Protein energy malnutrition pathophysiology: Difference between revisions
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=== Pathogenesis of edema in kwashiorkor === | === 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: | Several [[Theory|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. | '''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]]. | ||
*Albumin concentrations were also noted to increase steadily within two weeks after refeeding. | *[[Albumin]] [[concentrations]] were also noted to increase steadily within two weeks after [[refeeding]]. | ||
*Presence of features similar to congenital nephrotic syndrome, in which the primary pathology is renal loss of albumin.<ref name="pmid25223408">{{cite journal| author=Coulthard MG| title=Oedema in kwashiorkor is caused by hypoalbuminaemia. | journal=Paediatr Int Child Health | year= 2015 | volume= 35 | issue= 2 | pages= 83-9 | pmid=25223408 | doi=10.1179/2046905514Y.0000000154 | pmc=4462841 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25223408 }} </ref> | *Presence of features similar to [[congenital nephrotic syndrome]], in which the primary [[pathology]] is [[renal]] loss of [[albumin]].<ref name="pmid25223408">{{cite journal| author=Coulthard MG| title=Oedema in kwashiorkor is caused by hypoalbuminaemia. | journal=Paediatr Int Child Health | year= 2015 | volume= 35 | issue= 2 | pages= 83-9 | pmid=25223408 | doi=10.1179/2046905514Y.0000000154 | pmc=4462841 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25223408 }} </ref> | ||
Multiple evidences have now shown that inadequate intake of dietary protein is not the primary trigger for edematous malnutrition. | Multiple [[Evidence|evidences]] have now shown that inadequate intake of [[dietary]] [[protein]] is not the primary trigger for [[edematous malnutrition]]. | ||
*Some patients have edematous malnutrition without hypoalbuminemia | *Some [[patients]] have [[edematous malnutrition]] without [[hypoalbuminemia]] | ||
*Others develop edematous malnutrition (kwashiorkor) despite adequate proportion of protein in the diet (eg, in exclusively breastfed infants) | *Others develop [[edematous malnutrition]] ([[kwashiorkor]]) despite adequate proportion of [[protein]] in the diet (eg, in exclusively [[Breastfeeding|breastfed]] [[infants]]) | ||
*Others recover from edematous malnutrition with supportive care even without enhancing the protein content of the diet.<ref name="pmid9830208">{{cite journal| author=Golden MH| title=Oedematous malnutrition. | journal=Br Med Bull | year= 1998 | volume= 54 | issue= 2 | pages= 433-44 | pmid=9830208 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9830208 }} </ref><ref name="pmid20345018">{{cite journal| author=Manary MJ, Heikens GT, Golden M| title=Kwashiorkor: more hypothesis testing is needed to understand the aetiology of oedema. | journal=Malawi Med J | year= 2009 | volume= 21 | issue= 3 | pages= 106-7 | pmid=20345018 | doi= | pmc=3717490 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20345018 }} </ref><ref name="pmid25844980">{{cite journal| author=Golden MH| title=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. | journal=Paediatr Int Child Health | year= 2015 | volume= 35 | issue= 2 | pages= 90-109 | pmid=25844980 | doi=10.1179/2046905515Y.0000000010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25844980 }} </ref> | *Others recover from [[edematous malnutrition]] with supportive care even without enhancing the [[protein]] content of the [[diet]].<ref name="pmid9830208">{{cite journal| author=Golden MH| title=Oedematous malnutrition. | journal=Br Med Bull | year= 1998 | volume= 54 | issue= 2 | pages= 433-44 | pmid=9830208 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9830208 }} </ref><ref name="pmid20345018">{{cite journal| author=Manary MJ, Heikens GT, Golden M| title=Kwashiorkor: more hypothesis testing is needed to understand the aetiology of oedema. | journal=Malawi Med J | year= 2009 | volume= 21 | issue= 3 | pages= 106-7 | pmid=20345018 | doi= | pmc=3717490 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20345018 }} </ref><ref name="pmid25844980">{{cite journal| author=Golden MH| title=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. | journal=Paediatr Int Child Health | year= 2015 | volume= 35 | issue= 2 | pages= 90-109 | pmid=25844980 | doi=10.1179/2046905515Y.0000000010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25844980 }} </ref> | ||
'''2. Oxidant stress''' : Excessive oxidant stress was also proposed as a mechanism of development of | '''2. [[Oxidant]] stress''' : Excessive [[Oxidant|oxidant stress]] was also proposed as a mechanism of development of [[kwashiorkor]], however, it was discovered that that the administration of [[antioxidant]] was not successful in prevention of the development of this [[malnutrition]] in a series of trials. Hence the conclusion that [[antioxidant]] depletion is a consequence rather than cause of [[kwashiorkor]].<ref name="pmid15851401">{{cite journal| author=Ciliberto H, Ciliberto M, Briend A, Ashorn P, Bier D, Manary M| title=Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial. | journal=BMJ | year= 2005 | volume= 330 | issue= 7500 | pages= 1109 | pmid=15851401 | doi=10.1136/bmj.38427.404259.8F | pmc=557886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15851401 }} </ref> | ||
'''3. Microbiome''' : Changes in intestinal microbiome has also been suggested as a cause of the development of kwashiorkor. However, these has not been fully supported because evidences show that neither the fecal microbiota transfer nor the local diet alone was sufficient to cause the malnutrition leading to the conclusion that changes in fecal microbiota are only effects rather than causes of kwashiorkor.<ref name="pmid23363771">{{cite journal| author=Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J et al.| title=Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. | journal=Science | year= 2013 | volume= 339 | issue= 6119 | pages= 548-54 | pmid=23363771 | doi=10.1126/science.1229000 | pmc=3667500 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23363771 }} </ref><ref name="pmid23576812">{{cite journal| author=Prentice AM, Nabwera H, Kwambana B, Antonio M, Moore SE| title=Microbes and the malnourished child. | journal=Sci Transl Med | year= 2013 | volume= 5 | issue= 180 | pages= 180fs11 | pmid=23576812 | doi=10.1126/scitranslmed.3006212 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23576812 }} </ref><ref name="pmid25717097">{{cite journal| author=Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I et al.| title=Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. | journal=Sci Transl Med | year= 2015 | volume= 7 | issue= 276 | pages= 276ra24 | pmid=25717097 | doi=10.1126/scitranslmed.aaa4877 | pmc=4423598 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25717097 }} </ref> | '''3. Microbiome''' : Changes in intestinal microbiome has also been suggested as a cause of the development of kwashiorkor. However, these has not been fully supported because evidences show that neither the fecal microbiota transfer nor the local diet alone was sufficient to cause the malnutrition leading to the conclusion that changes in fecal microbiota are only effects rather than causes of kwashiorkor.<ref name="pmid23363771">{{cite journal| author=Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J et al.| title=Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. | journal=Science | year= 2013 | volume= 339 | issue= 6119 | pages= 548-54 | pmid=23363771 | doi=10.1126/science.1229000 | pmc=3667500 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23363771 }} </ref><ref name="pmid23576812">{{cite journal| author=Prentice AM, Nabwera H, Kwambana B, Antonio M, Moore SE| title=Microbes and the malnourished child. | journal=Sci Transl Med | year= 2013 | volume= 5 | issue= 180 | pages= 180fs11 | pmid=23576812 | doi=10.1126/scitranslmed.3006212 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23576812 }} </ref><ref name="pmid25717097">{{cite journal| author=Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I et al.| title=Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. | journal=Sci Transl Med | year= 2015 | volume= 7 | issue= 276 | pages= 276ra24 | pmid=25717097 | doi=10.1126/scitranslmed.aaa4877 | pmc=4423598 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25717097 }} </ref> | ||
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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]
Overview
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 understand. 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 wasting in a child. Marasmus always results from a negative energy balance.
Pathophysiology
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 propose that chronic infections such as helminthic infections are mainly responsible for the development of protein energy malnutrition.[1] The underlying mechanisms include the following:
- Decreased food intake because of anorexia
- Decreased nutrient absorption
- Increased metabolic requirements
- Direct nutrient losses
The pathologic changes involved in protein energy malnutrition include:[2]
- Immunologic deficiency in the humoral and cellular subsystem as a result of protein deficiency.
- Metabolic disturbances cause impaired intercellular degradation of fatty acids as a result of carbohydrate deficiency.
- Poor synthesis of pigments in the hair and skin observed with more frequency among children with low levels of Zinc.
Pathogenesis of marasmus
When subcutaneous fat and muscle are lost because of endogenous mobilization of all available energy and nutrients, marasmus is diagnosed. The overall metabolic adaptations that occur during marasmus are similar to those in starvation. Initially, gluconeogenesis aims at maintaining the energy requirements of the body leading to a perceived increased metabolic rate. As fasting progresses, gluconeogenesis is suppressed to minimize muscle protein breakdown, and ketones derived from fat become the main fuel for the brain. One of the main adaptations to long-standing energy deficiency is a decreased rate of linear growth, leading to permanent stunting.
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.
- Albumin concentrations were also noted to increase steadily within two weeks after refeeding.
- Presence of features similar to congenital nephrotic syndrome, in which the primary pathology is renal loss of albumin.[3]
Multiple evidences have now shown that inadequate intake of dietary protein is not the primary trigger for edematous malnutrition.
- Some patients have edematous malnutrition without hypoalbuminemia
- Others develop edematous malnutrition (kwashiorkor) despite adequate proportion of protein in the diet (eg, in exclusively breastfed infants)
- Others recover from edematous malnutrition with supportive care even without enhancing the protein content of the diet.[4][5][6]
2. Oxidant stress : Excessive oxidant stress was also proposed as a mechanism of development of kwashiorkor, however, it was discovered that that the administration of antioxidant was not successful in prevention of the development of this malnutrition in a series of trials. Hence the conclusion that antioxidant depletion is a consequence rather than cause of kwashiorkor.[7]
3. Microbiome : Changes in intestinal microbiome has also been suggested as a cause of the development of kwashiorkor. However, these has not been fully supported because evidences show that neither the fecal microbiota transfer nor the local diet alone was sufficient to cause the malnutrition leading to the conclusion that changes in fecal microbiota are only effects rather than causes of kwashiorkor.[8][9][10]
Genetics
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 kwashiokor include;
- Vitamin A deficiency
- Vitamin D deficiency
- Thiamine deficiency
- Zinc deficiency
- Iodine deficiency
- Iron deficiency
- Dehydration
- Sepsis
- Shigella and Campylobacter infections.
Gross pathology
Post mortem examination of the liver shows the presence of fatty infiltration and necrosis which disappears with adequate treatment.[11]
Microscopic pathology
In kwashiorkor, microscopic studies reveal a decreased proportion of hairs in anagen follicles. In marasmic patients, no hairs were in the anagen phase, with a shift to the telogen phase. Marasmic patients have many more broken hairs when compared with patients with kwashiorkor. 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.
References
- ↑ Cederholm T, Jägrén C, Hellström K (1995). "Outcome of protein-energy malnutrition in elderly medical patients". Am J Med. 98 (1): 67–74. doi:10.1016/S0002-9343(99)80082-5. PMID 7825621.
- ↑ Lerner AB (1971). "On the etiology of vitiligo and gray hair". Am J Med. 51 (2): 141–7. PMID 5095523.
- ↑ 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.
- ↑ Golden MH (1998). "Oedematous malnutrition". Br Med Bull. 54 (2): 433–44. PMID 9830208.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.