Protein energy malnutrition pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2], Syed Hassan A. Kazmi BSc, MD [3]


Protein-energy malnutrition represents a shift of the body from fed to fasting/starvation state. Starvation leads to a decreased basal plasma insulin concentration and in decrease of glucose-stimulated insulin secretion. Prolonged fasting results in a deficiency in amino acids used for gluconeogenesis. It is thought that kwashiorkor is produced by a deficiency in the adequate consumption of protein-rich foods during the weaning process. However, the associated edema is not fully understood. Several theories have been put forward to explain this finding. Marasmus on the other hand is thought to be due to the total caloric deficiency leading to wastingin a child. Marasmus always results from a negative energy balance.


Several studies have shown that a deficiency in the consumption of protein, carbohydrates and fat is responsible for the development of protein-energy malnutrition. However, other studies have proposed that chronic infections such as helminthic infections are mainly responsible for the development of protein-energy malnutrition.[1] The underlying mechanisms include the following:

The pathologic changes involved in protein-energy malnutrition include:[2]


Hormonal and molecular mechanisms (fed to starvation state)

Insulin and glucagon in starvation

Eventual decreased gluconeogenesis in protein-energy malnutrition

  • Prolonged fasting results in a deficiency in amino acids used for gluconeogenesis.
  • Glucagon concentrations have been found to be lower in children with kwashiorkor compared with marasmus but similar to normal controls.[6]

Malnutrition, Leptin, and Immunity

Pathogenesis of marasmus

Pathogenesis of edema in kwashiorkor

Several theories have been postulated to explain the mechanism of edema seen in children with kwashiorkor. Some of them include:

1. Protein deficiency / hypoalbuminemia

It was initially believed that a deficiency in the consumption of protein was responsible for the development of kwashiorkor in children.

Multiple evidences have now shown that inadequate intake of dietary protein is not the primary trigger for edematous malnutrition.

2. Oxidant stress

3. Microbiome


Protein-energy malnutrition is frequently reported in Cri du chat syndrome(CDS), a genetic disease that causes developmental delay and global growth retardation.

Associated conditions

Some of the conditions that are associated with kwashiorkor include:

Gross pathology

Post mortem examination of the liver shows the presence of fatty infiltration and necrosis which disappears with adequate treatment.[18]

Microscopic pathology

Both in kwashiorkor and marasmus hair analysis is therefore advocated as a useful diagnostic procedure for both conditions. In both cases, there is a decrease in the amount of melanin present in the scalp hair.




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  2. Lerner AB (1971). "On the etiology of vitiligo and gray hair". Am J Med. 51 (2): 141–7. PMID 5095523.
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  6. "Pediatric Research - Mechanisms Behind Decreased Endogenous Glucose Production in Malnourished Children".
  7. Scrimshaw NS, SanGiovanni JP (1997). "Synergism of nutrition, infection, and immunity: an overview". Am. J. Clin. Nutr. 66 (2): 464S–477S. PMID 9250134.
  8. Monk JM, Makinen K, Shrum B, Woodward B (2006). "Blood corticosterone concentration reaches critical illness levels early during acute malnutrition in the weanling mouse". Exp. Biol. Med. (Maywood). 231 (3): 264–8. PMID 16514171.
  9. Auphan N, Didonato JA, Helmberg A, Rosette C, Karin M (1997). "Immunoregulatory genes and immunosuppression by glucocorticoids". Arch. Toxicol. Suppl. 19: 87–95. PMID 9079197.
  10. Coulthard MG (2015). "Oedema in kwashiorkor is caused by hypoalbuminaemia". Paediatr Int Child Health. 35 (2): 83–9. doi:10.1179/2046905514Y.0000000154. PMC 4462841. PMID 25223408.
  11. Golden MH (1998). "Oedematous malnutrition". Br Med Bull. 54 (2): 433–44. PMID 9830208.
  12. Manary MJ, Heikens GT, Golden M (2009). "Kwashiorkor: more hypothesis testing is needed to understand the aetiology of oedema". Malawi Med J. 21 (3): 106–7. PMC 3717490. PMID 20345018.
  13. Golden MH (2015). "Nutritional and other types of oedema, albumin, complex carbohydrates and the interstitium - a response to Malcolm Coulthard's hypothesis: Oedema in kwashiorkor is caused by hypo-albuminaemia". Paediatr Int Child Health. 35 (2): 90–109. doi:10.1179/2046905515Y.0000000010. PMID 25844980.
  14. Ciliberto H, Ciliberto M, Briend A, Ashorn P, Bier D, Manary M (2005). "Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial". BMJ. 330 (7500): 1109. doi:10.1136/bmj.38427.404259.8F. PMC 557886. PMID 15851401.
  15. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J; et al. (2013). "Gut microbiomes of Malawian twin pairs discordant for kwashiorkor". Science. 339 (6119): 548–54. doi:10.1126/science.1229000. PMC 3667500. PMID 23363771.
  16. Prentice AM, Nabwera H, Kwambana B, Antonio M, Moore SE (2013). "Microbes and the malnourished child". Sci Transl Med. 5 (180): 180fs11. doi:10.1126/scitranslmed.3006212. PMID 23576812.
  17. Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I; et al. (2015). "Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy". Sci Transl Med. 7 (276): 276ra24. doi:10.1126/scitranslmed.aaa4877. PMC 4423598. PMID 25717097.
  18. Lefranc, Violaine; de Luca, Arnaud; Hankard, Régis (2016). "Protein-energy malnutrition is frequent and precocious in children with cri du chat syndrome". American Journal of Medical Genetics Part A. 170 (5): 1358–1362. doi:10.1002/ajmg.a.37597. ISSN 1552-4825.

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