Kwashiorkor

Kwashiorkor ( ) is a form of severe protein malnutrition characterized by edema and an enlarged liver with fatty infiltrates. However, the exact cause of kwashiorkor is still unknown. Inadequate food supply is correlated with kwashiorkor; occurrences in high-income countries are rare. It occurs amongst weaning children to ages of about five years old.

The disease's first formal description was published by Jamaican pediatrician Cicely Williams in 1933. She was the first to research kwashiorkor, and to suggest that it might be a protein deficiency to differentiate it from other dietary deficiencies.

The name, introduced by Williams in 1935, was 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 is most likely to develop after children are weaned from breast milk and begin consuming a diet high in carbohydrates, including maize, cassava, or rice. 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.

{| class="wikitable"

!Weight for age

!With edema

!Without edema

!General considerations

|65-85%

|Kwashiorkor

|Undernutrition

| rowspan="2" |

Weight for age ± oedema
Reference standard (50th percentile)

|<60%

|Marasmic kwashiorkor

|Marasmus

Signs and symptoms

The defining sign of kwashiorkor in children is bilateral edema in the feet. Edema may also involve the hands, trunk, and face. Kwashiorkor is characterized by a fatty liver. This fatty liver of the 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 to 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. However, AE is caused by zinc deficiency, not protein deficiency, and is associated with a significant decrease in serum zinc levels. Unlike kwashiorkor, which is diagnosed based on clinical signs like edema and low serum albumin levels, AE requires additional diagnostic tests, such as zinc uptake tests and genetic screening, to differentiate it from other disorders with similar symptoms. Therefore, while both conditions can present with dermatitis, the underlying etiology helps distinguish the two.

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

thumb|upright=1.2|[[Disability-adjusted life years per 100,000 inhabitants for protein-energy malnutrition in 2002:

]]

Kwashiorkor is a severe form of malnutrition associated with a low-protein diet.

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 and 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 thought 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. In particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine.

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 caused by an acute loss of salt and water. Children with severe albumin deficiency struggle physiologically to maintain their blood volume.

It is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation.

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 the risk for kwashiorkor.

Others

A proposed experimental theory suggests that alterations in the microbiome/virome contribute to edematous malnutrition, but further studies are required to understand the mechanism. 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).

In addition to anthropometric measures, laboratory tests can be critical for diagnosing kwashiorkor. Low serum albumin levels (hypoalbuminemia) are a hallmark of protein deficiency, and elevated liver enzymes may indicate liver dysfunction. Electrolyte imbalances and blood tests may also be used to assess the degree of organ involvement and complications.

Specifically in children, severe malnutrition, such as kwashiorkor, can lead to notable changes in brain function and behavior. Children with kwashiorkor tend to be irritable and may develop cerebral atrophy, whereas those with severe wasting frequently show apathy, reduced movement, and speech delays. 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.

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 recovery

Both clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly. Therefore, after concerns of refeeding syndrome have passed, children may require 120-140% of their estimated caloric needs to achieve catch-up growth. 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). Micronutrient deficiencies are common in malnourished children and contribute to immune dysfunction. Specific vitamin A supplementation is particularly important for preventing further damage to the liver and skin.

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. Routine antibiotics, even in the absence of clinical infection, are generally given as a prophylactic measure, especially in regions with a high risk of infectious diseases. However, due to concerns about antibiotic resistance, there is debate over their routine use.

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.

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. "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." Malnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drug's bioavailability, distribution, and elimination.