<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hereditary spherocytosis and explain in detail? [/INST] Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (spherocytosis), rather than the normal biconcave disk-shaped, their morphology interferes with these cells abilities to be flexible during circulation throughout the entirety of the body -  arteries, arterioles, capillaries, venules, veins, and organs. This difference in shape also makes the red blood cells more prone to rupture under osmotic and/or mechanical stress. Cells with these dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes resulting in hemolytic anemia.
HS was first described in 1871, and is the most common cause of inherited hemolysis in populations of northern European descent, with an incidence of 1 in 5000 births. The clinical severity of HS varies from mild (symptom-free carrier), to moderate (anemic, jaundiced, and with splenomegaly), to severe (hemolytic crisis, in-utero hydrops fetalis), because HS is caused by genetic mutations in a multitude of structural membrane proteins and exhibits incomplete penetrance in its expression.Early symptoms include anemia, jaundice, splenomegaly, and fatigue. Acute cases can threaten to cause hypoxia secondary to anemia and acute kernicterus through high blood levels of bilirubin, particularly in newborns. Most cases can be detected soon after birth. Testing for HS is available for the children of affected adults. Occasionally, the disease will go unnoticed until the child is about 4 or 5 years of age. A person may also be a carrier of the disease and show no signs or symptoms of the disease. Late complications may result in the development of pigmented gallstones, which is secondary to the detritus of the broken-down blood cells (unconjugated or indirect bilirubin) accumulating within the gallbladder. Also, patients who are heterozygous for a hemochromatosis gene may exhibit iron overload, despite the hemochromatosis genes being recessive. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. The resultant asplenic patient is susceptible to encapsulated bacterial infection, and prevented with vaccination. If other symptoms, such as abdominal pain persist, the removal of the gallbladder may be warranted for symptomatic cholelithiasis.

Epidemiology
Hereditary spherocytosis is the heritable hemolytic disorder, affecting 1 in 2,000 people of Northern European ancestry. According to Harrisons Principles of Internal Medicine, the frequency is at least 1 in 5,000 within the United States of America. While HS is most commonly (though not exclusively) found in Northern European and Japanese families, an estimated 25% of cases are due to spontaneous mutations.

Etiology
Hereditary spherocytosis is an erythrocytic disorder of that affects the following red cell membrane proteins in a congenital fashion:

Spectrin (alpha and beta)
Ankyrin
Band-3 Protein
Protein-4.2
Lesser proteins of significanceHereditary spherocytosis can be an autosomal recessive or autosomal dominant trait.  The autosomal recessive inheritance pattern accounts for close to 25% of the clinical cases. The autosomal dominant inheritance patter accounts for over 75% of the clinical cases. Many positive individuals will not present clinically, thus the etiologic data may be artificially skewed towards the more prominent dominant forms. These dominant forms tend to leave a family history that  yields generational splenectomies and black gallstones cholelithiasis. Lastly, an estimated 25% of cases are due to spontaneous mutations.

Pathophysiology
Causative Genetic Mutations and Phenotypic Expressions
Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other red blood cell membrane proteins:
*Online Mendelian Inheritance in Man (OMIM). The Alpha-1 refers the Alpha-1 Subunit of the Spectrin protein. The Beta refers the Beta Subunit of the Spectrin protein.
These genetic mutations are acted upon and executed by erythrocyte progenitor cells within the bone marrow, where red blood cells are normally produced in the non-pathological state (see Extramedullary Hematopoiesis for pathological production outside of the bone marrow).

Pathophysiology of Mutated Erythrocytic Membrane Proteins
These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk.  The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of spectrin to the greater actin cytoskeleton. This dysfunction of cytoskeletal instabilities ensue, and leave the plasma membrane of the cell less supported and/or weakened.

Cellular Implications
A secondary defect in hereditary spherocytosis is a deficiency of membrane surface area. The decrease in surface area leads to less efficient gas exchange of the erythrocyte at the alveoli of the lungs and throughout circulation. Decreased surface area may be produced by two different mechanisms:

Defects of Spectrin, Ankyrin (most commonly), or Protein 4.2 lead to reduced structural integrity of the plasma membrane, destabilizing the overlying lipid bilayer, and releasing band 3-containing microvesicles. Band-3 is important for gas exchange (as seen above).
Defects of band 3 lead to band 3 deficiency and loss of its lipid-stabilizing effect within the plasma membrane lipid bilayer. This results in the release of band 3-free microvesicles.Both pathways result in compromised plasma membrane integrity, decreased surface area, and formation of spherocytes with decreased mechanical compliance during circulation.

Cardiovascular and Organ Sequelae
Spherocytes have less plasma membrane compliance and fluidity, and this has implications throughout the entirety of circulation within the body, i.e. arteries, arterioles, capillaries, venules, veins, and organs. The lack of compliance and fluidity lead to a higher viscosity value for blood (thickened blood), which can have implications for both larger and smaller diameter vasculature. However, the most pronounced issues with the lack of compliance and fluidity declare themselves in the failure of the erythrocyte to deform itself when transiting arterioles, capillary beds, and venules. These vessels are smaller, and can become congested or blocked altogether. Studies have demonstrated that HS is related to deep vein thrombosis (DVT) and arterial cardiovascular disease for this reason.
The spleen typically acts as a filter for blood, and targets pathogens and other damaged cells within circulation. Removing blood contaminants promotes entire-body homeostasis. The following facts about the spleens role in normal body functioning are crucial to understanding the implications of HS on the overall health of the individual:

Removal of pathogens includes encapsulated bacteria, which reduces sepsis risk (see Complications below).
Removal of damaged erythrocytes reduces iron burden from heme via hepatosplenic recycling, which reduces sepsis risk (see Complications below).
Removal of damaged erythrocytes continues healthy signaling to bone marrow, where erythropoiesis replaces red blood cells lost to wear and tear.In relation to the three facts above, the spleen misguidedly filters spherocytes - regardless of the age or functional status of the cell. The spleen is not dysfunctional itself when selecting spherocytes for destruction, as this is the regular function of the spleen both at an anatomic structure level, and at the molecular cellular level. At the anatomic level, the passage from the Cords of Billroth into the Sinusoids may be seen as a "bottleneck", where red blood cells need to be flexible in order to pass through. In HS, the erythrocytes fail to pass through fenestrations, and this is where resident splenic macrophages sample, or "bite," part of the stuck spherocytes plasma membranes. The macrophages recognize that the spherocyte is not normal, and the macrophage is "programmed" to destroy irregularities filtered at the spleen from the blood. The resident splenic macrophages therefore phagocytose the spherocytes, causing extravascular hemolysis. This leads to both splenomegaly and anemia. Should this process continue unchecked chronically, inappropriate regulation of erythropoeisis leads to extramedullary hematopoiesis.

Clinical Presentation
HS patients present in a vast array of presentations from being asymptomatic, to the extreme situations of splenic rupture and/or hemolytic crisis, or in-utero demise.

Asymptomatic HS (mild): 20-30% of patients.
Infantile-Onset HS (moderate): 60-75% of patients.
Neonatal or In-Utero Onset HS (severe): <5% of patients.The most common presentation will demonstrate jaundice (due to increased unconjugated bilirubin), anemia (with secondary pallor), and a palpable spleen sometimes with concomitant tenderness (due to splenic congestion and splenomegaly). Its worth noting that a subsection of HS patients will also have incidental black pigmented gallstones (made of calcium bilirubinate consequence of the extravascular hemolysis), and some of these patients will develop cholelithiasis and/or the potential complex sequelae of this condition, i.e. cholecystisis, choledocholithiasis, etc.

Diagnostics
Laboratory Testing
Available lab testing that may aid in the diagnosis of HS is as follows:

Coombs Test
Osmotic Fragility Test
Acidified Glycerol Lysis Test
Supportive blood work: mean cell volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), red blood cell count (RBC), reticulocytes, unconjugated bilirubin, haptoglobin, lactate dehydrogenase (LDH).
Peripheral Blood Smear
Eosin-5-maleimide Binding Test

Common Laboratory Findings
The common findings of lab testing in setting of a patient with hereditary spherocytosis:

Coombs Test: Negative (rules-out autoimmune hemolytic anemia)
Osmotic Fragility Test: Positive (Spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture. Although the osmotic fragility test is no longer considered the gold standard for diagnosing hereditary spherocytosis, as it misses ~25% of cases).
Acidified Glycerol Lysis Test: Positive (A newer version of the osmotic fragility test that adds glycerol to a hypotonic solution. This produces lysis, a positive test, quicker that the traditional saline version).
Supportive blood work:
Mean Cell Volume (MCV): Normocytic (normal range: 80-100fL), or slightly lower. Spherocytes are slightly smaller than normal biconcave red blood cells.
Mean Corpuscular Hemoglobin Concentration (MCHC): Increased (normal range: 31-36% Hb/cell). This is secondary to less water being in the cell.
Red Blood Cell Distribution Width (RDW): Increased (normal range: 11-15%). The spherocytes create variation in the size of the red blood cells on average, thus expanding the distribution.
Red Blood Cell Count (RBC): Sometimes Increased Early (normal range males: 4.3-5.9 million/mm3; normal range females: 3.5-5.5million/mm3). The loss of surface area per cells cause the body to mass produce red blood cells. The spleen will filter spherocytes out and change this value.
Reticulocytes: Increased (normal range: 0.5%-1.5% of the RBC listed above). The body to mass produces red blood cells (reticulocytes being young erythrocytes) even as the spleen filters spherocytes out. This is known as reticulocytosis.
Unconjugated Bilirubin: Increased (normal range: 0.2-1.2 mg/dL). This is caused by heme released into the hepatosplenic circulation by macrophages that have phagocytosed erythrocytes. The unconjugated bilirubin is not soluble in water (blood), so it binds to albumin, and is processed in the liver.
Haptoglobin (Free): Decreased (normal range: 41–165 mg/dL). This is caused by hemoglobin binding to haptoglobin, thus making it no longer "free."
lactate dehydrogenase (LDH): Increased (Normal range: 110-295U/L in children). This is due to extravascular hemolysis.
Peripheral Blood Smear: Directly shows spherocytes on microscope.
Eosin-5-maleimide Binding Test: Positive (reduced mean fluorescence), as the test will demonstrate a reduced ability of the Eosin-5-maleimide dye to bind to erythrocyte plasma membrane proteins. The process relies upon flow cytometry.  Gold standard test that produces results at low cost within ~2 hours.In chronic cases, patients who have taken iron supplementation, have heterozygous hemochromatosis, or received numerous blood transfusions, iron overload may cause additional health issues. Measuring iron stores is sometimes considered part of the diagnostic approach to hereditary spherocytosis in older patients presenting with heart muscle damage of unknown etiology or liver disease without apparent cause.

Imaging
Ultrasound is often used to evaluate the dimensions of the spleen, and also the gallbladder in preparation for functionally curative splenectomy with or without cholecystectomy.

Treatment
Although research is ongoing, currently there is no genetic-level cure for the myriad of mutations that cause the various presentations of hereditary spherocytosis. Common current management focuses on interventions prevent the body from inappropriately destroying the functional spherocytes produced by erythrocyte progenitor cells within the bone marrow.
Typical treatment options include:

Splenectomy (operative): This is the operative removal of the entire spleen by a surgeon, thus stopping the extravascular hemolysis, but also removing the immune functions the spleen naturally provide to the body.
Partial splenectomy (operative): This is when only a section of the spleen is removed, instead of the entire organ. The goal is to lower the extravascular hemolysis to a level compatible with homeostasis of the patient, while preserving the immune function of the spleens presence. Research on outcomes is currently ongoing, and is routine at childrens hospitals within the United States of America.
Splenic ablation (interventional radiology): This option is non-operative, and is when an interventional radiologist (instead of a surgeon) uses radiologic techniques to coil or cauterize vasculature within the splenic circulation. There are various points in the circulatory pathway where the treatment can be applied to produces varying amounts of retained viability of the spleen, thus giving the option to attempt to preserve splenic immune function.All operative and interventional treaments require the immunization of HS patients against the influenza virus, SARS-CoV-2, and encapsulated bacteria such as Streptococcus pneumoniae and meningococcus </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Kwashiorkor and explain in detail? [/INST] Kwashiorkor ( KWOSH-ee-OR-kor, -kər, UK also  KWASH-) is a form of severe protein malnutrition characterized by edema and an enlarged liver with fatty infiltrates. It is thought to be caused by sufficient calorie intake, but with insufficient protein consumption (or lack of good quality protein), which distinguishes it from marasmus. Recent studies have found that a lack of antioxidant micronutrients such as β-carotene, lycopene, other carotenoids, and vitamin C as well as the presence of aflatoxins may play a role in the development of the disease. However, the exact cause of kwashiorkor is still unknown. Inadequate food supply is correlated with occurrences of kwashiorkor; occurrences in high income countries are rare.  It occurs amongst weaning children to ages of about five years old.Conditions analogous to kwashiorkor were well documented around the world throughout history. However, Jamaican pediatrician Cicely Williams introduced the term in 1935, two years after she published the diseases first formal description. Williams was the first to conduct research on kwashiorkor and differentiate it from other dietary deficiencies. She was the first to suggest that this might be a deficiency of protein.  The name is derived from the Ga language of coastal Ghana, translated as "the sickness the baby gets when the new baby comes" or "the disease of the deposed child", and reflecting the development of the condition in an older child who has been weaned from the breast when a younger sibling comes. Breast milk contains amino acids vital to a childs growth. In at-risk populations, kwashiorkor may develop after children are weaned from breast milk and begin consuming a diet high in carbohydrates, including maize, cassava or rice.

Classification
Children with severe malnutrition have an increased risk of serious illness and death.
Kwashiorkor is one of the main forms of childhood malnutrition living in low-income and middle-income countries. Kwashiorkor is oftentimes referred to as severe acute malnutrition (SAM). Severe forms of malnutritions are recognized, including stunting, marasmus, and kwashiorkor. Both kwashiorkor and marasmus fall under the umbrella of deficiencies called protein–energy malnutrition (PEM). These diseases are oftentimes discussed together, but can be distinguished. Kwashiorkor is classified by its insufficient protein consumption whereas marasmus is related to general energy deficiency and severe muscle wasting. Kwashiorkor is also distinguished from marasmus by the presence of edema. There is also marasmic kwashiorkor that is the deficiency in calories and in protein. Although they are both different types of severe acute malnutrition, there was greater consumption of antioxidants, vitamins, and minerals seen in those with kwashiorkor compared to those with marasmus.

Wellcomes classification
Wellcome classification is a system for classifying protein-energy malnutrition in children based on weight for their age and based on presence of edema. Other classifications include Gomez classification and Waterlow classification.

Signs and symptoms
The defining sign of kwashiorkor in a malnourished child is pitting edema (particularly swelling of the hands and feet). Unlike marasmus, where the liver and other essential organs are reduced in size, kwashiorkor is characterized by "an enlarged fatty liver, fibrosis, and dysfunction of several organs (such as the liver, kidneys, and nervous system)".  Other signs include a distended abdomen, thinning of hair, loss of teeth, skin or hair depigmentation, and dermatitis. Children with kwashiorkor often develop irritability and anorexia. Generally, the disease can be treated by adding protein to the diet; however, it can have a long-term impact on a childs physical and mental development, and in severe cases may lead to death.In dry climates, marasmus is the more frequent disease associated with malnutrition. Another malnutrition syndrome includes cachexia, although it is often caused by underlying illnesses.  These are important considerations in the treatment of individuals with kwashiorkor.

Causes
The precise etiology of kwashiorkor remains unclear. Several hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor. They include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes.

Low protein intake
Kwashiorkor is a severe form of malnutrition associated with a deficiency in dietary protein. The extreme lack of protein causes an osmotic imbalance in the gastrointestinal system causing swelling of the gut diagnosed as an edema or retention of water.Extreme fluid retention observed in individuals suffering from kwashiorkor is a direct result of irregularities in the lymphatic system and an indication of capillary exchange. The lymphatic system serves three major purposes: fluid recovery, immunity, and lipid absorption. Victims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption, all of which result from a state of severe undernourishment. Fluid recovery in the lymphatic system is accomplished by re-absorption of water and proteins which are then returned to the blood. Compromised fluid recovery results in the characteristic belly distension observed in highly malnourished children.Capillary exchange between the lymphatic system and the bloodstream is stunted due to the inability of the body to effectively overcome the hydrostatic pressure gradient. Proteins, mainly albumin, are responsible for creating the colloid osmotic pressure (COP) observed in the blood and tissue fluids. The difference in the COP of the blood and tissue is called the oncotic pressure. The oncotic pressure is in direct opposition with the hydrostatic pressure and tends to draw water back into the capillary by osmosis. However, due to the lack of proteins, no substantial pressure gradient can be established to draw fluids from the tissue back into the blood stream. This results in the pooling of fluids, causing the swelling and distention of the abdomen.The low protein intake leads to some specific signs: edema of the hands and feet, irritability, anorexia, a desquamative rash, hair discolouration, and a large fatty liver. The typical swollen abdomen is due to two causes: ascites because of hypoalbuminemia (low oncotic pressure), and enlarged fatty liver.Ignorance of nutrition can be a cause. A case was described where parents who fed their child cassava failed to recognize malnutrition because of the edema caused by the syndrome and believed the child was well-nourished despite the lack of dietary protein.Protein should be supplied only for anabolic purposes. The catabolic needs should be satisfied with carbohydrate and fat. Protein catabolism involves the urea cycle, which is located in the liver and can easily overwhelm the capacity of an already damaged organ. The resulting liver failure can be fatal.  This means in individuals suffering from kwashiorkor, protein must be introduced back into the diet gradually. Clinical solutions include weaning the affected with milk products and increasing the intake of proteinaceous material progressively to daily recommended amounts.

Aflatoxins
Recent studies have attempted to pinpoint a relationship between kwashiorkor and high levels of aflatoxins. Aflatoxins are naturally occurring toxins produced by the mold Aspergillus flavus, a fungus found in areas with hot and humid climates. These toxins tend to grow and can be found in agricultural crops such as millet, maize, and rice. An analysis found that the presence of aflatoxins was found more frequently and in higher concentrations in individuals with kwashiorkor when compared to individuals with marasmus (another form of severe acute malnutrition). In particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine. Aflatoxins were not found in liver samples of individuals with marasmus. It has been known that the liver organ is the main target of aflatoxins and chronic toxicity can result in immunosuppressive and carcinogenic effects. However, there is currently conflicting evidence to pinpoint a connection between kwashiorkor and aflatoxins. Studies have shown that not all children with kwashiorkor present with detectable aflatoxin levels. It has also been proposed that damage done by aflatoxins may be due to glutathione depletion (another proposed mechanism of the disease) in children with kwashiorkor.

Mechanisms
Peripheral edema and hypoalbuminemia
Kwashiorkor is a form of protein deficiency, which can result in both osmotic imbalances and irregularities in the lymphatic system.Kwashiorkor is most notable for peripheral edema. The presence of edema in kwashiorkor is correlated with very low albumin concentration (hypoalbuminemia). Edema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls due to the lack of protein which affects the bodys ability to draw fluid from the tissues into the bloodstream. Low albumin concentration influences negatively the strength of oncotic pressure. Failure leads to the fluid buildup in the abdomen, resulting in edema and belly distension.Furthermore, the release of antidiuretic hormone is stimulated by hypovolemia, also leading to the development of peripheral edema. Plasma renin is also stimulated, promoting sodium retention.It is important to distinguish the pathophysiology of marasmus and kwashiorkor when it comes to treating malnourished children who may have hypovolemic shock that is cause by an acute loss of salt and water. Children with severe albumin deficiency struggle physiologically to maintain their blood volume.

Low glutathione levels
Kwashiorkor is also marked by low glutathione levels. Glutathione is used in many of the body processes on a molecule level.It is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation. Glutathione serves vital functions including management of oxidative stress which is an imbalance that plays a key role in the pathogenesis of many diseases.
Cysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans. Factors that stimulate cysteine uptake by cells will increase glutathione levels and prevent glutathione deficiency in humans under various conditions including protein malnutrition.Evidence indicates that dietary amino acids balance has an important effect on protein nutrition and therefore on glutathione homeostasis.

Others
A proposed experimental theory suggests that alterations in the microbiome/virone contributes to edematous malnutrition, but further studies are required to understand the mechanism.

Diagnosis
Kwashiorkor, or edematous malnutrition, like many other malnutrition diseases, is indirectly assessed using anthropometry. Kwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema. According to the World Health Organization, the SAM diagnosis parameters are a "mid-upper arm circumference (MUAC) of < 115 mm, weight-for-height/length Z-score (WHZ) of < -3Z and nutritional edema or any combination of these parameters." Additional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.WHO criteria for clinical assessment of malnutrition are based on the degree of wasting (MUAC), stunting (weight-for-height Z-score), and the presence of edema (mild to severe).

Screening
Because it can be difficult to measure weight-for-height Z scores (WHZ) frequently, screening is performed using mid-upper arm circumference (MUAC) < 115 mm. To properly screen for severe malnutrition in children, MUAC measurements should be done every month to reduce the risk of complications. Additionally, getting a better sense of what they eat, how often they eat, and any issues they may have with eating, may give more insight on their nutrition and what changes may need to be made to improve it.

Prevention
As for the prevention of childhood malnutrition, there needs to be public health changes such as improving agriculture and improving access to healthcare to effectively reduce the rates of malnutrition in children. By educating individuals of childbearing age on proper nutrition and health during and after pregnancy, they can provide their children with the appropriate nutrients from a young age. By ensuring they are equipped with the proper education and resources, caretakers and infants are in better health, ultimately preventing childhood malnutrition.Because edema can hide decreased muscle mass, it can be hard to diagnose kwashiorkor in young children; however, if cases are overlooked, children become more susceptible to infections and can ultimately lead to morbidity and mortality. To prevent this from happening, parents can be educated on proper nutrition and the importance of breastfeeding infants to ensure they receive all the nutrients they need.A diet rich in carbohydrates, fats that make up 10% of the total caloric needs, and proteins that make up 15% of the caloric needs can prevent kwashiorkor.
Proteins can be found in the following foods

Seafood
Peas
Nuts
Seeds
Eggs
Lean meat
Beans

Treatment
WHO guidelines outline 10 general principles for the inpatient management of severely malnourished children.
Treat/prevent hypoglycemia
Treat/prevent hypothermia
Treat/prevent dehydration
Correct electrolyte imbalance
Treat/prevent infection
Correct micronutrient deficiencies
Start cautious feeding
Achieve catch-up growth
Provide sensory stimulation and emotional support
Prepare for follow-up after recoveryBoth clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly. Upon initial treatment, children with kwashiorkor may experience weight loss as their edema resolves. Therefore, after concerns of refeeding syndrome have passed, children may require 120-140% of their estimated caloric needs in order to achieve catch-up growth.The cause, type, and severity of malnutrition determines what type of treatment would be most appropriate. For primary acute malnutrition, children with no complications are treated at home and are encouraged to either continue breastfeeding (for infants) or start using ready-to-use therapeutic foods (for children). For secondary acute malnutrition, the underlying cause needs to be identified to appropriately treat children. Only after the primary disease is determined can an appropriate dietary plan be made, as fluid, vitamins, and macronutrients may need to be considered to not exacerbate the cause of the malnutrition.Ready-to-use therapeutic foods (RUTFs) and F-75 and F-100 milks were created to provide appropriate nutrition and caloric intake to those experiencing malnutrition. F-75 milk would be ideal when trying to reintroduce food into a malnourished person, and F-100 milk would be used to aid in weight gain. While RUTFs and F-100 milk were made to have the same nutritional value, RUTFs are beneficial as they are dehydrated and do not require much preparation.

Prognosis
Kwashiorkor is associated with a high risk of mortality and long-term complications. Treatment under the guidelines of the World Health Organization has proven to reduce this mortality risk and affected children tend to recover faster than children with other severe malnutrition diseases. However, physical and intellectual capabilities are not fully restored. Growth stunting and chronic disruption of microbiota are commonly observed after recovery.A high risk of death is identified by a brachial perimeter < 11 cm or by a weight-for-age threshold < −3 z-scores below the median of the WHO child growth standards. In practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition.

Epidemiology
Kwashiorkor is rare in high income countries. It is mostly observed in low-income and middle income nations and regions such as Southeast Asia, Central America, Congo, Ethiopia, Puerto Rico, Jamaica, South Africa, and Uganda, where poverty is prominent. Occurrences of severe malnutrition also tend to trend higher under conditions of food insecurity, higher prevalence of infectious diseases, lack of access to appropriate care, and poor living situations with inadequate sanitation. Communities experiencing famine are affected the most especially during the rainy season. Prevalence varies, but it affects children of either sex commonly under five years old. "Globally, kwashiorkor indirected accounted for 53% of deaths among children under five between 2000 and 2003 when associated with other common childhood diseases like acute respiratory infections, malaria, measles, HIV/AIDS and other causes of perinatal deaths."When compared to marasmus in developing countries, kwashiorkor has a lower prevalence, "0.2%-1.6% for kwashiorkor and 1.2%-6.8% for marasmus." Factors such as "diet, geographical locations, climate and aflatoxin exposure" are associated with the difference in prevalence for kwashiorkor and marasmus.

History
It is likely that kwashiorkor was commonly seen around the world long before 1933, when Cicely Williams published research which took the Ga name for the disease. There were already many names for the illness which referenced the cessation of breastfeeding, or the consumption of diets which were too high in starch. However, Williams was the first to suggest that this might be a deficiency of protein.   Despite publishing in 1933, it was only in 1949 that the World Health Organization officially recognized kwashiorkor as a public health concern. This period also correlated with the promotion of infant formula, often by European colonial powers. The substitution of breastmilk for formula contributed significantly to the increasing visibility of kwashiorkor throughout the twentieth century. Cicely Williams later described the promotion of formula as "the most criminal form of sedition, and that those deaths should be regarded as murder." These arguments underpinned the 1970s Nestlé boycott.

Effects on pharmacokinetics
Those experiencing poverty-related infectious diseases (PRDs) such as malaria and tuberculosis are also likely to be malnourished. Malnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drugs bioavailability, distribution, and elimination </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Vascular dementia and explain in detail? [/INST] Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting of a complex interaction of cerebrovascular disease and risk factors that lead to changes in brain structures due to strokes and lesions, resulting in changes in cognition. The temporal relationship between a stroke and cognitive deficits is needed to make the diagnosis.

Signs and symptoms
Differentiating dementia syndromes can be challenging, due to the frequently overlapping clinical features and related underlying pathology. In particular, Alzheimers disease often co-occurs with vascular dementia.People with vascular dementia present with progressive cognitive impairment, acutely or sub-acutely as in mild cognitive impairment, frequently step-wise, after multiple cerebrovascular events (strokes). Some people may appear to improve between events and decline after further silent strokes. A rapidly deteriorating condition may lead to death from a stroke, heart disease, or infection.The disease is described as both a mental disorder and behavioural disorder within the International Classification of Diseases. Signs and symptoms are cognitive, motor, behavioral, and for a significant proportion of patients, also affective. These changes typically occur over a period of 5–10 years. Signs are typically the same as in other dementias, but mainly include cognitive decline and memory impairment of sufficient severity as to interfere with activities of daily living, sometimes with presence of focal neurologic signs, and evidence of features consistent with cerebrovascular disease on brain imaging (CT or MRI). The neurologic signs localizing to certain areas of the brain that can be observed are hemiparesis, bradykinesia, hyperreflexia, extensor plantar reflexes, ataxia, pseudobulbar palsy, as well as gait problems and swallowing difficulties. People have patchy deficits in terms of cognitive testing. They tend to have better free recall and fewer recall intrusions when compared with patients with Alzheimers disease. In the more severely affected patients, or patients affected by infarcts in Wernickes or Brocas areas, specific problems with speaking called dysarthria and aphasias may be present.In small vessel disease, the frontal lobes are often affected. Consequently, patients with vascular dementia tend to perform worse than their Alzheimers disease counterparts in frontal lobe tasks, such as verbal fluency, and may present with frontal lobe problems: apathy, abulia (lack of will or initiative), problems with attention, orientation, and urinary incontinence. They tend to exhibit more perseverative behavior. VaD patients may also present with general slowing of processing ability, difficulty shifting sets, and impairment in abstract thinking. Apathy early in the disease is more suggestive of vascular dementia.Rare genetic disorders that cause vascular lesions in the brain have other presentation patterns. As a rule, they tend to occur earlier in life and have a more aggressive course. In addition, infectious disorders, such as syphilis, can cause arterial damage, strokes, and bacterial inflammation of the brain.

Causes
Vascular dementia can be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus. On rare occasion, infarcts in the hippocampus or thalamus are the cause of dementia. A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%. Brain vascular lesions can also be the result of diffuse cerebrovascular disease, such as small vessel disease.Risk factors for vascular dementia include age, hypertension, smoking, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease. Other risk factors include geographic origin, genetic predisposition, and prior strokes.Vascular dementia can sometimes be triggered by cerebral amyloid angiopathy, which involves accumulation of beta amyloid plaques in the walls of the cerebral arteries, leading to breakdown and rupture of the vessels. Since amyloid plaques are a characteristic feature of Alzheimers disease, vascular dementia may occur as a consequence. Cerebral amyloid angiopathy can, however, appear in people with no prior dementia condition. Amyloid beta accumulation is often present in cognitively normal elderly people.Two reviews of 2018 and 2019 found potentially an association between celiac disease and vascular dementia.

Diagnosis
Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the International Classification of Diseases, Tenth Edition (ICD-10) criteria, the National Institute of Neurological Disorders and Stroke criteria, Association Internationale pour la Recherche et lEnseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimers Disease Diagnostic and Treatment Center criteria, and the Hachinski Ischemic Score (after Vladimir Hachinski).The recommended investigations for cognitive impairment include: blood tests (for anemia, vitamin deficiency, thyrotoxicosis, infection, etc.), chest X-Ray, ECG, and neuroimaging, preferably a scan with a functional or metabolic sensitivity beyond a simple CT or MRI. When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging may be used to confirm a diagnosis of multi-infarct dementia in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating multi-infarct dementia from Alzheimers disease, compared to the usual mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.The screening blood tests typically include full blood count, liver function tests, thyroid function tests, lipid profile, erythrocyte sedimentation rate, C reactive protein, syphilis serology, calcium serum level, fasting glucose, urea, electrolytes, vitamin B-12, and folate. In selected patients, HIV serology and certain autoantibody testing may be done.Mixed dementia is diagnosed when people have evidence of Alzheimers disease and cerebrovascular disease, either clinically or based on neuro-imaging evidence of ischemic lesions.

Pathology
Gross examination of the brain may reveal noticeable lesions and damage to blood vessels. Accumulation of various substances such as lipid deposits and clotted blood appear on microscopic views. The white matter is most affected, with noticeable atrophy (tissue loss), in addition to calcification of the arteries. Microinfarcts may also be present in the gray matter (cerebral cortex), sometimes in large numbers.
Although atheroma of the major cerebral arteries is typical in vascular dementia, smaller vessels and arterioles are mainly affected.

Prevention
Early detection and accurate diagnosis are important, as vascular dementia is at least partially preventable. Ischemic changes in the brain are irreversible, but the patient with vascular dementia can demonstrate periods of stability or even mild improvement. Since stroke is an essential part of vascular dementia, the goal is to prevent new strokes. This is attempted through reduction of stroke risk factors, such as high blood pressure, high blood lipid levels, atrial fibrillation, or diabetes mellitus. Meta-analyses have found that medications for high blood pressure are effective at prevention of pre-stroke dementia, which means that high blood pressure treatment should be started early. These medications include angiotensin converting enzyme inhibitors, diuretics, calcium channel blockers, sympathetic nerve inhibitors, angiotensin II receptor antagonists or adrenergic antagonists. Elevated lipid levels, including HDL, were found to increase risk of vascular dementia. However, six large recent reviews showed that therapy with statin drugs was ineffective in treatment or prevention of this dementia. Aspirin is a medication that is commonly prescribed for prevention of strokes and heart attacks; it is also frequently given to patients with dementia. However, its efficacy in slowing progression of dementia or improving cognition has not been supported by studies. Smoking cessation and Mediterranean diet have not been found to help patients with cognitive impairment; physical activity was consistently the most effective method of preventing cognitive decline.

Treatment
Currently, there are no medications that have been approved specifically for prevention or treatment of vascular dementia. The use of medications for treatment of Alzheimers dementia, such as cholinesterase inhibitors and memantine, has shown small improvement of cognition in vascular dementia. This is most likely due to the drugs actions on co-existing AD-related pathology. Multiple studies found a small benefit in VaD treatment with: memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; cholinesterase inhibitors galantamine, donepezil, rivastigmine; Studies have been proposed to evaluate whether an extract of Ginkgo biloba EGb761 improves cognition, daily activities, and quality of life in treating vascular dementia.In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve symptoms of mild cognitive impairment. It should be started as soon as possible. There is no evidence that a gluten free diet is useful against advanced dementia. People with no digestive symptoms are less likely to receive early diagnosis and treatment.General management of dementia includes referral to community services, aid with judgment and decision-making regarding legal and ethical issues (e.g., driving, capacity, advance directives), and consideration of caregiver stress. Behavioral and affective symptoms deserve special consideration in this patient group. These problems tend to resist conventional psychopharmacological treatment, and often lead to hospital admission and placement in permanent care.

Prognosis
Many studies have been conducted to determine average survival of patients with dementia. The studies were frequently small and limited, which caused contradictory results in the connection of mortality to the type of dementia and the patients gender. A very large study conducted in Netherlands in 2015 found that the one-year mortality was three to four times higher in patients after their first referral to a day clinic for dementia, when  compared to the general population. If the patient was hospitalized for dementia, the mortality was even higher than in patients hospitalized for cardiovascular disease.  Vascular dementia was found to have either comparable or worse survival rates when compared to Alzheimers Disease; another very large 2014 Swedish study found that the prognosis for VaD patients was worse for male and older patients.Unlike Alzheimers disease, which weakens the patient, causing them to succumb to bacterial infections like pneumonia, vascular dementia can be a direct cause of death due to the possibility of a fatal interruption in the brains blood supply.

Epidemiology
Vascular dementia is the second-most-common form of dementia after Alzheimers disease (AD) in older adults. The prevalence of the illness is 1.5% in Western countries and approximately 2.2% in Japan. It accounts for 50% of all dementias in Japan, 20% to 40% in Europe and 15% in Latin America </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Labyrinthitis and explain in detail? [/INST] Labyrinthitis is inflammation of the labyrinth – a maze of fluid-filled channels in the inner ear. Vestibular neuritis is inflammation of the vestibular nerve – the nerve in the inner ear that sends messages related to motion and position to the brain. Both conditions involve inflammation of the inner ear.  Labyrinths that house the vestibular system sense changes in the heads position or the heads motion. Inflammation of these inner ear parts results in a sensation of the world spinning and also possible hearing loss or ringing in the ears. It can occur as a single attack, a series of attacks, or a persistent condition that diminishes over three to six weeks. It may be associated with nausea, vomiting, and eye nystagmus.
The cause is often not clear. It may be due to a virus, but it can also arise from bacterial infection, head injury, extreme stress, an allergy, or as a reaction to medication. 30% of affected people had a common cold prior to developing the disease. Either bacterial or viral labyrinthitis can cause a permanent hearing loss in rare cases. This appears to result from an imbalance of neuronal input between the left and right inner ears.

Signs and symptoms
The main symptoms are severe vertigo and nystagmus. The most common symptom for vestibular neuritis is the onset of vertigo that has formed from an ongoing infection or trauma. The dizziness sensation that is associated with vertigo is thought to be from the inner ear labyrinth. Rapid and undesired eye motion (nystagmus) often results from the improper indication of rotational motion.  Nausea, anxiety, and a general ill feeling are common due to the distorted balance signals that the brain receives from the inner ear system. Other common symptoms include tinnitus, ear ache, and a feeling of fullness in the ear.

Causes
Some people will report having an upper respiratory infection (common cold) or flu prior to the onset of the symptoms of vestibular neuritis; others will have no viral symptoms prior to the vertigo attack.
Some cases of vestibular neuritis are thought to be caused by an infection of the vestibular ganglion by the herpes simplex type 1 virus. However, the cause of this condition is not fully understood, and in fact, many different viruses may be capable of infecting the vestibular nerve.
Acute localized ischemia of these structures also may be an important cause. Especially in children, vestibular neuritis may be preceded by symptoms of a common cold.  However, the causative mechanism remains uncertain.This can also be brought on by pressure changes such as those experienced while flying or scuba diving.

Mechanism
In the vestibular system, there are three canals that are semicircular in shape that input sensory clues. These canals allow the brain to sense rotational motion and linear motion changes. The brain then uses the sensory input clues and the visual input clues from the vestibular system to retain balance. The vestibulo–ocular reflex retains continuous visual focus during motion which is also the vestibular systems job during activity.

Treatment
The treatment for vestibular neuritis depends on the cause. However, symptoms of vertigo can be treated in the same way as other vestibular dysfunctions with vestibular rehabilitation.

Physical therapy
Typical treatments include combinations of head and eye movements, postural changes, and walking exercises. Specifically, exercises that may be prescribed include keeping eyes fixated on a specific target while moving the head, moving the head right to left at two targets at a significant distance apart, walking while keeping eyes fixated on a specific target, and walking while keeping eyes fixated on a specific target while also turning the head in different directions.
The main function behind repeating a combination of head and eye movements, postural changes and walking is that through this repetition, compensatory changes for the dysfunctions arising from peripheral vestibular structures may be promoted in the central vestibular system (brainstem and cerebellum).Vestibular rehabilitation therapy is a highly effective way to substantially reduce or eliminate residual dizziness from labyrinthitis. VRT works by causing the brain to use already existing neural mechanisms for adaptation, neuroplasticity, and compensation. Vestibular neuritis rehabilitation is an effective and safe management to improve symptoms. The vestibular neuritis rehabilitation can improve symptoms or resolve the symptoms which is dependent on each individual. Rehabilitation strategies most commonly used are:
Gaze stability exercises – moving the head from side to side while fixated on a stationary object (aimed at assisting the eye to fixate during head rotation without the input from the lost canal vestibulo–ocular reflex).  An advanced progression of this exercise would be walking in a straight line while looking side to side by turning the head.
Habituation exercises – movements designed to provoke symptoms and subsequently reduce the negative vestibular response upon repetition. Examples of these include Brandt–Daroff exercises.
Functional retraining – including postural control, relaxation, and balance training.These exercises function by challenging the vestibular system.  Progression occurs by increasing the amplitude of the head or focal point movements, increasing the speed of movement, and combining movements such as walking and head turning.One study found that patients who believed their illness was out of their control showed the slowest progression to full recovery, long after the initial vestibular injury had healed </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cryptosporidiosis and explain in detail? [/INST] Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS or autoimmune disorders) individuals, resulting in watery diarrhea with or without an unexplained cough. In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water; recent evidence suggests that it can also be transmitted via fomites contaminated with respiratory secretions.Cryptosporidium is commonly isolated in HIV-positive patients presenting with diarrhea. Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The infection begins when a human consumes food or water containing cysts of the Cryptosporidium organism.

Signs and symptoms
Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals; symptoms are usually more severe and persist longer in immunocompromised individuals.  Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. The likelihood of re-infection is high in immunocompromised adults, and low in those with normal immune systems.In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well.  In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis.

Intestinal cryptosporidiosis
Common signs and symptoms of intestinal cryptosporidiosis include:

Moderate to severe watery diarrhea, sometimes contains mucus and rarely contains blood or leukocytesIn very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia
Low-grade fever
Crampy abdominal pain
Dehydration
Weight loss
Fatigue
Nausea and vomiting – suggests upper GI tract involvement and may lead to respiratory cryptosporidiosis
Epigastric or right upper quadrant tendernessLess common or rare signs and symptoms include:

Reactive arthritis (may affect the hands, knees, ankles, and feet)
Jaundice – suggests hepatobiliary involvement
Ascites – suggests pancreatic involvement

Respiratory cryptosporidiosis
Symptoms of upper respiratory cryptosporidiosis include:

Inflammation of the nasal mucosa, sinuses, larynx, or trachea
Nasal discharge
Voice change (e.g., hoarseness)Symptoms of lower respiratory cryptosporidiosis include:

Cough
Shortness of breath
Fever
Hypoxemia

Reason
Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis (previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans. Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route.  Other vectors of disease transmission also exist.The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborder Eimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serving for parasites spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species.These species possess a number of unusual features:
an endogenous phase of development in microvilli of epithelial surfaces
two morphofunctional types of oocysts
the smallest number of sporozoites per oocyst
a multi-membraneous "feeder" organelleDNA studies suggest a relationship with the gregarines rather than the coccidia. The taxonomic position of this group has not yet been finally agreed upon.
The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA. A closely related species, C. hominis, also has its genome sequence available. CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets.

Transfer
Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces.  The high resistance of Cryptosporidium oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective. Some outbreaks have happened in day care related to diaper changes.The following groups have an elevated risk of being exposed to Cryptosporidium:
Child care workers
Parents of infected children
People who take care of other people with cryptosporidiosis
International travelers
Backpackers, hikers, and campers who drink unfiltered, untreated water
People, including swimmers, who swallow water from contaminated sources
People who handle infected cattle
People exposed to human feces through sexual contactCases of cryptosporidiosis can occur even in cities that have a properly de-contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have other origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Cryptosporidium is causing serious illness  more frequently in immunocompromised than in apparently healthy individuals. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviors can transmit the parasite directly.

Life cycle
Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage). As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants. After being ingested, the sporozoites within oocysts excyst (i.e., are released) in the small intestine.  The released sporozoites subsequently attach to the microvilli of the epithelial cells of the small intestine.  From there they become trophozoites that reproduce asexually by multiple fission, a process known as schizogony.  The trophozoites develop into Type 1 meronts [1] that contain 8 daughter cells.These daughter cells are Type 1 merozoites, which get released by the meronts.  Some of these merozoites can cause autoinfection by attaching to epithelial cells.  Others of these merozoites become Type II meronts, which contain 4 Type II merozoites.  These merozoites get released and they attach to the epithelial cells.  From there they become either macrogamonts or microgamonts.  These are the female and male sexual forms, respectively.  This stage, when sexual forms arise, is called gametogony.Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts.  The zygotes develop into oocysts of two types.  20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again.  The thick-walled oocysts are excreted into the environment.  The oocysts are mature and infective upon being excreted.

Pathogenesis
The oocysts are ovoid or spherical and measure 5 to 6 micrometers across.  When in flotation preparations they appear highly refractile.  The oocysts contains up to 4 sporozoites that are bow-shaped.As few as 2 to 10 oocysts can initiate an infection.  The parasite is located in the brush border of the epithelial cells of the small intestine.  They are mainly located in the jejunum.  When the sporozoites attach the epithelial cells membrane envelops them.  Thus, they are "intracellular but extracytoplasmic".  The parasite can cause damage to the microvilli where it attaches.  The infected human excretes the most oocysts during the first week.  Oocysts can be excreted for weeks after the diarrhea subsides from infections by C. parvum or C. hominis; however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months.The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts.  This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite.
Previous infection in immunocompetent individuals produces little resistance to future infection, however it may decrease the severity of disease and the number of oocysts excreted.

Diagnosis
There are many diagnostic tests for Cryptosporidium.  They include microscopy, staining, and detection of antibodies. Microscopy can help identify oocysts in fecal matter.  To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples.  There are several techniques to concentrate either the stool sample or the oocysts.  The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool.  Both the modified zinc sulfate centrifugal flotation technique and the Sheathers sugar flotation procedure can concentrate the oocysts by causing them to float.  Another form of microscopy is fluorescent microscopy done by staining with auramine.Other staining techniques include acid-fast staining, which will stain the oocysts red.  One type of acid-fast stain is the Kinyoun stain.  Giemsa staining can also be performed.  Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.Detecting antigens is yet another way to diagnose the disease.  This can be done with direct fluorescent antibody (DFA) techniques.  It can also be achieved through indirect immunofluorescence assay.  Enzyme-linked immunosorbent assay (ELISA) also detects antigens.Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis.  It can even identify the specific species of Cryptosporidium.  If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography.  If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography.

Prevention
Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes, including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, including slow sand filters,  diatomaceous earth filters and membranes will remove 99% of Cryptosporidium. Membranes and bag and cartridge filters remove Cryptosporidium  product-specifically.While Cryptosporidium is highly resistant to chlorine disinfection, with high enough concentrations and contact time, Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UVs efficacy in inactivating Cryptosporidium.One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory.  Real-time monitoring technology is now able to detect Cryptosporidium with online systems, unlike the spot and batch testing methods used in the past.The most reliable way to decontaminate drinking water that may be contaminated by Cryptosporidium is to boil it.In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments.  These departments then report to the Center for Disease Control and Prevention.  The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation.  An example would be hand-washing.  Prevention is through washing hands carefully after going to the bathroom or contacting stool, and before eating.  People should avoid contact with animal feces.  They should also avoid possibly contaminated food and water.  In addition, people should refrain from engaging in sexual activities that can expose them to feces.Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it.  Heating milk at 71.7 °C (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts ability to infect.  Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for "cyst removal" by NSF International National Sanitation Foundation.  Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.People with cryptosporidiosis should not swim in communal areas because the pathogen can reside in the anal and genital areas and be washed off.  They should wait until at least two weeks after diarrhea stops before entering public water sources, since oocysts can still be shed for a while.  Also, they should stay away from immunosuppressed people.  Immunocompromised people should take care to protect themselves from water in lakes and streams.  They should also stay away from animal stools and wash their hands after touching animals.  To be safe, they should boil or filter their water.  They should also wash and cook their vegetables.The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3% hydrogen peroxide (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions.

Treatment
Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g., loperamide).  Supplemental zinc may improve symptoms, particularly in recurrent or persistent infections or in others at risk for zinc deficiency.

Immunocompetent
Immunocompetent individuals with cryptosporidiosis typically experience a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may require symptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms); however reinfection frequently occurs.As of 2015, nitazoxanide is the only antiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals; however, it lacks efficacy in severely immunocompromised patients. Certain agents such as paromomycin and azithromycin are sometimes used as well, but they only have partial efficacy.

Immunocompromised
In immunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication. Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together; these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons. A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.Currently, research is being done in molecular-based immunotherapy.  For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies.  Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro. rifaximin is also sometimes used for immunocompromised patients/patients with severe disease.

Epidemiology
Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries, 8–19% of diarrheal diseases can be attributed to Cryptosporidium. Ten percent of the population in developing countries excretes oocysts. In developed countries, the number is lower at 1–3%. The age group most affected are children from 1 to 9 years old.In Eastern Europe cryptosporidiosis in humans and animals is common, but there are considerable gaps in surveillance and a lack of comparable methods which is limit the understanding of the disease and detection of outbreaks. Research show a rich diversity of zoonotic subtypes of the parasite in animals indicating a rich potential of animal to human transmission.
Roughly 30% of adults in the United States are seropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives.

History
The organism was first described in 1907 by Tyzzer, who recognised it was a coccidian.

Research
A recombinant Cryptosporidium parvum oocyst surface protein (rCP15/60) vaccine has produced an antibody response in a large group of cows and also antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows.  This is very promising.  Human Cryptosporidium parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDS patients.  There is no commercially available effective vaccine against Cryptosporidium parvum, although passive immunization utilizing different zoite surface (glyco)proteins has shown promise.  Developmental stages of the life cycle of the parasite might act as possible targets for vaccine development. The organism is detected in 65–97% of the surface-water supply in the United States and is resistant to most disinfectants used for the treatment of drinking water. Antibodies in the serum of humans and animals infected with Cryptosporidium parvum react with several antigens, one of which is a 15 kDa protein (CP15) located on the surface of the organism. This protein is a good candidate for use as a molecular vaccine because previous studies have shown that a monoclonal antibody to CP15 confers passive immunity to mice.  Currently, there is no vaccine or completely effective drug therapy against Cryptosporidium parvum in HIV/AIDS individuals.A summary of discoveries presented at the most recent (June 2019) international symposium on Cryptosporidium has been published in 2020.

Other animals
The most important zoonotic reservoirs are cattle, sheep and goats. In addition, in recent years, cryptosporidiosis has plagued many commercial leopard gecko breeders.  Several species of the Cryptosporidium family (C. serpentes and others) are involved, and outside of geckos it has been found in monitor lizards, iguanas and tortoises, as well as several snake species.

Notable cases
Before 2000
In 1987, 13,000 people in Carrollton, Georgia, United States, became ill with cryptosporidiosis. This was the first report of its spread through a municipal water system that met all state and federal drinking water standards.
In 1993, a waterborne cryptosporidiosis outbreak occurred in Milwaukee, Wisconsin, US. An estimated 403,000 people became ill, including 4,400 people hospitalized. The source of the Cryptosporidium is believed to be overflow from the Milwaukee area combined sanitary and storm sewer system into Lake Michigan, which was then taken into the Howard Avenue Water Purification Plant and distributed to an estimated 880,000 residents (of the 1.61 million residents in the Milwaukee area who receive their drinking water from Lake Michigan). These residents, who receive their drinking water from Lake Michigan, were told to boil their water before drinking it. More people were affected in this one outbreak than the combined number of people affected in every cryptosporidiosis outbreak in the 24 years since then. An estimated 69 people died during the outbreak, according to the CDC.
The UKs biggest outbreak occurred in Torbay in Devon in 1995.
In the summer of 1996, Cryptosporidium affected approximately 2,000 people in Cranbrook, British Columbia, Canada. Weeks later, a separate incident occurred in Kelowna, British Columbia, where 10,000 to 15,000 people got sick.

2001–2009
In April 2001, an outbreak occurred in the city of North Battleford, Saskatchewan, Canada. Between 5800 and 7100 people had diarrheal illness, and 1907 cases of cryptosporidiosis were confirmed. Equipment failures at the citys antiquated water filtration plant following maintenance were found to have caused the outbreak.
In the summer of 2005, after numerous reports by patrons of gastrointestinal upset, a water park at Seneca Lake State Park, in the Finger Lakes region of upstate New York was found to have two water storage tanks infected with Cryptosporidium.  By early September 2005, over 3,800 people reported symptoms of a Cryptosporidium infection. The "Sprayground" was ordered closed for the season on 15 August.
In October 2005, the Gwynedd and Anglesey areas of North Wales, the United Kingdom, suffered an outbreak of cryptosporidiosis. The outbreak may have been linked to the drinking water supply from Llyn Cwellyn, but this is not yet confirmed. As a result, 231 people fell ill and the company Welsh Water (Dwr Cymru) advised 61,000 people to boil their water before use.
In March 2007, a suspected outbreak occurred in Galway, Ireland, after the source of water for much of the county, Lough Corrib, was suspected to be contaminated with the parasite. A large population (90,000 people), including areas of both Galway City and County, were advised to boil water for drinking, food preparation and for brushing teeth. On 21 March 2007, it was confirmed that the city and countys water supply was contaminated with the parasite. The areas water supply was finally given approval on 20 August 2007, five months after Cryptosporidium was first detected. Around 240 people are known to have contracted the disease; experts say the true figure could be up to 5,000.
Hundreds of public pools in 20 Utah counties were closed to young children in 2007, as children under 5 are most likely to spread the disease, especially children wearing diapers. As of 10 September 2007 the Utah Department of Health had reported 1302 cases Archived 25 September 2007 at the Wayback Machine of cryptosporidiosis in the year; a more usual number would be 30. On 25 September the pools were reopened to those not requiring diapers, but hyperchlorination requirements were not lifted.
On 21 September 2007, a Cryptosporidium outbreak attacked the Western United States: 230 Idaho residents, with hundreds across the Rocky Mountain area; in the Boise and Meridian areas; Utah, 1,600 illnesses; Colorado and other Western states — Montana, decrease.
On 25 June 2008, Cryptosporidium was found in England in water supplies in Northampton, Daventry, and some surrounding areas supplied from the Pitsford Reservoir, as reported on the BBC. People in the affected areas were warned not to drink tap water unless it had been boiled. Anglian Water confirmed that 108,000 households were affected, about 250,000 people. They advised that water might not be fit for human consumption for many weeks. The boil notice was lifted for all the affected customers on 4 July 2008.
Throughout the summer of 2008; many public swimming areas, water parks, and public pools in the Dallas/Fort Worth Metroplex of Texas suffered an outbreak of cryptosporidiosis. Burgers Lake in Fort Worth was the first to report such an outbreak. This prompted some, if not all, city-owned and private pools to close and hyperchlorinate. To the 13 August 2008 there were 400 reported cases of Cryptosporidium.
In September 2008, a gym in Cambridge, the United Kingdom, was forced to close its swimming pool until further notice after health inspectors found an outbreak of cryptosporidiosis. Environmental Health authorities requested that the water be tested after it was confirmed that a young man had been infected.

2010 and later
In May 2010, the Behana creek water supply south of Cairns, Australia, was found to be contaminated by cryptosporidium.
In July 2010, a local sports center in Cumbernauld (Glasgow, UK) detected traces of cryptosporidium in its swimming pools, causing a temporary closure of the swimming pools.
In November 2010, over 4000 cases of cryptosporidiosis were reported in Östersund, Sweden. The source of contamination was the tap water. In mid December 2010 the number of reported cases was 12,400 according to local media.
As of April 2011, there has been an ongoing outbreak in Skellefteå, Sweden. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Several tests have been taken around the water treatment unit "Abborren", but so far no results have turned up positive. Residents are being advised to boil the tap water as they continue to search for the contaminating source.
Since May 2011, there has been an ongoing outbreak in South Roscommon in Ireland. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Testing continues and Roscommon County Council are now considering introducing Ultra Violet Filtration to their water treatment process in the next 12 months. Residents are being advised to boil the tap water and there is no sign of this boil notice being lifted in the near future.
In May 2013, in Roscommon, Ireland, another outbreak of the cryptosporidiosis was reported and a boil water notice was issued. This was the second time the parasite was detected in a month in the Roscommon water supply. The source of one of the outbreaks had been linked to the agricultural community. At least 13 people were treated for Cryptosporidiosis.

See also
Cryptosporidium was the basis of the 1998 television film, Thirst, in which it mutates and passes through a towns water filters.
Cryptosporidium was shown on three episodes in three seasons of the television show, Monsters Inside Me

References
White, A. Clinton Jr. (2005). "Cryptosporidiosis".  In Mandell, G;  et al. (eds.). Principles and Practice of Infectious Diseases (6th ed.). Elsevier. pp. 3215–28.
Upton, Steve J </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Epidural abscess and explain in detail? [/INST] An epidural abscess refers to a collection of pus and infectious material located in the epidural space superficial to the dura mater which surrounds the central nervous system </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Primary aldosteronism and explain in detail? [/INST] Primary aldosteronism (PA), also known as primary hyperaldosteronism or Conns syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormality is caused by hyperplasia or tumors. Many experience fatigue, potassium deficiency and high blood pressure which may cause poor vision, confusion or headaches. Symptoms may also include: muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, dizziness/vertigo, nocturia and excessive urination. Complications include cardiovascular disease such as stroke, myocardial infarction, kidney failure and abnormal heart rhythms.Primary hyperaldosteronism has a number of causes. About 33% of cases are due to an adrenal adenoma that produces aldosterone, and 66% of cases are due to an enlargement of both adrenal glands. Other uncommon causes include adrenal cancer and an inherited disorder called familial hyperaldosteronism. Some recommend screening people with high blood pressure who are at increased risk, while others recommend screening all people with high blood pressure for the disease. Screening is usually done by measuring the aldosterone-to-renin ratio in the blood (ARR) whilst off interfering medications and a serum potassium over 4, with further testing used to confirm positive results. While low blood potassium is classically described in primary hyperaldosteronism, this is only present in about a quarter of people. To determine the underlying cause, medical imaging is carried out.Some cases may be cured by removing the adenoma by surgery after localization with adrenal venous sampling (AVS). A single adrenal gland may also be removed in cases where only one is enlarged. In cases due to enlargement of both glands, treatment is typically with medications known as aldosterone antagonists such as spironolactone or eplerenone. Other medications for high blood pressure and a low salt diet, e.g. DASH diet, may also be needed. Some people with familial hyperaldosteronism may be treated with the steroid dexamethasone.Primary aldosteronism is present in about 10% of people with high blood pressure. It occurs more often in women than men. Often, it begins in those between 30 and 50 years of age. Conns syndrome is named after Jerome W. Conn (1907–1994), an American endocrinologist who first described adenomas as a cause of the condition in 1955.

Signs and symptoms
People often have few or no symptoms. They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.High blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to low blood calcium), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.Secondary hyperaldosteronism is often related to decreased cardiac output, which is associated with elevated renin levels.

Causes
The condition is due to:
Bilateral idiopathic (micronodular) adrenal hyperplasia: 66% of cases
Adrenal adenoma (Conns disease): 33% of cases
Primary (unilateral) adrenal hyperplasia: 2% of cases
Aldosterone-producing adrenocortical carcinoma: <1% of cases
Familial Hyperaldosteronism (FH)
Glucocorticoid-remediable aldosteronism (FH type I): <1% of cases
FH type II (APA or IHA): <2% of cases
Ectopic aldosterone-producing adenoma or carcinoma: < 0.1% of cases

Genetics
40% of people with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5). This gene is mutated in inherited cases of early onset primary aldosteronism and bilateral adrenal hyperplasia, albeit less frequently. These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.Other genes commonly mutated in aldosterone producing adenomas are ATP1A1 ATP2B3, CACNA1D, and CTNNB1.

Epidemiology
In the past, the prevalence of primary aldosteronism was considered to be less than 1% of patients with hypertension. More recent studies have reported much higher prevalence of primary aldosteronism, up-to 12.7% in primary care and to 29.8% in referral centers. Very low rates of compliance with screening guidelines lead to the underdiagnoses of primary aldosteronism.

Pathophysiology
Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENaC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome, these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid.In summary, hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis.Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsorption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. Finally, epithelial cells of sweat gland ducts and distal colon surface respond exactly the same as the principal cells of the nephron. These responses are important in climate adaptation and as a cause of constipation with elevated aldosterone.
The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to increased glomerular filtration rate and cause a decrease in renin released from the granular cells of the juxtaglomerular apparatus in the kidney decreasing sodium reabsorption and returning sodium renal excretion to near normal levels allowing sodium to escape the effect of mineralocorticoids (also known as Aldosterone escape mechanism in primary hyperaldosteronism also contributed to by increased ANP level). If there is primary hyperaldosteronism, the decreased renin (and subsequent decreased angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in diagnosis of primary hyperaldosteronism).

Diagnosis
Screening may be considered in people with high blood pressure presenting with low blood potassium, high blood pressure that is difficult to treat, other family members with the same condition, or a mass on the adrenal gland.Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio (ARR) is used for case detection. A high aldosterone-to-renin ratio suggests the presence of primary hyperaldosteronism. The diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test.Measuring sodium and potassium concentrations simultaneously in serum and urine specimens has been suggested for screening purposes. Calculating the serum sodium over urinary sodium to serum potassium over urinary potassium (SUSPUP) and the (serum sodium to urinary sodium to (serum potassium)2 (SUSPPUP) ratios delivers calculated structure parameters of the RAAS, which may be used as a static function test. Its results have to be confirmed by calculating the ARR.If primary hyperaldosteronism is confirmed biochemically, CT scanning or other cross-sectional imaging can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma (aldosteronoma), adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. Imaging findings may ultimately lead to other necessary diagnostic studies, such as adrenal venous sampling, to clarify the cause. It is not uncommon for adults to have bilateral sources of aldosterone hypersecretion in the presence of a nonfunctioning adrenal cortical adenoma, making adrenal venous sampling (AVS) mandatory in cases where surgery is being considered. For cases where AVS is unable to provide lateralisation of the source/sources of aldosterone hypersecretion, radionuclide imaging such as NP-59 scintigraphy or PET/CT with 11C-Metomidate is an option. Since 11C-Metomidate is unspecific for CYP11B1/CYP11B2 the patient needs pre-treatment with dexamethasone to downregulate the expression of CYP11B1.The diagnosis is best accomplished by an appropriately-trained subspecialist, though primary care providers are critical in recognizing clinical features of primary aldosteronism and obtaining the first blood tests for case detection.

Classification
Some people only use Conns syndrome for when it occurs due to an adrenal adenoma (a type of benign tumor). In practice, however, the terms are often used interchangeably, regardless of the underlying physiology.

Differential diagnosis
Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).

Treatment
The treatment for hyperaldosteronism depends on the underlying cause. In people with a single benign tumor (adenoma), surgical removal (adrenalectomy) may be curative. This is usually performed laparoscopically, through several very small incisions. For people with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the aldosterone receptor. With its antiandrogen effect, spironolactone drug therapy may have a range of side effects in males and females, including gynecomastia and irregular menses. These symptoms occur less frequently with eplerenone drug therapy.In the absence of treatment, individuals with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure </s>