British Medical Bulletin (1981) Vol. 37, No. 1, pp.

19-24

BIOCHEMISTRY AND PHYSIOLOGY OF KWASHIORKOR AND MARASMUS WA Coward&PGLunn

but they do not, in any way, distinguish causes in the same
manner that the term protein-energy malnutrition quite
specifically suggests a dietary cause.
We can therefore make clinical distinctions between kwashi-
THE BIOCHEMISTRY AND orkor and marasmus, but the object of many experimental
PHYSIOLOGY OF KWASHIORKOR studies, and of dietary surveys in different parts of the world,
has been to find differences in their dietary aetiology. It is well
AND MARASMUS known that it is necessary to feed experimental animals
unrestricted amounts of diets low in protein to produce a
W A COWARD PhD syndrome resembling kwashiorkor; restricting the intake of any
diet will result in severe wasting. Survey work in Uganda
P G LUNN PhD (Whitehead et al. 1977) also showed that, when diets with a
wide range of protein: energy ratios are available within a
University of Cambridge
and community, it is the children who habitually consume diets from
Medical Research Council the low end of the range (protein: energy, 0.04-0.06) who are at
Dunn Nutritional Laboratory, Cambridge risk of developing kwashiorkor. These observations contrast
with others typified by those of Gopalan (1968). He showed
that, in Indian children eating cereal-based diets with a relatively
Concepts and definitions: protein-energy malnutrition, constant protein: energy ratio (0.08), either kwashiorkor or
kwashiorkor and marasmus marasmus could emerge if energy intakes were low. Taking
Adaptation to a deficiency of energy: the pathogenesis of extreme views would therefore suggest that kwashiorkor and
marasmus marasmus represent different aspects of the same disease (as the
Failure of adaptation to protein deficiency: the pathogenesis
term protein-energy malnutrition suggests) or that they are
of kwashiorkor
Pathogenesis of intermediate forms of protein-energy different diseases with distinguishable aetiologies.
malnutrition Protagonists of each idea have ample support for their
Regulation of body fluid volumes in protein-energy arguments but it is unrewarding to initiate a discussion of the
malnutrition aetiology of kwashiorkor and marasmus by emphasizing one
a The distribution of extracellular fluid volume theory to the exclusion of the other. A more realistic approach
b Sodium and water balance is to accept that each idea makes a worthwhile contribution in a
c Membrane defects and the sodium pump
worldwide context but that causes can differ in individual,
Plasma proteins in kwashiorkor and marasmus
References regional circumstances.

It is just four years since Alleyne et al. (1977) published their 2 Adaptation to a Deficiency of Energy: the Pathogenesis
comprehensive treatise on protein-energy malnutrition. In this of Marasmus
paper we will focus on a few developments in biochemistry and
physiology that we believe are important for our understanding It is now widely accepted that the severe wasting seen in
of how the clinical features of the disease emerge in children marasmic children represents the end-product of metabolic
subjected to a hostile environment and inadequate diet. adaptation to an inadequate energy intake, mediated by changes
in hormonal pattern. Although a child is not clinically identified
as a case of marasmus until weight-for-age falls below 60%, the
1 Concepts and Definitions: Protein-Energy Malnutrition,
relevant metabolic changes can be detected, within a community
Kwashiorkor and Marasmus
where marasmus occurs, well before this stage is reached.
In recent years it has been customary to use the term Whitehead et al. (1977) and Lunn et al. (1979a) showed that
"protein-energy malnutrition" to describe a group or spectrum fasting plasma cortisol and growth hormone (GH) levels were
of diseases that often affect children living in poor communities high but insulin concentrations were low in Gambian children
in most developing countries. The expression suggests impor- with faltering growth rates, and insulin: cortisol ratios were
tant concepts. These are that inadequate intakes of energy or strongly correlated with growth velocities (Lunn et al. 1979a).
protein, or both, are causative factors and that there is a The changes seen when children are admitted to hospital
continuous connection in terms of biochemistry and physiology (reviewed by Alleyne et al. 1977) are only more exaggerated
between the extreme forms of protein-energy malnutrition, examples of the same pattern.
which are kwashiorkor and marasmus. A reduction in plasma insulin concentration is a normal
For comprehensive clinical descriptions of the two syndromes response to a reduced food intake and extremely low values are
the reader may refer to Alleyne et al. (1977), but for the present seen in marasmic children admitted to hospital. Cahill (1970)
it will be sufficient to use a series of internationally accepted suggested that a decreased level of this hormone is the main
definitions suggested by a Wellcome Trust Working Party regulator for the release of energy metabolites from endogenous
(Lancet, 1970). The crucial diagnostic features are the degree sources. Raised plasma cortisol concentrations will augment
of body wasting and the presence of oedema. Thus, when the effect on the mobilization of skeletal muscle protein,
Harvard weight standards (Stuart & Stevenson, 1959) are used, releasing amino acids for gluconeogenesis and perhaps for the
children of 60-80% expected weight-for-age are called cases of hepatic synthesis of plasma proteins. Adipose tissue
kwashiorkor if oedema is present. Below 60% the diagnosis is mobilization will be enhanced by changes in GH concentra-
marasmic kwashiorkor if they have oedema or marasmus if tions, and free fatty acids will become available as alternative
oedema is absent. These definitions have the merit of simplicity sources of energy (Parra et al. 1973).

19

Vol. 37 No. 1

There is also an inverse relationship Edozien. There can be only two options: energy can be stored as fat or it potassium supplementation of rehabilitation diets results in a can be removed by oxidation. Kajubi & Okel. The considerable variation that exists between reports is not surprising. 1970). 1977) and a markedly elevated tri-iodothyronine likely explanations (see section 4). The those involved in the development of obesity and. is the one adopted. If true. the appearance of kwashiorkor in children who. and deficiencies in (J-lipoprotein synthesis dietary ideas we have already outlined. be no hypoglycaemic stress and consequently no shown that short-term fasting in healthy subjects results in elevation of plasma cortisol or GH to cause wasting. and much higher than those found in Gambian changes described are in most cases the expected responses to pre-school children of the same age (Whitehead et al. very different from that which existed earlier in his illness but much more like that found in marasmus. plasma insulin concentrations The study of Lunn et al. The mechanisms we have discussed are clearly similar to 1968. 1971. hied. assessed by plasma albumin concentrations (Pimstone el al. Mann et al. effect. Jaya Rao (1974) essential amino acids in muscle when protein intake is low is proposed that some children develop kwashiorkor rather than likely to produce a fall in hepatic synthesis of export proteins. 1978. Fasting plasma insulin concentrations in these GH concentration is elevated and thyroid hormone concentra- children were higher than in children who had recovered from tions are either normal or reduced (Alleyne et al. (1973) showed that this response occurs Enwonwu & Sreebny. but no fully understood. endemic. This latter Plasma GH concentrations are high in children with response enables the animals to "burn-off' any energy excess kwashiorkor and are not reduced by glucose loads (Pimstone et and will prevent the development of changes we have described al. amounts of cortisol adequate for adaptation to protein-energy Hypoalbuminaemia could lead to defects in body fluid homo. however. 1973). 1974). it has been demonstrated that they fall after in children. from an early stage. becomes easier to understand. problem of adaptation is how to deal with the energy excess. These non-essential amino acids typical of the developmental phases of results suggest that a defect in the adrenals' ability to produce kwashiorkor (Grimble & Whitehead. 1968). 1981) also exists in the response of children discussed by Pimstone et al. There need. since lowering the basal metabolic rate described as apathetic and anorexic and the hormone profile is will conserve the meagre supplies of energy available. 1981 . 1974. (1973) in Uganda remains the most are reduced but can be normal. By promoting muscle protein found in marasmic children with the same degree of anorexia synthesis. However. there is no evidence to support the suggestion (Grant el al. 1967. We believe. If the excess energy is not removed. hospital (Alleyne et al. 1968. Although plasma to low-protein diets. or marasmus on identical diets. 1979). as values 3 Failure of Adaptation to Protein Deficiency: the will be influenced by the duration and severity of the clinical Patbogenesls of Kwashlorkor phase of the illness. and stimulation of the adrenal cortex with essential amino acids. 1973. even when energy intakes could be argued that this might be expected in a child whose are lower than recommended requirements. 1979). but this was not found to be the case in Egyptian children school children indicates that the first of these possible pathways (Carter et al. Data from Jordan determine the kind of protein-energy malnutrition that even. Fiorotto & Coward. (1975) have shown that. marasmus because they fail. 1968). if the mechanisms regulating plasma GH concentrations in kwashi- considerable degree of individual variation to over-eating orkor have not been identified. because of in- Rats do not respond to low-protein diets in this way and adequate food intakes. The impaired glucose tolerance (Vance et al. The course taken may ultimately faster return to a normal insulin respose. 1977). 1977). Anthony & even after a single meal. indicate that adding chromium to the diet produces a similar The endocrine pattern in non-hospitalized Ugandan pre. then the situation described by Gopalan somatomedin concentrations are low in children with kwashi- (1968) in India. but a number of possibilities are (James & Trayhurn. 1975.BIOCHEMISTRY AND PHYSIOLOGY OF KWASHIORKOR AND MARASMUS W A Coward & P G Lunn Reductions in the plasma concentration of thyroid hormones cance of a high variability in the unrelated individual require- have also been reported for marasmic children admitted to ments for protein and energy. metabolism is geared to survival. This view is substantially different from the eostasis and oedema. In general. 1979). already in short supply. Lunn el al. level (Edozien et al. 1979) can this adaptation between GH levels and the severity of protein deficiency as be overcome. blood Although plasma cortisol concentrations are elevated • in glucose concentrations will tend to rise and result in hyper. feedback stimulus for GH release (Mohan & Jaya Rao. anorexia and hypoglycaemia. but there are some features not Plasma cortisol and GH levels were not elevated. 1977). that there are other more (Coward et al. to produce including albumin and apo-proteins for (J-lipoprotein synthesis. information on thyroid hormone concentrations was obtained. The malnutrition. (Hopkins et al. 1968) and Turkey (Giirson & Saner. they are usually lower than those insulinaemia and fat deposition. where children can develop either kwashiorkor orkor. 1968). 1967). only by feeding diets virtually free of protein (Edozien. and by inhibiting Synacthen (synthetic P'~24 adrenocorticotrophic hormone) gluconeogenesis will cause an accumulation of alanine and other results in a poor response (Jaya Rao et al. This change can be regarded as A child admitted to hospital with kwashiorkor is usually an effective adaptation. Children with all forms of protein-energy malnutrition have a When the low protein content of a diet limits growth there poor insulin response to a glucose load (Alleyne et al. Bull. 1977). 1971) tually develops (see MacLean & Graham. cortisol values are often elevated complete source of information on the hormonal profiles of and correlate with the degree of wasting and the severity of pre-school children living in an area where kwashiorkor is intercurrent infections (Abbassy et al. It must be a relative excess of energy. (1973). Thus the rat is a poor model for kwashiorkor and a few days of feeding meals containing protein (Pimstone el al. Locking away cortisol may be a feature of kwashiorkor. 20 Br. children with kwashiorkor. in South African children. Tulp et al. it would explain to a fatty liver. Philbrick & Hill. Robinson et al. 1973) that impaired somatomedin production might cause a Waterlow (1974) has previously pointed out the likely signifi. Lunn et al. high insulin concentrations will deplete the plasma of and infection. 1968). might otherwise be expected to become instead have a much reduced plasma insulin concentration marasmic. However. malnutrition. and certainly it has been therefore.

or protein deficiencies. control over the distribution of extracellular fluid volume will be Finally. again. when plasma protein rates in malnourished children but plasma concentrations were concentrations fall in protein-deficient rats. they are not specifically associated with the presence The appearance of oedema in malnourished children is an of oedema in children (Alleyne. Srikantia (1968) postulated a role for antidiuretic 21 Vol. two distinctly different views can now be low-protein diets and are not associated with evidence of identified. cumstances the task is to identify the reasons for phases of oedema and hypoproteinaemia have appeared precipitously as a sodium retention in malnourished children. evidence for a specific association with the believe that the most important factors are those that determine presence of oedema is ambiguous. contradicting much of the Malnutrition earlier work. as a result of the alternating dominance of energy leadingly large. plasma albumin concentrations will fall kwashiorkor can develop. Worthington et range of plasma protein concentrations. 1967). The differences could be attributed to different We have suggested that the endocrine response to a diet can methodologies. although Van der water filtration. because in normal animals the Westhuysen et al. 1979). sodium retention could result from a The Distribution of Extracellular Fluid Volume elevated plasma aldosterone levels and increased plasma renin Coward & Fiorotto (1979) and Fiorotto & Coward (1979) activity but. in preparation) showed that further reduction in plasma protein content will produce an changes in aldosterone concentration and plasma renin activity imbalance of the transcapillary forces and the organism's can precede the appearance of oedema by many months. result of an increased gastrointestinal loss of plasma proteins. Likely renal function. when plasma monkeys fed low-protein diets and found elevated levels when protein concentration is reduced by half. when a malnourished child develops sodium there may be another important way in which marasmic and water retention. irrespective of the presence of oedema. Active renal salt and water retention might then occur to of the development of kwashiorkor (Lunn et al. Viart suggested that in malnutrition plasma determine how available nutrients are used. severe wasting could be induced in b Sodium and Water Balance children who are otherwise likely to present as cases of The alternative. al. They observed that. 1973). 1973) and baboons (M tinguishes kwashiorkor from other forms of malnutrition. At this stage any (M Fiorotto & W A Coward. 1979b) that and suggests that. because albumin synthesis admitted to hospital with oedema have the underlying rates are unalterably low (Patrick. We believe that many children with the development of oedema. the concept that children with kwashiorkor are over-hydrated We have also recently suggested (Lunn et al. excessive salt and water retention. interstitial volume expansion will occur. in practice. (1975a) found increased plasma renin content of interstitial fluid that matched the changes in plasma. not In a review of the effects of protein-energy malnutrition on compensated for by increased rates of protein synthesis. In these cir- metabolic features of marasmus. it is more insistence that changes in plasma albumin concentration are likely that non-nutritional factors modulate the effects of the functionally important in the development of kwashiorkor and diet. activity in oedematous malnourished rats but not in non- This represented a proportionally larger change in interstitial oedematous animals. in the face of the unlikely that GH-mediated changes are directly involved in the circulation's reduced ability to hold retained fluid. Superimposed on these. interstitial fluid protein oedema was present. 1972). 4 Pathogenesis of Intermediate Forms of Protein-Energy 1977) show that this is the case. However. the distribution of extracellular fluid between the vascular and (1973) found either normal or increased aldosterone secretion interstitial spaces. but our own serial studies with baboons concentrations reach values close to zero. With only one exception (Srikantia. effects of diet and accelerate wasting in children developing marasmus. sodium loads. In addition. (1977) measured plasma aldosterone concentrations in anism does not possess infinite gain because. while these 5 Regulation of Body Fluid Volumes In Protein-Energy changes will undoubtedly limit the potential for salt and water Malnutrition excretion. but Fiorotto and W A Coward. Migeon et al. was maintained by a reduction in the colloid Westhuysen et al. marasmic kwashiorkor might emerge The development of these ideas was stimulated by an (Whitehead & Alleyne. ments with sheep (Rabinowitz et al. However. the homoeostatic mech. idea begins with kwashiorkor. While protein-energy malnutrition have elevated plasma renin ac- this adaptation to hypoproteinaemia is effective over a large tivities. preventing excessive those with kwashiorkor. BIOCHEMISTRY AND PHYSIOLOGY OF KWASHIORKOR AND MARASMUS WA Coward & P G Lunn Since plasma GH concentrations rise only in the terminal stages lost. 1975b) showed that children suffering from plasma: interstitial fluid concentration ratio is about 2. further early pathogenesis of this disease. At the tubular level. published data show that renal plasma flow (RPF) and glomerular filtration rate (GFR) are decreased but. 1 . by the recognition that the contribution of albumin to the total A conventional view was outlined by Whitehead & Lunn colloid osmotic pressure of plasma (>50%) is greater than that (1979). in preparation) have shown that until recently little progress had been made in identifying its reductions in RPF and GFR are early effects of feeding cause. but other abnormalities occur and elevate plasma glucocorticoid concentrations will alter the their importance has to be considered. Alternatively. experi- example of a failure of homoeostasis that specifically dis. Klahr & Alleyne (1973) identified factors that causes of such losses are a measles infection or the presence of could impair the ability of malnourished children to excrete intestinal helminths. Furthermore. It was proposed that the incidence of infections that of any other plasma protein. a normal balance of normal in children with marasmus and elevated in only half of transcapillary colloid osmotic pressures. For example. 1968). This idea indicates that blood and plasma volumes will be reduced in kwashiorkor and the most recent observations with labelled erythrocytes (Viart. it is prevent plasma volume contraction but. and it is theoretically volumes measured with protein-bound tracers could be mis- possible that. 37 No. or perhaps complementary. the same group of workers (Van der fluid protein concentration.

However. where the functional significance c Membrane Defects and the Sodium Pump of changes in the concentration of a plasma protein is In following up lines of thought developed by Metcoff (1975). 1980). 1973). 1973) is not clear. recognized. 1965. but it is suggested that centration of any protein is dependent not only on rates of findings for leucocytes (Patrick. Bull. Nichols et There are a multitude of reports on the usefulness of the al. Furthermore. Wright & Briggs (1979) have recently reviewed the butes to oedema formation. 1975. Delpeuch et al. marasmic children fed high-energy diets increase their are likely to be less ambiguous. malnutrition. Thus. Observations made by Patrick et al. Children with kwashiorkor can that a decrease in transferrin concentration caused by mal- lose their oedema and decrease their total body water from 77% nutrition can be masked by an increase due to a lack of iron to 63% of body weight when they are fed diets not known to (Ismadi et al. changes in its plasma environment in the renal medulla needed for salt and water concentration should be meaningful in terms of the ultimate reabsorption in later segments. In this way it is possible to build normal children.23-30 of thiiBuBttm. a thermogenic response involving nourished children although albumin concentrations were not increased sodium pumping might be relevant Others have also advocated the use of plasma transferrin It will be clear that we are some way from integrating all these concentration as a most sensitive index of protein-energy observations into a concise framework. 22 Br. since the plasma con- tubule cell physiology in malnutrition. rates of intravascular- leucocytes it was shown that there were dramatically increased extravascular exchange and the degree of hydration. kwashiorkor but not in marasmus. other workers report even indicators of nutritional status (Ingenbleek et al. (1971) showed that low transferrin concentrations were could cause increased fractional sodium resorption. up a comprehensive picture of the development and resolution of kwashiorkor. if we accept water losses could be prevented only by reductions in RPF and that a low plasma albumin concentration specifically contri- GFR. The protein-energy malnutrition. 1981 . in experimental animals (Olusi et al. if an energy intake in excess of requirements is a related to deficits in weight. PP. We have therefore often found it distal tubule fluid. and in these circumstances other indices of malnutrition However. McFarlane et al. 1979) and erythrocytes synthesis (the diet. al. There associated with a poor prognosis in children with kwashiorkor. where it was found that have consistently attracted attention: these are transferrin.and substrate-dependent component) but (Kaplay. 31-36 of this Bulletin.—ED. pp. There is no information on this aspect of renal This strategy is inevitably empirical. and in protein deficiency reduced rates of urea for malnutrition. the the interstitium and cells. the problem of the relationship of these and Reeds & Laditan (1976) extended this observation to changes to dietary and environmental causes of kwashiorkor. Ingenbleek et al. In the first instance it should be responsive to synthesis would lead to the dissipation of the hypertonic changes in nutrient intake and. produce substantial changes in rates of plasma protein synthesis. However. 1975). (1969). and sensitivity to reduced protein intake responsible for the distribution of body water between plasma. The connection between these observations and those 6 Plasma Proteins in Kwashiorkor and Marasmus showing that fractional sodium reabsorption can be decreased in malnourished oedematous children (Alleyne. S « Nirumg* R«o. Fondu et al. malnourished children can complicate the situation to the extent (1978) illustrate the problem. It could be argued (Fiorotto. never elevated in malnourished children. but this idea has not been 1965). Thus excessive sodium and pathology of protein-energy malnutrition. 1980) that measurement of plasma protein concentrations for the assess- hypoproteinaemia and low plasma oncotic pressure in the ment of nutritional status. secondly. In contrast to this situation. 1971. the latter workers Trace element deficiencies1 could provide the link (Patrick. hied.—ED. Delpeuch et al. 1978. because their concentrations are greatly 1 1 See Golden & Golden. however. which could be balance between these processes that determines whether the achieved only by an increase in membrane permeability to concentration of a specific protein reflects the degree of sodium and subsequent stimulation of the sodium pump. total body water from 64% to over 70% of body weight in 14 Plasma RBP and TBPA have also been proposed as sensitive days but oedema does not appear. but before discussing them it is peritubular capillaries would limit sodium reabsorption in the necessary to develop a concept that describes an ideal marker proximal tubules. 1979) may be relevant. For also on utilization and catabolism. In these circumstances the manner in which convenient to classify children according to their albumin the kidney regulates salt and water balance in relationship to concentration and to relate other biochemical changes to these intake may not have the precision of response available in values (Whitehead et al.and length-for-age in under- significant dietary component. It is unlikely that changes in only one aspect of universally accepted. It is the transport rates of sodium in kwashiorkor. showed that serum transferrin concentrations were linearly 1980) or. 1975. higher values in oedema-free marasmic children (Hansen et al. Our general view is that malnutrition because of its rapid response to refeeding in there is a need to separate the influence of those factors malnourished children. 1980). 1972. are compatible with these McFarlane et al. three plasma proteins results obtained for erythrocytes. (1970) and Gabr et observations and. if mirrored at the level of the renal tubule. we can describe the "sensitivity" of a particular Patrick (1979) commented on the significance of changes in protein in malnutrition without simultaneously considering membrane permeability and the activity of the sodium pump in nutrient intake or the final form of malnutrition that emerges. it is clear that its measurement is evidence for the existence of a mechanism by which GFR in a useful in communities where kwashiorkor is the predominant single nephron is regulated by the composition or rate of flow of form of malnutrition. ouabain-sensitive Na-K adenosinetriphosphatase activity is thyroxine-binding prealbumin (TBPA) and retinol-binding pro- increased (compared with normal and recovery values) in tein (RBP). and those controlling the general frequency with which iron-deficiency anaemia2 occurs in degree of hydration. remains. include those with marasmus. BIOCHEMISTRY AND PHYSIOLOGY OF KWASHIORKOR AND MARASMUS W A Coward & P G Lunn hormone in oedema formation. essentially because urine osmolality is regulative physiology will be able to explain these findings.

In this respect. Jamaican children (Thesis for MD degree). Mar M-H. Nutr. (1978). Nutr. Pediatr. Trop. Ada. Fiorotto M & Coward W A (1979) Br. proconvertin. Susheela T P & Narasinga Rao B S (1971) Indian J. nutritional problem most frequently encountered by doctors In reviewing the relationship between diet and plasma protein working in developing countries. transferrin. Mandelbaum I M & Vis H L (1979) Am. 21-31 13. 49—58 (Proceedings of a Protein-energy malnutrition. Stanfield J P & Whitehead R G (1977) deficiencies and protein deficiencies. we accept the concentrations. marasmus and marasmic kwashiorkor.87-95. Workers in metrically. Mikhail M. identified as diet-independent plasma proteins. Nutr. Nutr. J. This result therefore indicates that RBP synthesis is less affected in marasmus than in We recognize that marasmus. Trop. Soc. It was not possible convincingly minority of the world's malnourished children are likely to suffer to relate these differences in responsiveness to normal fractional from it.918-921 Patwardhan V N (1968) Am. 1974) that in a universal context it is necessary groups of proteins on the basis of the responsiveness to dietary to appreciate that a lack of nutrients in general. Thailand (Schelp et al. 2. (1980) metabolically distinct diseases. malnutrition (Thesis for PhD degree). orkor.115—126 491-195 Delpeuch F. Arnold. but will also provide a more complete usefulness of an index for malnutrition is defined only in terms of understanding of how nutritional and other environmental sensitivity to a dietary change. many aspects of the biochemistry and tion when only 1 g protein/kg body weight per day was fed physiology of kwashiorkor have not yet been explained. 38. Ogunshina & Hussain different indices from the dietary and metabolic points of view. Med.400-411 Gopalan C (1968) In: McCance R A & Widdowson E M. De Visscher M & De Nayer P (1972) Lancet. Cornu A & Chevalier P (1980) Br.106-109 108. Olson (1975) found it possible to distinguish view (McLaren.g. Niehaus N. (3. 21. Becker D & Pimstone B L (1973) Arch. The theory. (1980) have also shown that TBPA concentrations decrease Another group of proteins that has recently attracted with increasing severity of malnutrition assessed anthropo. Nutr.1313-1319 Coward W A S Fiorotto M (1979) Proc. Brinkman G L & Bowie M D (1965) S. with an energy therapy. Med. RBP from the liver. Hay R W. 38.375-379 Hopkins L L Jr. April 1967). The peak levels were lowest in kwashi. marasmus appears. However. Davis I T . Res. recognizes that kwashiorkor and marasmus are marasmus (Smith et al. / . Elucidation of the mechanisms involved will not only or absolute rates of synthesis.631-648 Grant D B.721-722 Alleyne G A O (1965) Renal and cardiac function In severely malnourished Gabr M. Makoui T & Switzer B R (1978)/. 1977. 39. However. Abd-FJ-Hadi K. Ingenbleek Y. pp. Experimental studies on obese women (Shetty et al.917-919 203-211 Edozien J C. awakening an interest in the latter disease.195-202 Gurson C T & Saner G (\91\)Am.(1971) / . Nutr. Nutr. 63. but suggests that proteinase have recently investigated RBP and TBPA in children suffering inhibitor levels determine the extent to which a malnourished the combined effects of vitamin A deficiency and protein-energy child can mobilize endogenous proteins to provide amino acids malnutrition and have shown that. Hyg.501-514 Clin. 74. 42. 1979) attach crucial 1979) indicate that TBPA and RBP concentrations are sensitive metabolic importance to changes in the plasma concentration of to changes in either energy or protein intake and this finding a1-antitrypsin and a1-antichymotrypsin in the development of supports the observations that TBPA and RBP concentrations malnutrition. 43. 21. Med. Zeitoun M M & Ragab M (1967)/.J. Ransome-Kuti O & Majaj A S (1968) Am. It would be wrong to suggest stresses interact to produce the diseases identified as kwashi- that RBP and TBPA are better indices than albumin concentra. Clin. Hambley J. attention are the plasma proteinase inhibitors. The immunoglobulins (IgA. Nuxr.596-600 Carter J P. so the authors considered that the peak concentrations provided some measure of the liver's ability to synthesize RBP from the outset. 1. 101. is the kwashiorkor. Child. this leads orkor and highest in marasmus. novel idea. J. When proteinase inhibitor levels are high as a protein with the ligand retinol attached) increased. or to their sites of synthesis. 24. it is possible that a balanced relationship hours after treatment. Afr. 32. following intramuscular for the synthesis of proteins (e. BIOCHEMISTRY AND PHYSIOLOGY OF KWASHIORKOR AND MARASMUS WA Coward & P G Lunn reduced in malnourished children admitted to hospital and tion and more appropriate to suggest instead that they are rapidly return to normal with refeeding. J. For (prothrombin. / . Schrieck Van den H-G. De Nayer P & De Visscher M (1975) Enwonwu C O & Sreebny L M (1971)/. The values achieved are kwashiorkor. most concisely outlined by Schelp et are equally low in kwashiorkor. rather than kwashiorkor. IgG and IgM) were gap rather than a protein gap.1581-1587 23 Vol. but lead to improvements in the prevention and treatment of the differences illustrate the difficulties that exist when the nutritional disease.61-67 Fiorotto M (1980) Studies on oedema/unction in experimental protein-energy Ismadi S D. Clin. Whitehead R G & Lunn P G (1977) Br. Picou D I. 282. 1975). El-Hawary M F S & El-Dali M. 1 . Coward W A. between proteinases and their inhibitors is destroyed. 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