Etiology

The etiology is unknown.[10] Most frequently, diets that are based on maize or cassava are associated with kwashiorkor. It is not the result of prolonged breastfeeding.[11][12] Neither deficiency in protein intake nor low levels of antioxidants in the diet are considered primary causal factors of kwashiorkor, as the diets of children with marasmus have similar deficiencies.[13][14][15]

Higher levels of aflatoxins have been found in the serum and liver of children with kwashiorkor than in malnourished children without kwashiorkor or in healthy children. However, some evidence suggests that the correlation between aflatoxin levels and kwashiorkor varies by geographic area, and kwashiorkor is also seen in populations without evidence of ingestion of aflatoxin.[16][17][18]

Hypotheses over the last 100 years have suggested causative roles for protein deficiency, hypoalbuminemia, and excessive oxidant stress.[19][20][21][22][23] However, dietary supplements of protein and antioxidants in children who are at high risk have not reduced the risk of kwashiorkor, and edema resolves even on a restricted-protein diet.[24]

Recent measles infection has been suggested as a risk factor, and diarrhea is often reported as a precipitating factor.

Social and economic risk factors have also been implicated, including recent cessation of breastfeeding, high birth order, and incomplete immunization. Uncertain family status such as parental death, not living with a parent, unmarried caretaker, young age of mother, living in a temporary home, or parents not owning land have also been suggested as contributing factors but remain unproven.[11][13]

Underlying tuberculosis (TB) or HIV is more common when children over the age of 5 years present with kwashiorkor. There is no evidence that HIV is a direct cause, but it is associated with poverty, and it predisposes to oral pathology, persistent diarrhea, enteropathy, malabsorption, and overgrowth of bowel flora.[25]

TB may present as kwashiorkor that is unresponsive to the usual therapeutic interventions, particularly in older children, and should be considered in such patients.

Metagenomic advances in the interrogation of the intestinal microbiome have suggested that children with kwashiorkor may suffer from a delay in the age-dependent maturation of their microbiome that may precede the development of kwashiorkor. Restoration of specific missing bacterial species can contribute to nutritional recovery in a mouse model.[26][27][28]

Pathophysiology

The unifying pathophysiologic concept of kwashiorkor is that cell membranes are damaged throughout the body. This damage results in the egress of potassium and water from cells and dysfunction of most major organ systems. It is not a condition of water retention but one where intracellular water moves to the extracellular space, resulting in edema. There is a profound reduction in whole body potassium, often to 35 mmol/kg or less (44 mmol/kg is normal). This corresponds to the loss of intracellular potassium. Profound, life-threatening hypokalemia, and hypophosphatemia are observed in severe cases. Though hyponatremia occurs, total body sodium is elevated. Cardiac output is diminished on average by 30% in kwashiorkor and renal fractional sodium excretion reduced by up to 70%.[29][30] Moderate anemia (Hb 8-10 g/dL) is seen in most cases, but plasma free iron is elevated. Fat accumulates in the intracellular space of the liver, which is the result of a decreased ability to transport and metabolically process fat. The villi of the small bowel and white matter of the brain usually show some degree of atrophy.

Classification

World Health Organization (WHO) classification of malnutrition in children 6-59 months of age[1]

Moderate malnutrition

  • No symmetric edema present

  • A weight for height z-score of between -2 and -3 or a mid upper arm circumference (MUAC) of 11.5 cm to 12.4 cm defines moderate wasting (also called moderate acute malnutrition)

  • Height for age z-score between -2 and -3 defines moderate stunting.

Severe malnutrition (includes kwashiorkor, a form of severe acute malnutrition)

  • Symmetric edema defines kwashiorkor, regardless of other anthropometric parameters

  • A weight for height z-score of <-3 or MUAC <11.5 cm defines severe wasting (also called marasmus, a form of severe acute malnutrition)

  • Height for age z-score of <-3 defines severe stunting.

The standard deviation score (or z-score) is defined as the deviation of the value from the median of the reference population, divided by the standard deviation of the reference population.[2]

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