups were found to disappear after adjustment for place of birth.From 2015 to 2018, rates of serious mental illness in young adult Latin Americans increased by 60%, from 4% to 6.4%. The prevalence of major depressive episodes in young and adult Latin Americans increased from 8.4% to 11.3%. More than a third of Latin Americans reported more than one bad mental health day in the last three months. The rate of suicide among Latin Americans was about half the rate of non-Latin American white Americans in 2018, and this was the second-leading cause of death among Latin Americans ages 15 to 34. However, Latin American suicide rates rose steadily after 2020 in relation to the COVID-19 pandemic, even as the national rate declined.Family relations are an integral part of the Latin American community. Some research has shown that Latin Americans are more likely rely on family bonds, or familismo, as a source of therapy while struggling with mental health issues. Because Latin Americans have a high rate of religiosity, and because there is less stigma associated with religion than with psychiatric services, religion may play a more important therapeutic role for the mentally ill in Latin American communities. However, research has also suggested that religion may also play a role in stigmatizing mental illness in Latin American communities, which can discourage community members from seeking professional help. Religion Religious, spiritual, or transpersonal experiences and beliefs meet many criteria of delusional or psychotic disorders. A belief or experience can sometimes be shown to produce distress or disability—the ordinary standard for judging mental disorders. There is a link between religion and schizophrenia, a complex mental disorder characterized by a difficulty in recognizing reality, regulating emotional responses, and thinking in a clear and logical manner. Those with schizophrenia commonly report some type of religious delusion, and in come cases religion plays a role in chronic schizophrenia. Movements Controversy has often surrounded psychiatry, and the term anti-psychiatry was coined by the psychiatrist David Cooper in 1967. The anti-psychiatry message is that psychiatric treatments are ultimately more damaging than helpful to patients, and psychiatrys history involves what may now be seen as dangerous treatments. Electroconvulsive therapy was one of these, which was used widely between the 1930s and 1960s. Lobotomy was another practice that was ultimately seen as too invasive and brutal. Diazepam and other sedatives were sometimes over-prescribed, which led to an epidemic of dependence. There was also concern about the large increase in prescribing psychiatric drugs for children. Some charismatic psychiatrists came to personify the movement against psychiatry. The most influential of these was R.D. Laing who wrote a series of best-selling books, including The Divided Self. Thomas Szasz wrote The Myth of Mental Illness. Some ex-patient groups have become militantly anti-psychiatric, often referring to themselves as survivors. Giorgio Antonucci has questioned the basis of psychiatry through his work on the dismantling of two psychiatric hospitals (in the city of Imola), carried out from 1973 to 1996. The consumer/survivor movement (also known as user/survivor movement) is made up of individuals (and organizations representing them) who are clients of mental health services or who consider themselves survivors of psychiatric interventions. Activists campaign for improved mental health services and for more involvement and empowerment within mental health services, policies and wider society. Patient advocacy organizations have expanded with increasing deinstitutionalization in developed countries, working to challenge the stereotypes, stigma and exclusion associated with psychiatric conditions. There is also a carers rights movement of people who help and support people with mental health conditions, who may be relatives, and who often work in difficult and time-consuming circumstances with little acknowledgement and without pay. An anti-psychiatry movement fundamentally challenges mainstream psychiatric theory and practice, including in some cases asserting that psychiatric concepts and diagnoses of mental illness are neither real nor useful.Alternatively, a movement for global mental health has emerged, defined as the area of study, research and practice that places a priority on improving mental health and achieving equity in mental health for all people worldwide. Cultural bias Diagnostic guidelines of the 2000s, namely the DSM and to some extent the ICD, have been criticized as having a fundamentally Euro-American outlook. Opponents argue that even when diagnostic criteria are used across different cultures, it does not mean that the underlying constructs have validity within those cultures, as even reliable application can prove only consistency, not legitimacy. Advocating a more culturally sensitive approach, critics such as Carl Bell and Marcello Maviglia contend that the cultural and ethnic diversity of individuals is often discounted by researchers and service providers.Cross-cultural psychiatrist Arthur Kleinman contends that the Western bias is ironically illustrated in the introduction of cultural factors to the DSM-IV. Disorders or concepts from non-Western or non-mainstream cultures are described as "culture-bound", whereas standard psychiatric diagnoses are given no cultural qualification whatsoever, revealing to Kleinman an underlying assumption that Western cultural phenomena are universal. Kleinmans negative view towards the culture-bound syndrome is largely shared by other cross-cultural critics. Common responses included both disappointment over the large number of documented non-Western mental disorders still left out and frustration that even those included are often misinterpreted or misrepresented.Many mainstream psychiatrists are dissatisfied with the new culture-bound diagnoses, although for partly different reasons. Robert Spitzer, a lead architect of the DSM-III, has argued that adding cultural formulations was an attempt to appease cultural critics, and has stated that they lack any scientific rationale or support. Spitzer also posits that the new culture-bound diagnoses are rarely used, maintaining that the standard diagnoses apply regardless of the culture involved. In general, mainstream psychiatric opinion remains that if a diagnostic category is valid, cross-cultural factors are either irrelevant or are significant only to specific symptom presentations.Clinical conceptions of mental illness also overlap with personal and cultural values in the domain of morality, so much so that it is sometimes argued that separating the two is impossible without fundamentally redefining the essence of being a particular person in a society. In clinical psychiatry, persistent distress and disability indicate an internal disorder requiring treatment; but in another context, that same distress and disability can be seen as an indicator of emotional struggle and the need to address social and structural problems. This dichotomy has led some academics and clinicians to advocate a postmodernist conceptualization of mental distress and well-being.Such approaches, along with cross-cultural and "heretical" psychologies centered on alternative cultural and ethnic and race-based identities and experiences, stand in contrast to the mainstream psychiatric communitys alleged avoidance of any explicit involvement with either morality or culture. In many countries there are attempts to challenge perceived prejudice against minority groups, including alleged institutional racism within psychiatric services. There are also ongoing attempts to improve professional cross cultural sensitivity. Laws and policies Three-quarters of countries around the world have mental health legislation. Compulsory admission to mental health facilities (also known as involuntary commitment) is a controversial topic. It can impinge on personal liberty and the right to choose, and carry the risk of abuse for political, social, and other reasons; yet it can potentially prevent harm to self and others, and assist some people in attaining their right to healthcare when they may be unable to decide in their own interests. Because of this it is a concern of medical ethics. All human rights oriented mental health laws require proof of the presence of a mental disorder as defined by internationally accepted standards, but the type and severity of disorder that counts can vary in different jurisdictions. The two most often used grounds for involuntary admission are said to be serious likelihood of immediate or imminent danger to self or others, and the need for treatment. Applications for someone to be involuntarily admitted usually come from a mental health practitioner, a family member, a close relative, or a guardian. Human-rights-oriented laws usually stipulate that independent medical practitioners or other accredited mental health practitioners must examine the patient separately and that there should be regular, time-bound review by an independent review body. The individual should also have personal access to independent advocacy. For involuntary treatment to be administered (by force if necessary), it should be shown that an individual lacks the mental capacity for informed consent (i.e. to understand treatment information and its implications, and therefore be able to make an informed choice to either accept or refuse). Legal challenges in some areas have resulted in supreme court decisions that a person does not have to agree with a psychiatrists characterization of the issues as constituting an "illness", nor agree with a psychiatrists conviction in medication, but only recognize the issues and the information about treatment options.Proxy consent (also known as surrogate or substituted decision-making) may be transferred to a personal representative, a family member, or a legally appointed guardian. Moreover, patients may be able to make, when they are considered well, an advance directive stipulating how they wish to be treated should they be deemed to lack mental capacity in the future. The right to supported decision-making, where a person is helped to understand and choose treatment options before they can be declared to lack capacity, may also be included in the legislation. There should at the very least be shared decision-making as far as possible. Involuntary treatment laws are increasingly extended to those living in the community, for example outpatient commitment laws (known by different names) are used in New Zealand, Australia, the United Kingdom, and most of the United States. The World Health Organization reports that in many instances national mental health legislation takes away the rights of persons with mental disorders rather than protecting rights, and is often outdated. In 1991, the United Nations adopted the Principles for the Protection of Persons with Mental Illness and the Improvement of Mental Health Care, which established minimum human rights standards of practice in the mental health field. In 2006, the UN formally agreed the Convention on the Rights of Persons with Disabilities to protect and enhance the rights and opportunities of disabled people, including those with psychosocial disabilities.The term insanity, sometimes used colloquially as a synonym for mental illness, is often used technically as a legal term. The insanity defense may be used in a legal trial (known as the mental disorder defence in some countries). Perception and discrimination Stigma The social stigma associated with mental disorders is a widespread problem. The US Surgeon General stated in 1999 that: "Powerful and pervasive, stigma prevents people from acknowledging their own mental health problems, much less disclosing them to others." Additionally, researcher Wulf Rössler in 2016, in his article, "The Stigma of Mental Disorders" stated "For millennia, society did not treat persons suffering from depression, autism, schizophrenia and other mental illnesses much better than slaves or criminals: they were imprisoned, tortured or killed". In the United States, racial and ethnic minorities are more likely to experience mental health disorders often due to low socioeconomic status, and discrimination. In Taiwan, those with mental disorders are subject to general publics misperception that the root causes of the mental disorders are "over-thinking", "having a lot of time and nothing better to do", "stagnant", "not serious in life", "not paying enough attention to the real life affairs", "mentally weak", "refusing to be resilient", "turning back to perfectionistic strivings", "not bravery" and so forth.Employment discrimination is reported to play a significant part in the high rate of unemployment among those with a diagnosis of mental illness. An Australian study found that having a mental illness is a bigger barrier to employment than a physical disability. The mentally ill are stigmatized in Chinese society and can not legally marry.Efforts are being undertaken worldwide to eliminate the stigma of mental illness, although the methods and outcomes used have sometimes been criticized. Media and general public Media coverage of mental illness comprises predominantly negative and pejorative depictions, for example, of incompetence, violence or criminality, with far less coverage of positive issues such as accomplishments or human rights issues. Such negative depictions, including in childrens cartoons, are thought to contribute to stigma and negative attitudes in the public and in those with mental health problems themselves, although more sensitive or serious cinematic portrayals have increased in prevalence.In the United States, the Carter Center has created fellowships for journalists in South Africa, the U.S., and Romania, to enable reporters to research and write stories on mental health topics. Former US First Lady Rosalynn Carter began the fellowships not only to train reporters in how to sensitively and accurately discuss mental health and mental illness, but also to increase the number of stories on these topics in the news media. There is also a World Mental Health Day, which in the US and Canada falls within a Mental Illness Awareness Week. The general public have been found to hold a strong stereotype of dangerousness and desire for social distance from individuals described as mentally ill. A US national survey found that a higher percentage of people rate individuals described as displaying the characteristics of a mental disorder as "likely to do something violent to others", compared to the percentage of people who are rating individuals described as being troubled. In the article, "Discrimination Against People with a Mental Health Diagnosis: Qualitative Analysis of Reported Experiences," an individual who has a mental disorder, revealed that, "If people dont know me and dont know about the problems, theyll talk to me quite happily. Once theyve seen the problems or someones told them about me, they tend to be a bit more wary." In addition, in the article,"Stigma and its Impact on Help-Seeking for Mental Disorders: What Do We Know?" by George Schomerus and Matthias Angermeyer, it is affirmed that "Family doctors and psychiatrists have more pessimistic views about the outcomes for mental illnesses than the general public (Jorm et al.,1999), and mental health professionals hold more negative stereotypes about mentally ill patients, but, reassuringly, they are less accepting of restrictions towards them."Recent depictions in media have included leading characters successfully living with and managing a mental illness, including in bipolar disorder in Homeland (2011) and posttraumatic stress disorder in Iron Man 3 (2013). Violence Despite public or media opinion, national studies have indicated that severe mental illness does not independently predict future violent behavior, on average, and is not a leading cause of violence in society. There is a statistical association with various factors that do relate to violence (in anyone), such as substance use and various personal, social, and economic factors. A 2015 review found that in the United States, about 4% of violence is attributable to people diagnosed with mental illness, and a 2014 study found that 7.5% of crimes committed by mentally ill people were directly related to the symptoms of their mental illness. The majority of people with serious mental illness are never violent.In fact, findings consistently indicate that it is many times more likely that people diagnosed with a serious mental illness living in the community will be the victims rather than the perpetrators of violence. In a study of individuals diagnosed with "severe mental illness" living in a US inner-city area, a quarter were found to have been victims of at least one violent crime over the course of a year, a proportion eleven times higher than the inner-city average, and higher in every category of crime including violent assaults and theft. People with a diagnosis may find it more difficult to secure prosecutions, however, due in part to prejudice and being seen as less credible.However, there are some specific diagnoses, such as childhood conduct disorder or adult antisocial personality disorder or psychopathy, which are defined by, or are inherently associated with, conduct problems and violence. There are conflicting findings about the extent to which certain specific symptoms, notably some kinds of psychosis (hallucinations or delusions) that can occur in disorders such as schizophrenia, delusional disorder or mood disorder, are linked to an increased risk of serious violence on average. The mediating factors of violent acts, however, are most consistently found to be mainly socio-demographic and socio-economic factors such as being young, male, of lower socioeconomic status and, in particular, substance use (including alcohol use) to which some people may be particularly vulnerable.High-profile cases have led to fears that serious crimes, such as homicide, have increased due to deinstitutionalization, but the evidence does not support this conclusion. Violence that does occur in relation to mental disorder (against the mentally ill or by the mentally ill) typically occurs in the context of complex social interactions, often in a family setting rather than between strangers. It is also an issue in health care settings and the wider community. Mental health The recognition and understanding of mental health conditions have changed over time and across cultures and there are still variations in definition, assessment, and classification, although standard guideline criteria are widely used. In many cases, there appears to be a continuum between mental health and mental illness, making diagnosis complex.: 39  According to the World Health Organization, over a third of people in most countries report problems at some time in their life which meet the criteria for diagnosis of one or more of the common types of mental disorder. Corey M Keyes has created a two continua model of mental illness and health which holds that both are related, but distinct dimensions: one continuum indicates the presence or absence of mental health, the other the presence or absence of mental illness. For example, people with optimal mental health can also have a mental illness, and people who have no mental illness can also have poor mental health. Other animals Psychopathology in non-human primates has been studied since the mid-20th century. Over 20 behavioral patterns in captive chimpanzees have been documented as (statistically) abnormal for frequency, severity or oddness—some of which have also been observed in the wild. Captive great apes show gross behavioral abnormalities such as stereotypy of movements, self-mutilation, disturbed emotional reactions (mainly fear or aggression) towards companions, lack of species-typical communications, and generalized learned helplessness. In some cases such behaviors are hypothesized to be equivalent to symptoms associated with psychiatric disorders in humans such as depression, anxiety disorders, eating disorders and post-traumatic stress disorder. Concepts of antisocial, borderline and schizoid personality disorders have also been applied to non-human great apes.The risk of anthropomorphism is often raised concerning such comparisons, and assessment of non-human animals cannot incorporate evidence from linguistic communication. However, available evidence may range from nonverbal behaviors—including physiological responses and homologous facial displays and acoustic utterances—to neurochemical studies. It is pointed out that human psychiatric classification is often based on statistical description and judgment of behaviors (especially when speech or language is impaired) and that the use of verbal self-report is itself problematic and unreliable.Psychopathology has generally been traced, at least in captivity, to adverse rearing conditions such as early separation of infants from mothers; early sensory deprivation; and extended periods of social isolation. Studies have also indicated individual variation in temperament, such as sociability or impulsiveness. Particular causes of problems in captivity have included integration of strangers into existing groups and a lack of individual space, in which context some pathological behaviors have also been seen as coping mechanisms. Remedial interventions have included careful individually tailored re-socialization programs, behavior therapy, environment enrichment, and on rare occasions psychiatric drugs. Socialization has been found to work 90% of the time in disturbed chimpanzees, although restoration of functional sexuality and caregiving is often not achieved.Laboratory researchers sometimes try to develop animal models of human mental disorders, including by inducing or treating symptoms in animals through genetic, neurological, chemical or behavioral manipulation, but this has been criticized on empirical grounds and opposed on animal rights grounds. See also List of mental disorders Mental illness portrayed in media Mental disorders in film Mental illness in fiction Mental illness in American prisons Parity of esteem Psychological evaluation References Further reading External links Overcoming Mental Health Stigma in the Latino Community – Consult QD clevelandclinic.org National Institute of Mental Health International Committee of Women Leaders on Mental Health

Would you describe Blackwater fever, to me Aarogya

Blackwater fever

Blackwater fever is a complication of malaria infection in which red blood cells burst in the bloodstream (hemolysis), releasing hemoglobin directly into the blood vessels and into the urine, frequently leading to kidney failure. The disease was first linked to malaria by the Sierra Leone Creole physician John Farrell Easmon in his 1884 pamphlet entitled The Nature and Treatment of Blackwater Fever. Easmon coined the name "blackwater fever" and was the first to successfully treat such cases following the publication of his pamphlet. Signs and symptoms Within a few days of onset there are chills, with rigor, high fever, jaundice, vomiting, rapidly progressive anemia, and dark red or black urine. Causes The cause of hemolytic crises in this disease is unknown (mainly due to intravascular haemolysis). There is rapid and massive destruction of red blood cells resulting in hemoglobinemia (hemoglobin in the blood, but outside the red blood cells), hemoglobinuria (hemoglobin in urine), intense jaundice, anuria (passing less than 50 milliliters of urine in a day), and finally death in the majority of cases.The most probable explanation for blackwater fever is an autoimmune reaction apparently caused by the interaction of the malaria parasite and the use of quinine. Blackwater fever is caused by heavy parasitization of red blood cells with Plasmodium falciparum. However, there have been other cases attributed to Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi.Blackwater fever is a serious complication of malaria, but cerebral malaria has a higher mortality rate. Blackwater fever is much less common today than it was before 1950. It may be that quinine plays a role in triggering the condition, and this drug is no longer commonly used for malaria prophylaxis. Quinine remains important for treatment of malaria. Diagnosis Treatment The treatment is antimalarial chemotherapy, intravenous fluid and sometimes supportive care such as intensive care and dialysis. Society and culture Prominent victims Prior to his photography career, Henri Cartier-Bresson contracted blackwater fever while hunting in Western Africa. Expecting to die, he sent instructions to his family on his wishes for a funeral. He made a full recovery. Zoologist John Samuel Budgett died from the disease in 1904, after returning from a collecting trip to West Africa, in search of specimens of the fish Polypterus. Missionary and explorer George Grenfell died after a bad attack of blackwater fever at Basoko on 1 July 1906. Jesse Brand, a missionary to the Chat Mountains in India, died of blackwater fever in 1928. Actor Don Adams, best known as Maxwell Smart from the popular sitcom Get Smart and as the title character in Inspector Gadget, contracted blackwater fever after being shot in combat at Guadalcanal during World War II. Adams was evacuated from his United States Marine Corps unit to a hospital in New Zealand where he ultimately made a full recovery. Humanitarian and MMA fighter Justin Wren contracted malaria, which devolved into blackwater fever, while drilling water-wells for Congo Pygmies in 2013. The affliction nearly claimed Wrens life. He was misdiagnosed four times and required airlift to Uganda, where he narrowly recovered from severe symptoms. Aeneas, Jeannie Gunns husband, is described as having died from Blackwater Fever or Malarial Dysentry at Elsey Station in the Northern Territory in 1903. She later authored the classic account We of the Never Never. Bernard Deacon Peter Cameron Scott, a Scottish-American missionary and founder of Africa Inland Mission, died from the disease in December 1896. Henry Stricker, South African cricketer Cultural references Out of Africa, a 1985 film based on the experiences of author Isak Dinesen The Power of One, a 1992 film based on the book of the same name The Bridge on the River Kwai, a 1957 film about prisoners of war in a jungle environment At Play in the Fields of the Lord, a 1965 novel by Peter Matthiessen West with the Night (1942), African memoir by aviator Beryl Markham Burmese Days, a 1934 novel by George Orwell; several associates of Flory are noted to have died of blackwater fever in chapter 5 Showdown, a 1946 novel by Errol Flynn The Heart of the Matter, a 1948 novel by Graham Greene Green Hills of Africa, a 1935 novel by Ernest Hemingway The Book of Secrets, a 1994 novel by M. G. Vassanji The Blackwater Fever, a blues band out of Australia An Ice-Cream War, a 1982 novel by William Boyd set during the First World War in German East Africa Liberia as I Know It, a 1929 memoir by medical missionary Clinton Caldwell Boone Showa: A History of Japan, a 2014 four-part autobiographical graphic novel of the Showa period in Japanese history Shigeru Mizuki Stand on Zanzibar, a 1968 science-fiction novel by John Brunner quotes a line from the sea chanty "The Bight of Benin": "The bight of Benin, the bight of Benin! Blackwater fever and pounds of quinine!" Blackwater: A True Epic of the Sea, a 1958 memoir of a ships crew stricken with blackwater fever, by H.L. Tredree The Mottled Lizard, a 1962 memoir of Kenya by Elspeth Huxley Wolfenstein: The Old Blood, referenced by Wesley (Agent One) near the beginning of the game See also Malarial nephropathy == References ==

Hey Aarogya, could you help me understand about Cannabinoid hyperemesis syndrome

Cannabinoid hyperemesis syndrome

Cannabinoid hyperemesis syndrome (CHS) is recurrent nausea, vomiting, and cramping abdominal pain that can occur due to prolonged, high-dose cannabis use. These symptoms may be relieved temporarily by taking a hot shower or bath. Complications may include kidney failure and electrolyte problems, and the condition can be fatal if not properly managed.Weekly cannabis use is generally required for the syndrome to occur; synthetic cannabinoids can also cause CHS. The underlying mechanism is unclear, with several possibilities proposed. Diagnosis is based on the symptoms, as well as the history of cannabis use (including a urine screen test if necessary). The condition is typically present for some time before the diagnosis is made. Another condition that presents similarly is cyclic vomiting syndrome (CVS).The only known effective treatment for CHS is to stop using cannabis. Two weeks (or possibly more) may be required to see a benefit. The primary differentiation between CHS and CVS is that cessation of cannabis use only relieves CHS.Treatments during an episode of vomiting are generally supportive in nature (e.g., hydration). There is tentative evidence for the use of capsaicin cream on the abdomen during an acute episode.The syndrome was first described in 2004, and simplified diagnostic criteria were published in 2009. Signs and symptoms The long-term and short-term effects of cannabis use are associated with behavioral effects leading to a wide variety of effects on the body systems and physiological states. CHS is a paradoxical syndrome characterized by hyperemesis (persistent vomiting), as opposed to the better known antiemetic properties of cannabinoids. Specifically, CHS takes the pattern of cyclical nausea, vomiting, and abdominal pain in the setting of chronic cannabinoid use. The abdominal pain tends to be mild and diffused. There are three phases of CHS: the prodromal phase, the hyperemetic phase, and the recovery phase. Prodromal phase The prodromal phase is characterized by mild symptoms of CHS, including nausea, anxiety, mild discomfort, sweating, and increased thirst; symptoms are more severe in the morning. Prior to the use of compensatory exposure to hot water to treat symptoms, people sometimes increase their intake of cannabinoids in an effort to treat the persistent nausea they experience. This phase can last for months or even years. Hyperemetic phase The hyperemetic phase is characterized by the full syndromal symptoms of CHS, including persistent nausea, vomiting, abdominal pain, and retching. Retching can occur up to 5 times per hour. Acute episodes of cannabinoid hyperemesis typically last for 24–48 hours. The symptoms experienced in this phase are cyclical, and can recur unpredictably in intervals of weeks to months. It is very difficult to take food or medicine by mouth during this stage, and patients may develop a fear of eating. Weight loss and dehydration due to decreased oral intake and vomiting are possible. It is during this hyperemetic phase that people with CHS are likely to present to the emergency department of the hospital for treatment.Treatment via hot water, sometimes for hours at a time, relieves symptoms for many patients, which can result in compulsive bathing or showering. People have described the hot water relief as "temperature-dependent," meaning that hotter temperatures provide greater relief. Recovery phase The recovery phase begins after the patient abstains from cannabis consumption, but the time for resolution of symptoms is unclear: it has been reported to occur within two weeks, or to take one to three months. Lost weight can be regained due to a restoration of normal oral intake, and compulsive bathing/showering can give way to normal patterns of behavior. If a person in this phase consumes cannabis again, their symptoms tend to come back. Relapses are common due to reinitiation of cannabis consumption, following which many people use or increase their use of cannabis due to concerns about nausea. Increased patient education may be necessary. Complications Two deaths were reported as complications of associated kidney failure and electrolyte disorders. Pathogenesis Cannabis contains more than 400 different chemicals, of which about 60 are cannabinoids. The chemical composition of cannabis may vary between cannabis products, making it difficult to identify the specific chemical(s) responsible for the syndrome. The pathophysiology of CHS is complicated by the complex action of these chemicals throughout the body, both in the central nervous system and in the gastrointestinal system. Cannabis-related factors, such as the amount of THC in the cannabis, the amount of use, and the duration of use likely play a role, but are not yet well understood. Other factors, such as chronic stress, genetics, and emotional factors, may influence the risk for CHS.Various pathogenic mechanistic theories attempting to explain symptoms have been put forward: dose dependent buildup of cannabinoids and related effects of cannabinoid toxicity the functionality of cannabinoid receptors in the brain and particularly in the hypothalamus (which regulates body temperature and the digestive system) direct stimulation of cannabinoid receptors in the gut Cannabinoid buildup theory Tetrahydrocannabinol (THC) is a fat-soluble cannabinoid that can be deposited into a persons fat stores, accounting for the long elimination half-life of THC. During periods of stress or food deprivation, a persons fat stores can be mobilized (lipolysis) for energy consumption, releasing the previously stored THC back into the blood. The mechanism can be characterized as a "reintoxication effect." Another cannabinoid called cannabigerol acts as an antagonist at cannabinoid(CB1) and serotonin(5HT1A) receptors, antagonizing the anti-emetic effects of cannabidiol that occurs through its effects on serotonin. Diagnosis The diagnostic criteria for CHS were ill-defined prior to the establishment of the Rome IV criteria of 2016. The criteria specify symptoms which resemble cyclic vomiting syndrome and which occur after long-term cannabis use, but which cease after cannabis use is halted. A retrospective application of these criteria to cases recorded in prior literature suggested that the number of people with CHS had been over-estimated.Various diagnostic frameworks for CHS have been proposed. As of 2015, the modified criteria by Simonetto et al. are the most frequently used. The most important feature is detecting a history of cannabinoid use, the denial of which can delay proper diagnosis. A urine drug screen can be useful for objectively determining the presence of cannabinoids in a persons system. Cannabinoid metabolites (specifically 11-nor-Δ9-carboxylic acid) can be detected in urine for about 2–8 days with short-term use, and for 14–42 days of chronic use.It has been hypothesized that certain people may be genetically pre-disposed to metabolize cannabinoids in an atypical manner, making them susceptible to CHS.Other commonly used diagnostic tests include laboratory blood tests (complete blood count and differential, blood glucose, basic metabolic panel, pancreatic and liver enzymes), pregnancy test, urinalysis, and plain flat radiographic series.Prior to diagnosing and treating for a presumed CHS, more serious medical conditions need to be ruled out. Medical conditions that may present similarly to CHS include cyclic vomiting syndrome, bowel perforation or obstruction, gastroparesis, cholangitis, pancreatitis, nephrolithiasis, cholecystitis, diverticulitis, ectopic pregnancy, pelvic inflammatory disease, heart attack, acute hepatitis, adrenal insufficiency, and ruptured aortic aneurysm. In general, CHS is most often misdiagnosed as cyclic vomiting syndrome. However, if simple laboratory tests and imaging have excluded more serious conditions, it is reasonable to monitor for a worsening of the patients status to prevent the unnecessary application of more invasive, and potentially dangerous, diagnostic procedures (e.g. exploratory surgery). A complete history of the persons use of cannabinoids is important in establishing the correct diagnosis.CHS has often been undiagnosed, even for years. This may be due to reluctance on behalf of patients to fully disclose their use of cannabis to healthcare professionals, especially when another person is accompanying the patient to an appointment or emergency department visit. Identifying the correct diagnosis saves money for the healthcare system and reduces morbidity associated with the condition. Treatment Many traditional medications for nausea and vomiting are ineffective. Treatment is otherwise supportive and focuses on stopping cannabis use. Proper patient education includes informing patients that their symptoms are due to their use of cannabis/cannabinoids, and that exposure to cannabinoids in the future are likely to cause their symptoms to return. Clinical pharmacists can play a role in administering this education, as well as encouraging patients to seek the assistance of mental health providers. Abstinence from cannabinoids currently remains the only definitive treatment. Cognitive behavioral therapy and motivational enhancement therapy are evidence-based outpatient treatment options for patients with cannabis use disorder.Symptomatic relief is noted with exposure to hot water (greater than 41 degrees C), which is mediated by TRPV–the capsaicin receptor. Assessing for dehydration due to vomiting and hot showers is important as it can lead to acute kidney failure, and this is easily treated with IV fluids. If dehydration is severe, hospitalization may be required. Based on the mechanism of the effect, some clinicians have used topical capsaicin cream applied to the periumbilical area in the treatment of acute CHS. The use of capsaicin as first-line treatment for CHS has been well tolerated, though the evidence for efficacy is limited. The use of hot water showers in the emergency department setting has been advocated in situations where topical capsaicin cream is unavailable, though the same precautions to hot water use (dehydration, burn injury) are required.The use of antipsychotics, such as haloperidol and olanzapine, have provided complete relief of symptoms in case-reports. The evidence for the use of benzodiazepines, such as lorazepam, has shown mixed results. Other drug treatments that have been tried, with unclear efficacy, include neurokinin-1 receptor antagonists, first-generation antihistamines (e.g. diphenhydramine), 5-HT3 receptor antagonists (e.g. ondansetron), and non-antipsychotic antidopaminergics (e.g. metoclopramide).Acetaminophen has shown some benefit in case reports for alleviating headaches associated with CHS. Opioids can provide some relief of abdominal pain, but their use is discouraged due to the risk of worsening nausea and vomiting. Epidemiology As of 2017 a French pharmacovigilance program for drug users had received reports of 29 cases of CHS. At the time there were 113 case described in the international medical literature. CHS incidence is likely to have been substantially under-reported.In the United States, an analysis of data from the National Emergency Department Sample between 2006 and 2013 found an increase in emergency room attendees with vomiting who also had cannabis use disorder, to a rate of approximately 13 per 100,000 attendees. It is possible this rise, of around 5+1⁄2 times, may be affected by sampling bias, as initial awareness of CHS prompted more diligent questioning and recording of when such ER attendees were also cannabis users.The number of people affected was unclear as of 2015. CHS has been reported more frequently in people that use cannabis daily (47.9% of people with CHS) and greater than daily (23.7% of people with CHS), compared to once weekly users (19.4% of people with CHS) and less frequent users (2.4% of people with CHS). A significant increase in the incidence of CHS (and other cannabis-related visits to the emergency department) has been noted in U.S. states that have legalized cannabis, with the incidence of cyclic vomiting prominently doubling in the US state of Colorado after legalization. As the use of cannabis continues to be legalized at the state level, the prevalence of CHS is expected to increase in the US. History Cannabinoid hyperemesis was first reported in the Adelaide Hills of South Australia in 2004.The name "cannabinoid hyperemesis syndrome" was also coined at this time. The report focused on nine patients who were chronic cannabis users who presented with cyclical vomiting illness. One woman in the study reported that warm baths provided the only relief from the nausea, severe vomiting, and stomach pain, and reportedly burned herself in a hot water bath three times trying to get relief. Society and culture CHS is not very well known. In lieu of a correct diagnosis, the average patient in the US may be charged $100,000 or more in medical bills through emergency department visits. An emergency department physician in 2018 commented that the condition wasnt on their "radar" in the five years prior, though the condition was being diagnosed more often now. Many people are surprised by the notion that cannabis can induce symptoms of nausea and vomiting, given the fact that cannabis is used to prevent nausea and vomiting. The portmanteau "scromiting" (scream + vomiting) has been used as a colloquial name for the condition, though it is not clear how widespread the use of the term is. Research directions It is unclear why CHS is disproportionately uncommon in recognition of how widely used cannabis is throughout the world. There may be genetic differences between cannabis users that affect ones risk for developing CHS, e.g., a genetic difference affecting cannabinoid metabolism that increases the level of pro-emetic cannabinoids. The pathophysiology of the syndrome is also unclear, especially with regards to the effect of cannabinoids on the gut. The long-term outcomes of patients that have had CHS are unknown. References Further reading == External links ==

Could you describe Fecal incontinence, to me Aarogya

Fecal incontinence

Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referred to as anal incontinence. FI is a sign or a symptom, not a diagnosis. Incontinence can result from different causes and might occur with either constipation or diarrhea. Continence is maintained by several interrelated factors, including the anal sampling mechanism, and incontinence usually results from deficiency of multiple mechanisms. The most common causes are thought to be immediate or delayed damage from childbirth, complications from prior anorectal surgery (especially involving the anal sphincters or hemorrhoidal vascular cushions), altered bowel habits (e.g., caused by irritable bowel syndrome, Crohns disease, ulcerative colitis, food intolerance, or constipation with overflow incontinence), and receptive anal sex. An estimated 2.2% of community dwelling adults are affected. However, reported prevalence figures vary. A prevalence of 8.39% among non-institutionalized U.S adults between 2005 and 2010 has been reported, and among institutionalized elders figures come close to 50%.Fecal incontinence has three main consequences: local reactions of the perianal skin and urinary tract, including maceration (softening and whitening of skin due to continuous moisture), urinary tract infections, or decubitus ulcers (pressure sores); a financial expense for individuals (due to cost of medication and incontinence products, and loss of productivity), employers (days off), and medical insurers and society generally (health care costs, unemployment); and an associated decrease in quality of life. There is often reduced self-esteem, shame, humiliation, depression, a need to organize life around easy access to a toilet and avoidance of enjoyable activities. FI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others. FI is one of the most psychologically and socially debilitating conditions in an otherwise healthy individual, but it is generally treatable. More than 50% of hospitalized seriously ill patients rated bladder or fecal incontinence as "worse than death". Management may be achieved through an individualized mix of dietary, pharmacologic, and surgical measures. Health care professionals are often poorly informed about treatment options, and may fail to recognize the effect of FI. Signs and symptoms FI affects virtually all aspects of peoples lives, greatly diminishing physical and mental health, and affecting personal, social and professional life. Emotional effects may include stress, fearfulness, anxiety, exhaustion, fear of public humiliation, feeling dirty, poor body-image, reduced desire for sex, anger, humiliation, depression, isolation, secrecy, frustration and embarrassment. Some people may need to be in control of life outside of FI as means of compensation. The physical symptoms such as skin soreness, pain and odor may also affect quality of life. Physical activity such as shopping or exercise is often affected. Travel may be affected, requiring careful planning. Working is also affected for most. Relationships, social activities and self-image likewise often suffer. Symptoms may worsen over time. Causes FI is a sign or a symptom, not a diagnosis, and represents an extensive list of causes. Usually, it is the result of a complex interplay of several coexisting factors, many of which may be simple to correct. Up to 80% of people may have more than one abnormality that is contributing. Deficits of individual functional components of the continence mechanism can be partially compensated for a certain period of time, until the compensating components themselves fail. For example, obstetric injury may precede onset by decades, but postmenopausal changes in the tissue strength reduce in turn the competence of the compensatory mechanisms. The most common factors in the development are thought to be obstetric injury and after effects of anorectal surgery, especially those involving the anal sphincters and hemorrhoidal vascular cushions. The majority of incontinent persons over the age of 18 fall into one of several groups: those with structural anorectal abnormalities (sphincter trauma, sphincter degeneration, perianal fistula, rectal prolapse), neurological disorders (multiple sclerosis, spinal cord injury, spina bifida, stroke, etc.), constipation/fecal loading (presence of a large amount of feces in the rectum with stool of any consistency), cognitive and/or behavioral dysfunction (dementia, learning disabilities), diarrhea, inflammatory bowel diseases (e.g. ulcerative colitis, Crohns disease), irritable bowel syndrome, disability related (people who are frail, acutely unwell, or have chronic/acute disabilities), and those cases which are idiopathic (of unknown cause). Diabetes mellitus is also known to be a cause, but the mechanism of this relationship is not well understood. Congenital Anorectal anomalies and spinal cord defects may be a cause in children. These are usually picked up and operated upon during early life, but continence is often imperfect thereafter. Anal canal The functioning of the anal canal can be damaged, traumatically or atraumatically. The resting tone of the anal canal is not the only factor which is important; both the length of the high pressure zone and its radial translation of force are required for continence. This means that even with normal anal canal pressure, focal defects such as the keyhole deformity can be the cause of substantial symptoms. External anal sphincter (EAS) dysfunction is associated with impaired voluntary control, whereas internal anal sphincter (IAS) dysfunction is associated with impaired fine tuning of fecal control. Lesions which mechanically interfere with, or prevent the complete closure of the anal canal can cause a liquid stool or mucous rectal discharge. Such lesions include piles (inflamed hemorrhoids), anal fissures, anal cancer or fistulae. Obstetric injury may tear the anal sphincters, and some of these injuries may be occult (undetected). The risk of injury is greatest when labor has been especially difficult or prolonged, when forceps are used, with higher birth weights or when an midline episiotomy is performed. Only when there is post operative investigation of FI such as endoanal ultrasound is the injury discovered. FI is a much under-reported complication of surgery. The IAS is easily damaged with an anal retractor (especially the Parks anal retractor), leading to reduced resting pressure postoperatively. Since the hemorrhoidal vascular cushions contribute 15% of the resting anal tone, surgeries involving these structures may affect continence status. Partial internal sphincterotomy, fistulotomy, anal stretch (Lords operation), hemorrhoidectomy or transanal advancement flaps may all lead to FI post operatively, with soiling being far more common than solid FI. The "keyhole deformity" refers to scarring within the anal canal and is another cause of mucus leakage and minor incontinence. This defect is also described as a groove in the anal canal wall, and may occur after posterior midline fissurectomy or fistulotomy, or with lateral IAS defects. Rare causes of traumatic injury to the anal sphincters include military or traffic accidents complicated by pelvic fractures, spine injuries or perineal lacerations, insertion of foreign bodies in the rectum, and sexual abuse. Nontraumatic conditions causing anal sphincter weakness include scleroderma, damage to the pudendal nerves and IAS degeneration of unknown cause. Radiation induced FI may involve the anal canal as well as the rectum, when proctitis, anal fistula formation and diminished function of internal and external sphincter occur. Irradiation may occur during radiotherapy, e.g. for prostate cancer. Pelvic floor Many people with FI have a generalized weakness of the pelvic floor, especially puborectalis. A weakened puborectalis leads to widening of the anorectal angle, and impaired barrier to stool in the rectum entering the anal canal, and this is associated with incontinence to solids. Abnormal descent of the pelvic floor can also be a sign of pelvic floor weakness. Abnormal descent manifests as descending perineum syndrome (>4 cm perineal descent). This syndrome initially gives constipation, and later FI. The pelvic floor is innervated by the pudendal nerve and the S3 and S4 branches of the pelvic plexus. With recurrent straining, e.g. during difficult labour or long term constipation, then stretch injury can damage the nerves supplying levator ani. The pudendal nerve is especially vulnerable to irreversible damage, (stretch induced pudendal neuropathy) which can occur with a 12% stretch. If the pelvic floor muscles lose their innervation, they cease to contract and their muscle fibres are in time replaced by fibrous tissue, which is associated with pelvic floor weakness and incontinence. Increased pudendal nerve terminal motor latency may indicate pelvic floor weakness. The various types of pelvic organ prolapse (e.g. external rectal prolapse, mucosal prolapse and internal rectal intussusception & solitary rectal ulcer syndrome) may also cause coexisting obstructed defecation. Rectum The rectum needs to be of a sufficient volume to store stool until defecation. The rectal walls need to be "compliant" i.e. able to distend to an extent to accommodate stool. Rectal sensation is required to detect the presence, nature and amount of rectal contents. The rectum must also be able to evacuate its contents fully. There must also be efficient co-ordination of rectal sensation and relaxation of the anal canal. Rectal storage capacity (i.e. rectal volume + rectal compliance) may be affected in the following ways. Surgery involving the rectum (e.g. lower anterior resection, often performed for colorectal cancer), radiotherapy directed at the rectum, and inflammatory bowel disease can cause scarring, which may result in the walls of the rectum becoming stiff and inelastic, reducing compliance. Reduced rectal storage capacity may lead to urge incontinence, where there is an urgent need to defecate as soon as stool enters the rectum, where normally stool would be stored until there was enough to distend the rectal walls and initiate the defecation cycle. Tumors and strictures also may impair reservoir function. Conversely, increased rectal volume (megarectum), may cause fecal loading and overflow FI. Reduced rectal sensation may be a contributory factor. If the sensory nerves are damaged, detection of stool in the rectum is dulled or absent, and the person will not feel the need to defecate until too late. Rectal hyposensitivity may manifest as constipation, FI, or both. Rectal hyposensitivity was reported to be present in 10% of people with FI. Pudendal neuropathy is one cause of rectal hyposensitivity, and may lead to fecal loading/impaction, megarectum and overflow FI. Normal evacuation of rectal contents is 90-100%. If there is incomplete evacuation during defecation, residual stool will be left in the rectum and threaten continence once defecation is finished. This is a feature of people with soiling secondary to obstructed defecation. Obstructed defecation is often due to anismus (paradoxical contraction or relaxation failure of the puborectalis).: 38  Whilst anismus is largely a functional disorder, organic pathologic lesions may mechanically interfere with rectal evacuation. Other causes of incomplete evacuation include non-emptying defects like a rectocele. Straining to defecate pushes stool into the rectocele, which acts like a diverticulum and causes stool sequestration. Once the voluntary attempt to defecate, albeit dysfunctional, is finished, the voluntary muscles relax, and residual rectal contents are then able to descend into the anal canal and cause leaking.: 37 Central nervous system Continence requires conscious and subconscious networking of information from and to the anorectum. Defects/brain damage may affect the central nervous system focally (e.g. stroke, tumor, spinal cord lesions, trauma, multiple sclerosis) or diffusely (e.g. dementia, multiple sclerosis, infection, Parkinsons disease or drug-induced). FI (and urinary incontinence) may also occur during epileptic seizures. Dural ectasia is an example of a spinal cord lesion that may affect continence. Diarrhea Liquid stool is more difficult to control than formed, solid stool. Hence, FI can be exacerbated by diarrhea. Some consider diarrhea to be the most common aggravating factor. Where diarrhea is caused by temporary problems such as mild infections or food reactions, incontinence tends to be short lived. Chronic conditions, such as irritable bowel syndrome or Crohns disease, can cause severe diarrhea lasting for weeks or months. Diseases, drugs, and indigestible dietary fats that interfere with the intestineal absorption may cause steatorrhea (oily rectal discharge & fatty diarrhea) and degrees of FI. Respective examples include cystic fibrosis, orlistat, and olestra. Postcholecystectomy diarrhea is diarrhea that occurs following gall bladder removal, due to excess bile acid. Orlistat is an anti-obesity (weight loss) drug that blocks the absorption of fats. This may give side effects of FI, diarrhea and steatorrhea. Overflow incontinence This may occur when there is a large mass of feces in the rectum (fecal loading), which may become hardened (fecal impaction). Liquid stool elements are able to pass around the obstruction, leading to incontinence. Megarectum (enlarged rectal volume) and rectal hyposensitivity are associated with overflow incontinence. Hospitalized patients and care home residents may develop FI via this mechanism, possibly a result of lack of mobility, reduced alertness, constipating effect of medication and/or dehydration. Pathophysiology The mechanisms and factors contributing to normal continence are multiple and inter-related. The puborectalis sling, forming the anorectal angle (see diagram), is responsible for gross continence of solid stool. The IAS is an involuntary muscle, contributing about 55% of the resting anal pressure. Together with the hemorrhoidal vascular cushions, the IAS maintains continence of flatus and liquid during rest. The EAS is a voluntary muscle, doubling the pressure in the anal canal during contraction, which is possible for a short time. The rectoanal inhibitory reflex (RAIR) is an involuntary IAS relaxation in response to rectal distension, allowing some rectal contents to descend into the anal canal where it is brought into contact with specialized sensory mucosa to detect consistency. The rectoanal excitatory reflex (RAER) is an initial, semi-voluntary contraction of the EAS and puborectalis which in turn prevents incontinence following the RAIR. Other factors include the specialized anti-peristaltic function of the last part of the sigmoid colon, which keeps the rectum empty most of the time, sensation in the lining of the rectum and the anal canal to detect when there is stool present, its consistency and quantity, and the presence of normal rectoanal reflexes and defecation cycle which completely evacuates stool from the rectum and anal canal. Problems affecting any of these mechanisms and factors may be involved in the cause. Diagnosis Identification of the exact causes usually begins with a thorough medical history, including detailed questioning about symptoms, bowel habits, diet, medication and other medical problems. Digital rectal examination is performed to assess resting pressure and voluntary contraction (maximum squeeze) of the sphincter complex and puborectalis. Anal sphincter defects, rectal prolapse, and abnormal perineal descent may be detected. Anorectal physiology tests assess the functioning of the anorectal anatomy. Anorectal manometry records the pressure exerted by the anal sphincters and puborectalis during rest and during contraction. The procedure is also able to assess sensitivity of the anal canal and rectum. Anal electromyography tests for nerve damage, which is often associated with obstetric injury. Pudendal nerve terminal motor latency tests for damage to the pudendal motor nerves. Proctography, also known as defecography, shows how much stool the rectum can hold, how well the rectum holds it, and how well the rectum can evacuate the stool. It will also highlight defects in the structure of the rectum such as internal rectal intussusception. Dynamic pelvic MRI, also called MRI defecography is an alternative which is better for some problems but not as good for other problems. Proctosigmoidoscopy involves the insertion of an endoscope (a long, thin, flexible tube with a camera) into the anal canal, rectum and sigmoid colon. The procedure allows for visualization of the interior of the gut, and may detect signs of disease or other problems that could be a cause, such as inflammation, tumors, or scar tissue. Endoanal ultrasound, which some consider to be the gold standard for detection of anal canal lesions, evaluates the structure of the anal sphincters, and may detect occult sphincter tears that otherwise would go unseen. Functional FI is common. The Rome process published diagnostic criteria for functional FI, which they defined as "recurrent uncontrolled passage of fecal material in an individual with a developmental age of at least 4 years". The diagnostic criteria are, one or more of the following factors present for the last 3 months: abnormal functioning of normally innervated and structurally intact muscles, minor abnormalities of sphincter structure/innervation (nerve supply), normal or disordered bowel habits, (i.e., fecal retention or diarrhea), and psychological causes. Furthermore, exclusion criteria are given. These are factors which all must be excluded for a diagnosis of functional FI, and are abnormal innervation caused by lesion(s) within the brain (e.g., dementia), spinal cord (at or below T12), or sacral nerve roots, or mixed lesions (e.g., multiple sclerosis), or as part of a generalized peripheral or autonomic neuropathy (e.g., due to diabetes), anal sphincter abnormalities associated with a multisystem disease (e.g., scleroderma), and structural or neurogenic abnormalities that are the major cause. Definition There is no globally accepted definition, but fecal incontinence is generally defined as the recurrent inability to voluntarily control the passage of bowel contents through the anal canal and expel it at a socially acceptable location and time, occurring in individuals over the age of four. "Social continence" has been given various precise definitions for the purposes of research; however, generally it refers to symptoms being controlled to an extent that is acceptable to the individual in question, with no significant effect on their life. There is no consensus about the best way to classify FI, and several methods are used. Symptoms can be directly or indirectly related to the loss of bowel control. The direct (primary) symptom is a lack of control over bowel contents which tends to worsen without treatment. Indirect (secondary) symptoms, which are the result of leakage, include pruritus ani (an intense itching sensation from the anus), perianal dermatitis (irritation and inflammation of the skin around the anus), and urinary tract infections. Due to embarrassment, people may only mention secondary symptoms rather than acknowledge incontinence. Any major underlying cause will produce additional signs and symptoms, such as protrusion of mucosa in external rectal prolapse. Symptoms of fecal leakage (FL) are similar, and may occur after defecation. There may be loss of small amounts of brown fluid and staining of the underwear. Types FI can be divided into those people who experience a defecation urge before leakage (urge incontinence), and those who experience no sensation before leakage (passive incontinence or soiling). Urge incontinence is characterized by a sudden need to defecate, with little time to reach a toilet. Urge and passive FI may be associated with weakness of the external anal sphincter (EAS) and internal anal sphincter (IAS) respectively. Urgency may also be associated with reduced rectal volume, reduced ability of the rectal walls to distend and accommodate stool, and increased rectal sensitivity.There is a continuous spectrum of different clinical presentations from incontinence of flatus (gas), through incontinence of mucus or liquid stool, to solids. The term anal incontinence often is used to describe flatus incontinence, however it is also used as a synonym for FI generally. It may occur together with incontinence of liquids or solids, or it may present in isolation. Flatus incontinence may be the first sign of FI. Once continence to flatus is lost, it is rarely restored. Anal incontinence may be equally disabling as the other types. Fecal leakage, fecal soiling and fecal seepage are minor degrees of FI, and describe incontinence of liquid stool, mucus, or very small amounts of solid stool. They cover a spectrum of increasing symptom severity (staining, soilage, seepage and accidents). Rarely, minor FI in adults may be described as encopresis. Fecal leakage is a related topic to rectal discharge, but this term does not necessarily imply any degree of incontinence. Discharge generally refers to conditions where there is pus or increased mucus production, or anatomical lesions that prevent the anal canal from closing fully, whereas fecal leakage generally concerns disorders of IAS function and functional evacuation disorders which cause a solid fecal mass to be retained in the rectum. Solid stool incontinence may be called complete (or major) incontinence, and anything less as partial (or minor) incontinence (i.e. incontinence of flatus (gas), liquid stool and/or mucus).In children over the age of four who have been toilet trained, a similar condition is generally termed encopresis (or soiling), which refers to the voluntary or involuntary loss of (usually soft or semi-liquid) stool. The term pseudoincontinence is used when there is FI in children who have anatomical defects (e.g. enlarged sigmoid colon or anal stenosis). Encopresis is a term that is usually applied when there are no such anatomical defects present. The ICD-10 classifies nonorganic encopresis under "behavioural and emotional disorders with onset usually occurring in childhood and adolescence" and organic causes of encopresis along with FI. FI can also be classified according to gender, since the cause in females may be different from males, for example it may develop following radical prostatectomy in males, whereas females may develop FI as an immediate or delayed consequence of damage whilst giving birth. Pelvic anatomy is also different according to gender, with a wider pelvic outlet in females. Clinical measurement Several severity scales exist. The Cleveland Clinic (Wexner) fecal incontinence score takes into account five parameters that are scored on a scale from zero (absent) to four (daily) frequency of incontinence to gas, liquid, solid, of need to wear pad, and of lifestyle changes. The Parks incontinence score uses four categories: those continent for solid and liquid stool and also for flatus. those continent for solid and liquid stool but incontinent for flatus (with or without urgency). those continent for solid stool but incontinent for liquid stool or flatus. those incontinent to formed stool (complete incontinence).The fecal incontinence severity index is based on four types of leakage (gas, mucus, liquid stool, solid stool) and five frequencies (once to three times per month, once per week, twice per week, once per day, twice or more per day). Other severity scales include: AMS, Pescatori, Williams score, Kirwan, Miller score, Saint Marks score and the Vaizey scale. Differential diagnosis FI may present with signs similar to rectal discharge (e.g. fistulae, proctitis or rectal prolapse), pseudoincontinence, encopresis (with no organic cause) and irritable bowel syndrome. Management FI is generally treatable with conservative management, surgery or both. The success of treatment depends upon the exact causes and how easily these are corrected. Treatment choice depends on the cause and severity of disease, and the motivation and general health of the person affected. Commonly, conservative measures are used together, and if appropriate surgery carried out. Treatments may be attempted until symptoms are satisfactorily controlled. A treatment algorithm based upon the cause has been proposed, including conservative, non-operative and surgical measures (neosphincter refers to either dynamic graciloplasty or artificial bowel sphincter, lavage refers to retrograde rectal irrigation). Conservative measures include dietary modification, drug treatment, retrograde anal irrigation, biofeedback retraining anal sphincter exercises. Incontinence products refer to devices such as anal plugs and perineal pads and garments such as diapers/nappies. Perineal pads are efficient and acceptable for only minor incontinence. If all other measures are ineffective removing the entire colon may be an option. Diet Dietary modification may be important for successful management. Both diarrhea and constipation can contribute to different cases, so dietary advice must be tailored to address the underlying cause or it may be ineffective or counter productive. In persons with disease aggravated by diarrhea or those with rectal loading by soft stools, the following suggestions may be beneficial: increase dietary fiber; reduce wholegrain cereals/bread; reduce fruit and vegetables which contain natural laxative compounds (rhubarb, figs, prunes/plums); limit beans, pulses, cabbage and sprouts; reduce spices (especially chilli); reduce artificial sweeteners (e.g. sugar free chewing gum); reduce alcohol (especially stout, beer and ale); reduce lactose if there is some degree of lactase deficiency; and reduce caffeine. Caffeine lowers the resting tone of the anal canal and also causes diarrhea. Excessive doses of vitamin C, magnesium, phosphorus and/or calcium supplements may increase FI. Reducing olestra fat substitute, which can cause diarrhea, may also help. Medication Pharmacological management may include anti-diarrheal/constipating agents and laxatives/stool bulking agents. Stopping or substituting any previous medication that causes diarrhea may be helpful in some (see table). There is not good evidence for the use of any medications, however.In people who have undergone gallbladder removal, the bile acid sequestrant cholestyramine may help minor degrees of FI. Bulking agents also absorb water, so may be helpful for those with diarrhea. A common side effect is bloating and flatulence. Topical agents to treat and prevent dermatitis may also be used, such as topical antifungals when there is evidence of perianal candidiasis or occasionally mild topical anti-inflammatory medication. Prevention of secondary lesions is carried out by perineal cleansing, moisturization, and use of a skin protectant. Other measures Evacuation aids (suppositories or enemas) e.g. glycerine or bisacodyl suppositories may be prescribed. People may have poor resting tone of the anal canal, and consequently may not be able to retain an enema, in which case transanal irrigation (retrograde anal irrigation) may be a better option, as this equipment utilizes an inflatable catheter to prevent loss of the irrigation tip and to provide a water tight seal during irrigation. A volume of lukewarm water is gently pumped into the colon via the anus. People can be taught how to perform this treatment in their own homes, but it does require special equipment. If the irrigation is efficient, stool will not reach the rectum again for up to 48 hours. By regularly emptying the bowel using transanal irrigation, controlled bowel function is often re-established to a high degree in patients with bowel incontinence and/or constipation. This enables control over the time and place of evacuation and development of a consistent bowel routine. However, persistent leaking of residual irrigation fluid during the day may occur and make this option unhelpful, particularly in persons with obstructed defecation syndrome who may have incomplete evacuation of any rectal contents. Consequently, the best time to carry out the irrigation is typically in the evening, allowing any residual liquid to be passed the next morning before leaving the home. Complications such as electrolyte imbalance and perforation are rare. The effect of transanal irrigation varies considerably. Some individuals experience complete control of incontinence, and other report little or no benefit. It has been suggested that if appropriate, people be offered home retrograde anal irrigation.Biofeedback (the use of equipment to record or amplify and then feed back activities of the body) is a commonly used and researched treatment, but the benefits are uncertain. Biofeedback therapy varies in the way it is delivered, but it is unknown if one type has benefits over another.The role of pelvic floor exercises and anal sphincter exercises in FI is poorly determined. While there may be some benefit they appear less useful than implanted sacral nerve stimulators. These exercises aim to increase the strength of the pelvic floor muscles (mainly levator ani). The anal sphincters are not technically part of the pelvic floor muscle group, but the EAS is a voluntary, striated muscle which therefore can be strengthened in a similar manner. It has not been established whether pelvic floor exercises can be distinguished from anal sphincter exercises in practice by the people doing them. This kind of exercise is more commonly used to treat urinary incontinence, for which there is a sound evidence base for effectiveness. More rarely are they used in FI. The effect of anal sphincter exercises are variously stated as an increase in the strength, speed or endurance of voluntary contraction (EAS).Electrical stimulation can also be applied to the anal sphincters and pelvic floor muscles, inducing muscle contraction without traditional exercises (similar to transcutaneous electrical nerve stimulation, TENS). The evidence supporting its use is limited, and any benefit is tentative. In light of the above, intra-anal electrical stimulation (using an anal probe as electrode) appears to be more efficacious than intra-vaginal (using a vaginal probe as electrode). Rarely, skin reactions may occur where the electrodes are placed, but these issues typically resolve when the stimulation is stopped. Surgically implanted sacral nerve stimulation may be more effective than exercises, and electrical stimulation and biofeedback may be more effective than exercises or electrical stimulation by themselves. TENS is also sometimes used to treat FI by transcutaneous tibial nerve stimulation.In a minority of people, anal plugs may be useful for either standalone therapy or in concert with other treatments. Anal plugs (sometimes termed tampons) aim to block involuntary loss of fecal material, and they vary in design and composition. Polyurethane plugs were reported to perform better than those made of polyvinyl-alcohol. Plugs are less likely to help those with frequent bowel movements, and many find them difficult to tolerate.In women, a device that functions as an inflatable balloon in the vagina, has been approved for use in the United States. Surgery Surgery may be carried out if conservative measures alone are not sufficient to control incontinence. There are many surgical options, and their relative effectiveness is debated due to a lack of good quality evidence. The optimal treatment regime may be a both surgical and non-surgical treatments. The surgical options can be considered in four categories: restoration and improvement of residual sphincter function (sphincteroplasty, sacral nerve stimulation, tibial nerve stimulation, correction of anorectal deformity), replacement / imitation of the sphincter or its function (anal encirclement, SECCA procedure, non-dynamic graciloplasty, perianal injectable bulking agents), dynamic sphincter replacement (artificial bowel sphincter, dynamic graciloplasty), antegrade continence enema (Malone procedure), and finally fecal diversion (e.g. colostomy). A surgical treatment algorithm has been proposed. Isolated sphincter defects (IAS/EAS) may be initially treated with sphincteroplasty and if this fails, the person can be assessed for sacral nerve stimulation. Functional deficits of the EAS and/or IAS (i.e. where there is no structural defect, or only limited EAS structural defect, or with neurogenic incontinence) may be assessed for sacral nerve stimulation. If this fails, neosphincter with either dynamic graciloplasty or artificial anal sphincter may be indicated. Substantial muscular and/or neural defects may be treated with neosphincter initially. Epidemiology FI is thought to be very common, but much under-reported due to embarrassment. One study reported a prevalence of 2.2% in the general population. It affects people of all ages, but is more common in older adults (but it should not be considered a normal part of aging). Females are more likely to develop it than males (63% of those with FI over 30 may be female). In 2014, the National Center for Health Statistics reported that one out of every six seniors in the U.S. who lived in their own home or apartment had FI. Men and women were equally affected. 45–50% of people with FI have severe physical and/or mental disabilities. People with dementia are four times more likely to have fecal incontinence compared to people of similar ages.Risk factors include age, female gender, urinary incontinence, history of vaginal delivery (non-Caesarean section childbirth), obesity, prior anorectal surgery, poor general health and physical limitations. Combined urinary and fecal incontinence is sometimes termed double incontinence, and it is more likely to be present in those with urinary incontinence.Traditionally, FI was thought to be an insignificant complication of surgery, but it is now known that a variety of different procedures are associated with this possible complication, and sometimes at high levels. Examples are midline internal sphincterotomy (8% risk), lateral internal sphincterotomy, fistulectomy, fistulotomy (18-52%), hemorrhoidectomy (33%), ileo-anal reservoir reconstruction, lower anterior resection, total abdominal colectomy, ureterosigmoidostomy, and anal dilation (Lords procedure, 0-50%). Some authors consider obstetric trauma to be the most common cause. History While the first mention of urinary incontinence occurs in 1500 BC in the Ebers Papyrus, the first mention of FI in a medical context is unknown. For many centuries, colonic irrigation was the only treatment available. Stoma creation was described in 1776, FI associated with rectal prolapse in 1873 and anterior sphincter repair in 1875. During the mid 20th Century, several operations were developed for instances where the sphincters were intact but weakened. Muscle transpositions using the gluteus maximus or the gracilis were devised, but did not become used widely until later. End-to-end sphincteroplasty is shown to have a high failure rate in 1940. In 1971, Parks and McPartlin first describe an overlapping sphincteroplasty procedure. Biofeedback is first introduced in 1974. In 1975, Parks describes post anal repair, a technique to reinforce the pelvic floor and EAS to treat idiopathic cases. Endoanal ultrasound is invented in 1991, which starts to demonstrate the high number of occult sphincter tears following vaginal deliveries. In 1994, the use of an endoanal coil during pelvic MRI shows greater detail of the anal canal than previously. During the last 20 years, dynamic graciliplasty, sacral nerve stimulation, injectable perianal bulking agents and radiofrequency ablation have been devised, mainly due to the relatively poor success rates and high morbidity associated with the earlier procedures. Society and culture Persons with this symptom are frequently ridiculed and ostracized in public. It has been described as one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. In older people, it is one of the most common reasons for admission into a care home. Persons who develop FI earlier in life are less likely to marry and obtain employment. Often, people will go to great lengths to keep their condition secret. It has been termed "the silent affliction" since many do not discuss the problem with their close family, employers or clinicians. They may be subject to gossip, hostility, and other forms of social exclusion. The economic cost has not received much attention. In the Netherlands, outpatients were reported to have total costs of €2169 annually, and over half of this was productivity loss in work. In the US, the average lifetime cost (treatment and follow-up) was $17,166 per person in 1996. The average hospital charges for sphincteroplasty was $8555 per procedure. Overall, in the US, the total charges associated with surgery increased from $34 million in 1998 to $57.5 million in 2003. Sacral nerve stimulation, dynamic graciloplasty and colostomy were all shown to be cost effective. Japan Some insults in Japan relate to incontinence, such as kusotare/kusottare and shikkotare which mean shit hanger/leaker/oozer and piss leaker/oozer respectively, though these have not been in common use since the 1980s. Law The case Hiltibran et al v. Levy et al in the United States District Court for the Western District of Missouri resulted in that court issuing an order in 2011. That order requires incontinence briefs funded by Medicaid to be given by Missouri to adults who would be institutionalized without them. Research Engineered anal sphincters grown from stem cells have been successfully implanted in mice. New blood vessels developed and the tissue displayed normal contraction and relaxation. In the future, these methods may become part of the management of FI, replacing the need for high morbidity implanted devices such as the artificial bowel sphincter. See also Open defecation References Further reading External links Independent continence product advisor

Hey Aarogya!, what is Ichthyosis

Ichthyosis

Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cause and mode of inheritance (e.g., dominant, recessive, autosomal or X-linked). Ichthyosis comes from the Greek ἰχθύς ichthys, literally "fish", since dry, scaly skin is the defining feature of all forms of ichthyosis.The severity of symptoms can vary enormously, from the mildest, most common, types such as ichthyosis vulgaris, which may be mistaken for normal dry skin, up to life-threatening conditions such as harlequin-type ichthyosis. Ichthyosis vulgaris accounts for more than 95% of cases. Types Many types of ichthyoses exist, and an exact diagnosis may be difficult. Types of ichthyoses are classified by their appearance, if they are syndromic or not, and by mode of inheritance. For example, non-syndromic ichthyoses that are inherited recessively come under the umbrella term autosomal recessive congenital ichthyosis (ARCI). Ichthyosis caused by mutations in the same gene can vary considerably in severity and symptoms. Some ichthyoses do not appear to fit exactly into any one type while mutations in different genes can produce ichthyoses with similar symptoms. Of note, X-linked ichthyosis is associated with Kallmann syndrome (close to the KAL1 gene). The most common or well-known types are: Non-syndromic ichthyosis Syndromic Ichthyosis Non-genetic ichthyosis Ichthyosis acquisita Diagnosis A physician often can diagnose ichthyosis by looking at the skin. A family history is also useful in determining the mode of inheritance. In some cases, a skin biopsy is done to help to confirm the diagnosis while in others genetic testing may be helpful in making a diagnosis. Diabetes has not been definitively linked to acquired ichthyosis or ichthyosis vulgaris; however, there are case reports associating new onset ichthyosis with diabetes.Ichthyosis has been found to be more common in Native American, Asian, Mongolian groups. There is no way to prevent ichthyosis. Ichthyosis is a genetically and phenotypically heterogeneous disease that can be isolated and restricted to the skin manifestations or associated with extracutaneous symptoms. One of which is limb reduction defect known as CHILD syndrome; a rare inborn error of metabolism of cholesterol biosynthesis that is usually restricted to one side of the body. One case with symptoms matching CHILD syndrome has been described as having a likely-different cause. Treatments Treatments for ichthyosis often take the form of topical application of creams and emollient oils, in an attempt to hydrate the skin. Creams containing a high percentage of urea or lactic acid have been shown to work exceptionally well in some cases. Application of propylene glycol is another treatment method. Retinoids are used for some conditions. Exposure to sunlight may improve or worsen the condition. In some cases, excess dead skin sloughs off much better from wet tanned skin after bathing or a swim, although the dry skin might be preferable to the damaging effects of sun exposure. There can be ocular manifestations of ichthyosis, such as corneal and ocular surface diseases. Vascularizing keratitis, which is more commonly found in congenital keratitis-ichythosis-deafness (KID), may worsen with isotretinoin therapy. Other animals Ichthyosis or ichthyosis-like disorders exist for several types of animals, including cattle, chickens, llamas, mice, and dogs. Ichthyosis of varying severity is well documented in some popular breeds of domestic dogs. The most common breeds to have ichthyosis are Golden retrievers, American bulldogs, Jack Russell terriers, and Cairn terriers. See also European Network for Ichthyosis – International patients network run by national European patients associations Skin disease Ichthyosis en confetti List of cutaneous conditions List of cutaneous neoplasms associated with systemic syndromes References External links DermAtlas 1896838546 Ichthyosis Overview - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Hi Aarogya, could you help me understand about Lichen planus

Lichen planus

Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, and is only named that because it looks like one. It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale (Wickhams striae), commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa. The hue may be gray-brown in people with darker skin. Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement. The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms. The term lichenoid reaction (lichenoid eruption or lichenoid lesion) refers to a lesion of similar or identical histopathologic and clinical appearance to lichen planus (i.e., an area which resembles lichen planus, both to the naked eye and under a microscope). Sometimes dental materials or certain medications can cause a lichenoid reaction. They can also occur in association with graft versus host disease.: 258 Classification Lichen planus lesions are so called because of their "lichen-like" appearance and can be classified by the site they involve, or by their morphology. Site Lichen planus may be categorized as affecting mucosal or cutaneous surfaces. Cutaneous forms are those affecting the skin, scalp, and nails. Mucosal forms are those affecting the lining of the gastrointestinal tract (mouth, pharynx, esophagus, stomach, anus), larynx, and other mucosal surfaces including the genitals, peritoneum, ears, nose, bladder and conjunctiva of the eyes. Pattern Lichen planus lesions can occur in many different forms: Overlap syndromes Occasionally, lichen planus is known to occur with other conditions. For example: Lupus erythematosus overlap syndrome. Lesions of this syndrome share features of both lupus erythematosus and lichen planus. Lesions are usually large and hypopigmented, atrophic, and with a red to blue colour and minimal scaling. Telangectasia may be present. Lichen sclerosus overlap syndrome, sharing features of lichen planus and lichen sclerosus. Signs and symptoms Although lichen planus can present with a variety of lesions, the most common presentation is as a well defined area of purple-coloured, itchy, flat-topped papules with interspersed lacy white lines (Wickhams striae). This description is known as the characteristic "6 Ps" of lichen planus: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques. This rash, after regressing, is likely to leave an area of hyperpigmentation that slowly fades. That said, a variety of other lesions can also occur. Skin Variants of cutaneous lichen planus are distinguished based upon the appearance of the lesions and/or their distribution. Lesions can affect the: Extremities (face, dorsal hands, arms, and nape of neck). This is more common in Middle Eastern countries in spring and summer, where sunlight appears to have a precipitating effect. Palms and soles Intertriginous areas of the skin. This is also known as "inverse lichen planus." Nails characterized by irregular longitudinal grooving and ridging of the nail plate, thinning of the nail plate, pterygium formation, shedding of the nail plate with atrophy of the nail bed, subungual keratosis, longitudinal erthronychia (red streaks), and subungual hyperpigmentation. A sand-papered appearance is present in around 10% of individuals with nail lichen planus. Hair and scalp. The scalp is rarely affected by a condition known as lichen planopilaris, acuminatus, follicular lichen planus, and peripilaris, characterised by violaceous, adherent follicular scale with progressive scarring alopecia. While lichen planus and lichen planopilaris may occur together, aside from sharing the term lichen and revealing inflammation on skin biopsy, there is neither established data on their co-occurrence nor data to suggest a common etiology. Lichen planopilaris is considered an orphan disease with no definitive prevalence data and no proven effective treatments.Other variants may include: Lichen planus pemphigoides characterized by the development of tense blisters atop lesions of lichen planus or the development vesicles de novo on uninvolved skin. Keratosis lichenoides chronica (also known as "Nekams disease") is a rare dermatosis characterized by violaceous papular and nodular lesions, often arranged in a linear or reticulate pattern on the dorsal hands and feet, extremities, and buttock, and some cases manifest by seborrheic dermatitis-like eruption on the scalp and face; also palmo plantar keratosis has been reported. Lichenoid keratoses (also known as "benign lichenoid keratosis," and "Solitary lichen planus") is a cutaneous condition characterized by brown to red scaling maculopapules, found on sun-exposed skin of extremities. Restated, this is a cutaneous condition usually characterized by a solitary dusky-red to violaceous papular skin lesion. Lichenoid dermatitis represents a wide range of cutaneous disorders characterized by lichen planus-like skin lesions. Mucous membranes Lichen planus affecting mucosal surfaces may have one lesion or be multifocal. Examples of lichen planus affecting mucosal surfaces include: Esophageal lichen planus, affecting the esophageal mucosa. This can present with difficulty or pain when swallowing due to oesophageal inflammation, or as the development of an esophageal stricture. It has also been hypothesized that it is a precursor to squamous cell carcinoma of the esophagus. Genital lichen planus, which may cause lesions on the glans penis or skin of the scrotum in males, and the vulva or vagina in females. Symptoms may include lower urinary tract symptoms associated with stenosis of the urethra, painful sexual intercourse, and itching. In females, Vulvovaginal-gingival syndrome, is severe and distinct variant affecting the vulva, vagina, and gums, with complications including scarring, vaginal stricture formation, or vulva destruction. The corresponding syndrome in males, affecting the glans penis and gums, is the peno-gingival syndrome. It is associated with HLA-DQB1. Mouth Oral lichen planus (also termed oral mucosal lichen planus), is a form of mucosal lichen planus, where lichen planus involves the oral mucosa, the lining of the mouth. This may occur in combination with other variants of lichen planus. Six clinical forms of oral lichen planus (OLP) are recognized: These types often coexist in the same individual. Oral lichen planus (OLP) tends to present bilaterally as mostly white lesions on the inner cheek, although any mucosal site in the mouth may be involved. Other sites, in decreasing order of frequency, may include the tongue, lips, gingivae, floor of the mouth, and very rarely, the palate.Generally, oral lichen planus tends not to cause any discomfort or pain, although some people may experience soreness when eating or drinking acidic or spicy foodstuffs or beverages. When symptoms arise, they are most commonly associated with the atrophic and ulcerative subtypes. These symptoms can include a burning sensation to severe pain. They may also experience mucosal bleeding in response to mild trauma, such as toothbrushing. Additionally, the Koebner phenomenon (the development of new lesions at sites of trauma) is not only present in cutaneous lichen planus (CLP) but can also occur in the setting of OLP. Residual postinflammatory hyperpigmentation has been reported in association with OLP, manifesting as brown to black pigmentation on the oral mucosa and may most likely occur in dark-skinned individuals.OLP may occur as a sole manifestation of the disease or in conjunction with other clinical manifestations of LP, including cutaneous LP, genital LP, nail LP, and lichen planopilaris (scalp LP). Causes Cutaneous LP is a self-limiting condition. It usually resolves within 6 to 12 months. Oral LP is a non infectious, chronic inflammatory condition that involves the oral mucosa and may be accompanied by skin lesions. The etiology of oral LP are unknown.It is not clear whether the mechanisms causing isolated oral LP are different from those causing oral LP with cutaneous LP. An immune-mediated mechanism where basal keratinocytes are being targeted as foreign antigens by activated T cells, especially CD8+ T cells, has been proposed. Upregulation of intercellular adhesion molecule-1 (ICAM-1) and cytokines associated with T-helper 1 immune response, may also play an important role in the pathogenesis of lichen planus.Stress is thought to play a role in the pathogenesis of oral LP. Patients with anxiety and depression are reported more commonly with oral LP if compared to normal healthy individuals. Some studies have indicated that stressful events can induce LP lesions in otherwise healthy individuals. However, a cause effect relationship between stress and the onset of oral LP has not been demonstrated. Autoimmune response to epithelial self-antigens remains a possibility. A single study of cutaneous LP reported evidence in support of autoimmunity by expanding in vitro T cells isolated from the skin lesions of two patients, followed by testing the ability of these T cells to kill autologous keratinocytes (cytotoxicity). Several potential triggers of oral LP have been proposed over the years, mainly Hypersensitivity reaction Restorative material (e.g. amalgam and composite) or drugs can cause hypersensitivity reaction and lead to oral LP. Oral LP usually resolve upon removal of the trigger, as is characteristics of oral LP Viral infection Pathogenesis Oral LP is considered to be a T-cell mediated chronic inflammatory tissue reaction that results in a cytotoxic reaction against epithelial basal cells. The inflammatory infiltrate in oral LP is primarily composed of CD8+ T cells. A potential pathway for CD8+ T cell-mediated cytotoxicity in oral LP is described as follows:Antigens presented on MHC 1 molecules activates CD8+ T cells on keratinocytes or by encounters with activated CD4+ helper T cells or cytokines produced by activated CD4+ helper T cells Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF)-alpha, secretion of granzyme B, or Fas-Fas ligand interactions. Chemokines are produced by activated CD8+ T cells that attract additional inflammatory cells, thereby promoting continued inflammation. Other mechanisms that have been proposed include: upregulation of matrix metalloproteinases that disrupt the epithelial basement membrane zone and allow entry of immune cells into the epidermis, the release of proinflammatory mediators and proteases by mast cells, and perturbations in the innate immune response that may involve toll-like receptors.Oral LP may also be caused by genetic factor which influence the immune function. A separate study performed in China found an association between a polymorphism in the TNF-alpha gene and risk for oral LP in a subset of patients. An Italian study found a significant increase in a genetic polymorphism of the first intron of the interferon (IFN)-gamma promoter in patients with oral LP compared with controls. Diagnosis Skin Patient history and clinical presentation need to be taken to diagnose lichen planus. Patients with suspected cutaneous lichen planus need to be evaluated clinically through patient interviews and physical examinations. Patients should be questioned about their medication history, any history of pruritus or genital pain and history of dysphagia or odynophagia. Examination of entire cutaneous surface including the scalp, oral cavity and external genitalia need to be included. Wickhams striae often can be seen during microscopic examination of cutaneous lesions of lichen planus.To confirm the diagnosis of cutaneous lichen planus, a skin biopsy can be done. A punch biopsy of sufficient depth to the mid dermis is usually significant. Immunofluorescence studies are not always needed. Direct immunofluorescence (DIF) can be useful in patients with bullous lesions to differentiate the condition from an autoimmune vesiculobullous disease. Mouth A diagnosis of oral lichen planus (LP) is confirmed through review of the patient history, physical examination, and histologic findings.The clinical evaluation should include a patient history that assesses the following: History of LP involving other body sites or other skin disorders that may present with similar findings (e.g., autoimmune blistering diseases) Presence of associated symptoms (e.g., pain, burning) Medication the patients are taking within the few weeks to months after drug initiation e.g. antihypertensives, antidepressants, diuretics, antidiabetics, NSAIDs, etc. to evaluate for the possibility of an oral lichenoid drug eruption History of dental restorations, use of dental appliances, or oral exposure to substances that may cause oral lichenoid contact eruptions (e.g. dental composites, cobalt chromium based dentures etc.)A full examination that includes the evaluation of the mucosal and cutaneous surfaces, including the vulva, vagina, penis, scalp, and nails should be performed. Thorough examination may lead to the detection of extraoral manifestations of LP that provide additional support for the diagnosis or the identification of clinical findings that suggest another diagnosis. Tissue biopsies of oral LP help to confirm the diagnosis and are particularly of value for erythematous and erosive LP, which share features with multiple other mucosal disorders, including oral malignancy. Biopsies to confirm oral LP are less essential in patients who present with classic reticular LP, particularly in patients in whom a diagnosis of LP has already been confirmed through biopsy of an extraoral manifestation of this disorder. Differential diagnosis Skin Lichenoid drug eruption The cutaneous manifestations resemble idiopathic lichen planus. Chronic graft-versus-host disease The history of preceding hematopoietic cell transplant is helpful for diagnosis Psoriasis Atopic dermatitis Cutaneous lupus erythematosus Discoid lupus erythematosus Mouth Oral lichenoid drug reaction Lichenoid drug eruptions may be caused by a variety of systemic medications and share clinical features with oral LP. Histologic findings of a deep mixed infiltrate with lymphocytes, plasma cells, and neutrophils (with or without eosinophils) and perivascular inflammation favor this diagnosis. Oral lichenoid contact reaction (allergic contact mucositis) Oral lichenoid contact reactions may be caused by a variety of substances. The clinical and histologic features of oral lichenoid contact reactions are similar to oral LP. Patch testing and recognition of the proximity of an offending substance to the eruption can aid with diagnosis. Autoimmune blistering diseases Mucous membrane pemphigoid and other autoimmune blistering diseases may present with oral erosions and desquamative gingivitis similar to that seen in erosive LP. Biopsies for routine histologic examination and direct immunofluorescence are useful for distinguishing these disorders from oral LP. Graft-versus-host disease (GVHD) Lacy, reticulated plaques or erosions that resemble oral LP may occur in GVHD. The histologic findings of these disorders are also similar. The patient history is useful for differentiating chronic GVHD from oral LP. Oral involvement in acute GVHD is less well characterized than chronic GVHD, but has been associated with erythematous, erosive, ulcerative, or lichenoid oral lesions. Leukoplakia Leukoplakia is a manifestation of squamous epithelial hyperplasia that may be a precursor to oral squamous cell carcinoma. White patches or plaques usually appear on the oral mucosa. To rule out malignancy, a biopsy of leukoplakia is indicated. Oral squamous cell carcinoma Oral squamous cell carcinoma (SCC) can present as erythematous or white patches, ulcers, or exophytic masses. The highest risk for oral SCC may occur in patients with erythematous or erosive oral LP. A biopsy is indicated. Leukoedema Leukoedema is a common, benign finding in the oral cavity that presents as white-gray, somewhat translucent plaques on the mucosa. The buccal mucosa is the most common site for involvement. Symptoms are absent, and no treatment is necessary. Oropharyngeal candidiasis Oropharyngeal candidiasis (also known as thrush) is a common infection that has a predilection for infants, older adults with dentures, immunosuppressed individuals, and individuals utilizing intraoral corticosteroid therapy. Patients present with white plaques or erythematous patches on the buccal mucosa, palate, tongue, or oropharynx that may be mistaken for reticular LP. Histopathology The histologic findings of oral LP can offer strong support for the diagnosis, but are not pathognomonic. Clinical correlation is required. Common histologic findings of oral LP include: Parakeratosis and slight acanthosis of the epithelium Saw-toothed rete ridges Liquefaction (hydropic) degeneration of the basal layer with apoptotic keratinocytes (referred to as Civatte, colloid, hyaline, or cytoid bodies) An amorphous band of eosinophilic material at the basement membrane composed of fibrin or fibrinogen. A lichenoid (band-like) lymphocytic infiltrate immediately subjacent to the epithelium.Nonetheless, interpreting the histopathological features of oral LP has been associated historically with high intra-observer and inter-observer variabilities. Treatment There is no cure for lichen planus, and so treatment of cutaneous and oral lichen planus is for symptomatic relief or due to cosmetic concerns. When medical treatment is pursued, first-line treatment typically involves either topical or systemic corticosteroids, and removal of any triggers. Without treatment, most lesions will spontaneously resolve within 6–9 months for cutaneous lesions, and longer for mucosal lesions. Skin Many different treatments have been reported for cutaneous lichen planus, however there is a general lack of evidence of efficacy for any treatment. Treatments tend to be prolonged, partially effective and disappointing. The mainstay of localized skin lesions is topical steroids. Additional treatments include retinoids, such as acitretin, or sulfasalazine. Narrow band UVB phototherapy or systemic PUVA therapy are known treatment modalities for generalized disease. Mouth Reassurance that the condition is benign, elimination of precipitating factors and improving oral hygiene are considered initial management for symptomatic OLP, and these measures are reported to be useful. Treatment usually involves topical corticosteroids (such as betamethasone, clobetasol, dexamethasone, and triamcinolone) and analgesics, or if these are ineffective and the condition is severe, then systemic corticosteroids may be used. Calcineurin inhibitors (such as pimecrolimus, tacrolimus or cyclosporin) are sometimes used. While topical steroids are widely accepted as first line treatment for mucosal lichen planus, there is only weak evidence to support their effectiveness for erosive oral lichen planus. Prognosis Cutaneous lichen planus lesions typically resolve within six months to a year. However, some variant such as the hypertrophic variant might persist for years if left untreated or unmonitored.It is found that cutaneous lichen planus does not carry a risk of skin cancer. In contrast to cutaneous LP, which is self limited, lichen planus lesions in the mouth may persist for many years, and tend to be difficult to treat, with relapses being common.Although this condition was first described almost a century ago, it has been reported that its associated oral cancer risk has been exaggerated. Overall, it is found that patients with erythematous or erosive oral lichen planus have a higher risk of oral squamous cell carcinoma compared to patients diagnosed with other variants.Due to the possibility that oral LP may increase risk for oral cancer, patients with oral lichen planus are encouraged to avoid activities known to increase the risk for oral cancer, such as smoking and alcohol use.Patients with oral lichen planus should be followed-up at least every 6 to 12 months, to assess the disease activity, changes in symptoms or even detect early signs of malignancy. Epidemiology The overall estimated prevalence of lichen planus in worldwide population is in the range of 0.2% to 5%.It generally occurs more commonly in females, in a ratio of 3:2, and most cases are diagnosed between the ages of 30 and 60, but it can occur at any age.Lichen planus can occur in patients as diverse cutaneous manifestations alone or in combination with mucosal lichen planus and, or lichen planus of the nails. Study shows that frequency of mucosal involvement of lichen planus patients is 30- 70%.Oral lichen planus is relatively common, It is one of the most common mucosal diseases. The prevalence in the general population is about 1.27–2.0%, and it occurs more commonly in middle aged people. Oral lichen planus in children is rare. About 50% of females with oral lichen planus were reported to have undiagnosed vulvar lichen planus.Some studies suggest that cutaneous lichen planus is more commonly found in men whilst oral lichen planus lesions are more commonly found in women. History Lichen planus was first reported in 1869 by Erasmus Wilson.The origin of the word is believed to be from the Greek word Leichen, which means tree moss, and also from Latin word planus, which means flat and even surface. Dr Wilson explained the condition as an inflammatory disorder with unknown etiology. Initially, the characteristic surface markings or striae was described by Weyl in 1885. In 1895, Wickham further explained the characteristic of the lesion, now known as Wickham striae. Further on, Darier explained the presence of such characteristic markings by correlating with an increase thickness of the granular cell layer. The coexistence of oral, cervical and stomach lichen planus lesions were described by Guogerot and Burnier in 1937. A similar variant of mucosal lichen planus as the vulvovaginal-gingival syndrome with erosive lesions involving oral and vulvovaginal mucosa were introduced by Pelisse and colleagues in year 1982. Research Apremilast is undergoing investigation as a potential treatment. Notes References External links Lichen planus at Curlie

Aarogya, give me a short description about Erythema multiforme major

Erythema multiforme major

Erythema multiforme major is a form of rash with skin loss or epidermal detachment. The term "erythema multiforme majus" is sometimes used to imply a bullous (blistering) presentation.According to some sources, there are two conditions included on a spectrum of this same disease process: Stevens–Johnson syndrome (SJS) Toxic epidermal necrolysis (TEN) which described by Alan Lyell and previously called Lyell syndrome[5].In this view, EM major, SJS and TEN are considered a single condition, distinguished by degree of epidermal detachment.However, a consensus classification separates erythema multiforme minor, erythema multiforme major, and SJS/TEN as three separate entities. References 5. Orphanet Journal of Rare Diseases 2010, 5:39 doi:10.1186/1750-1172-5-39 == External links ==

Hey Aarogya, could you help me understand about Prelabor rupture of membranes

Prelabor rupture of membranes

Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complications in the baby may include premature birth, cord compression, and infection. Complications in the mother may include placental abruption and postpartum endometritis.Risk factors include infection of the amniotic fluid, prior PROM, bleeding in the later parts of pregnancy, smoking, and a mother who is underweight. Diagnosis is suspected based on symptoms and speculum exam and may be supported by testing the vaginal fluid or by ultrasound. If it occurs before 37 weeks it is known as PPROM (preterm prelabor rupture of membranes) otherwise it is known as term PROM.Treatment is based on how far along a woman is in pregnancy and whether complications are present. In those at or near term without any complications, induction of labor is generally recommended. Time may also be provided for labor to begin spontaneously. In those 24 to 34 weeks of gestation without complications corticosteroids and close observation is recommended. A 2017 Cochrane review found waiting generally resulted in better outcomes in those before 37 weeks. Antibiotics may be given for those at risk of Group B streptococcus. Delivery is generally indicated in those with complications, regardless of how far along in pregnancy.About 8% of term pregnancies are complicated by PROM while about 30% of preterm births are complicated by PROM. Before 24 weeks PROM occurs in fewer than 1% of pregnancies. Prognosis is primarily determined by complications related to prematurity such as necrotizing enterocolitis, intraventricular hemorrhage, and cerebral palsy. Signs and symptoms Most women will experience a painless leakage of fluid out of the vagina. They may notice either a distinct "gush" or a steady flow of small amounts of watery fluid in the absence of steady uterine contractions. Loss of fluid may be associated with the baby becoming easier to feel through the belly (due to the loss of the surrounding fluid), decreased uterine size, or meconium (fetal stool) seen in the fluid. Risk factors The cause of PROM is not clearly understood, but the following are risk factors that increase the chance of it occurring. In many cases, however, no risk factor is identified. Infections: urinary tract infection, sexually transmitted diseases, lower genital tract infections (e.g. bacterial vaginosis), infections within the amniotic sac membranes (chorioamnionitis) Tobacco use during pregnancy Illicit drug use during pregnancy Having had PROM or preterm delivery in previous pregnancies Polyhydramnios: too much amniotic fluid Multiple gestation: being pregnant with two or more fetuses at one time Having had episodes of bleeding anytime during the pregnancy Invasive procedures (e.g. amniocentesis) Nutritional deficits Cervical insufficiency: having a short or prematurely dilated cervix during pregnancy Low socioeconomic status Being underweight Pathophysiology Weak membranes Fetal membranes likely break because they become weak and fragile. This weakening is a normal process that typically happens at term as the body prepares for labor and delivery. However, this can be a problem when it occurs before 37 weeks (preterm). The natural weakening of fetal membranes is thought to be due to one or a combination of the following. In PROM, these processes are activated too early: Cell death: when cells undergo programmed cell death, they release biochemical markers that are detected in higher concentrations in cases of PPROM. Poor assembly of collagen: collagen is a molecule that gives fetal membranes, as well as other parts of the human body such as the skin, their strength. In cases of PPROM, proteins that bind and cross-link collagen to increase its tensile strength are altered. Breakdown of collagen: collagen is broken down by enzymes called matrix metalloproteinases (MMPs), which are found at higher levels in PPROM amniotic fluid. This breakdown results in prostaglandin production which stimulates uterine contractions and cervical ripening. MMPs are inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs) which are found at lower levels in PPROM amniotic fluid. Infection Infection and inflammation likely explains why membranes break earlier than they are supposed to. In studies, bacteria have been found in the amniotic fluid from about one-third of cases of PROM. Often, testing of the amniotic fluid is normal, but a subclinical infection (too small to detect) or infection of maternal tissues adjacent to the amniotic fluid, may still be a contributing factor. In response to infection, the resultant infection and release of chemicals (cytokines) subsequently weakens the fetal membranes and put them at risk for rupture. PROM is also a risk factor in the development of neonatal infections. Genetics Many genes play a role in inflammation and collagen production, therefore inherited genes may play a role in predisposing a person to PROM. Diagnosis To confirm if a woman has experienced PROM, a clinician must prove that the fluid leaking from the vagina is amniotic fluid, and that labor has not yet started. To do this, a careful medical history is taken, a gynecological exam is conducted using a sterile speculum, and an ultrasound of the uterus is performed. History: a person with PROM typically recalls a sudden "gush" of fluid loss from the vagina, or steady loss of small amounts of fluid. Sterile speculum exam: a clinician will insert a sterile speculum into the vagina in order to see inside and perform the following evaluations. Digital cervical exams, in which gloved fingers are inserted into the vagina to measure the cervix, are avoided until the women is in active labor to reduce the risk of infection.Pooling test: Pooling is when a collection of amniotic fluid can be seen in the back of the vagina (vaginal fornix). Sometimes leakage of fluid from the cervical opening can be seen when the person coughs or performs a valsalva maneuver. Nitrazine test: A sterile cotton swab is used to collect fluid from the vagina and place it on nitrazine (phenaphthazine) paper. Amniotic fluid is mildly basic (pH 7.1–7.3) compared to normal vaginal secretions which are acidic (pH 4.5–6). Basic fluid, like amniotic fluid, will turn the nitrazine paper from orange to dark blue. Fern test: A sterile cotton swab is used to collect fluid from the vagina and place it on a microscope slide. After drying, amniotic fluid will form a crystallization pattern called arborization which resembles leaves of a fern plant when viewed under a microscope. Fibronectin and alpha-fetoprotein blood tests Classification Prelabor rupture of membranes (PROM): when the fetal membranes rupture early, at least one hour before labor has started. Prolonged PROM: a case of prelabor rupture of membranes in which more than 18 hours has passed between the rupture and the onset of labor. Preterm prelabor rupture of membranes (PPROM): prelabor rupture of membranes that occurs before 37 weeks gestation. Midtrimester PPROM or pre-viable PPROM: prelabor rupture of membranes that occurs before 24 weeks gestation. Before this age, the fetus cannot survive outside of the mothers womb. Additional tests The following tests should only be used if the diagnosis is still unclear after the standard tests above. Ultrasound: Ultrasound can measure the amount of fluid still in the uterus surrounding the fetus. If the fluid levels are low, PROM is more likely. This is helpful in cases when the diagnosis is not certain, but is not, by itself, definitive. Immune-chromatological tests are helpful, if negative, to rule out PROM, but are not that helpful if positive since the false-positive rate is relatively high (19–30%). Indigo carmine dye test: a needle is used to inject indigo carmine dye (blue) into the amniotic fluid that remains in the uterus through the abdominal wall. In the case of PROM, blue dye can be seen on a stained tampon or pad after about 15–30 minutes. This method can be used to definitively make a diagnosis, but is rarely done because it is invasive and increases risk of infection. But, can be helpful if the diagnosis is still unclear after the above evaluations have been done.It is unclear if different methods of assessing the fetus in a woman with PPROM affects outcomes. False positives Like amniotic fluid, blood, semen, vaginal secretions in the presence of infection, soap, urine, and cervical mucus also have an alkaline pH and can also turn nitrazine paper blue. Cervical mucus can also make a pattern similar to ferning on a microscope slide, but it is usually patchy and with less branching. Differential diagnosis Other conditions that may present similarly to premature rupture of membranes are the following: Urinary incontinence: leakage of small amounts of urine is common in the last part of pregnancy Normal vaginal secretions of pregnancy Increased sweat or moisture around the perineum Increased cervical discharge: this can happen when there is a genital tract infection Semen Douching Vesicovaginal fistula: an abnormal connection between the bladder and the vagina Loss of the mucus plug Prevention Women who have had PROM are more likely to experience it in future pregnancies. There is not enough data to recommend a way to specifically prevent future PROM. However, any woman that has had a history of preterm delivery, because of PROM or not, is recommended to take progesterone supplementation to prevent recurrence. Management The management of PROM remains controversial, and depends largely on the gestational age of the fetus and other complicating factors. The risks of quick delivery (induction of labor) vs. watchful waiting in each case is carefully considered before deciding on a course of action.As of 2012, the Royal College of Obstetricians and Gynaecologists advised, based on expert opinion and not clinical evidence, that attempted delivery during maternal instability increases the rates of both fetal death and maternal death, unless the source of instability is an intrauterine infection.In all women with PROM, the age of the fetus, its position in the uterus, and its well-being should be evaluated. This can be done with ultrasound, Doppler fetal heart rate monitoring, and uterine activity monitoring. This will also show whether or not uterine contractions are happening which may be a sign that labor is starting. Signs and symptoms of infection should be closely monitored, and, if not already done, a group B streptococcus (GBS) culture should be collected.At any age, if the fetal well-being appears to be compromised, or if intrauterine infection is suspected, the baby should be delivered quickly by induction of labour. Term Both expectant management (watchful waiting) and an induction of labor (artificially stimulating labor) are considered in this case. 90% of women start labor on their own within 24 hours, and therefore it is reasonable to wait for 12–24 hours as long as there is no risk of infection. However, if labor does not begin soon after the PROM, an induction of labor is recommended because it reduces rates of infections, decreases the chances that the baby will require a stay in the neonatal intensive care unit (NICU), and does not increase the rate of caesarean sections. If a woman strongly does not want to be induced, watchful waiting is an acceptable option as long as there is no sign of infection, the fetus is not in distress, and she is aware and accepts the risks of PPROM. There is not enough data to show that the use of prophylactic antibiotics (to prevent infection) is beneficial for mothers or babies at or near term because of the potential side effects and development of antibiotic resistance. 34 to 37 weeks When the fetus is 34 to 37 weeks gestation, the risk of being born prematurely must be weighed against the risk of PROM. Previously it was recommended that delivery be carried out as if the baby was term. A 2017 Cochrane review however found waiting resulted in better outcomes when pregnancy is before 37 weeks. 24 to 34 weeks Before 34 weeks, the fetus is at a much higher risk of the complications of prematurity. Therefore, as long as the fetus is doing well, and there are no signs of infection or placental abruption, watchful waiting (expectant management) is recommended. The younger the fetus, the longer it takes for labor to start on its own, but most women will deliver within a week. Waiting usually requires a woman to stay in the hospital so that health care providers can watch her carefully for infection, placental abruption, umbilical cord compression, or any other fetal emergency that would require quick delivery by induction of labor.In 2017, a review of watchful waiting vs the early birth strategy was conducted to ascertain which was associated with a lower overall risk. Focusing on the 24–37-week range, the review analysed twelve randomised controlled trials from the "Cochrane Pregnancy and Childbirths Trials Register", concluding that "In women with PPROM before 37 weeks gestation with no contraindications to continuing the pregnancy, a policy of expectant management with careful monitoring was associated with better outcomes for the mother and baby."There is believed to be a correlation between volume of amniotic fluid retained and neonatal outcomes before 26 weeks gestation. Amniotic fluid levels are an important consideration when debating expectant management vs clinical intervention, as low levels, or oligohydramnios, can result in lung and limb abnormalities. Additionally, labor and infection are less likely to occur when there are sufficient levels of amniotic fluid remaining in the uterus. Serial amnioinfusion in pregnancies with PPROM-related oligohydramnios at less than 26 weeks gestation, successfully alleviates oligohydramnios, with perinatal outcomes that are significantly better than the outcome in those with the persistent condition and is comparable with gestations with PPROM in which oligohydramnios never develops. Recommended Monitoring for infection: signs of infection include a fever in the mother, fetal tachycardia (fast heart rate of the fetus, more than160 beats per minute), or tachycardia in the mother (more than 100 beats per minute). White blood cell (WBC) counts are not helpful in this case because WBCs are normally high in late pregnancy. Steroids before birth: corticosteroids (betamethasone) given to the mother of a baby at risk of being born prematurely can speed up fetal lung development and reduce the risk of death of the infant, respiratory distress syndrome, brain bleeds, and bowel necrosis. It is recommended that mothers receive one course of corticosteroids between 24 and 34 weeks when there is a risk of preterm delivery. In cases of PPROM these medications do not increase the risk of infection even though steroids are known to suppress the immune system. More than two courses is not recommended because three or more can lead to small birth weight and small head circumference. In pregnancies between 32 and 34 weeks (right around the time that fetal lungs mature) vaginal fluid can be tested to determine fetal lung maturity using chemical markers which can help to decide if corticosteroids should be given. Magnesium sulfate: Intravenous magnesium sulfate is given to the mother in cases when there is a risk of preterm birth before 32 weeks. This has been shown to protect the fetal brain and reduce the risk of cerebral palsy. Latency antibiotics: The time from PROM to labor is termed the latency period, and there is an inverse relationship between gestational age and the length of latency, meaning that the earlier the rupture, the longer it will take for labor to begin naturally. As expected, antibiotics given to mothers that experience PPROM serve to protect against infections during this lengthened latency period. Additionally, antibiotics increase the time that babies stay in the womb. Antibiotics dont seem to prevent death or make a difference in the long-term (years after the baby is born). But, because of the short-term benefits, routine use of antibiotics in PPROM is still recommended. The American Congress of Obstetricians and Gynecologists (ACOG) recommends a seven-day course of intravenous ampicillin and erythromycin followed by oral amoxicillin and erythromycin if watchful waiting is attempted before 34 weeks. Amoxicillin/clavulanic acid increases the risk of fetal bowel death (necrotizing enterocolitis) and should be avoided in pregnancy. Prophylactic antibiotics: If a woman is colonized with GBS, than the typical use of antibiotics during labor is recommended to prevent transmission of this bacteria to the fetus, regardless of earlier treatments. Controversial or not recommended Preventative tocolysis (medications to prevent contractions): the use of tocolytic medications to prevent labor contractions is controversial. On the one hand, this can delay delivery and allow the fetus more time to develop and benefit from antenatal corticosteroid medication, on the other hand it increases the risk of infection or chorioamnionitis. The use of tocolysis has not shown to benefit mom or baby and currently there is not enough data to recommend or discourage its use in the case of preterm PROM. Therapeutic tocolysis (medications to stop contractions): Once labor has started, using tocolysis to stop labor has not been shown to help, and is not recommended. Amnioinfusion: This treatment attempts to replace the lost amniotic fluid from the uterus by infusing normal saline fluid into the uterine cavity. This can be done through the vagina and cervix (transcervical amnioinfusion) or by passing a needle through the abdominal wall (transabdominal amnioinfusion). Current data suggests that this treatment prevents infection, lung problems, and fetal death. However, there have not been enough trials to recommend its routine use in all cases of PPROM. Home care: Typically women with PPROM are managed in the hospital, but, occasionally they opt to go home if watchful waiting is attempted. Since labor usually starts soon after PPROM, and infection, umbilical cord compression, and other fetal emergencies can happen very suddenly, it is recommended that women stay in the hospital in cases of PPROM after 24 weeks. Currently, there is not enough evidence to determine meaningful differences in safety, cost, and womens views between management at home vs. the hospital. Sealing membranes after rupture: Infection is the major risk associated with PROM and PPROM. By closing the ruptured membranes, it is hoped that there would be a decrease in infection, as well as encouraging the re-accumulation of amniotic fluid in the uterus to protect the fetus and allow for further lung development. Common techniques include placing a sponge over the ruptured membrane and the use of oral autoimmune stimulating drugs to encourage the bodys immune system to repair the rupture. There is currently insufficient research to determine whether these or other resealing techniques improve maternal or neonatal outcomes when compared to the current standard of care. Before 24 weeks Before 24 weeks, a fetus is not viable meaning it cannot live outside the mother. In this case, either watchful waiting at home or an induction of labor done.Because the risk of infection is so high, the mother should check her temperature often and return to the hospital if she develops any signs or symptoms of infection, labor, or vaginal bleeding. These women are typically admitted to the hospital once their fetus reaches 24 weeks and then managed the same as women with PPROM before 34 weeks (discussed above). When possible, these deliveries should take place in a hospital that has expertise in the management of the potential maternal and neonatal complications, and has the necessary infrastructure in place to support the care of these patients (i.e. neonatal intensive care unit). Antenatal corticosteroids, latency antibiotics, magnesium sulfate, and tocolytic medications are not recommended until the fetus reaches viability (24 weeks). In cases of pre-viable PPROM, chance of survival of the fetus is between 15 and 50%, and the risk of chorioamnionitis is about 30%. Chorioamnionitis Chorioamnionitis is a bacterial infection of the fetal membranes, which can be life-threatening to both mother and fetus. Women with PROM at any age are at high risk of infection because the membranes are open and allow bacteria to enter. Women are checked often (usually every 4 hours) for signs of infection: fever (more than 38 °C or 100.5 °F), uterine pain, maternal tachycardia, fetal tachycardia, or foul-smelling amniotic fluid. Elevated white blood cells are not a good way to predict infection because they are normally high in labor. If infection is suspected, artificial induction of labor is started at any gestational age and broad antibiotics are given. Caesarean section should not be automatically done in cases of infection, and should only be reserved for the usual fetal emergencies. Outcomes The consequences of PROM depend on the gestational age of the fetus. When PROM occurs at term (after 36 weeks), it is typically followed soon thereafter by the start of labor and delivery. About half of women will give birth within 5 hours, and 95% will give birth within 28 hours without any intervention. The younger the baby, the longer the latency period (time between membrane rupture and start of labor). Rarely, in cases of preterm PROM, amniotic fluid will stop leaking and the amniotic fluid volume will return to normal.If PROM occurs before 37 weeks, it is called preterm prelabor rupture of membranes (PPROM), and the baby and mother are at greater risk of complications. PPROM causes one-third of all preterm births. PROM provides a path for disease-causing organisms to enter the womb and puts both the mother and baby at risk for infection. Low levels of fluid around the baby also increase the risk of umbilical cord compression and can interfere with lung and body formation of the baby in early pregnancy. Infection (any age) At any gestational age, an opening in the fetal membranes provides a route for bacteria to enter the womb. This can lead to chorioamnionitis (an infection of the fetal membranes and amniotic fluid) which can be life-threatening to both the mother and fetus. The risk of infection increases the longer the membranes remain open and baby undelivered. Women with preterm PROM will develop an intra-amniotic infection 15–25% of the time, and the chances of infection increase at earlier gestational ages. Pre-term birth (before 37 weeks) PROM occurring before 37 weeks (PPROM) is one of the leading causes of preterm birth. Thirty to 35% of all preterm births are caused by PPROM. This puts the fetus at risk for the many complications associated with prematurity such as respiratory distress, brain bleeds, infection, necrotizing enterocolitis (death of the fetal bowels), brain injury, muscle dysfunction, and death. Prematurity from any cause leads to 75% of perinatal mortality and about 50% of all long-term morbidity. PROM is responsible for 20% of all fetal deaths between 24 and 34 weeks gestation. Fetal development (before 24 weeks) Before 24 weeks the fetus is still developing its organs, and the amniotic fluid is important for protecting the fetus against infection, physical impact, and for preventing the umbilical cord from becoming compressed. It also allows for fetal movement and breathing that is necessary for the development of the lungs, chest, and bones. Low levels of amniotic fluid due to mid-trimester or previable PPROM (before 24 weeks) can result in fetal deformity (e.g. Potter-like facies), limb contractures, pulmonary hypoplasia (underdeveloped lungs), infection (especially if the mother is colonized by group B streptococcus or bacterial vaginosis), prolapsed umbilical cord or compression, and placental abruption. PROM after second-trimester amniocentesis Most cases of PROM occur spontaneously, but the risk of PROM in women undergoing a second trimester amniocentesis for prenatal diagnosis of genetic disorders is 1%. Although no studies are known to account for all cases of PROM that stem from amniocentesis. This case, the chances of the membranes healing on their own and the amniotic fluid returning to normal levels is much higher than spontaneous PROM. Compared to spontaneous PROM, about 70% of women will have normal amniotic fluid levels within one month, and about 90% of babies will survive. Epidemiology Of term pregnancies (more than 37 weeks) about 8% are complicated by PROM, 20% of these become prolonged PROM. About 30% of all preterm deliveries (before 37 weeks) are complicated by PPROM, and rupture of membranes before viability (before 24 weeks) occurs in less than 1% of all pregnancies. Since there are significantly fewer preterm deliveries than term deliveries, the number of PPROM cases make up only about 5% of all cases of PROM. See also Placental alpha microglobulin-1 (PAMG-1) IGFBP1 (Insulin-like growth factor binding protein-1) References == External links ==

Would you describe Pleocytosis, to me Aarogya

Pleocytosis

In medicine, pleocytosis (or pleiocytosis) is an increased cell count (from Greek pleion, "more"), particularly an increase in white blood cell count, in a bodily fluid, such as cerebrospinal fluid. It is often defined specifically as an increased white blood cell count in cerebrospinal fluid.Increased white blood cell count in the blood is called leukocytosis. == References ==

Aarogya what is Precordium

Precordium

In anatomy, the precordium or praecordium is the portion of the body over the heart and lower chest.Defined anatomically, it is the area of the anterior chest wall over the heart. It is therefore usually on the left side, except in conditions like dextrocardia, where the individuals heart is on the right side. In such a case, the precordium is on the right side as well. The precordium is naturally a cardiac area of dullness. During examination of the chest, the percussion note will therefore be dull. In fact, this area only gives a resonant percussion note in hyperinflation, emphysema or tension pneumothorax. Precordial chest pain can be an indication of a variety of illnesses, including costochondritis and viral pericarditis. See also Precordial thump Precordial examination Commotio cordis Hyperdynamic precordium Precordial catch syndrome == References ==

Hi Aarogya , Do you know what is Milk-alkali syndrome,

Milk-alkali syndrome

Milk-alkali syndrome (MAS), also referred to as calcium-alkali syndrome, is the third most common cause of hypercalcemia. Milk-alkali syndrome is characterized by elevated blood calcium levels, metabolic alkalosis, and acute kidney injury.Milk-alkali syndrome can be caused by the excessive intake of calcium and absorbable alkali. Sources of calcium and alkali include dietary supplements taken for the prevention of osteoporosis or hyperparathyroidism and antacids taken for peptic ulcer disease. Common acute symptoms of milk-alkali syndrome include nausea and vomiting, dry mouth, confusion, lethargy, and distaste for milk. If left untreated, milk-alkali syndrome may lead to kidney failure or even death. Signs and symptoms The signs and symptoms of milk-alkali syndrome can develop after only a few days and up to several months following the initial ingestion of absorbable calcium and alkali. However, the severity of signs and symptoms of milk-alkali syndrome is largely dependent upon the duration and quantity of calcium and alkali ingested.Acute milk-alkali syndrome is characterized by several biochemical alterations, mainly alkalosis, hypochloremia, hypokalemia, and hypercalcemia. In the acute phase of milk-alkali syndrome (Cope syndrome), the first symptoms of toxicity are nausea, vomiting, anorexia, headache, dizziness, vertigo, apathy, weakness, confusion, irritability, dry mouth, and repulsion to milk. In individuals with chronic milk-alkali syndrome (Burnett syndrome), symptoms may include muscle aches, psychosis, tremor, polyuria (producing large volumes of dilute urine), polydipsia (intense thirst), pruritus (itchy sensation on skin), band keratopathy and abnormal calcifications. These abnormal calcium deposits often collect metastatically in the body, including throughout the periarticular tissue, subcutaneous tissue, central nervous system, liver, kidneys, adrenal, bones, and lungs. If ingestion of calcium and alkali is continued, neurologic symptoms such as memory loss, personality changes, lethargy, stupor, and coma will persistently develop over time, as a result of the extreme hypercalcemia and electrolyte imbalances.People with milk-alkali syndrome commonly show signs of renal dysfunction, a hallmark symptom of milk-alkali syndrome, at early stages of disease progression. Several lab test results, such as elevated blood urea nitrogen (BUN) and elevated creatinine, are illustrative of azotemia and kidney impairment. Histologically, the kidneys of individuals with milk-alkali syndrome have been shown to have "complete glomerulus hyalinization, thickening of the Bowmans capsule, tubular atrophy, vascular changes, and diffuse lymphocytic infiltration."Other laboratory tests, such as measuring serum bicarbonate, pH, 1,25-OH vitamin D, and parathyroid hormone (PTH) can show signs of milk-alkali syndrome. Specifically, bicarbonate and pH would be elevated while 1,25-OH vitamin D and PTH would be suppressed. Causes Milk-alkali syndrome is caused by ingesting excessive amounts of both calcium (usually in the form of dietary supplements such as calcium carbonate, which is commonly taken to prevent or treat osteoporosis) and absorbable alkali (as are found in antacid drugs).Presently, consumption of extensively large amounts of calcium carbonate has replaced the over-ingestion of milk products, or milk and bicarbonate, as the most prominent cause of MAS. Excessive consumption of calcium generally means taking in more than 4 to 5 g of calcium carbonate every day. This can be attributed to the greater availability of over-the-counter calcium carbonate supplements to treat osteoporosis and dyspepsia, as well as the growing awareness among consumers of the potential health benefits of calcium intake. Calcium carbonate is also often prescribed to people with chronic kidney disease for the prevention of secondary hyperparathyroidism and to people receiving prolonged corticosteroid therapy that may lead to bone loss, putting them at a higher risk of calcium over-consumption and developing MAS.Other drugs reported to be associated with the development of MAS include thiazide diuretics, which causes increased reabsorption of calcium in the kidneys and hypovolemia that leads to contraction alkalosis. Angiotensin-converting enzyme (ACE) inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) are also drugs associated with MAS because they decrease glomerular filtration rate (GFR) and thus reduce calcium excretion. Taking medications such as aluminum hydroxide and magnesium hydroxide, which are absorbable alkali, can also contribute to MAS in those who already consume a large amount of calcium.Pregnant individuals have an increased risk for developing MAS due to hyperemesis (which can cause hypovolemia) and enhanced gastrointestinal calcium absorption as a result of higher levels of prolactin or placental lactose signaling (resulting in hypercalcemia). Calcium carbonate is also commonly used in pregnant individuals to treat acid reflux, further putting them at risk for overconsumption of calcium and developing MAS. Mechanism The mechanism of how milk-alkali syndrome develops from ingesting too much of calcium and absorbable alkali is still unclear. However, it is well known that MAS is usually associated with a triad of symptoms that include hypercalcemia, alkalosis, and acute kidney injury. In general, milk-alkali syndrome starts with excess calcium levels in the body (hypercalcemia), which causes the bodys pH to increase (become more alkaline) resulting in metabolic alkalosis and ultimately contributes to a decrease in renal function.Factors involved in the development of hypercalcemia include excess intestinal absorption of calcium, saturation of the bones buffering capacity for calcium, decreased renal excretion, and abnormal vitamin D metabolism. Underlying kidney disease is a risk factor for MAS, but even people with healthy kidneys can develop the syndrome.For a healthy individual, if calcium levels are high, the kidneys will decrease its production of calcitriol (active vitamin D) by reducing the hydroxylation of calcidiol (inactive vitamin D); lower calcitriol levels means a lower rate of calcium absorption in the small intestine, which eventually offsets the elevated calcium levels. However, excessive ingestion of calcium of more than 10-15 g per day has been reported to cause calcium levels too high for renal calcitriol suppression to control, resulting in net calcium absorption that ultimately causes hypercalcemia.Hypercalcemia affects the kidneys in multiple ways that altogether contributes to hypovolemia. Prolonged hypercalcemia can decrease glomerular filtration rate (GFR) via vasoconstriction, reduce creatinine clearance, and eventually cause renal insufficiency. Hypercalcemia also causes natriuresis by blocking the Na-K-Cl cotransporter (NKCC) in the medullary thick ascending limb of the loop of Henle, leading increased sodium excretion followed by water excretion that leads to hypovolemia. Additionally, hypercalcemia can decrease the reabsorption of water in the kidneys collecting ducts by suppressing antidiuretic hormone (ADH) receptors, contributing to more hypovolemia. Hypercalcemia also results in lower parathyroid hormone (PTH) levels via a negative feedback loop, in which calcium-sensing receptors in the PTH gland are activated by the elevated calcium levels to inhibit PTH production, thus decreasing renal reabsorption of calcium.Hypovolemia then leads to metabolic alkalosis (increase in blood pH) by stimulating bicarbonate reabsorption in order to maintain extracellular volume. In summary, the symptoms of alkalosis is the net result of over-consumption of absorbable alkali, hypercalcemia-induced hypovolemia, and impaired glomerular filtration rate. Alkalosis, in turn, increases calcium-reabsorption from the distal tubules of the nephron, thus exacerbating the hypercalcemia and hypovolemia.Altogether, these result in a cycle of hypercalcemia, alkalosis, and renal injury characteristic of MAS. Diagnosis Prior to an official diagnosis of milk-alkali syndrome, other causes of hypercalcemia must be ruled out. Other causes of hypercalcemia can include elevated vitamin D levels, hyperthyroidism, and hyperparathyroidism. Physical Examination:Symptoms such as vertigo, confusion, apathy, nausea and vomiting, anorexia, tremors, psychosis, myalgia, polyuria, abnormal calcifications such as renal calcifications, and pruitus could be observed in people. Lab work: Lab work must be done to diagnose milk-alkali syndrome. Lab workup includes serum calcium levels, parathyroid hormone (PTH), phosphorus, creatinine, blood urea nitrogen (BUN), magnesium, and vitamin D levels. Primary hyperparathyroidism has to be excluded. Diagnosis is made by looking at past medical history and laboratory studies. Serum calcium levels: high serum calcium levels. PTH: low serum PTH levels are indicative of MAS. Low serum PTH levels also exclude primary hyperthyroidism. Phosphorus: low serum phosphorus levels due to low PTH. Creatinine and BUN: high levels can indicate severity of renal damage. Magnesium: serum magnesium levels are low as hypercalcemia inhibits mg^2+ reabsorption in the renal tubules. Vitamin D levels: low vitamin D levels are found. Normal vitamin D levels eliminate primary hypercalcemia. Electrocardiograms (ECG): An ECG can also be used to diagnose MAS. The following findings related to hypercalcemia could appear on an ECG: Short QT interval: most commonly seen as short OoT or OaT changes. Prolongation of PR and QRS intervals. Increased Amplitude of QRS complex. Osborn wave Short ST segment.Radiology: Chest x-rays can help exclude any malignancy or sarcoidosis when evaluating for hypercalcemia. Prevention Increasing education in both people and clinicians surrounding milk-alkali syndrome can help prevent the disease. Over recent years, people have become more aware of the benefits of calcium and how to access it, leading to a consequential rise in cases of milk-alkali syndrome. It is crucial that people are educated by their healthcare provider(s) about how hypercalcemia can develop and the hallmark symptoms to monitor for. Often unknown to the person, calcium can come from many different dietary sources in addition to self- or prescribed-supplementation. Unfortunately, this can lead to the intake of amounts of calcium that exceeds recommended doses, causing harmful effects. Particularly in persons with any degree of renal disease, supplementation of calcium can more easily result in deadly hypercalcemia and alkalosis. Generally, the daily intake of less than 2 grams of calcium is considered to be safe. Prior to starting any calcium supplementation, it is recommended to discuss the individualized calcium requirements of the person. If a person begins a calcium supplementation regimen, they should be educated on the common signs and symptoms of hypercalcemia and milk-alkali syndrome, as well as how to reverse the syndrome by discontinuing the offending agent and seeking medical attention. Treatment For mild cases of MAS, the only intervention needed is to withdraw the offending agent. By having the person stop taking any calcium supplements and any other alkali agents they have been taking rapidly corrects hypercalcemia and alkalosis in MAS.In severe cases, hospitalization may be required to manage this syndrome. Withholding calcium and initiating IV fluids such as saline to correct hypovolemia. The initial rate of infusion is generally around 200-300 mL/h in people not experiencing edema then it is adjusted to maintain urine output of 100 - 150 mL/h. However, the rate is variable depending on the individuals age, renal status, comorbidities, and the severity of hypercalcemia.Furosemide can be used to treat hypercalcemia as it induces caliuresis (excreting calcium in the urine). Standard practice of adequate rehydration and electrolyte monitoring should be used to avoid alkalosis and renal insufficiency.If kidney failure is advanced then treatment for that is required, namely chronic dialysis.Calcimimetic agents may be necessary, e.g. Cinacalcet. Outcomes In mild cases of milk-alkali syndrome, full recovery is expected and reduction to renal function is reversible. However, in severe cases that are chronic, permanent kidney failure or death may result. Long term consumption of large amounts of calcium supplementation associated with milk-alkali syndrome has also been linked to adverse cardiovascular outcomes. It was found that over supplementation of calcium can lead to an increased risk for myocardial infarction and vascular calcification. Epidemiology In the early years after the discovery of milk-alkali syndrome, the prevalence of the disease among people treated with Sippys treatment varied from 2% to 18%. The wide range was attributed to the differing amounts of alkali absorbed among people. In the 1900s, the mortality rate of people with milk-alkali syndrome was found to be 4.4%.The use of milk and alkali to treat gastric ulcers greatly contributed to the development of milk-alkali syndrome in people but the incidence of milk-alkali syndrome greatly diminished when the true cause of most gastric ulcers was identified and drugs other than antacids were developed to treat heartburn, such as acid-reducing drugs like H2-receptor antagonists or proton pump inhibitors. These new drugs replaced Sippys diet treatment for peptic ulcers. However, the incidence of milk-alkali syndrome has increased again since the 1990s due to increased osteoporosis awareness and the preventative routine use of calcium supplements. The consumption of calcium supplementation in todays society, mostly to prevent osteoporosis, has aided in the resurgence of milk-alkali syndrome and has sparked conversation about changing the name of milk-alkali syndrome to calcium alkali syndrome as it more accurately reflects the cause of this syndrome. Currently, milk-alkali syndrome is the third most common cause of people hospitalized with high blood calcium, after hyperparathyroidism and cancer.In regards to populations at risk, there has been a shift in the conditions demographic over time. Previously, milk-alkali syndrome was predominantly seen amongst males with ulcers. As new treatments for peptic ulcers arose, there was change in the causation of hypercalcemia. Presently, individuals who are at a higher risk of developing milk-alkali syndrome are pregnant or postmenopausal individuals and the elderly. History Milk-alkali syndrome is an illness that is characterized by hypercalcaemia, kidney damage, and metabolic alkalosis. This syndrome was discovered in the early 1900s when people began experiencing adverse effects from Bertrand Sippys gastric ulcer treatment consisting of milk and alkali. Sippy prescribed patients with ulcers milk and alkali, on the theory that ulcers were caused by excessive gastric acid. Further research by Cuthbert Cope and Charles H. Burnett revealed varying degrees of milk-alkali syndrome. Cope identified an acute phase which was named Copes Syndrome while Burnett described a more severe chronic form which was named Burnetts Syndrome. However, both the acute and chronic form of this illness involve renal impairment which is a key contributor to the hypercalcemia seen in people with MAS. Cope and Burnett believe that the kidney damage caused by ingesting high amounts of calcium and alkali occurs first which subsequently makes removal of calcium from the body difficult. References == External links ==

Would you describe Aseptic meningitis, to me Aarogya

Aseptic meningitis

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause. The most common cause of aseptic meningitis is by viral infection. Other causes may include side-effects from drugs and connective tissue disorders. Signs and symptoms Aseptic meningitis is a disease that can depend on the patients age, however, research has shown some distinct symptoms that indicate the possibility of aseptic meningitis. A variety of patients notice a change in body temperatures (higher than normal temperatures 38-40 °C), marked with the possibility of vomiting, headaches, firm neck pain, and even lack of appetite. In younger patients, like babies, a meningeal inflammation can be noticed along with the possibility of hepatic necrosis and myocarditis. In serious cases, a multiple organ failure can also signal aseptic meningitis and oftentimes, in babies, seizures and focal neurological deficits can be early symptoms of aseptic meningitis. In fact, in newborns, the mortality rate is 70%. The next set of age group, like children, have similar but varying symptoms of sore throat, rashes, and diarrhea. In adults, symptoms and the harshness of them tend to be less in duration. Additionally, the probability of developing aseptic meningitis increases when patients have a case of mumps or herpes.Symptoms of meningitis caused by an acute viral infection last between one and two weeks. When aseptic meningitis is caused by cytomegalovirus 20 percent of individuals face mortality or morbidity. If left untreated it can affect an individuals hearing and learning abilities. Causes The most common cause of aseptic meningitis is a viral infection, specifically by enteroviruses. In fact, 90 percent of all meningitis cases that are viral are caused by enteroviruses. Other viruses that may cause aseptic meningitis are varicella zoster virus, herpes, and mumps. Other causes may include mycobacteria, fungi, spirochetes, and complications from HIV. Side effects of certain drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (e.g., trimethoprim-sulfamethoxazole or amoxicillin), and antiepileptic drugs can also cause aseptic meningitis.There are multiple types of aseptic meningitis that are differentiated based on their cause. Viral meningitis Enterovirus (EV) caused meningitis. This is the most common cause of viral meningitis, with 90% of viral meningitis cases being caused by EVs. Human immunodeficiency virus (HIV) Mumps meningoencephalitis Mosquito carried viruses of the flavivirus family. Saint Louis encephalitis (SLE) and West Nile virus (WNV) are the most typical. Specific types of Herpes can result in aseptic meningitis. These are (HSV)-1, (HSV)-2, varicella-zoster virus, and (HHV6). Bacteria Lyme disease Syphilis Leptospirosis Fungi Cryptococcal infection Coccidioidal infection Drug-induced aseptic meningitis (DIAM) Irritation of the meninges from drugs administered directly to the spinal canal or subarachnoid space. The hypersensitivity to the drug results in an immune response. Autoimmune diseases Systemic lupus erythematosus. Cancer-caused aseptic meningitis such as neoplastic meningitis This affects about 5% of all cancer cases, with a predominance in leukemias. Neurosarcoidosis Diagnosis The term aseptic can be misleading, implying a lack of infection. On the contrary, many cases of aseptic meningitis represent infection with viruses or mycobacteria that cannot be detected with routine methods. Medical professionals will take into consideration the season of the year, the medical history of the individual and family, physical examination, and laboratory results when diagnosing aseptic meningitis.One common medical test used when diagnosing aseptic meningitis is lumbar puncture. A medical professional inserts a needle between two vertebrae to remove cerebrospinal fluid (CSF) from the spinal cord. The cerebrospinal fluid collected from the lumbar puncture is analyzed by microscope examination or by culture to distinguish between bacterial and aseptic meningitis. Samples of CSF undergo cell count, Gram stains, and viral cultures, and polymerase chain reaction (PCR). Polymerase chain reaction has increased the ability of clinicians to detect viruses such as enterovirus, cytomegalovirus, and herpes virus in the CSF, but many viruses can still escape detection. Other laboratory tests include blood, urine, and stool collection. Medical professionals also have the option of performing a computed tomographic (CT) scan or magnetic resonance imaging (MRI), these tests help observe calcifications or abscesses. Treatment If CSF levels are irregular among individuals, they will undergo hospitalization where they receive antiviral therapy. If aseptic meningitis was caused by herpes simplex virus (HSV), the individual will receive acyclovir, an antiviral drug. If infants are diagnosed, medical professionals will order regular check-ins for hearing and learning disabilities. History Aseptic meningitis was first described by Wallgren in 1925. Aseptic meningitis cases have varied historically. Aseptic meningitis caused by mumps has declined in the United States due to the increased use of vaccination which prevents mumps cases from occurring. See also Central nervous system infections Meningitis References == External links ==

Hey Aarogya , Do you know what is Irregular menstruation,

Irregular menstruation

Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods). The possible causes of irregular menstruation may vary. The common factors of it are related to lifestyle, such as stress, body weight, and smoking status. Several studies indicate that COVID-19 vaccine of any type may disrupt the menstrual cycle, although only momentarily. This side effect should resolve on its own in the following month. Irregular cycles or periods Irregular cycles or irregular periods is an abnormal variation in length of menstrual cycles. An individual usually experiences cycle length variations of up to eight days between the shortest and longest cycle lengths. Lengths ranging between eight and 20 days are considered moderately irregular. Variation of 21 days or more is considered very irregular.Alternatively, a single menstruation cycle may be defined as irregular if it is less than 24 days or more than 38 days. If they are regularly shorter than 21 days or longer than 36 (or 35) days, the condition is termed polymenorrhea or oligomenorrhea, respectively.Additionally, irregular menstruation is common in adolescence. A regular menstrual cycle can be set within a year of menarche. However, other studies suggest that it can take anywhere between 2 and 7 years to establish regularity after an individuals first menses. Other types Other types of conditions that can be referred to by "irregular menstruation" include: Metrorrhagia, which generally refers to vaginal bleeding that occurs between the expected menstrual periods. The distinction between irregular cycle lengths and metrorrhagia is not always clear. It may depend on whether the bleeding is regarded as marking the menstrual period (favoring the term "irregular cycles") or being separate from it (favoring the term "metrorrhagia"). Oligomenorrhea generally refers to infrequent menstruation, More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Menstrual periods should have been regularly established before the development of infrequent flow and often (but not always) involves irregular intervals. In contrast to "irregular cycles", the interval between one cycle and the next may be consistent but can be regarded as "irregular" compared to the cycle length of a female without oligomenorrhea. Women with oligomenorrhea often have irregular cycles as well. Polymenorrhea is the medical term for cycles with intervals of 21 days or fewer. It can be regarded as the opposite of oligomenorrhea. References == External links ==

Aarogya, can you share information about a health condition involving Hemarthrosis

Hemarthrosis

Hemarthrosis is a bleeding into joint spaces. It is a common feature of hemophilia. Causes It usually follows injury but occurs mainly in patients with a predisposition to hemorrhage such as those being treated with warfarin (or other anticoagulants) and patients with hemophilia.It can be associated with knee joint arthroplasty.It has also been reported as a part of hemorrhagic syndrome in the Crimean-Congo Hemorrhagic Fever, suggesting a viral cause to the bleeding in a joint space. Diagnosis Hemarthrosis is diagnosed through the methods listed below: A physical examination is the first step, the joints of the patient are moved and bent to study the functioning.Synovial Fluid analysis is another method to diagnose Hemarthrosis. It involves a small needle being inserted into the joint to draw the fluid. Reddish-colored hue of the sample is an indication of the blood being present. Imaging tests are normally done. The tests also include MRI, Ultrasound and X-ray test, which give better information about the joint inflammation. Treatment In hemophilia it may occur spontaneously, and recurrent hemarthroses are a major cause of disability in that patient group due to hemophilic arthropathy, requiring synovectomy, joint replacement and increased medical therapy to prevent further bleeding episodes. Reducing hemarthroses events using intravenous administration of blood clotting factor concentrate on a regular basis starting in early childhood, reduces joint deterioration and increases the persons quality of life compared to "on demand" treatment (treating after a bleed). The minimal effective dose and best dosage frequency have not been established. It is not clear, due to lack of sufficient data, if preventative therapy with clotting factor concentrate is also effective at reducing joint deterioration if treatment is started after joint damage has occurred. Complications Up to a quarter of all severe ligament or capsular knee injuries leading to a hemarthrosis are associated with cartilage damage that can lead to progressive degenerative arthritis. References == External links ==

Aarogya what is Type 1 diabetes

Type 1 diabetes

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks.The cause of type 1 diabetes is unknown, but it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves an autoimmune destruction of the insulin-producing beta cells in the pancreas. Diabetes is diagnosed by testing the level of sugar or glycated hemoglobin (HbA1C) in the blood. Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies.There is no known way to prevent type 1 diabetes. Treatment with insulin is required for survival. Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump. A diabetic diet and exercise are important parts of management. If left untreated, diabetes can cause many complications. Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma. Long-term complications include heart disease, stroke, kidney failure, foot ulcers and damage to the eyes. Furthermore, since insulin lowers blood sugar levels, complications may arise from low blood sugar if more insulin is taken than necessary.Type 1 diabetes makes up an estimated 5–10% of all diabetes cases. The number of people affected globally is unknown, although it is estimated that about 80,000 children develop the disease each year. Within the United States the number of people affected is estimated at one to three million. Rates of disease vary widely, with approximately one new case per 100,000 per year in East Asia and Latin America and around 30 new cases per 100,000 per year in Scandinavia and Kuwait. It typically begins in children and young adults. Signs and symptoms Type 1 diabetes begins suddenly, typically in childhood or adolescence. The major sign of type 1 diabetes is very high blood sugar, which typically manifests in children as a few days to weeks of polyuria (increased urination), polydipsia (increased thirst), and weight loss. Children may also experience increased appetite, blurred vision, bedwetting, recurrent skin infections, candidiasis of the perineum, irritability, and performance issues at school. Adults with type 1 diabetes tend to have more varied symptoms that come on over months rather than days to weeks.Prolonged lack of insulin can also result in diabetic ketoacidosis, characterized by persistent fatigue, dry or flushed skin, abdominal pain, nausea or vomiting, confusion, trouble breathing, and a fruity breath odor. Blood and urine tests reveal unusually high glucose and ketones in the blood and urine. Untreated ketoacidosis can rapidly progress to loss of consciousness, coma, and death. The percentage of children whose type 1 diabetes begins with an episode of diabetic ketoacidosis varies widely by geography, as low as 15% in parts of Europe and North America, and as high as 80% in the developing world. Cause Type 1 diabetes is caused by the destruction of β-cells – the only cells in the body that produce insulin – and the consequent progressive insulin deficiency. Without insulin, the body is unable to respond effectively to increases in blood sugar and diabetics have persistent hyperglycemia. In 70–90% of cases, β-cells are destroyed by someones own immune system, for reasons that are not entirely clear. The best-studied components of this autoimmune response are β-cell-targeted antibodies that begin to develop in the months or years before symptoms arise. Typically someone will first develop antibodies against insulin or the protein GAD65, followed eventually by antibodies against the proteins IA-2, IA-2β, and/or ZNT8. People with more of these antibodies, and who develop them earlier in life, are at higher risk for developing symptomatic type 1 diabetes. The trigger for the development of these antibodies remains unclear. A number of explanatory theories have been put forward, and the cause may involve genetic susceptibility, a diabetogenic trigger, and/or exposure to an antigen. The remaining 10–30% of type 1 diabetics have β-cell destruction but no sign of autoimmunity; this is called idiopathic type 1 diabetes and its cause remains unclear. Environmental Various environmental risks have been studied in an attempt to understand what triggers β-cell autoimmunity. Many aspects of environment and life history are associated with slight increases in type 1 diabetes risk, however the connection between each risk and diabetes often remains unclear. Type 1 diabetes risk is slightly higher for children whose mothers are obese or older than 35, or for children born by caesarean section. Similarly, a childs weight gain in the first year of life, total weight, and BMI are associated with slightly increased type 1 diabetes risk. Some dietary habits have also been associated with type 1 diabetes risk, namely consumption of cows milk and dietary sugar intake. Animal studies and some large human studies have found small associations between type 1 diabetes risk and intake of gluten or dietary fiber; however, other large human studies have found no such association. Many potential environmental triggers have been investigated in large human studies and found to be unassociated with type 1 diabetes risk including duration of breastfeeding, time of introduction of cow milk into the diet, vitamin D consumption, blood levels of active vitamin D, and maternal intake of omega-3 fatty acids.A longstanding hypothesis for an environmental trigger is that some viral infection early in life contributes to type 1 diabetes development. Much of this work has focused on enteroviruses, with some studies finding slight associations with type 1 diabetes, and others finding none. Large human studies have searched for, but not yet found an association between type 1 diabetes and various other viral infections, including infections of the mother during pregnancy. Conversely, some have postulated that reduced exposure to pathogens in the developed world increases the risk of autoimmune diseases, often called the hygiene hypothesis. Various studies of hygiene-related factors – including household crowding, daycare attendance, population density, childhood vaccinations, antihelminth medication, and antibiotic usage during early life or pregnancy – show no association with type 1 diabetes. Genetics Type 1 diabetes is partially caused by genetics, and family members of type 1 diabetics have a higher risk of developing the disease themselves. In the general population, the risk of developing type 1 diabetes is around 1 in 250. For someone whose parent has type 1 diabetes, the risk rises to 1–9%. If a sibling has type 1 diabetes, the risk is 6–7%. If someones identical twin has type 1 diabetes, they have a 30–70% risk of developing it themselves.About half of the diseases heritability is due to variations in three HLA class II genes involved in antigen presentation: HLA-DRB1, HLA-DQA1, and HLA-DQB1. The variation patterns associated with increased risk of type 1 diabetes are called HLA-DR3 and HLA-DR4-HLA-DQ8, and are common in people of European descent. A pattern associated with reduced risk of type 1 diabetes is called HLA-DR15-HLA-DQ6. Large genome-wide association studies have identified dozens of other genes associated with type 1 diabetes risk, mostly genes involved in the immune system. Chemicals and drugs Some medicines can reduce insulin production or damage β cells, resulting in disease that resembles type 1 diabetes. The antiviral drug didanosine triggers pancreas inflammation in 5 to 10% of those who take it, sometimes causing lasting β-cell damage. Similarly, up to 5% of those who take the anti-protozoal drug pentamidine experience β-cell destruction and diabetes. Several other drugs cause diabetes by reversibly reducing insulin secretion, namely statins (which may also damage β cells), the post-transplant immunosuppressants cyclosporin A and tacrolimus, the leukemia drug L-asparaginase, and the antibiotic gatifloxicin. Pyrinuron (Vacor), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 diabetes after accidental poisoning. Pyrinuron was withdrawn from the U.S. market in 1979. Diagnosis Diabetes is typically diagnosed by a blood test showing unusually high blood sugar. The World Health Organization defines diabetes as blood sugar levels at or above 7.0 mmol/L (126 mg/dL) after fasting for at least eight hours, or a glucose level at or above 11.1 mmol/L (200 mg/dL) two hours after an oral glucose tolerance test. The American Diabetes Association additionally recommends a diagnosis of diabetes for anyone with symptoms of hyperglycemia and blood sugar at any time at or above 11.1 mmol/L, or glycated hemoglobin (hemoglobin A1C) levels at or above 48 mmol/mol.Once a diagnosis of diabetes is established, type 1 diabetes is distinguished from other types by a blood test for the presence of autoantibodies that target various components of the beta cell. The most commonly available tests detect antibodies against glutamic acid decarboxylase, the beta cell cytoplasm, or insulin, each of which are targeted by antibodies in around 80% of type 1 diabetics. Some healthcare providers also have access to tests for antibodies targeting the beta cell proteins IA-2 and ZnT8; these antibodies are present in around 58% and 80% of type 1 diabetics respectively. Some also test for C-peptide, a byproduct of insulin synthesis. Very low C-peptide levels are suggestive of type 1 diabetes. Management The mainstay of type 1 diabetes treatment is the regular injection of insulin to manage hyperglycemia. Injections of insulin – via subcutaneous injection using either a syringe or an insulin pump – are necessary multiple times per day, adjusting dosages to account for food intake, blood glucose levels and physical activity. The goal of treatment is to maintain blood sugar in a normal range – 80–130 mg/dL before a meal; <180 mg/dL after – as often as possible. To achieve this, people with diabetes often monitor their blood glucose levels at home. Around 83% of type 1 diabetics monitor their blood glucose by capillary blood testing – pricking the finger to draw a drop of blood, and determining blood glucose with a glucose meter. The American Diabetes Association recommends testing blood glucose around 6–10 times per day: before each meal, before exercise, at bedtime, occasionally after a meal, and any time someone feels the symptoms of hypoglycemia. Around 17% of people with type 1 diabetes use a continuous glucose monitor, a device with a sensor under the skin that constantly measures glucose levels and communicates those levels to an external device. Continuous glucose monitoring is associated with better blood sugar control than capillary blood testing alone; however, continuous glucose monitoring tends to be substantially more expensive. Healthcare providers can also monitor someones hemoglobin A1C levels which reflect the average blood sugar over the last three months. The American Diabetes Association recommends a goal of keeping hemoglobin A1C levels under 7% for most adults and 7.5% for children.The goal of insulin therapy is to mimic normal pancreatic insulin secretion: low levels of insulin constantly present to support basic metabolism, plus the two-phase secretion of additional insulin in response to high blood sugar – an initial spike in secreted insulin, then an extended phase with continued insulin secretion. This is accomplished by combining different insulin preparations that act with differing speeds and durations. The standard of care for type 1 diabetes is a bolus of rapid-acting insulin 10–15 minutes before each meal or snacks, and as-needed to correct hyperglycemia. In addition, constant low levels of insulin are achieved with one or two daily doses of long-acting insulin, or by steady infusion of low insulin levels by an insulin pump. The exact dose of insulin appropriate for each injection depends on the content of the meal/snack, and the individual persons sensitivity to insulin, and is therefore typically calculated by the individual with diabetes or a family member by hand or assistive device (calculator, chart, mobile app, etc.). People unable to manage these intensive insulin regimens are sometimes prescribed alternate plans relying on mixtures of rapid- or short-acting and intermediate-acting insulin, which are administered at fixed times along with meals of pre-planned times and carbohydrate composition.The only non-insulin medication approved by the U.S. Food and Drug Administration for treating type 1 diabetes is the amylin analog pramlintide, which replaces the beta-cell hormone amylin. Addition of pramlintide to mealtime insulin injections reduces the boost in blood sugar after a meal, improving blood sugar control. Occasionally, metformin, GLP-1 receptor agonists, Dipeptidyl peptidase-4 inhibitors, or SGLT2 inhibitor are prescribed off-label to people with type 1 diabetes, although fewer than 5% of type 1 diabetics use these drugs. Lifestyle Besides insulin, the major way type 1 diabetics control their blood sugar is by learning how various foods impact their blood sugar levels. This is primarily done by tracking their intake of carbohydrates – the type of food with the greatest impact on blood sugar. In general, people with type 1 diabetes are advised to follow an individualized eating plan rather than a pre-decided one. There are camps for children to teach them how and when to use or monitor their insulin without parental help. As psychological stress may have a negative effect on diabetes, a number of measures have been recommended including: exercising, taking up a new hobby, or joining a charity, among others.Regular exercise is important for maintaining general health, though the effect of exercise on blood sugar can be challenging to predict. Exogenous insulin can drive down blood sugar, leaving those with diabetes at risk of hypoglycemia during and immediately after exercise, then again seven to eleven hours after exercise (called the "lag effect"). Conversely, high-intensity exercise can result in a shortage of insulin, and consequent hyperglycemia. The risk of hypoglycemia can be managed by beginning exercise when blood sugar is relatively high (above 100 mg/dL), ingesting carbohydrates during or shortly after exercise, and reducing the amount of injected insulin within two hours of the planned exercise. Similarly, the risk of exercise-induced hyperglycemia can be managed by avoiding exercise when insulin levels are very low, when blood sugar is extremely high (above 350 mg/dL), or when one feels unwell. Transplant In some cases, people can receive transplants of the pancreas or isolated islet cells to restore insulin production and alleviate diabetic symptoms. Transplantation of the whole pancreas is rare, due in part to the few available donor organs, and to the need for lifelong immunosuppressive therapy to prevent transplant rejection. The American Diabetes Association recommends pancreas transplant only in people who also require a kidney transplant, or who struggle to perform regular insulin therapy and experience repeated severe side effects of poor blood sugar control. Most pancreas transplants are done simultaneously with a kidney transplant, with both organs from the same donor. The transplanted pancreas continues to function for at least five years in around three quarters of recipients, allowing them to stop taking insulin.Transplantations of islets alone have become increasingly common. Pancreatic islets are isolated from a donor pancreas, then injected into the recipients portal vein from which they implant onto the recipients liver. In nearly half of recipients, the islet transplant continues to work well enough that they still dont need exogenous insulin five years after transplantation. If a transplant fails, recipients can receive subsequent injections of islets from additional donors into the portal vein. Like with whole pancreas transplantation, islet transplantation requires lifelong immunosuppression and depends on the limited supply of donor organs; it is therefore similarly limited to people with severe poorly controlled diabetes and those who have had or are scheduled for a kidney transplant. Pathogenesis Type 1 diabetes is a result of the destruction of pancreatic beta cells, although what triggers that destruction remains unclear. People with type 1 diabetes tend to have more CD8+ T-cells and B-cells that specifically target islet antigens than those without type 1 diabetes, suggesting a role for the adaptive immune system in beta cell destruction. Type 1 diabetics also tend to have reduced regulatory T cell function, which may exacerbate autoimmunity. Destruction of beta cells results in inflammation of the islet of Langerhans, called insulitis. These inflamed islets tend to contain CD8+ T-cells and – to a lesser extent – CD4+ T cells. Abnormalities in the pancreas or the beta cells themselves may also contribute to beta-cell destruction. The pancreases of people with type 1 diabetes tend to be smaller, lighter, and have abnormal blood vessels, nerve innervations, and extracellular matrix organization. In addition, beta cells from people with type 1 diabetes sometimes overexpress HLA class I molecules (responsible for signaling to the immune system) and have increased endoplasmic reticulum stress and issues with synthesizing and folding new proteins, any of which could contribute to their demise.The mechanism by which the beta cells actually die likely involves both necroptosis and apoptosis induced or exacerbated by CD8+ T-cells and macrophages. Necroptosis can be triggered by activated T cells – which secrete toxic granzymes and perforin – or indirectly as a result of reduced blood flow or the generation of reactive oxygen species. As some beta cells die, they may release cellular components that amplify the immune response, exacerbating inflammation and cell death. Pancreases from people with type 1 diabetes also have signs of beta cell apoptosis, linked to activation of the janus kinase and TYK2 pathways.Partial ablation of beta-cell function is enough to cause diabetes; at diagnosis, people with type 1 diabetes often still have detectable beta-cell function. Once insulin therapy is started, many people experience a resurgence in beta-cell function, and can go some time with little-to-no insulin treatment – called the "honeymoon phase". This eventually fades as beta-cells continue to be destroyed, and insulin treatment is required again. Beta-cell destruction is not always complete, as 30–80% of type 1 diabetics produce small amounts of insulin years or decades after diagnosis. Alpha cell dysfunction Onset of autoimmune diabetes is accompanied by impaired ability to regulate the hormone glucagon, which acts in antagonism with insulin to regulate blood sugar and metabolism. Progressive beta cell destruction leads to dysfunction in the neighboring alpha cells which secrete glucagon, exacerbating excursions away from euglycemia in both directions; overproduction of glucagon after meals causes sharper hyperglycemia, and failure to stimulate glucagon upon hypoglycemia prevents a glucagon-mediated rescue of glucose levels. Hyperglucagonemia Onset of type 1 diabetes is followed by an increase in glucagon secretion after meals. Increases have been measured up to 37% during the first year of diagnosis, while c-peptide levels (indicative of islet-derived insulin), decline by up to 45%. Insulin production will continue to fall as the immune system destroys beta cells, and islet-derived insulin will continue to be replaced by therapeutic exogenous insulin. Simultaneously, there is measurable alpha cell hypertrophy and hyperplasia in the early stage of the disease, leading to expanded alpha cell mass. This, together with failing beta cell insulin secretion, begins to account for rising glucagon levels that contribute to hyperglycemia. Some researchers believe glucagon dysregulation to be the primary cause of early stage hyperglycemia. Leading hypotheses for the cause of postprandial hyperglucagonemia suggest that exogenous insulin therapy is inadequate to replace the lost intraislet signalling to alpha cells previously mediated by beta cell-derived pulsatile insulin secretion. Under this working hypothesis intensive insulin therapy has attempted to mimic natural insulin secretion profiles in exogenous insulin infusion therapies. Hypoglycemic glucagon impairment Glucagon secretion is normally increased upon falling glucose levels, but normal glucagon response to hypoglycemia is blunted in type 1 diabetics. Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.Autonomic inputs to alpha cells are much more important for glucagon stimulation in the moderate to severe ranges of hypoglycemia, yet the autonomic response is blunted in a number of ways. Recurrent hypoglycemia leads to metabolic adjustments in the glucose sensing areas of the brain, shifting the threshold for counter regulatory activation of the sympathetic nervous system to lower glucose concentration. This is known as hypoglycemic unawareness. Subsequent hypoglycemia is met with impairment in sending of counter regulatory signals to the islets and adrenal cortex. This accounts for the lack of glucagon stimulation and epinephrine release that would normally stimulate and enhance glucose release and production from the liver, rescuing the diabetic from severe hypoglycemia, coma, and death. Numerous hypotheses have been produced in the search for a cellular mechanism of hypoglycemic unawareness, and a consensus has yet to be reached. The major hypotheses are summarized in the following table: In addition, autoimmune diabetes is characterized by a loss of islet specific sympathetic innervation. This loss constitutes an 80–90% reduction of islet sympathetic nerve endings, happens early in the progression of the disease, and is persistent though the life of the patient. It is linked to the autoimmune aspect of type 1 diabetics and fails to occur in type 2 diabetics. Early in the autoimmune event, the axon pruning is activated in islet sympathetic nerves. Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75NTR), which acts to prune off axons. Axons are normally protected from pruning by activation of tropomyosin receptor kinase A (Trk A) receptors by NGF, which in islets is primarily produced by beta cells. Progressive autoimmune beta cell destruction, therefore, causes both the activation of pruning factors and the loss of protective factors to the islet sympathetic nerves. This unique form of neuropathy is a hallmark of type 1 diabetes, and plays a part in the loss of glucagon rescue of severe hypoglycemia. Complications The most pressing complication of type 1 diabetes are the always present risks of poor blood sugar control: severe hypoglycemia and diabetic ketoacidosis. Hypoglycemia – typically blood sugar below 70 mg/dL – triggers the release of epinephrine, and can cause people to feel shaky, anxious, or irritable. People with hypoglycemia may also experience hunger, nausea, sweats, chills, dizziness, and a fast heartbeat. Some feel lightheaded, sleepy, or weak. Severe hypoglycemia can develop rapidly, causing confusion, coordination problems, loss of consciousness, and seizure. On average, people with type 1 diabetes experience a hypoglycemia event that requires assistance of another 16–20 times in 100 person-years, and an event leading to unconsciousness or seizure 2–8 times per 100 person-years. The American Diabetes Association recommends treating hypoglycemia by the "15-15 rule": eat 15 grams of carbohydrates, then wait 15 minutes before checking blood sugar; repeat until blood sugar is at least 70 mg/dL. Severe hypoglycemia that impairs someones ability to eat is typically treated with injectable glucagon, which triggers glucose release from the liver into the bloodstream. People with repeated bouts of hypoglycemia can develop hypoglycemia unawareness, where the blood sugar threshold at which they experience symptoms of hypoglycemia decreases, increasing their risk of severe hypoglycemic events. Rates of severe hypoglycemia have generally declined due to the advent of rapid-acting and long-acting insulin products in the 1990s and early 2000s; however, acute hypoglycemic still causes 4–10% of type 1 diabetes-related deaths.The other persistent risk is diabetic ketoacidosis – a state where lack of insulin results in cells burning fat rather than sugar, producing toxic ketones as a byproduct. Ketoacidosis symptoms can develop rapidly, with frequent urination, excessive thirst, nausea, vomiting, and severe abdominal pain all common. More severe ketoacidosis can result in labored breathing, and loss of consciousness due to cerebral edema. People with type 1 diabetes experience diabetic ketoacidosis 1–5 times per 100 person-years, the majority of which result in hospitalization. 13–19% of type 1 diabetes-related deaths are caused by ketoacidosis, making ketoacidosis the leading cause of death in people with type 1 diabetes less than 58 years old. Long-term complications In addition to the acute complications of diabetes, long-term hyperglycemia results in damage to the small blood vessels throughout the body. This damage tends to manifest particularly in the eyes, nerves, and kidneys causing diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy respectively. In the eyes, prolonged high blood sugar causes the blood vessels in the retina to become fragile.People with type 1 diabetes also have increased risk of cardiovascular disease, which is estimated to shorten the life of the average type 1 diabetic by 8–13 years. Cardiovascular disease as well as neuropathy may have an autoimmune basis, as well. Women with type 1 DM have a 40% higher risk of death as compared to men with type 1 DM.About 12 percent of people with type 1 diabetes have clinical depression. About 6 percent of people with type 1 diabetes also have celiac disease, but in most cases there are no digestive symptoms or are mistakenly attributed to poor control of diabetes, gastroparesis or diabetic neuropathy. In most cases, celiac disease is diagnosed after onset of type 1 diabetes. The association of celiac disease with type 1 diabetes increases the risk of complications, such as retinopathy and mortality. This association can be explained by shared genetic factors, and inflammation or nutritional deficiencies caused by untreated celiac disease, even if type 1 diabetes is diagnosed first. Urinary tract infection People with diabetes show an increased rate of urinary tract infection. The reason is bladder dysfunction is more common in people with diabetes than people without diabetes due to diabetes nephropathy. When present, nephropathy can cause a decrease in bladder sensation, which in turn, can cause increased residual urine, a risk factor for urinary tract infections. Sexual dysfunction Sexual dysfunction in people with diabetes is often a result of physical factors such as nerve damage and poor circulation, and psychological factors such as stress and/or depression caused by the demands of the disease. The most common sexual issues in males with diabetes are problems with erections and ejaculation: "With diabetes, blood vessels supplying the peniss erectile tissue can get hard and narrow, preventing the adequate blood supply needed for a firm erection. The nerve damage caused by poor blood glucose control can also cause ejaculate to go into the bladder instead of through the penis during ejaculation, called retrograde ejaculation. When this happens, semen leaves the body in the urine." Another cause of erectile dysfunction is reactive oxygen species created as a result of the disease. Antioxidants can be used to help combat this. Sexual problems are common in women who have diabetes, including reduced sensation in the genitals, dryness, difficulty/inability to orgasm, pain during sex, and decreased libido. Diabetes sometimes decreases estrogen levels in females, which can affect vaginal lubrication. Less is known about the correlation between diabetes and sexual dysfunction in females than in males.Oral contraceptive pills can cause blood sugar imbalances in women who have diabetes. Dosage changes can help address that, at the risk of side effects and complications.Women with type 1 diabetes show a higher than normal rate of polycystic ovarian syndrome (PCOS). The reason may be that the ovaries are exposed to high insulin concentrations since women with type 1 diabetes can have frequent hyperglycemia. Autoimmune disorders People with type 1 diabetes are at an increased risk for developing several autoimmune disorders, particularly thyroid problems – around 20% of people with type 1 diabetes have hypothyroidism or hyperthyroidism, typically caused by Hashimoto thyroiditis or Graves disease respectiveley. Celiac disease affects 2–8% of people with type 1 diabetes, and is more common in those who were younger at diabetes diagnosis, and in white people. Type 1 diabetics are also at increased risk of rheumatoid arthritis, lupus, autoimmune gastritis, pernicious anemia, vitiligo, and Addisons disease. Conversely, complex autoimmune syndromes caused by mutations in the immunity-related genes AIRE (causing autoimmune polyglandular syndrome), FoxP3 (causing IPEX syndrome), or STAT3 include type 1 diabetes in their effects. Epidemiology Type 1 diabetes makes up an estimated 10–15% of all diabetes cases or 11–22 million cases worldwide. Symptoms can begin at any age, but onset is most common in children, with diagnoses slightly more common in 5 to 7 year olds, and much more common around the age of puberty. In contrast to most autoimmune diseases, type 1 diabetes is slightly more common in males than in females.In 2006, type 1 diabetes affected 440,000 children under 14 years of age and was the primary cause of diabetes in those less than 15 years of age.Rates vary widely by country and region. Incidence is highest in Scandinavia, at 30–60 new cases per 100,000 children per year, intermediate in the U.S. and Southern Europe at 10–20 cases per 100,000 per year, and lowest in China, much of Asia, and South America at 1–3 cases per 100,000 per year.In the United States, type 1 and 2 diabetes affected about 208,000 youths under the age of 20 in 2015. Over 18,000 youths are diagnosed with Type 1 diabetes every year. Every year about 234,051 Americans die due to diabetes (type I or II) or diabetes-related complications, with 69,071 having it as the primary cause of death.In Australia, about one million people have been diagnosed with diabetes and of this figure 130,000 people have been diagnosed with type 1 diabetes. Australia ranks 6th-highest in the world with children under 14 years of age. Between 2000 and 2013, 31,895 new cases were established, with 2,323 in 2013, a rate of 10–13 cases per 100,00 people each year. Aboriginals and Torres Strait Islander people are less affected.Since the 1950s, the incidence of type 1 diabetes has been gradually increasing across the world by an average 3–4% per year. The increase is more pronounced in countries that began with a lower incidence of type 1 diabetes. History The connection between diabetes and pancreatic damage was first described by Martin Schmidt, who in a 1902 paper noted inflammation around the pancreatic islet of a child who had died of diabetes. The connection between this inflammation and diabetes onset was further developed through the 1920s by Shields Warren, and the term "insulitis" was coined by Hanns von Meyenburg in 1940 to describe the phenomenon.Type 1 diabetes was described as an autoimmune disease in the 1970s, based on observations that autoantibodies against islets were discovered in diabetics with other autoimmune deficiencies. It was also shown in the 1980s that immunosuppressive therapies could slow disease progression, further supporting the idea that type 1 diabetes is an autoimmune disorder. The name juvenile diabetes was used earlier as it often first is diagnosed in childhood. Society and culture Type 1 and 2 diabetes was estimated to cause $10.5 billion in annual medical costs ($875 per month per diabetic) and an additional $4.4 billion in indirect costs ($366 per month per person with diabetes) in the U.S. In the United States $245 billion every year is attributed to diabetes. Individuals diagnosed with diabetes have 2.3 times the health care costs as individuals who do not have diabetes. One in ten health care dollars are spent on individuals with type 1 and 2 diabetes. Research Funding for research into type 1 diabetes originates from government, industry (e.g., pharmaceutical companies), and charitable organizations. Government funding in the United States is distributed via the National Institutes of Health, and in the UK via the National Institute for Health Research or the Medical Research Council. The Juvenile Diabetes Research Foundation (JDRF), founded by parents of children with type 1 diabetes, is the worlds largest provider of charity-based funding for type 1 diabetes research. Other charities include the American Diabetes Association, Diabetes UK, Diabetes Research and Wellness Foundation, Diabetes Australia, the Canadian Diabetes Association. A number of approaches have been explored to understand causes and provide treatments for type 1. Prevention Type 1 diabetes is not currently preventable. Several trials have attempted dietary interventions with the hope of reducing the autoimmunity that leads to type 1 diabetes. Trials that withheld cows milk or gave infants formula free of bovine insulin decreased the development of β-cell-targeted antibodies, but did not prevent the development of type 1 diabetes. Similarly, trials that gave high-risk individuals injected insulin, oral insulin, or nicotinamide did not prevent diabetes development.Other research has focused on treating high-risk individuals with immunosuppressive agents to prevent beta cell destruction. Large trials of cyclosporine treatment suggested that cyclosporine could improve insulin secretion in those recently diagnosed with type 1 diabetes; however, people who stopped taking cyclosporine rapidly stopped making insulin, and cyclosporines kidney toxicity and increased risk of cancer prevented people from using it long-term. Several other immunosuppressive agents – prednisone, azathioprine, anti-thymocyte globulin, mycophenolate, and antibodies against CD20 and IL2 receptor α – have been the subject of research, but none have provided lasting protection from development of type 1 diabetes. Antibodies against CD3 have been shown to delay the development of type 1 diabetes in those at high risk; however, they have not been widely adopted due to concerns over the duration of their effect, and activation of Epstein-Barr virus infections in those undergoing treatment.Vitamin D supplementation may help with preventing type one diabetes. This is believed to be the case due to vitamin D receptors affecting the B-cells involved in promoting pancreatic homeostasis.Vaccines are being looked at to treat or prevent type 1 diabetes by inducing immune tolerance to insulin or pancreatic beta cells. While Phase II clinical trials of a vaccine containing alum and recombinant GAD65, an autoantigen involved in type 1 diabetes, were promising, as of 2014 Phase III had failed. As of 2014, other approaches, such as a DNA vaccine encoding proinsulin and a peptide fragment of insulin, were in early clinical development. Organ replacement Pluripotent stem cells can be used to generate beta cells but previously these cells did not function as well as normal beta cells. In 2014 more mature beta cells were produced which released insulin in response to blood sugar when transplanted into mice. Before these techniques can be used in humans more evidence of safety and effectiveness is needed.There has also been substantial effort to develop a fully automated insulin delivery system or "artificial pancreas" that could sense glucose levels and inject appropriate insulin without conscious input from the user. Current "hybrid closed-loop systems" use a continuous glucose monitor to sense blood sugar levels, and a subcutaneous insulin pump to deliver insulin; however, due to the delay between insulin injection and its action, current systems require the user to initiate insulin before taking meals. Several improvements to these systems are currently undergoing clinical trials in humans, including a dual-hormone system that injects glucagon in addition to insulin, and an implantable device that injects insulin intraperitoneally where it can be absorbed more quickly. Disease models Various animal models of disease are used to understand the pathogenesis and etiology of type 1 diabetes. Currently available models of T1D can be divided into spontaneously autoimmune, chemically induced, virus induced and genetically induced.The nonobese diabetic (NOD) mouse is the most widely studied model of type 1 diabetes. It is an inbred strain that spontaneously develops type 1 diabetes in 30–100% of female mice depending on housing conditions. Diabetes in NOD mice is caused by several genes, primarily MHC genes involved in antigen presentation. Like diabetic humans, NOD mice develop islet autoantibodies and inflammation in the islet, followed by reduced insulin production and hyperglycemia. Some features of human diabetes are exaggerated in NOD mice, namely the mice have more severe islet inflammation than humans, and have a much more pronounced sex bias, with females developing diabetes far more frequently than males. In NOD mice the onset of insulitis occurs at 3–4 weeks of age. The islets of Langerhans are infiltrated by CD4+, CD8+ T lymphocytes, NK cells, B lymphocytes, dendritic cells, macrophages and neutrophils, similar to the disease process in humans. In addition to sex, breeding conditions, gut microbiome composition or diet also influence the onset of T1D.The BioBreeding Diabetes-Prone (BB) rat is another widely used spontaneous experimental model for T1D. The onset of diabetes occurs, in up to 90% of individuals (regardless of sex) at 8–16 weeks of age. During insulitis, the pancreatic islets are infiltrated by T lymphocytes, B lymphocytes, macrophages, and NK cells, with the difference from the human course of insulitis being that CD4 + T lymphocytes are markedly reduced and CD8 + T lymphocytes are almost absent. The aforementioned lymphopenia is the major drawback of this model. The disease is characterized by hyperglycemia, hypoinsulinemia, weight loss, ketonuria, and the need for insulin therapy for survival. BB Rats are used to study the genetic aspects of T1D and are also used for interventional studies and diabetic nephropathy studies.LEW-1AR1 / -iddm rats are derived from congenital Lewis rats and represent a rarer spontaneous model for T1D. These rats develop diabetes at about 8–9 weeks of age with no sex differences unlike NOD mice. In LEW mice, diabetes presents with hyperglycemia, glycosuria, ketonuria, and polyuria. The advantage of the model is the progression of the prediabetic phase, which is very similar to human disease, with infiltration of islet by immune cells about a week before hyperglycemia is observed. This model is suitable for intervention studies or for the search for predictive biomarkers. It is also possible to observe individual phases of pancreatic infiltration by immune cells. The advantage of congenic LEW mice is also the good viability after the manifestation of T1D (compared to NOD mice and BB rats). Chemically induced The chemical compounds aloxan and streptozotocin (STZ) are commonly used to induce diabetes and destroy β-cells in mouse/rat animal models. In both cases, it is a cytotoxic analog of glucose that passes GLUT2 transport and accumulates in β-cells, causing their destruction. The chemically induced destruction of β-cells leads to decreased insulin production, hyperglycemia and weight loss in the experimental animal. The animal models prepared in this way are suitable for research into blood sugar-lowering drugs and therapies (e.g. for testing new insulin preparations). They are also The most commonly used genetically induced T1D model is the so-called AKITA mouse (originally C57BL/6NSIc mouse). The development of diabetes in AKITA mice is caused by a spontaneous point mutation in the Ins2 gene, which is responsible for the correct composition of insulin in the endoplasmic reticulum. Decreased insulin production is then associated with hyperglycemia, polydipsia and polyuria. If severe diabetes develops within 3–4 weeks, AKITA mice survive no longer than 12 weeks without treatment intervention. The description of the etiology of the disease shows that, unlike spontaneous models, the early stages of the disease are not accompanied by insulitis. AKITA mice are used to test drugs targeting endoplasmic reticulum stress reduction, to test islet transplants, and to study diabetes-related complications such as nephropathy, sympathetic autonomic neuropathy, and vascular disease. for testing transplantation therapies. Their advantage is mainly the low cost, the disadvantage is the cytotoxicity of the chemical compounds. Genetically induced Virally induced Viral infections play a role in the development of a number of autoimmune diseases, including human type 1 diabetes. However, the mechanisms by which viruses are involved in the induction of type 1 DM are not fully understood. Virus-induced models are used to study the etiology and pathogenesis of the disease, in particular the mechanisms by which environmental factors contribute to or protect against the occurrence of type 1 DM. Among the most commonly used are Coxsackie virus, lymphocytic choriomeningitis virus, encephalomyocarditis virus, and Kilham rat virus. Examples of virus-induced animals include NOD mice infected with coxsackie B4 that developed type 1 DM within two weeks. References Works cited External links National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – Diabetes in America Textbook (PDFs) IDF Diabetes Atlas Type 1 Diabetes Archived 30 October 2009 at the Wayback Machine at the American Diabetes Association ADAs Standards of Medical Care in Diabetes 2019

Can you describe Fatty liver disease, to me Aarogya

Fatty liver disease

Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.There are two types of fatty liver disease: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease. NAFLD is made up of simple fatty liver and non-alcoholic steatohepatitis (NASH). The primary risks include alcohol, type 2 diabetes, and obesity. Other risk factors include certain medications such as glucocorticoids, and hepatitis C. It is unclear why some people with NAFLD develop simple fatty liver and others develop NASH. Diagnosis is based on the medical history supported by blood tests, medical imaging, and occasionally liver biopsy.Treatment of NAFLD is generally by dietary changes and exercise to bring about weight loss. In those who are severely affected, liver transplantation may be an option. More than 90% of heavy drinkers develop fatty liver while about 25% develop the more severe alcoholic hepatitis. NAFLD affects about 30% of people in Western countries and 10% of people in Asia. NAFLD affects about 10% of children in the United States. It occurs more often in older people and males. Signs and symptoms Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications Fatty liver can develop into a fibrosis or a liver cancer. For people affected by NAFLD, the 10-year survival rate was about 80%. The rate of progression of fibrosis is estimated to be one per 7 years in NASH and one per 14 years in NAFLD, with an increasing speed. There is a strong relationship between these pathologies and metabolic illnesses (diabetes type II, metabolic syndrome). These pathologies can also affect non-obese people, who are then at a higher risk.Less than 10% of people with cirrhotic alcoholic FLD will develop hepatocellular carcinoma, the most common type of primary liver cancer in adults, but up to 45% people with NASH without cirrhosis can develop hepatocellular carcinoma.The condition is also associated with other diseases that influence fat metabolism. Causes Fatty liver (FL) is commonly associated with metabolic syndrome (diabetes, hypertension, obesity, and dyslipidemia), but can also be due to any one of many causes: Alcohol Alcohol use disorder is one of the causes of fatty liver due to production of toxic metabolites like aldehydes during metabolism of alcohol in the liver. This phenomenon most commonly occurs with chronic alcohol use disorder. Metabolic abetalipoproteinemia, glycogen storage diseases, Weber–Christian disease, acute fatty liver of pregnancy, lipodystrophy Nutritional obesity, malnutrition, total parenteral nutrition, severe weight loss, refeeding syndrome, jejunoileal bypass, gastric bypass, jejunal diverticulosis with bacterial overgrowth Drugs and toxins amiodarone, methotrexate, diltiazem, expired tetracycline, highly active antiretroviral therapy, glucocorticoids, tamoxifen, environmental hepatotoxins (e.g., phosphorus, mushroom poisoning) Other celiac disease, inflammatory bowel disease, HIV, hepatitis C (especially genotype 3), and alpha 1-antitrypsin deficiency Pathology Fatty change represents the intracytoplasmatic accumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus (microvesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring appearance (macrovesicular fatty change). These vesicles are well-delineated and optically "empty" because fats dissolve during tissue processing. Large vacuoles may coalesce and produce fatty cysts, which are irreversible lesions. Macrovesicular steatosis is the most common form and is typically associated with alcohol, diabetes, obesity, and corticosteroids. Acute fatty liver of pregnancy and Reyes syndrome are examples of severe liver disease caused by microvesicular fatty change. The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight. Defects in fatty acid metabolism are responsible for pathogenesis of FLD, which may be due to imbalance in energy consumption and its combustion, resulting in lipid storage, or can be a consequence of peripheral resistance to insulin, whereby the transport of fatty acids from adipose tissue to the liver is increased. Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute to fat accumulation. In addition, alcohol use disorder is known to damage mitochondria and other cellular structures, further impairing cellular energy mechanism. On the other hand, non-alcoholic FLD may begin as excess of unmetabolised energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying cause is reduced or removed. Severe fatty liver is sometimes accompanied by inflammation, a situation referred to as steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH) depends on the persistence or severity of the inciting cause. Pathological lesions in both conditions are similar. However, the extent of inflammatory response varies widely and does not always correlate with degree of fat accumulation. Steatosis (retention of lipid) and onset of steatohepatitis may represent successive stages in FLD progression.Liver disease with extensive inflammation and a high degree of steatosis often progresses to more severe forms of the disease. Hepatocyte ballooning and necrosis of varying degrees are often present at this stage. Liver cell death and inflammatory responses lead to the activation of hepatic stellate cells, which play a pivotal role in hepatic fibrosis. The extent of fibrosis varies widely. Perisinusoidal fibrosis is most common, especially in adults, and predominates in zone 3 around the terminal hepatic veins.The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors. In alcoholic FLD, the transition to cirrhosis related to continued alcohol consumption is well-documented, but the process involved in non-alcoholic FLD is less clear. Diagnosis Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver enzymes are found in 50% of patients with simple steatosis. The serum alanine transaminase (ALT) level usually is greater than the aspartate transaminase (AST) level in the nonalcoholic variant and the opposite in alcoholic FLD (AST:ALT more than 2:1). Simple blood test may help to determine the magnitude of the disease by assessing the degree of liver fibrosis. For example, AST-to-platelets ratio index (APRI score) and several other score, calculated from the results of blood test, can detect the degree of liver fibrosis and predict the future formation of liver cancer.Imaging studies are often obtained during the evaluation process. Ultrasonography reveals a "bright" liver with increased echogenicity. Medical imaging can aid in diagnosis of fatty liver; fatty livers have lower density than spleens on computed tomography (CT), and fat appears bright in T1-weighted magnetic resonance images (MRIs). Magnetic resonance elastography, a variant of magnetic resonance imaging, is investigated as a non-invasive method to diagnose fibrosis progression. Histological diagnosis by liver biopsy is the most accurate measure of fibrosis and liver fat progression as of 2018. Conventional imaging methods, such as ultrasound, CT and MRI, are not specific enough to detect fatty liver disease unless fat occupies at least 30% of the liver volume. Treatment Decreasing caloric intake by at least 30% or by approximately 750–1,000 kcal/day results in improvement in hepatic steatosis. For people with NAFLD or NASH, weight loss via a combination of diet and exercise was shown to improve or resolve the disease. In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those that induce weight loss such as bariatric surgery as well as Vitamin E have been shown to improve or resolve liver function.Bariatric surgery, while not recommended in 2017 as a treatment for fatty liver disease (FLD) alone, has been shown to revert FLD, NAFLD, NASH and advanced steatohepatitis in over 90% of people who have undergone this surgery for the treatment of obesity.In the case of long-term total parenteral nutrition induced fatty liver disease, choline has been shown to alleviate symptoms. This may be due to a deficiency in the methionine cycle. Epidemiology NAFLD affects about 30% of people in Western countries and 10% of people in Asia. In the United States rates are around 35% with about 7% having the severe form NASH. NAFLD affects about 10% of children in the United States. Recently the term Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace NAFLD. MAFLD is a more inclusionary diagnostic name as it is based on the detection of fatty liver by histology (biopsy),medical imaging or blood biomarkers but should be accompanied by either overweight/obesity, type 2 diabetes mellitus, or metabolic dysregulation. The new definition no longer excludes alcohol consumption or coexistence of other liver diseases such as viral hepatitis. Using this more inclusive definition, the global prevalence of MAFLD is an astonishingly high 50.7%. Indeed, also using the old NAFLD definition, the disease is observed in up to 80% of obese people, 35% of whom progress to NASH, and in up to 20% of normal weight people, despite no evidence of excessive alcohol consumption. FLD is the most common cause of abnormal liver function tests in the United States. Fatty liver is more prevalent in Hispanic people than white, with black people having the lowest susceptibility.In the study of Children of the 90s, 2.5% born in 1991 and 1992 were found by ultrasound at the age of 18 to have non-alcoholic fatty liver disease; five years later transient elastography (fibroscan) found over 20% to have the fatty deposits on the liver, indicating non-alcoholic fatty liver disease; half of those were classified as severe. The scans also found that 2.4% had the liver scarring, which can lead to cirrhosis.After the lockdown of the COVID-19 pandemic, a study demonstrated that 48% of patients with liver steatosis gained weight, while 16% had a worsened steatosis grade. Weight gain was associated with poor adherence to the suggested diet, reduced levels of physical activity, and increased prevalence of PNPLA3 GG gene. PNPLA3 genes are already known risk factors for NAFLD. In animals Fatty liver disease can occur in pets such as reptiles (particularly turtles) and birds as well as mammals like cats and dogs. The most common cause is overnutrition. A distinct sign in birds is a misshapen beak. Fatty livers can be induced via gavage in geese or ducks to produce foie gras. Fatty liver can also be induced in ruminants such as sheep by a high caloric diet. References External links 00474 at CHORUSPhoto at Atlas of Pathology Healthdirect

Aarogya, could you share information about a health condition involving Stomach rumble

Stomach rumble

A stomach rumble, also known as a bowel sound, peristaltic sound, abdominal sound, bubble gut or borborygmus (pronounced ; plural borborygmi), is a rumbling, growling or gurgling noise produced by movement of the contents of the gastro-intestinal tract as they are propelled through the small intestine by a series of muscle contractions called peristalsis. A trained healthcare provider can listen to these intestinal noises with a stethoscope, but they may be audible enough to be heard with the naked ear as the fluid and gas move forward in the intestines (in the vicinity of, but not actually within the stomach). The lack of bowel sounds is indicative of ileus, intestinal obstruction, or some other serious pathology. Etymology The scientific name borborygmus is related to the 16th-century French word borborygme, itself from Latin, ultimately from Ancient Greek βορβορυγμός (borborygmós). The Greeks probably onomatopoetically coined the word. Other causes Other causes of stomach rumbles: Incomplete digestion of food can lead to excess gas in the intestine. In humans, this can be due to incomplete digestion of carbohydrate-containing foods, including milk and other dairy products (lactose intolerance or the use of α-glucosidase inhibitors by diabetics), gluten (protein in wheat, barley, and rye) (coeliac disease), fruit, vegetables, beans, legumes, and high-fiber whole grains. In rare instances, excessive abdominal noise may be a sign of digestive disease, especially when accompanied by abdominal bloating, abdominal pain, diarrhea or constipation. Some examples of diseases that may be associated with this symptom include carcinoid neoplasm and coeliac sprue. Louder rumbles may occur when one is hungry. The sound of air moving around the lumen of the stomach is amplified by the empty space. Around two hours after the stomach has been emptied, it sends signals to the brain, which tells the digestive muscles to restart peristalsis in a wave called the migrating motor complex. Food left behind after the first cycle is swept up, and the vibrations of the empty stomach cause hunger. Appetite plays a big role in this situation. Peristalsis recurs about every hour, and ones appetite may cause 10- to 20-minute food cravings. Stomach rumbles can form further along the gastrointestinal system when air is swallowed while talking, eating, and drinking. This phenomenon occurs in most people and is typical. Diseases and conditions Celiac disease is a condition that prevents the small intestine from absorbing parts of food that are needed to stay healthy. Consuming food containing gluten is dangerous for people with this disease: Intestinal villi help to absorb nutrients from food, but when gluten is consumed, the immune system attacks these villi as a result. Symptoms may include abdominal pain, nausea, and bulky or foul smelling stools. Colitis is swelling of the large intestine. The many different forms of colitis include cytomegalovirus or Cryptosporidium infection, and necrotizing and pseudomembranous colitis. The usual causes of colitis are infection and lack of blood flow. Symptoms may include bloody stools, chills, dehydration, diarrhea, and fever. Diverticulitis is a condition where small bulging sacs, usually found in the large intestine, become inflamed or infected. The most probable cause is a low-fiber diet, possibly a result of eating processed food. Diverticulitis is usually seen in about half the American population over the age of 60. Symptoms may include bloating, fever, and nausea. Irritable bowel syndrome, a disorder in the lower intestinal tract, is usually accompanied by other symptoms, such as abdominal pain and diarrhea. It is more common in women and it usually occurs during early adulthood. There are many risk factors such as emotional stress and a low-fiber diet. These can all cause stomach disorders. Nonmedical usage The word borborygmic has been used in literature to describe noisy plumbing. In Ada, Vladimir Nabokov wrote: "All the toilets and waterpipes in the house had been suddenly seized with borborygmic convulsions". In A Long Way Down (New York: Harper, 1959, p. 54), Elizabeth Fenwick wrote: "The room was very quiet, except for its borborygmic old radiator".Graham Greenes short story "Alas, Poor Maling" tells the tale of a luckless individual whose borborygmus takes the form of irritating noises that he has recently heard. The word borborygmus has also been used in journalism to describe political turbulence. In an article in The Atlantic, Graeme Wood used the word to describe the effects of mass refugee migration into Europe: "Central Europe had to digest a massive refugee flow from Syria and Afghanistan, and the resulting borborygmus upended European politics and enabled a populist wave that has yet to crest." See also Flatulence Ileus Migrating motor complex == References ==

Hello Aarogya, what is Microhematuria

Microhematuria

Microhematuria, also called microscopic hematuria (both usually abbreviated as MH), is a medical condition in which urine contains small amounts of blood; the blood quantity is too low to change the color of the urine (otherwise, it is known as gross hematuria). While not dangerous in itself, it may be a symptom of kidney disease, such as IgA nephropathy or Sickle cell trait, which should be monitored by a doctor. The American Urological Association (AUA) recommends a definition of microscopic hematuria as three or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens.Microhematuria is usually asymptomatic, and there are medical guidelines on how to handle asymptomatic microhematuria (AMH) so as to avoid problems such as overtreatment or misdiagnosis. See also Proteinuria Hematuria Myoglobinuria Hemoglobinuria References External links Cohen RA, Brown RS (2003). "Clinical practice. Microscopic hematuria". N. Engl. J. Med. 348 (23): 2330–8. doi:10.1056/NEJMcp012694. PMID 12788998. 2012 AUA Guidelines [1]

Do you know what is Necrolytic migratory erythema, Aarogya

Necrolytic migratory erythema

Necrolytic migratory erythema is a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and distal extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin. It is strongly associated with glucagonoma, a glucagon-producing tumor of the pancreas, but is also seen in a number of other conditions including liver disease and intestinal malabsorption. Signs and symptoms Clinical features NME features a characteristic skin eruption of red patches with irregular borders, intact and ruptured vesicles, and crust formation. It commonly affects the limbs and skin surrounding the lips, although less commonly the abdomen, perineum, thighs, buttocks, and groin may be affected. Frequently these areas may be left dry or fissured as a result. All stages of lesion development may be observed synchronously. The initial eruption may be exacerbated by pressure or trauma to the affected areas. Associated conditions William Becker first described an association between NME and glucagonoma in 1942 and since then, NME has been described in as many as 70% of persons with a glucagonoma. NME is considered part of the glucagonoma syndrome, which is associated with hyperglucagonemia, diabetes mellitus, and hypoaminoacidemia. When NME is identified in the absence of a glucagonoma, it may be considered "pseudoglucagonoma syndrome". Less common than NME with glucagonoma, pseudoglucagonoma syndrome may occur in a number of systemic disorders: Celiac disease Ulcerative colitis Crohns disease Hepatic cirrhosis Hepatocellular carcinoma Lung cancer, including small cell lung cancer Tumors that secrete insulin- or insulin-like growth factor 2 Duodenal cancer Cause The cause of NME is unknown, although various mechanisms have been suggested. These include hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia, and liver disease. Mechanism The pathogenesis is also unknown. Diagnosis Histology The histopathologic features of NME are nonspecific and include: epidermal necrosis subcorneal pustules confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal hyperplasia in a psoriasiform pattern angioplasia of papillary dermis suppurative folliculitisThe vacuolated, pale, swollen epidermal cells and necrosis of the superficial epidermis are most characteristic. Immunofluorescence is usually negative. Management Managing the original condition, glucagonoma, by octreotide or surgery. After resection, the rash typically resolves within days. See also List of cutaneous conditions References == External links ==

Can you describe Hemoglobinuria, to me Aarogya

Hemoglobinuria

Hemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is caused by excessive intravascular hemolysis, in which large numbers of red blood cells (RBCs) are destroyed, thereby releasing free hemoglobin into the plasma. Excess hemoglobin is filtered by the kidneys, which excrete it into the urine, giving urine a purple color. Hemoglobinuria can lead to acute tubular necrosis which is an uncommon cause of a death of uni-traumatic patients recovering in the ICU. Causes Acute glomerulonephritis Burns Renal cancer Malaria Paroxysmal nocturnal hemoglobinuria Microangiopathies, e.g. hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP) leading to microangiopathic hemolytic anemia Transfusion reactions IgM autoimmune hemolytic anemia Glucose-6-phosphate dehydrogenase deficiency Pyelonephritis Sickle cell anemia Tuberculosis of the urinary tract March hemoglobinuria secondary to repetitive impacts on the body, usually the feet Athletic nephritis secondary to strenuous exercise Acute lead poisoning Diagnosis The diagnosis is often made based on the medical history, blood samples, and a urine sample. The absence of urine RBCs and RBC casts microscopically despite a positive dipstick test suggests hemoglobinuria or myoglobinuria. The medical term for RBCs in the urine is hematuria. See also Hematuria References == External links ==

Aarogya, can you share information about a health condition involving Uterine rupture

Uterine rupture

Uterine rupture is when the muscular wall of the uterus tears during pregnancy or childbirth. Symptoms, while classically including increased pain, vaginal bleeding, or a change in contractions, are not always present. Disability or death of the mother or baby may result.Risk factors include vaginal birth after cesarean section (VBAC), other uterine scars, obstructed labor, induction of labor, trauma, and cocaine use. While typically rupture occurs during labor it may occasionally happen earlier in pregnancy. Diagnosis may be suspected based on a rapid drop in the babys heart rate during labor. Uterine dehiscence is a less severe condition in which there is only incomplete separation of the old scar.Treatment involves rapid surgery to control bleeding and delivery of the baby. A hysterectomy may be required to control the bleeding. Blood transfusions may be given to replace blood loss. Women who have had a prior rupture are generally recommended to have C-sections in subsequent pregnancies.Rates of uterine rupture during vaginal birth following one previous C-section, done by the typical technique, are estimated at 0.9%. Rates are greater among those who have had multiple prior C-sections or an atypical type of C-section. In those who do have uterine scarring, the risk during a vaginal birth is about 1 per 12,000. Risk of death of the baby is about 6%. Those in the developing world appear to be affected more often and have worse outcomes. Signs and symptoms Symptoms of a rupture may be initially quite subtle. An old cesarean scar may undergo dehiscence; with further labor the woman may experience abdominal pain and vaginal bleeding, though these signs are difficult to distinguish from normal labor. Often a deterioration of the fetal heart rate is a leading sign, but the cardinal sign of uterine rupture is loss of fetal station on manual vaginal exam. Intra-abdominal bleeding can lead to hypovolemic shock and death. Although the associated maternal mortality is now less than one percent, the fetal mortality rate is between two and six percent when rupture occurs in the hospital. In pregnancy uterine rupture may cause a viable abdominal pregnancy. This is what accounts for most abdominal pregnancy births. Abdominal pain and tenderness. The pain may not be severe; it may occur suddenly at the peak of a contraction. The woman may describe a feeling that something "gave way" or "ripped." Chest pain, pain between the scapulae, or pain on inspiration—Pain occurs because of the irritation of blood below the womans diaphragm Hypovolemic shock caused by bleeding, evidenced by falling blood pressure, tachycardia, tachypnea, pallor, cool and clammy skin, and anxiety. The fall in blood pressure is often a late sign of haemorrhage Signs associated with fetal oxygenation, such as late deceleration, reduced variability, tachycardia, and bradycardia Absent fetal heart sounds with a large disruption of the placenta; absent fetal heart activity by ultrasound examination Cessation of uterine contractions Palpation of the fetus outside the uterus (usually occurs only with a large, complete rupture). The fetus is likely to be dead at this point. Signs of an abdominal pregnancy Post-term pregnancy Risk factors A uterine scar from a previous cesarean section is the most common risk factor. (In one review, 52% had previous cesarean scars.) Other forms of uterine surgery that result in full-thickness incisions (such as a myomectomy), dysfunctional labor, labor augmentation by oxytocin or prostaglandins, and high parity may also set the stage for uterine rupture. In 2006, an extremely rare case of uterine rupture in a first pregnancy with no risk factors was reported.Uterine rupture during pregnancy without a prior cesarean section is one of the major diagnostic criterion for vascular Ehlers-Danlos syndrome (vEDS). Mechanism In an incomplete rupture the peritoneum is still intact. With a complete rupture the contents of the uterus spill into the peritoneal cavity or the broad ligament. Treatment Emergency exploratory laparotomy with cesarean delivery accompanied by fluid and blood transfusion are indicated for the management of uterine rupture. Depending on the nature of the rupture and the condition of the patient, the uterus may be either repaired or removed (cesarean hysterectomy). Delay in management places both mother and child at significant risk. See also Uterine perforation References == External links ==

Give me a short description about Takotsubo cardiomyopathy , Aarogya

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy or Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart. It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome. Examples of physical stressors that can cause TTS are sepsis, shock, and pheochromocytoma, and emotional stressors include bereavement, divorce, or the loss of a job. Reviews suggest that of patients diagnosed with the condition, about 70–80% recently experienced a major stressor, including 41–50% with a physical stressor and 26–30% with an emotional stressor. TTS can also appear in patients who have not experienced major stressors.The pathophysiology is not well understood, but a sudden massive surge of catecholamines such as adrenaline and norepinephrine from extreme stress or a tumor secreting these chemicals is thought to play a central role. Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or "stunning". Further, this adrenaline surge triggers the arteries to tighten, thereby raising blood pressure and placing more stress on the heart, and may lead to spasm of the coronary arteries that supply blood to the heart muscle. This impairs the arteries from delivering adequate blood flow and oxygen to the heart muscle. Together, these events can lead to congestive heart failure and decrease the hearts output of blood with each squeeze.Takotsubo cardiomyopathy occurs worldwide. The condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals. Although TTS has generally been considered a self-limiting disease, spontaneously resolving over the course of days to weeks, contemporary observations show that "a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure, pulmonary oedema, stroke, cardiogenic shock, or cardiac arrest". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome (ACS), but that patients with acute complications may co-occur with TTS. These cases of shock and death have been associated with the occurrence of TTS secondary to an enciting physical stressor such as hemorrhage, brain injury sepsis, pulmonary embolism or severe COPD.It occurs more commonly in postmenopausal women. The name "takotsubo" comes from the Japanese word takotsubo "octopus trap", because the left ventricle of the heart takes on a shape resembling an octopus trap when affected by this condition.A study published in the Journal of the American Heart Association in October 2021 found a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older. Signs and symptoms The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking a myocardial infarction of the anterior wall. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome its name takotsubo "octopus trap", in Japan, where it was first described.Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms. Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems. Acute asthma, surgery, chemotherapy, and stroke are examples of physical stressors. In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday. Risk factors Stress trigger Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful event. Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury, asthma attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers. Roughly one-third of patients have no preceding stressful event. A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter. Sex Women, specifically postmenopausal women, are at greatest risk of developing TTS. This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS. Genetic risk factors It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS. There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process. Hormonal dysregulation Certain endocrine diseases including pheochromocytoma and thyrotoxicosis have been identified as potential risk factors for TTS. The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena. A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS. Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality. Pathophysiology The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed. It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals and the effects these chemicals have on areas of the heart. More specifically, adrenal stimulation by the sympathetic nervous system has been noted in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one. How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood. Research supports the widely-held understanding that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes results in apical stunning and transient cardiomyopathy. Microvascular dysfunction/Transient vasospasm: Some of the original researchers of takotsubo suggested that multiple simultaneous spasms of coronary arteries could cause enough loss of blood flow to cause transient stunning of the myocardium. Other researchers have shown that vasospasm is much less common than initially thought. It has been noted that when there are vasospasms, even in multiple arteries, that they do not correlate with the areas of myocardium that are not contracting. However, the idea of coronary artery vasospasm is still believed to contribute to the TTS disease process. The theory of vasospasm is not easily separated from that of microvascular dysfunction and in fact, microvascular dysfunction could explain vasospasticity. Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is currently one of the most supported theories. Most of the dysfunction occurs as a result of abnormalities within the endothelial linings of blood vessels supplying the heart. In TTS, these highly sensitive interior linings of the vessels have reduced functionality which create dysregulation of vascular tone and predispose the individual to vasoconstriction. When the increased vasoconstrictor effects of catecholamines are introduced, the result is acute cardiac ischemia. Catecholamine-induced myocyte injury: It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy. The effects of this toxicity can be greater in those with a predisposition to anxiety or panic disorders. Delivery of catecholamines (epinephrine, norepinephrine) via circulating blood and through direct delivery from cardiac nerves is increased by the stimulation of stress control centers of the brain. During an emotionally or physically stressful event, brain centers initiate the sympathetic nervous pathways and increase myocardial activity. Excessive catecholamine stimulation has a toxic effect on cardiac muscle cells which creates necrosis of the contractile units of cells similarly seen during acute myocardial infarction. The increased workload of cardiac muscle created by the stimulation of catecholamines, increases the need for more blood and oxygen to these muscles to sustain function. When these demands are unable to be met, the heart is starved of blood and oxygen and begins to die. Included in the cytotoxic sequela of catecholamine toxicity is the molecular transformation of the cardiac myocyte to produce apical stunning. Mid-ventricular obstruction, apical stunning: It has been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology. This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell. Overstimulation of catecholamine receptors create physiological changes in the receptor which has an inverse effect on cardiac cellular function. Termed cellular-trafficking, this property of the cardiac muscle cell is actually a molecular transformation of the cell to produce a down-regulation of catecolaminergic sensitivity. This means that in the presence of excess epinephrine, a normal cardiac contraction is inhibited in an effort to reduce energy demands, prevent hyperactivity and spare the integrity of the cell. Further bolstering this idea is the concentration of these kinds of receptors in the heart. Higher concentrations of the receptor effected to produce cardiac stunning are found closer to the apex of the ventricle. This is what creates the classic ballooning effect of the ventricle.It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality. For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia. An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction. Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS.A 2019 case involved a 60-year-old woman presenting with Takotsubo cardiomyopathy due to over-consumption of wasabi, mistaking it for avocado. Diagnosis Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, Gothenburg University, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology. All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin.Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome. While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram to rule out occlusion of the left anterior descending artery, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months.The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings often are confused with those found during an acute anterior wall myocardial infarction. It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease.The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments.The ballooning patterns were classified by Shimizu et al. as takotsubo type for apical akinesia and basal hyperkinesia, reverse takotsubo for basal akinesia and apical hyperkinesia, mid-ventricular type for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and localised type for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction.In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patients ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time. Treatment The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder. Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months. Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases. After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of supporting the patient. There is currently no internationally agreed protocol for treatment of this condition.While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations.Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated. These most commonly include congestive heart failure and very low blood pressure, and less commonly include blood clotting in the apex of the left ventricle, irregular heart beat, and tearing of the heart wall. Heart failure For patients in acute heart failure, ACE inhibitors, angiotensin receptor blockers, and beta blockers, are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit. Low blood pressure For people with cardiogenic shock, medical treatment is based on whether a left ventricular outflow tract (LVOT) obstruction is present. Therefore, early echocardiography is necessary to determine proper management. For those with obstructed LVOTs inotropic agents should not be used, but instead should be managed like patients with hypertrophic cardiomyopathy, (e.g. phenylephrine and fluid resuscitation). For cases in which the LVOT is not obstructed, inotropic therapy (e.g. dobutamine and dopamine) may be used, but with the consideration that takotsubo is caused by excess catecholamines.Furthermore, mechanical circulatory support (MCS) with an intra-aortic balloon pump (IABP) is well-established as supportive treatment. Prognosis Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most. Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months. Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger. Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall. Epidemiology Takotsubo cardiomyopathy is common, affecting between 1.2% and 2.2% of people in Japan and 2% to 3% in Western countries who experience a myocardial infarction. It also affects far more women than men with 90% of cases being women, most postmenopausal. Scientists believe one reason is that estrogen causes the release of catecholamine and glucocorticoid in response to mental stress. It is not likely for the same recovered patient to experience the syndrome twice, although it has happened in rare cases. The average ages at onset are between 58 and 75 years. Less than 3% of cases occurred in patients under age 50. History Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven.Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: (1) on the impact of the collapse or death of a close person; (2) during acute grief; (3) on threat of loss of a close person; (4) during mourning or on an anniversary; (5) on loss of status or self-esteem; (6) personal danger or threat of injury; (7) after the danger is over; (8) reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease.Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in Cuyahoga County, Ohio, the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had myofibrillar degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart".The first studied case of takotsubo cardiomyopathy was in Japan in 1991 by Sato et al. More cases of the syndrome appeared in Japan within the next decade, although western medicine had still not acknowledged it. The syndrome finally occurred in 1997 when Pavin, et al., wrote about two cases of "reversible LV dysfunction precipitated by acute emotional stress". The western world had not heard of such a thing at the time, as it was incredibly rare and often misdiagnosed. The Japanese at last reported about the syndrome to the west in 2001 under the name "transient LV apical ballooning" though at this point the west had already heard of numerous cases. The syndrome reached international audiences through the media in 2005 when the New England Journal of Medicine wrote about the syndrome.In the bible, when Jacob was told his long lost son, Joseph, is still alive, "his heart faltered, because he did not believe them". The medieval commentator, Nachmanides, further explains: "This condition is known when joy suddenly comes upon one, and it is mentioned in the books of medicines that old or feeble persons cannot withstand the shock, for many of them faint when joy comes to them very suddenly. The heart widens and opens suddenly, and its natural heat goes out and scatters throughout the outer parts of the body, and the heart thus ceases to function because of its coolness." In popular culture The name and title track of the 2021 album Tako Tsubo by French band LImpératrice refers to the intense emotional stress which may provoke this syndrome. See also Widowhood effect References External links Krishnan, Lakshmi; Marchalik, Daniel (8 September 2018). "Understanding Heartbreak: From Takotsubo to Wuthering Heights". The Lancet. 392 (10150): 812. doi:10.1016/S0140-6736(18)32061-0. S2CID 54271789. Retrieved 25 September 2019. Wagner, Judith N. (Fall 2014). "Death by voodoo: truth or tale?". Hektoen International Journal. 6 (4). ISSN 2155-3017. Takotsubo Network - website for professionals and people who have experienced Takotsubo