436

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1984), 78, 436-441

Kwashiorkor revisited: the pathogenesis of oedema in kwashiorkor

and its significance
J. C. WATERLOW
Dept. of Human Nutrition, London School of Hygiene and Tropical Medicine, Keppel Street,
London WClE 7HT

Summary
Cicely Williams, in her original description of kwashiorkor, implied that deficiency of protein in the

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babv’s food could be a main cause of the syndrome. The hallmark of kwashiorkor is oedema.
According to the ‘classical’ theory, an inadequate intake of protein leads to a low plasma albumin
concentration, which in turn causesoedema. This theory has been contested from several points of
view: that hypoalbuminaemia is not the major factor determining the presenceof oedema, and that
there is no real evidence of dietary protein deficiency. The resolution of this question 1s of some
importance from the point of view of public health diagnosis and prevention.
A crucial point in the argument is the pathogenesisof oedema, which is discussedin some detail.
Although it is clearly multifactorial, with electrolyte disturbance+potassium deficiency and sodium
retention-playing an important role, it is contended that the classicaltheory is essentially correct. On
the dietary side, recent experimental work supports the earlier view that the development of oedema
depends on a relative deficiency of protein with a relative excessof energy. Comparisons of intakes
with requirements are unconvincing in view of uncertainty about the validity of the estimates of
children’s needs for protein.

Introduction in the early days put emphasis on one or another as

Cicely Williams’s 90th birthday has just been
celebratedand it may be useful, after 50 years, to look
back briefly on the way in which ideas have developed
since her first description of kwashiorkor (WILLIAMS,
1933). One of her contributions which has not been
adequately recognized was the new and original idea
that perhaps kwashiorkor represents a state of protein
deficiency. Earlier accounts, mainly from Latin
America, had attributed it to a multiple deficiency of
vitamins (summarized by WATERLOWet al., 1960).
The evidence for protein deficiency was the observa-
tion that kwashiorkor develops in a child when it is
replaced by a new baby and is weaned from the breast
on to starchy paps, and that it responds to treatment
with milk. This evidence is not. of course. conclusive
and after the war, Brock of Cape Town tried to test it
more rigorously by treating children with mixtures of
pure aminoacids, which had just become available
(BROCKet al., 1955). When, at a meeting in Uganda,
Brock claimed that this treatment produced “initia-
tion of cure”, as judged by the loss of oedema,the tart
criticism was made: “You have a headacheand it goes
away with aspirin: does this mean that you are
suffering from aspirin deficiency?“. This remark
illustrates the kind of difficulty that besets the
problem of establishing a causal relationship.
On the basis of Williams’s work arosewhat may be
called the “classical theory” differentiating marasmus
from kwashiorkor: marasmus results from a total
deficiency of food (semi-starvation); kwashiorkor
from a specific defiiency of protein, with energy in
relative excess.
The name kwashiorkor denotes a clinical syn-
drome in the literal sense of the word-that is, a
group of characteristics which occur together. These
features, as originally described by Cicely WILLIAMS
(1933), are: oedema, dermatosis, fatty liver, discol-
oured hair and irritability. Many casespresent some
but not all of these characteristics. Different authors
the essential feature, without which the diagnosis of
kwashiorkor could not be made, e.g., red hair
(BROCK & AUTRET, 1952), dermatosis (TROWELL,
1941), fatty liver (WATERLOW,1948). The confusion
about diagnosis became so great that the Wellcome
Trust convened a working party in Jamaica to try to
establish someagreed diagnostic criteria. The conclu-
sion of this group was that the essential feature for
making the diagnosis of kwashiorkor was the presence
of oedema, together with some degree of weight
deficit (Wellcome Trust Working Party, 1970).
The Wellcome definition leads to the key question
which is the subject of this paper: doesthe presenceof
oedema in malnourished children imply that they,
and presumably others in their community, have an
inadequate protein intake? It may be noted that an
inadequate protein intake is not exactly synonymous
with a nrotein-deficient diet which is likelv to be low
in othei factors associatedwith protein in animal and
plant cells, such as potassium, magnesium, trace
elements and vitamins of the B complex.
To answer this question it is necessary to under-
stand the cause of the oedema which differentiates
kwashiorkor from general malnutrition or marasmus.
The question may be divided into two parts: the
immediate physiopathological causeswithin the body
and the more remote environmental causewhich sets
the metabolic events in motion.
Pathophysiology of oedema in kwashiorkor
The word “oedema” is used here to denote an
excessof fluid in the extracellular space.,as is obvious
visually and by the clinical sign of pitting, or, in the
early stages,by a kind of tensenessof the tissue which
can be felt better than it can be described (WATER-
LOW, 1948). Intracellular overhydration is a separate
entity, much more difficult to establish. We do not
know how far the very great increases in total body
water found in oedematous malnutrition represent
 J. C.
expansion of both water compartments, but it is
probable that in most cases the increase is largely
extracellular (WATERLOW & ALLEYNE, 1971).
The class&l theory of the causal chain is very
simple: (i) oedemais caused by low plasma albumin;
(ii) hypoalbuminaemia results from an inadequate
protein intake.
The theory has come under strong attack in recent
years and therefore it is important to re-examine the
evidence for and against it.
It is not disputed that plasma albumin concentra-
tions are generally reduced in children with oedema-
tous malnutrition, nor is there any dispute about the
validity of the Starling hypothesis defining the forces
controlling the exchange of fluid between intra- and
extra-vascular compartments. However, there is not
an invariable relationship between albumin concen-
tration and the presenceor degreeof oedema(MONT-
GOMERY, 1963)or the rate of its clearance(GOLDEN et
al., 1980). Therefore some other factor or factors
must be involved, the most important of which are
probably changes in cardiac and renal function and
potassium deficiency.
Cardiac and renal function
Cardiac output is reduced in severemalnutrition to
one half to one third of normal (ALLEYNE, 1966;
VIART, 1977a,b). ALLEYNE(1967) also demonstrated
decreasesin renal blood flow and glomerular filtration
rate. Thirdly, there is impairment of the capacity to
concentrate the urine and to handle a sodium load.
KLAHR & ALLEYNE (1973) gave an excellent discus-
sion of the interrelationships of these factors in
producing oedema in malnutrition. An important
point is that these changes were found equally in
children with marasmus and kwashiorkor. Therefore
they represent an underlying complex of factors
which tend to promote fluid retention but cannot be
regarded as the sole cause of it.
Decreasedinterstitial pressure, from loss of muscle
and fat, is another factor which will upset the balance
of the Starling equation. The fact that in some
children gross oedemaof the legs co-exists with signs
of dehydration in the upper part of the body suggests
that local circulatory factors must be important.
Potassium deficiency
It is well established that potassium deficiency is
often found in severely malnourished children. The
evidence comes from balance experiments, showing
during treatment increased retention of K compared
to N (HANSEN, 1956), from tissue analyses,showing a
reduced K/N ratio, particularly in muscle (ALLEYNE
et al., 1969), and thirdly, from decreasedwhole body
K, as measured by 40K counting (GARROW,1965).
This latter evidence is lessclear-cut.,becausemeasure-
ment of whole body K cannot distinguish between
decreasedK capacity, secondary to shrinkage of the
cell mass, and specific K depletion.
It seemsto be acceptedthat K depletion can cause
retention of water and sodium, although the mechan-
ism is not very clear. I know frbm personal experience
that a low K intake, combined with a mild remiratorv
alkalosis can cause gross oedema, which r&pond>
immediately to administration of potassium (WATER-
LOW & BUNJE, 1966).
Other minerals, notably magnesium and zinc, are
deficient in severemalnutrition. GOLDEN & GOLDEN
WATERLOW
437
(1981) have discussedthe possible role of vanadium in
controlling water and electrolyte balances across cell
membranes. It is not within the scopeof this paper to
discuss the difficult question of intracellular over-
hydration, but it is important to realize, as first
pointed out by Gomez and co-workers in Mexico 40
years ago, that in some casesof severe malnutrition
there is hypotonicity and hyponatraemia. In this
situation one might expect water to enter the cells to
maintain osmotic balance, and perhaps sodium also.
PATRICK (1979) in studies on leucocytes has produced
evidence of leaky membranes in severely mal-
nourished children. The capacity of the cell mem-
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brane to keep K in and Na out dependson the sodium
pump, which is fuelled by ATP. Many years ago I
found evidence of defective oxidative phosphorylation
in the fatty livers of children with kwashiorkor
(WATERLOW, 1961).
The purpose of this digression from the main theme
is to emphasize that in these patients there are
profound and complex changes in electrolyte and
water balance. Consider the following hypothet+l
but not impossible scenario: in a severely ill child
excessof water and sodium has entered the cells. The
first effect of treatment with a high energy-high
protein diet is an improvement in cellular function
with a massivedischarge of water and sodium into the
extracellular and intravascular compartments. This in
turn leads to interstitial oedema, circulatory overload
and pulmonary oedema,just asin a child who is given
over-energetic intravenous therapy. It would clearly
be incorrect to deduce from such a sequenceof events
that the kind of diet used in treatment is in general the
cause of oedema.
My clinical impression, not supported by concrete
evidence, is that these disturbances of fluid and
electrolyte balance tend to be more severein children
with marasmic kwashiorkor, who are wasted aswell as
oedematous and whose greater stunting in height is
evidence of long-standing malnutrition (ALLEYNE,
1970; WATERLOW, 1974).
What of the relationship between oedema in
children with kwashiorkor and in adults with famine
oedema?GOLDEN(1982a) argues that the pathogene-
sis is probably the same, the main cause being an
inadequate energy intake. I originally supposed that
the two were different conditions (WATERLOW,
1948), becausein famine oedemain post-war Europe
there was no great reduction in plasma albumin
concentration. However, in India, although I did not
know it at the time, the situation was different.
Hypoalbuminaemia was found in some but not all
adults with famine oedema (G~PALAN et aE., 1952)
and in the Bengal famine albumin concentrations ai
low as 1.0 g Der 100 ml were recorded (BOSEet al..
1946). On &is evidence there does not seemto be ani
greai inconsistency between children and adults. -
To conclude this Dart of the discussion, I believe
that in classical k\;ashiorkor, as defineh by the
Wellcome system, hypoalbuminaemia remains the
front runner asthe proximate causeof oedema.I admit
that there are many difficulties, but no other candi-
date is stronger. The fmding of GOLDENet al. f 1980)
that somechyldren lost oedeha without any chaige ih
plasma albumin concentration is not conclusive evi-
dence against the hypothesis. These children were
routinely treated with potassium; moreover, a small
438 SYMPOSIUM-KWASHIORKOR:
change in haemodynamic factors, such as a decrease
in venous capillary pressure, could produce a large
shift of fluid between extra- and intra-vascular com-
partments.
My conclusion is in no sense a claim that all
manifestations of oedemacan be explained by a single
hypothesis. If we go outside the field of malnutrition,
we immediately meet the contradiction that in the
nephrotic syndrome there is gross oedema with
hypoalbuminaemia, whereas in the rare condition of
congenital absenceof albumin if oedemais present at
all it is only mild (BENNHOLD & KALLEE, 1959).
The cause of hypoalbuminaemia
The evidence here is mainly experimental. The
classical study of JAMES& HAY (1968) showed that
when either well nourished or malnourished children
were given a reduced protein intake, there was an
immediate fall in the rate of albumin svnthesis.
Compensatory factors then cameinto play to ~maintain
the circulating albumin mass: a fall in the rate of
albumin breakdown and a shift from the extra- to the
intravascular compartment. Loss of albumin from the
gut may in some cases be a factor contributing to
hypoalbuminaemia (DOSSETOR& WHITTLE, 1975).
Albumin is synthesized in the liver. It was shown
long ago in Jamaica that there is a statistically
significant associationbetween oedemaand fatty liver.
According to current ideas, the most probable cause
of the fatty liver is failure of fat transport out of the
liver, resulting from decreased hepatic synthesis of
the carrier proteins (apolipoproteins). The sugges-
tion, therefore, is that aminoacid deficiency causesa
preferential reduction in the synthesis of “export”
proteins by the liver-a conclusion which has been
confirmed by animal experiments (QUARTEY-PAPAFIO
et al.. 1980). The reduction in svnthesis is more likelv
to be a causerather than effect 6f fatty liver, because
in malnourished children it is reversed very rapidly
when protein is given (JAMES & HAY, 1968) whereas
the fatty infiltration disappearsrather slowly (WATER-
LOW, 1975). Moreover, in acute rat experiments
impairment in synthesis produced by low protein
diets is not accompanied by fatty liver.
The next question is why hypoalbuminaemia and
fatty liver are less prominent in marasmus than in
kwashiorkor. The classical exulanation was neatlv
summarized by Trowel1 in the phrase: “the marasmic
lives on his own meat”. Munro’s demonstration many
years ago, that insulin promotes the uptake of
aminoacids into muscle (MUNRO, 1951) focussed
attention on the endocrine responsesto low protein
and low energy intakes. When energy supply is
restricted and muscle protein is being broken down to
supply aminoacids for gluconeogenesis, one would
expect plasma insulin levels to be low and cortisol
high. Whitehead and co-workers, in a comparison of
kwashiorkor and marasmus in Uganda and The
Gambia, obtained results which fit in well with this
expectation. Plasma insulin levels were higher, and
cortisol levels lower, in Uganda, where kwashiorkor is
common, than in the Gambia, where marasmusis the
prevailing form of malnutrition (WHITEHEAD et aE.,
1977).These differences were found in children in the
co&unity. Once children became severely mal-
nourished and ill the patterns were less clear-cut, as
might be expected.
P~ZTHOGENE~IS OF OEDEMA
The hypothesis therefore is that when muscle
protein is broken down to provide energy, the
aminoacids liberated are transported to the liver,
where some of them are oxidized but some are taken
up for protein synthesis. A difficulty with this
hypothesis is that in fasting the greater part of the net
efflux of amino-N from muscle is in the form of
alanine and glutamine, which have received their N
by transamination from other aminoacids, particular-
ly the branched chain aminoacids @CA). If the liver
is to be presented with a complete aminoacid mixture
for the synthesis of albumin, then it is necessarythat
some part of the carbon skeletons of the BCA should
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escapeoxidation and be reaminated in the liver. This
is possible, because the transaminases exist in the
liver, but in low concentration. Although many gaps
remain to be tilled, in my view the general concept of
a redistribution of protein synthesis in the body in
response to different dietary conditions is entirely
plausible (WATERLOW,1959).
Recently LUNN & AUSTIN (1983), in an important
series of experiments on the rat, have examined in
great detail the influence of energy and protein intakes
on plasma albumin concentration. At a lixed low
protein intake there was an inverse relationship
between energy intake and albumin level, so that the
rats with the highest energy intake had the lowest
concentrations. Similar results were obtained in
baboons (LUNN & BAKER, 1984). Although in these
experiments the authors did not fmd any relation
between plasma insulin and cortisol levels on the one
hand and that of albumin on the other, they made the
very interesting observation that on a high energy
intake, when albumin concentration was low, the
plasma T3 level was raised. There was in fact an
inverse correlation between albumin and T3. The
suggestion is made that in this situation T3 has taken
over the role of insulin and is stimulating muscle
protein synthesis (BROWN& MILLWARD, 1983).
Although many details of the mechanisms remain
to be worked out, the experimental evidence seemsto
me convincing, that albumin synthesis and plasma
albumin concentration are sensitive to protein intake
and their responseis modulated by the energy intake.
Protein deficiency as a cause of oedema
Having considered two links in the chain-the link
between oedema and hypoalbuminaemia and that
between hypoalbuminaemia and a low protein in-
takewe now come to the over-all relationship
between oedema and protein deficiency. GOLDEN
(1982b) has questioned whether the concept of
protein deficiency has any meaning when used to
describe a state of the body. As he rightly points out, it
is a circular argument to saythat oedema is diagnostic
of orotein deficiencv and therefore urotein deficiencv
causesoedema. If we are considering the state of the
body, we are on firmer ground with the concept of
fmtein deDZetion.Objective evidence of protein deple-
tion is a reduction in the amount of protein per cell,
i.e.. in the ratio orotein/DNA (WATERLOW & WEISZ,
1956). There i$ no reason to suppose that in this
respect there is any important difference between
kwashiorkor and marasmus. Protein depletion is
present in both and does not provide any basis for a
distinction.
In the present context it is more useful to consider
 J. C.
“protein deficiency” as referring to what goesinto the
body. Here it is necessary to distinguish between
“intake” and “diet”. Intake refers to the amount, diet
to the composition. This is the general usage in
nutrition, but not in dietetics. Thus in hospital
practice, a “diabetic diet” is a prescription of quantity
as well as of composition. In this discussion, a “low
protein intake” means an intake (grams per day)
below the estimated requirement. A “low protein
diet” is one with a low ratio of protein to energy.
Expzrimental and clinical evidence
There is a very large body of experimental work on
the effects of low protein diets fed to animals, and
specifically on the production of oedema.As GOLDEN
(1982b) points out, the results are conflicting and
confusing. In this caseI think we have to reverse the
maxim of Popper, that a hypothesis can only be
disproved, never proved, and regard as significant any
casewhere oedemahas been produced, becausethere
are many confounding factors which can prevent it
from occurrina. Accordina to the ‘Lclassical” hvooth-
esis, confirmid by the ixperiments of LU<N &
AUSTIN (1983) already referred to, one of these is a
low energy intake. The problem with many animals is
that it is difficult to get them to eat enough of a low
protein diet. An exception is the pig, which, as
WIDDOWSON(1968) showed, will eat such a diet
voraciously and develop both oedemaand fatty liver.
This work provides important support for the classic-
al theory of the pathogenesis of nutritional oedema.
A strong attack on that theory has come from
GOLDEN(1982a), who made a retrospective study of
the response of malnourished children to treatment
with different diets and showed that the rate of loss of
oedema was positively correlated with the energy
intake and had no relation to the protein intake. The
basis of these calculations has been questioned by
FIOROTTO& NICHOLS(1982). I have suggestedabove
that it may be misleading to suppose that the factors
which make oedemadisappear are simply the inverse
of those which make it accumulate. One could also
argue that high energy intakes were effective because
they allowed protein to be utilized with maximum
efficiency. Finally, these responsesto treatment have
to be reconciled with the results of an earlier study in
which it was shown that total body water, measured
with labelled water, increased dramatically when
children were transferred from a maintenance to a
high energy intake (PATRICK et al., 1978). Perhaps
some of this extra water may be intracellular, bound
to glycogen. It may be recalled that nearly a century
ago German paediatricians stressed the “water-
binding capacity of carbohydrates”.
Epidemiological evidence
The classical theory of kwashiorkor as a syndrome
of protein deficiency fell into disrepute when dietary
surveys in many countries showed that virtually all
children were getting more than their protein require-
ment, as estimated by FAOWHO (1973) (WATER-
LOW & PAYNE, 1975) but not enough energy. Thus
the pendulum swung right away from the earlier and
undoubtedly exaggerated emphasis on protein de-
ficiency and in 1980 LANDMAN & IACKSONwere able
to write: “The interpretation of-the data we have
reviewed appears to be that energy was generally a
limiting nutrient before protein”.
WATERLOW 439
This interpretation rests on the assumption that the
estimates of the requirements of young children
produced in 1973were correct. Current evidence now
suggeststhat for energy they were too high (WHITE-
HEAD et al.. 1981). In the case of nrotein. the safe
levels were’ prescribed for an ideal situation of
complete health, and as the Protein Advisory Group
(1973) emnhasized. did not allow for the less favour-
able conditions of ‘developing countries. Although I
was a member of the Committee which produced the
1973 report, I also now think that the protein
requirements of children may have been set too low
for children in developing countries. The estimatesdo
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not allow for irregularity of growth nor for catch-up
after infections, both of which will increase the
relative and absolute need for orotein (FAOKVHOI
UNU, 1984). It is also possible ihat the requirements
for synthesis of specific proteins such as albumin may
be greater than the average requirements for growth
in body protein mass.Early observations of Whipple’s
group on dogs, that after depletion by plasma-
phoresis, animal proteins were more effective in
restoring plasma albumin than vegetable proteins,
have never been entirely explained.
There is unfortunately no good epidemiological
evidence on the relative prevalence of kwashiorkor
and marasmus in different countries. Observations
basedon hospital statistics are inevitably biassed, but
may give some indications. The literature, such as it
is, suggeststhat kwashiorkor is relatively frequent in
countries where the staple is low in protein, e.g.,
plantains, starchy roots (Uganda, parts of Zaire), or
rice (southern India), or when the protein is of poor
quality, as in maize (Mexico, Central America, parts
of Brazil, South Africa). Marasmus predominates
where the diet is relatively high in protein, based on
wheat or millet and milk (Middle East, Sahel), but
inadequate in quantity. There is an urgent need for
properly designed surveys on this subject.
A study frequently quoted as evidence against the
classical theory was reported by GOPALAN(1968),
who made a prospective survey of a group of Indian
children on a poor diet. Somedeveloped kwashiorkor,
some marasmus, but there was no quantitative or
qualitative difference in their preceding diet. It was
therefore suggested that the difference lay in the
host’s response and that kwashiorkor represented a
failure to adapt. The concept of dysadaptation is not
narticularlv heloful, becauseit describes but does not
explain. Howe;er, the general idea of a difference in
host response is important and not inconsistent with
the classical theorv. Individual children differ in their
requirements for protein and for energy, but there is
no evidence that these requirements are linked. A
child with a high protein requirement does not
necessarily have a high energy requirement, and vice
versa. If that is so, we can conceive a situation where,
on a diet marginally inadequate in both energy and
protein, the limiting factor for some children is
protein and they will develop kwashiorkor; for others
it is energy and they will develop marasmus (WATER-
LOW, 1974).
No doubt all the arguments I have produced against
the objections to the classical theory may be regarded
as special pleading. That may be so. The purpose of
440 SYMPOSIUM-KWASHIORKOR:
this paper is to emphasize that although the evidence
in support of the classical theory may be incomplete
and inconclusive, we cannot ignore the possibility that
oedematous malnutrition is a sign of an inadequate
protein intake? becauseif it is true it has important
practical apphcations.
In the last decade attention has moved away from
severemalnutrition in hospitals to concentrate, quite
rightly, on the definition and prevention of the more
moderate and more widespread malnutrition that
exists in the community. Perhaps the movement has
gone a little too far; perhaps the severe casesgive us
clues which we should not ignore; perhaps it is not in
the best interests of Third World children to regard
$G&&investigations of pathophysiology as purely
To test the hypothesis discussed in this paper
researchalong two lines is needed: better epidemiolo-
gical studies of the prevalence of kwashiorkor in
relation to diet and other background factors; and
more work on the physiology and pathology of
oedema ifi malnutrition. It is sad that, compared
with a decade ago, there are now very few places in
the world where research in depth on the effects of
severe malnutrition is being actively pursued. The
fact that a large proportion of the papers quoted here
were published more than 10 years ago illustrates the
extent of the decline.
References
Alleyne, G. A. 0. (1966). Cardiac function in severely
malnourished children. Clinical Science, 30, 553-562.
Alleyne, G. A. 0. (1967). The effect of severeprotein calorie
malnutrition on the renal function of Jamaican children.
Pediatrics, 39, 400-411.
Alleyne, G. A. 0. (1970). Some features of infantile
malnutrition in Jamaica. West Indian Medical Journal,
19, 32-36.
Alleyne, G. A. O., Halliday, D. & Waterlow, J. C. (1969).
Chemical composition of organs of children who died of
malnutrition. British Journal of Nutrition, 23, 783-790.
Benhold, H. & Kallee, E. (1959). Comparative studies on
the half-life of ‘311-labelledalbumins and non-radioactive
human serum albumin in a case of analbuminaemia.
Journal of Clinical Investigation, 38, 863-872.
Bose, J. I’., De, U. N. & Mukherjee, P. (1946). A
preliminary study of the biochemical changes in starva-
tion cases. Indian Journal of Medical Research, 34,
143-150.
Brock, J. F. & Autret, M. (1952). Kwashiorkor in Africa.
WHO Monograph Series No. 8. Geneva: WHO.
Brock, J. F., Hansen, J. D. L., Howe, E. E., Pretorius, I’.
J., Davel, J. G. A. & Hendrickse, R. G. (1955).
Kwashiorkor and protein malnutrition: a dietary thera-
peutic trial. Lance& ii, 355-360.
Brown, J. G. & Millward, D. J. (1983). Dose response of
protein turnover in rat skeletal muscle to tri-
iodothvronine treatment. Biochimica et Biophysics Acta,
757, i82-190.
Dossetor. I. F. B. & Whittle, H. C. (1975). Protein losing
enter&athy and malabsorption in acute measles enteri-
tis. British Medical Journal, ii, 592-593.
FAOiWHO (1973). Energy and protein requirements.
WHO Technical Report SeriesNo. 522. Geneva: WHO.
FAO/WHOIUNU (1984). Energy and protein requirements.
Report of an Expert Consultation. (In press).
Fiorotto, M. L. & Nichols, B. L. (1982). Oedema of
malnutrition. Lancet, ii, 871.
Garrow, J. S. (1965). Total body potassium in kwashiorkor
and marasmus. Lancet, ii, 455-458.
I’ATHOGENESIS OF OEDEMA
Golden, M. H. N. (1982a). Protein deficiency, energy
deficiency and the oedema of malnutrition. Lance& i,
1261-1265.
Golden, M. H. N. (1982b). Transport proteins as indices of
protein status. AmericanJournal of Clinical Nutrition, 35,
1159-1165.
Golden, M. H. N. & Golden, B. E. (1981). Trace elements:
potential importance in human nutrition with particular
reference to zinc and vanadium. British Medical Bulletin,
37, 31-36.
Golden, M. H. N., Golden, B. E. & Jackson, A. A. (1980).
Albumin and nutritional oedema. Lance& i, 114-116.
Gopalan, C. (1968). Kwashiorkor and marasmus: evolution
and distinguishing features. In: Calorie DeJicienciesand
Downloaded from https://academic.oup.com/trstmh/article/78/4/436/1893691 by guest on 25 January 2024
Protein Deficiencies, McCance, R. A. & Widdowson, E.
M. (Editors). London: Churchill, pp. 49-58.
Gopalan, C., Venkatachalam, P. S., SomeswaraRoa, K. &
Menon, P. S. (1952). Studies on nutritional oedema.
Indian Journal of Medical Sciences, 6, 277-295.
Hansen, J. D. L. (1956). Electrolyte and nitrogen metabol-
ism in kwashiorkor. South African Journal of Laboratory
Clinical Medicine, 2, 206-231.
James, W. P. T. & Hay, A. M. (1968). Albumin metabol-
ism: effect of the nutritional state and the dietary protein
intake. Journal of Clinical Investigation, 47, 1958-1972.
Klahr, S. & Alleyne, G. A. 0. (1973). Effects of chronic
protein-calorie malnutrition on the kidney. Kidney Inter-
national, 3, 129-141.
Landman, J. & Jackson?A. A. (1980). The role of protein
deficiency in the aeuology of kwashiorkor. West Indian
Medical Journal, 29, 229-238.
Lunn, P. G. & Austin, S. (1983). Excess energy intake
promotes the development of hypoalbuminaemia in rats
fed on low protein diets. BritishJournal of Nutrition, 49,
9-16.
Lunn, P. G. & Baker, B. A. (1984). Effects of energy
restriction on babies given low-protein diets. Proceedings
of the Nutrition Society, 43, (In press).
Montgomery, R. D. (1963). The relation of oedemato serum
proteins and pseudocholinesterase levels in the mal-
nourished infants. Archives of Diseases in Childhood, 38,
343-348.
Munro, H. N. (1951). Carbohydrate and fat as factors in
protein utilization and metabolism. Physiological Re-
views, 31, 449-488.
Patrick, J. (1979). Oedema in protein energy malnutrition:
the role of the sodium pump. Proceedings of the Nutrition
Sociezy, 38, 61-68.
Patrick, J., Reeds, P. J., Jackson, A. A., Seakins, A. &
Picou, D. I. M. (1978).Total body water in malnutrition:
the possible role of energy intake. British Journal of
Nutrition, 39, 417-424.
Protein Advisorv Grouo of the United Nations Svstem
(1973). The Protein -Problem. PAG Statement No. 20.
New York: United Nations.
Quartey-Papafio, P., Garlick, P. J. & Pain, V. M. (1980).
Effect of dietarv urotein on liver protein synthesis.
Biochemical Socbty- Transactions, 8, j57. -
Trowel& H. C. (1941). Infantile pellagra. Transactionsof the
Royal SocieFy of Tropical Medicine and Hygiene, 33,
389-404.
Viart, P. (1977a). Haemodynamic changes in severe PEM.
American 3ournal of Clinical Nutrition, 30, 334-348.
Viart, P. (1977b). Blood volume changesdurkg, treatment of
f5Ey. Amencan Journal of Chmcal Numtlon, 30, 349-
Waterlow, J. C. (1948). Fatzy liver disease in infants in the
British West Indies. Medical Research Council Special
Report Series No. 263. London: HMSO.
Waterlow, J. C. (1959). Effect of protein depletion on the
distribution of protein synthesis. Nature, 184, 1875-
1877.
Waterlow, J. C. (1961). Oxidative phosphorylation in the
livers of normal and malnourished human infants.
Proceedingsof the Royal Society, Series B, 155, 96-l 14.
 J. C.
Waterlow, J. C. (1974). Evolution of kwashiorkor and
marasmus. Lancet, ii, 712.
Waterlow, J. C. (1975). Amount and rate of disappearanceof
liver fat in malnourished infants in Jamaica. American
Journal of Clinical Nutrition, 28, 1330-1336.
Waterlow, J. C. & Alleyne, G. A. 0. (1971). Protein
malnutrition in children: advances in knowledge in the
last 10 years. Advances in Protein Chemistty, 25, 117-235.
Waterlow, J. C. & Bunje, H. W. (1966). Observations on
mountain sickness in the Colombian Andes. Lancet, ii,
655661.
Waterlow, J. C. & Payne, I’. R. (1975). The protein gap.
Nature, 258, 113-117.
Waterlow. 1. C. & Weisz, T. (1956). The fat, motein and
nucleic acid content of the l&er in malnou%hed human
infants. Journal of Clinical Investigation, 35, 346-354.
Waterlow, J. C., Cravioto, J. & Stephen, J. M. L. (1960).
Protein malnutrition in man. Advances in Protein Chemis-
try, 15, 131-238.
WATERLOW 441
Wellcome Trust Working Party (1970). Classification of
infantile malnutrition. Lancet, ii, 302-303.
Whitehead, R. G., Paul, A. A. & Cole, T. J. (1981). A
critical analysis of measured food energy intakes during
infancy and early childhood in comparison with current
international recommendations.3ournal of Human Nutri-
tion, 35, 339-348.
Whitehead, R. G., Coward, W. A., Lunn, P. G. &
Rutishauser, I. (1977). A comparison of the pathogenesis
of protein-energy malnutrition in Uganda and the
Gambia. Transactions of the Royal Society of Tropical
Medicine and Hygiene, 71, 189-195.
Widdowson, E. M. (1968). The place of experimental
animals in the study of human malnutrition. In: Caloriz
Downloaded from https://academic.oup.com/trstmh/article/78/4/436/1893691 by guest on 25 January 2024
Deficiencies and Protein Deficiencies. McCance, R. A. &
Widdowson,
*-L _^, E. M. (Editors). London: Churchill, pp.
W&%~~:. D. (1933). Nutritional disease of childhood
associatedwith maize diet. Archives of Disease in Child-
hood, 8, 423-433.