Liver Function in Kwashiorkor

Kinnear, Ann; Pretorius, P. J.

doi:10.1136/bmj.1.4982.1528

Cited by 24 publications

(8 citation statements)

References 9 publications

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“…The usual range of biochemical tests do not seem to indicate functional damage (Waterlow, 1950;Sherlock and Walshe, 1951;Altmann, 1953;Kinnear and Pretorius, 1956) either in children or adults. Serum enzymes like alkaline phosphatase, serum bilirubin values and floculation tests have been reported to be within the normal range.…”

Section: Hepatic Changesmentioning

confidence: 99%

Drug Metabolism and Pharmacokinetics in Malnutrition

Krishnaswamy

1978

Clinical Pharmacokinetics

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Malnutrition is usually complex. many deficiencies occurring simultaneously. Changes occur in almost every organ oj the body. Apart jrom the pathophysiological changes which occur in protein-calorie malnutrition. vitamin. mineral and trace element deficiency is accompanied by diverse metabolic changes in tissues. As a consequence there is large potentialjor alteration oj drug response in malnutrition. not only because of possible changes in drug kinetics but also because of changes in tissue uptake and localisation of drugs and potential alteration in drugreceptor interactions. The risk of susceptibility to drug-induced damage may also be increased.The functional status oj the gastroinlestinal tract is markedly altered in malnourished individuals and as a consequence the rate and extent of drug absorption is likely to be altered. First pass metabolism (intestinal and hepatic) is also likely to-be altered. The prqfi/eoj-plasma-proteins is considerably changed in malnourished individuals. In most cases. there is hypoalbuminaemia. the degree varying with the severity oj malnutrition. Globulins however. are elevated. particularly in cases oj injection. Lipoproteins are also reduced in states oj malnutri--'ion but there is no -it!formation ort ai-acid glycoproteins. which bind basic drugs. Malnutrition.by altering. the total body water. body composition and drug binding can lead to changes in the volume of distribution oj a drug. depending on its physicochemical properties and its ability to bind to macromolecules.Although electronmicroscopc studies indicate changes ill endoplasmic reticulum. liver junction in malnutrition seems to be generally well preserved. However. biotranllformation oj drugs may be altered due to changes in drug metabolising hepatic enzyme activity. alteration in drug binding characteristics qf proteins and the significant metabolic and hormonal changes in malnutrition. There may be abnormalities in biliary excretion which may affect drug elimination. at least in severe jorms of protein-calorie malnutrition. Severe malnutrition can lead to changes in cardiac and renal junction. These changes may be indirectly responsiblejor alterations in excretion mechanisms.Malnutrition can lead to changes in renal junction. although this may not be a uni/orm change and there are very little data on renal excretion mechanisms and their relationship to drug elimination in malnutrition. Cardiac function also seems to be affected in malnutrition. particularly in children. There is reduction in cardiac output and prolonged circulation time; changes which may indirectly be responsible for decreased renal and hepatic blood flow.Animal studies reveal that a number of macro-and micronutrient deficiencies can result in alteration in the rate qf drug metabolism. Deficiencies in proteins. dietary jat. minerals and vitamins have all been shown to influence the activity oj the mixed function oxidases. However. nutritional-pharmacological interactions in human populations are not as simple as observed

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Section: Hepatic Changesmentioning

confidence: 99%

Drug Metabolism and Pharmacokinetics in Malnutrition

Krishnaswamy

1978

Clinical Pharmacokinetics

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“…The average score in the first week was 223. In the *--Lipids -* Alkaline phosphatase Kinnear and Pretorius (1957) found that in kwashiorkor the total serum lipids are low initially, rise to a peak in a week and then decline. The latter biochemical findings show some analogy to the white cell lipid data of the first type, but not to those of the second type.…”

Section: Resultsmentioning

confidence: 99%

“…The present investigation was carried out in conjunction with a series of biochemical and haematological studies of the blood in kwashiorkor conducted at the Pretoria General Hospital (Kinnear andPretorius, 1956 and1957) in order to extend the overall picture of the state of various tissues in this malnutrition syndrome. For a complete review of the application of histochemical procedures to leucocytes the reader is referred to Wachstein (1955).…”

mentioning

confidence: 99%

A Histochemical Investigation of the Leucocytes in Kwashiorkor

Theron¹,

Coetzee²,

Pretorius³

1959

J Clin Pathol

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“…Serum enzymes are reported to be in the normal range. Only in severe cases is bromosulphaphthaline excretion decreased (Kinnear & Pretorius 1956). Available literature indicates that protein-energy malnutrition in childhood does not lead to permanent liver damage (Bhramara pra- McLaren et al 1972;Tandon et al 1974).…”

Section: Hepatic Changesmentioning

confidence: 94%

Drug Metabolism and Pharmacokinetics in Malnourished Children

Krishnaswamy

1989

Clinical Pharmacokinetics

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Malnutrition is a complex condition in which many deficiencies occur simultaneously. Protein-energy malnutrition is a major public health and clinical problem in paediatric practice that accounts for high child mortality and morbidity. It includes many different clinical syndromes with protean manifestations.The malnourished often have several concomitant diseases; drugs are therefore as widely used as in the well-nourished. The pathophysiological profile in malnutrition can alter pharmacokinetic processes, drug responses and toxicity. This review summarises the available knowledge on nutrient-drug interactions in malnourished children.Although there is much evidence in the literature that diet and nutritional status are 2 important environmental variables determining the pharmacotoxicological properties of chemicals, there are few data on humans. Recently, intense effort has been initially directed at studying drug kinetics in grade III malnutrition, namely kwashiorkor and marasmus. Studies on drugs and nutrients indicate delayed or decreased absorption, reduced protein binding of several drugs, fluctuations in volume of distribution, altered hepatic oxidative drug biotransformations and conjugations, reduced elimination of conjugates and reduced elimination of renally excreted drugs. The estimated steady-state levels of a few drugs suggest accumulation. Bioavailability problems with certain drugs are due to divergent effects of pharmacokinetic processes. Clinical risk of toxicity appears to be higher in malnourished children. Rehabilitation studies suggest that a number of these pharmacological abnormalities can be reversed.The majority of studies have concentrated on single-dose pharmacokinetics in severely malnourished children. A number of abnormalities seen in drug disposition during the' acute phase Qf malnutrition need to be confirmed for other grades of malnutrition. For practical purposes, it is important to consider steady-state levels and data in mild and moderate forms of growth-retarded children; drug-induced nutritional deficiencies can occur more easily in these populations. Although some of the drugs described in this review have been in use for many years, knowledge on drug response and toxicity is still only approximate. There is at present enough evidence to support monitoring plasma drug concentrations in malnourished children, particularly for those drugs which have dosedependent kinetics and narrow margins of safety.The metabolism and disposition of xenobiotics seem to vary widely in children with protein-energy malnutrition. Therapeutic inadequacies and toxicities need careful evaluation in malnourished children.

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Liver Function in Kwashiorkor

Cited by 24 publications

References 9 publications

Drug Metabolism and Pharmacokinetics in Malnutrition

Drug Metabolism and Pharmacokinetics in Malnutrition

A Histochemical Investigation of the Leucocytes in Kwashiorkor

Drug Metabolism and Pharmacokinetics in Malnourished Children

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