User:J.Choi, Future UCSF Pharm.D./Kwashiorkor

Kwashiorkor (“kwah-shee-awr-kawr” or “-ker”, IPA:, ) is 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 good-quality protein), which distinguishes it from marasmus. Recent studies have found that antioxidant micronutrients, such as Vitamin C, β-carotene, lycopene, and carotenoids may play a role in the development of Kwashiorkor. Kwashiorkor cases occur primarily in areas of famine or poor food supply; cases in the developed world are rare. It occurs in children more than 1 year of age. Usually children of age around 5 years are affected by it.

Jamaican pediatrician Cicely Williams introduced the term in 1935, two years after she published the disease's first formal description. 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 a mother weans her child from breast milk, replacing it with a diet high in carbohydrates, such as maize, cassava or rice based diets.

Classification
....(Jeremy) Types of malnutrition:

Kwashiorkor: insufficient protein consumption

Marasmus: energy deficiency

Marasmic kwashiorkor: deficiency of both calories and proteins (Jeremy).....

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.

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 pancreatic, renal, and mental functions). (swelling of the ankles and feet) . Other clinical characteristics observed signs include a distended abdomen, an enlarged liver with fatty infiltrates, thinning of hair, loss of teeth, variable skin or hair dyspigmentation'', 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 child's 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 the patients.

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 gastro-intestinal 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 patients 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.

Mechanisms
.......(Jeremy)

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 or hypoalbuminemia. Edema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls. Lack of protein results in lack of pressure gradient, and 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. The low albumin concentration especially among children with Kwashiorkor became intravascularly depleted. 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 will struggle physiologically to maintain their blood volume by driving hormonal pathways.

Low gluthaione levels
Kwashiorkor is also marked by low gluthaione levels. It is believed it relates to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation.

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. (Jeremy).....

Diagnosis
Kwashiorkor, 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, low mid-upper arm circumference (MUAC < 115 mm), and a low weight-for-height Z-score (WHZ, Z < -3). Additional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly. Kwashiorkor is distinguished from marasmus by the presence of edema.

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).

Prevention or Screening
...(Jeremy) 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

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.
 * Seafood
 * Peas
 * Nuts
 * Seeds
 * Eggs
 * Lean meat
 * Beans (Jeremy)...

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 teenage girls and young women on proper nutrition and health during and after pregnancy, they can provide their children with the appropriate nutrients from a young age. By ensuring pregnant women are equipped with the proper education and resources, mothers 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.

Treatment
WHO guidelines outline 10 general principles for the inpatient management of severely malnourished children.


 * 1) Treat/prevent hypoglycemia
 * 2) Treat/prevent hypothermia
 * 3) Treat/prevent dehydration
 * 4) Correct electrolyte imbalance
 * 5) Treat/prevent infection
 * 6) Correct micronutrient deficiencies
 * 7) Start cautious feeding
 * 8) Achieve catch-up growth
 * 9) Provide sensory stimulation and emotional support
 * 10) Prepare for follow-up after recovery

Both clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly.

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 don't require much preparation.

Outcomes or Prognosis
Kwashiorkor is associated with a high risk of mortality and complications. Treatment has proven to reduce this mortality risk and children tend to recover faster than children with other severe malnutrition disease. 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 developed nations. It is mostly observed in Southeast Asia, Central America, Congo, Puerto Rico, Jamaica, South Africa, and Uganda, where poverty is prominent. Cases of severe malnutrition also tend to trend higher under conditions of food insecurity, higher prevalence of infectious diseases, and poor living situation 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.

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
The World Health Organization officially recognized Kwashiorkor as a public health crisis in the 1950s. Despite Kwashiorkor initially being described and introduced by Jamaican pediatrician Cicely Williams in 1933 '', there was a delay in the recognition of the disease. This delay was because most reported cases of childhood deaths at the time were classified as being due to diseases of the gastrointestinal system or of infectious nature. During that time, it was been found that children who were presenting with digestive system diseases and symptoms of infections were also exhibiting classic symptoms of Kwashiorkor. Kwashiorkor has since been concluded to be a secondary cause of death.''

Effects on PK
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 drug's bioavailability, distribution, and elimination. To optimize treatment of those diseases, there needs to be more research into how severe malnutrition, specifically kwashiorkor, can affect treatment response.

Society and Culture
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Research Directions
Current research and recommendations to manage severe acute malnutrition (SAM), such as kwashiorkor, in children are based on expert opinions. Further studies are needed in order to "improve treatment outcomes in a large number of children with SAM.

Special Populations
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Other Animals
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See also[edit]

 * Anemia
 * Emaciation
 * Starvation and Edema