kwashiorkor kwashiorkor kwashiorkor (/ˌkwɒʃiˈɔːrkɔːr, -kər/ kwosh-ee-or-kor, -⁠kər, is also kwash-) 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. kwashiorkora young girl with kwashiorkor in a relief camp during the biafra warspecialtypediatrics 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 disease's 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 child's 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 kwashiorkor is a type of severe acute malnutrition (sam). sam is a category, composed of two conditions: marasmus and kwashiorkor. both kwashiorkor and marasmus fall under the umbrella of protein–energy malnutrition (pem). these diseases are oftentimes discussed together, but are distinctly separate conditions of malnutrition. kwashiorkor is marked by an array of metabolic disturbances of uncertain etiology. in contrast, marasmus is more clearly a syndrome of energy deficiency, which is marked by weight loss. on physical exam, kwashiorkor is also distinguished from marasmus by the presence of edema. when children present with both kwashiorkor and marasmus, the condition is referred to as "marasmic-kwashiorkor". in general, kwashiorkor is marked by more profound serum depletions of antioxidant molecules and minerals, relative to marasmus. wellcome's 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. weight for age with edema without edema general considerations 60-80% kwashiorkor undernutrition weight for age +/- oedema reference standard (50th percentile) <60% marasmic kwashiorkor marasmus signs and symptoms the defining sign of kwashiorkor in children is bilateral pitting edema in the feet. edema may also involve the hands, trunk, and face. kwashiorkor is characterized by a fatty liver. this fatty liver of undernutrition phenotype is often accompanied by evidence of inflammation and fibrosis. whereas a fatty liver of undernutrition is a consistent feature of kwashiorkor, it is only encountered sometimes in children with marasmus. in addition this characteristic hepatic steatosis, kwashiorkor is marked by a parallel pattern of multi-organ dysfunction. organs often affected in children with kwashiorkor include the kidneys, pancreas, heart, and nervous system". other findings that may be encountered on physical exam include a distended abdomen, hair thinning, loss of teeth, skin or hair depigmentation, and dermatitis. children with kwashiorkor often develop irritability and anorexia. generally, kwashiorkor is treated by introducing a high quality source of protein to the diet. ready to use therapeutic food (rutf) as well as f-100 and f-75 milk powders, which both include skim milk powder, are recommended for the treatment of kwashiorkor. these products are designed for use in low resource settings. the limited number of kwashiorkor cases that occur in high resource settings, where there is good access to advanced therapeutic tools, are typically treated with partially hydrolyzed or elemental enteral formulas, with parenteral nutrition provided in extreme cases. 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 disability-adjusted life years per 100,000 inhabitants for protein–energy malnutrition in 2002. no data fewer than 10 10–100 100–200 200–300 300–400 400–500 500–600 600–700 700–800 800–1000 1000–1350 more than 1350 kwashiorkor is a severe form of malnutrition associated with a low protein diet. 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 accompanied by irregularities in the lymphatic system as well as disruptions 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. fluid recovery by the lymphatic system is accomplished by re-vascularization of fluid and macromolecules from the interstitial space, allowing these constituents of whole blood to be returned to the venous circulation. compromised fluid recovery may contribute to the phenomenon of extravascular fluid accumulation in kwashiorkor. the low protein theory for the pathogenesis of kwashiorkor has been used to teach that capillary exchange between the lymphatic system and circulating blood is impaired by a reduced oncotic (i.e. colloid osmotic pressure, cop) in the blood, as a consequence of inadequate protein intake, so that the hydrostatic pressure gradient, which favors extravasation of fluid from small vessels, is not overcome. proteins, mainly albumin, are responsible for creating the cop observed in the blood and tissue fluids. the difference in the cop of the blood and tissue tends to favor the reentry of fluid from the extravascular space, into the circulatory system. this tendency is opposed by the venous hydrostatic pressure, which tends to favor the exit of fluid from small vessels, into the interstitial space. the low protein theory for the pathogenesis of kwashiorkor held that a deficiency of serum proteins, caused by inadequate protein intake, disrupted this balance, and thus impaired the return flow of fluid from the interstitium into the capillary and venous structures. it has been taught that this is what accounts for the accumulation of extravascular fluid in kwashiorkor, and the subsequent pedal edema and abdominal distension. the low protein theory, which relies heavily upon starling's theory for the movement of fluid in biological systems, provided a compelling rationale for the pathogenesis of edema in kwashiorkor. what it does not explain however, is the entire array of disturbances that define the kwashiorkor syndrome. these include, irritability, anorexia, skin desquamation, skin depigmentation, hair discoloration, reduced mitochondrial respiration, impaired lipid export from the liver without an accompanying reduction of lipoprotein synthesis, 'oxidative stress', glutathione depletions, transsulfuration disturbances, diffuse dna hypomethylation, immune dysfunction, decreased transmethylation activity, and sulfated glycosaminoglycan deficiencies. it is now generally acknowledged that by itself, the low protein theory does not adequately account for the pathogenesis of kwashiorkor. more complex deficiencies are at work. these have still not been established. social factors are also relevant. 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 development of kwashiorkor. 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 body's 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. evidence indicates that amino acid balance has an important effect on protein nutrition and therefore on glutathione homeostasis. cysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans. factors that increase demand for glutathione may increase demand for cysteine, and hence methionine. such demands have been hypothesized to increase risk for kwashiorkor. 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 by physical exam, with careful examination of the child's feet to detect the presence of bilateral pitting edema. screening for edema is essential for the diagnosis of kwashiorkor, since nearly two thirds of kwashiorkor cases do not have evidence of acute wasting (i.e. mid-upper arm circumference (muac) < 125 mm, or whz < -2) when diagnosed with kwashiorkor. 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