Chapter 4 Page 1
CHAPTER 4. PROTEIN ENERGY MALNUTRITION (PEM)
Protein calorie malnutrition is a term used to denote a deficiency in calories and protein which leads, in
children, to a deficiency in growth. This growth deficiency expresses itself in both wasting and
stunting. When the deficiency becomes more important certain body functions and metabolic pathways
will change or deteriorate and a clinical picture will develop either as marasmus, kwashiorkor or as a
mixture of both: marasmic kwashiorkor.
1. Epidemiology
1.1. The magnitude of the problem.
An estimated 190 million children < 5 suffer from PEM. Of those 4% are severely malnourished, 20-30
% moderately malnourished. About 60 % of the children < 5 are stunted.
1.2. Distribution.
At world level.: N «» S
At national level:
in between countries
Cities «» rural areas; causality is different
Differences in regions, over all country not energy deficient but poorer and
richer zones, Thailand NE and central; Nepal: terai Vs mountains.
1.3. Variations
In time: - In relation to harvesting; prevalence of malnutrition is usually higher before harvest.
- In relation to climatic season: in rainy season more waterborne infections  more
diarrhoea  malnutrition. Take into account in surveys, evaluations, etc.
- Year by year: crop failures, drought
- Linked to international market: cassava, coffee, middle man stimulation of crops: chilli.
- Exceptional environment: Sahel, Ethiopia, wars (Somalia), etc.
Long term variations
A research over the last years, performed by FAO and the United Nations concluded that, if the
population growth stays the same as it is now,
50 percent of the African countries will have severe problem producing enough food for their population
if agricultural practices do not change.
If attitudes towards food production changes, with alternative crops, more intensive production and
improved crops, only 20 percent of the countries will continue to have problems.
The Sahel countries, Mauritania and Ethiopia will continue to be high risk countries, even with
intensified food production.
The causality changes also over time. In many new industrialised countries the causes are more social
in combination with a changing social pattern. This is certainly related to the urbanisation and the
micro-economic changes where people are more directly income dependent.
Related to people
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Age:
Mainly children below five are at risk, where the highest risk period is between 6 months and
three years. (see recommendations for anthropometry) if breastfeeding is practised.
Breastfeeding protects the child the first six months. The weaning period is the first period of
high risk due to contact with contaminants and a diet, possibly not adequate for the child.
Around one the child is walking and crawling away from the direct environment of the mother
and comes into contact with soil  parasites, and other children  all kinds of infections
(remember that children are immunological virgins protected, only partially and only during the
first six months by the immunoglobulins transmitted to them during intra-uterine life from the
mother). The relative energy need is also substantially higher in the first years of life (130 ®
100 Kcal/Kg/day). Adults 40-50 Kcal/Kg/day. It is for this reason that the composition of the
food for children has to be less rich in proteins.
Many children are "used" for child labour at a very young age. They have to work many hours,
are poorly paid and are usually not well fed. Attraction of the big city, poverty of the family,
etc.
Sex:
Females >Males. Relative importance of the male in some societies, even leading to infanticide.
The higher workload of women combined with sexual maturation, pregnancy and lactation.
Social environment: Ethnic groups: Indians in Lat Am, Lao in Thailand, Mountain people, etc.
Castes: untouchable.
Landless people,
Workers
4.2. Causes
The possible causes are best explained by looking at the life cycle of a child from conception to the age
of three.
Different classifications exist such as the UNICEF on with immediate, underlying and basic causes, but
they are too restrictive in their subdivisions. The best way is to represent them in a causal model. At this
stage I would like to propose two broad categories: direct causes which disturb the equilibrium and the
underlying causes.
Direct causes:
-
Underlying causes
insufficient energy intake (proteins ???)
infections (see fig 4.3 from Mata).
breastfeeding/weaning
intra-uterine life as expressed in birthweight
-
safe water, water availability
health services access
environment
schooling, job opportunities
........
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4.3. Changes in body composition in PEM
Brain weight
The brain weight in children with PEM is very well preserved. With decreasing body weight the ratio of
brain weight to body weight increases considerably from 9% for a normal child of one year to 20% for
the same child severely malnourished.
Muscle mass
In severe malnutrition muscle mass bares the lion's share of tissue loss. In children with PEM the
muscle mass can be reduced to 10 % of body weight where after recovery it is 20%.
Body water
There is a substantial increase in total body water in PEM. This will result in oedema. Pitting oedema
appears first on the feet and lower legs and then may become generalised. Ascites can be found in very
severe cases.
Lean body mass and body fat
Structural lean body mass stays the same as measured by collagen. Cellular protein and body fat are
considerable decreased.
Figure 4.1. synthesises the above discussion. Remark that water, although less than in a normal child in
absolute terms increases if one takes the total loss in weight into account.
Fig 4.1 Changes in body composition in PEM
Absolute amounts compared with normal children of the
same hights
10
8
Collagen protein
Cellular protein
Fat
Water
6
4
2
0
Normal
PEM
Electrolytes and major minerals
a)
Potassium is decreased as measured by total body potassium. Intracellular potassium concentration
is decreased. Serum potassium can be normal or lower and does not reflect the true state. When
recovery starts potassium concentration can drop dangerously if no supplementation is provided.
Hypokaliemia is not a constant of PEM.
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There is good evidence that potassium deficiency promotes retention of water and therefore may
produce oedema. It also leads to intracellular acidosis which in turn allows for an accumulation of
Ca++ which is toxic for the cell membrane, deteriorates protein metabolism. It could decrease the
contractile power of the muscle fibres and together with Hypokaliemia be responsible for the
reduction in cardiac output, a feature of severe PEM.
b)
Magnesium is frequently low in PEM. The concentration at admission is frequently normal, the
depletion being mainly intracellular. On recovery a drop in serum concentration can be seen.
Supplementation in the treatment is necessary. Mg has the same function for chlorophyll as iron for
haemoglobin.
c)
Ca++ is for 99 % stored in the bone and its concentration is very tightly regulated by three
hormones. It has not received much attention, but is seems reasonable to state that Ca++ deficiency
may be common in PEM. As long as the child is breast-fed his supply is adequate. Later his main
sources are milk, green leafy vegetables and nuts.
4. Effects of PEM on structure and functions of organs
a)
b)
c)
d)
e)
f)
g)
h)
i)
The heart: Cardiac output is reduced; Cardiac function is impaired.
Intra vascular volume is decreased.
Anaemia is a consistent finding, the cause of it is not clear. Plasma ferritin is normal or decreased.
Iron stocks are blocked. Fe concentration drops sometimes during the recovery phase. Treatment is
not necessary in the beginning. Wait until recovery is well under way. Fe in the beginning could
even be dangerous.
Liver: fatty infiltration. Prognostic significance. Probably due to a block in transport factors from
the liver. Beta-lipoproteins are decreased and increase rapidly on recovery. Liver changes
particular for Kwashiorkor.
Pancreas: reduction in enzyme production.
Variable degrees of atrophy of vili. Infections certainly explain a great degree of the variability
observed. Mucosal enzymatic activity also decreased. Bacterial overgrowth commonly found due
to decreased acidity of gastric fluid, more available material due to a certain degree of
malabsorption, decreased motility, increased transit time, etc. This in turn enhances the degree of
malabsorption.
Kidney: reduction in glomerular filtration rate, renal plasma flow, ability to concentrate urine,
ability to excrete sodium, ability to excrete acid.
Skin and hair changes are commonly found in PEM. A dermatosis develops resembling pellagra,
with a hyperpigmentation and a flaky paint rash. The hyperpigmented patches can come off
leaving an erosive exudation area. The hair becomes thin and looses pigment. The curliness of the
hair is lost. Hair is easily pulled out.
Many neurological changes have been demonstrated in the brain, but there seem to be no lasting
effect on neurological development.
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5. Clinical picture of PEM
As mentioned before, PEM will lead to a growth deficit, clinically noticeable as thinness (wasting) and a
deficit in linear growth (stunting). When energy intake is deficient the degree of malnutrition will
become more pronounced and the child will become clearly wasted. When this becomes severe, the
child will develop a situation of severe malnutrition where a number of pathophysiological changes will
occur and clinical signs become noticeable. Two very typical clinical pictures can emerge in such a
situation: marasmus and kwashiorkor. A mixed type of clinical picture with signs of both also exists:
marasmic-kwashiorkor.
5.1. Marasmus
Generally earlier than kwashiorkor
Severely wasted; most of the subcutaneous fat has gone
Sunken eye balls, depressed cheeks (old man face)
Skin hangs loosely, and in folds, over the bones that are sticking out.
Through the thin skin, the abdominal peristalsis can be observed.
Hair is sometimes thin
Child looks around alert but is generally miserable.
Hungry
Biochemical:
-
Serum proteins are normal
-
Immunoglobulins are normal or increased, reflecting infection
Cellular immunity responds normally. Mantoux test is negative probably due to skin factors.
Thymus is atrophied
-
Serum potassium can be normal or low; but there is a very considerable potassium loss.
Glyconeogenesis and glycolysis are slow, glycogen stocks virtually non existent  very easy
hypoglycaemia.
Children are in negative nitrogen balance with high levels of cortisol, low levels of insulin and
growth hormone.
-
Gastro intestinal changes are frequent, as is lactose intolerance.
-
Anaemia
5.2. Kwashiorkor
Usually above the age of one (older than marasmus)
Difficult to give a general picture, large variations possible.
Generally :
Biochemical:
Oedema
Skin and hair changes
Apathy
Liver changes
Different degrees of wasting; sometimes almost none.
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-
Potassium concentration decreased
Magnesium concentration decreased
Intracellular sodium is high
Hypoalbuminemia
Zinc, Copper and Selenium are depressed in varying degrees, not a consistent finding.
Anaemia
Immune system:
Atrophy of the thymus
Local resistance is decreased
Intracellular bactericidal activity is decreased
Complement is decreased
T-cell activity is decreased
Immunoglobulins are increased but their reaction is atypical.
Kidney, heart, liver and gastro intestinal system all have the changes mentioned above in 3.
6. Pathophysiology
Oedema in Kwashiorkor
Oedema is a pathognomonic sign for kwashiorkor, but there is no complete consensus on its causes. It is
probably multifactorial, with albumin on the first place of importance, then probably potassium, and
then the other factors.
Hypoalbuminaemia is found, and could explain through the changed oncotic pressure the formation of
oedema. But oedema disappears before there has been a normalisation of the albumin levels, it also
when the diet only contains sugars.
Depletion of potassium can lead to a sodium retention
The lowered cardiac output through the renin-angiotensin axis at the kidney, retains water.
The kidney changes all lead to a sodium and water retention.
In situations where free radical scavenging mechanism are not functioning properly, cell membranes can
be damaged, causing leakiness and so oedema.
The classical theory on the aetiology of kwashiorkor
"The chief cause is lack of protein and energy in the diet".
- Multifactorial
- Low protein in the diet because
link albumin  oedema
link low protein  low albumin
 low beta lipoproteins  fatty liver
large body of circumstantial evidence of low protein diets (largely debated)
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The following conclusion has been taken from Waterlow:
a)
Kwashiorkor develops when the diet has a low protein-energy ratio, so that protein and the vitamins and
minerals associated with it are limiting.
The P/E ratio might be adequate for some but not all children; there is a variability in requirements.
The endocrine response is in response to the P/E ratio. Low P/E ratio, insulin is high and cortisol low 
muscle take up AA and energy. The liver is largely bypassed in AA. Thus low albumin production, low
lipoproteins  Kwashiorkor. Infection further decreases the availability of AA for the liver.
In Marasmus where the over all food energy content is low, insulin levels drop and cortisol increases 
muscle is broken down, AA circulate, E is burnt.
b)
c)
d)
The free radical theory
Free radicals are defined as molecules or fragments containing a single unpaired electron, which makes
them highly reactive, frequently with toxic effects. They are represented as OH.
Free radicals are produced under normal circumstances as bactericidal elements by leukocytes or as a
side effect in oxidative phosphorylation. A number of enzymatic pathways exist to keep the production
of free radicals under control, and so see to it that no toxic reactions happen. In the red blood cells we
have gluthationperoxidase GSH and intracellular superoxide dysmutase (SOD), and catalase. GSH is
selenium dependent, mitochondrial SOD is Manganese dependent and cytosol SOD is zinc and copper
dependant. ß- carotene, vit E and C and polyunsaturated essential fatty acids also captivate free radicals.
Under severe stress situations the production of free radicals can exceed the controlling capacity and
lead to membrane damage. Chain reactions occur in those situations with polyunsaturated fatty acids on
the membrane. This changes the morphology of the membrane and its characteristics; membranes
become "leaky".
Free ferrous iron Fe2+ is potentially very toxic in creating free radicals in the reaction : Fe2+ + H2O2 =
Fe3+ + OH. + OH- . Limiting the amount of free iron protects therefore the formation of free radicals.
This underlines the importance of transferrin and ferroxidase. Transferrin levels are inversely related to
mortality in kwashiorkor.
The basis of the theory is that kwashiorkor is the expression of an imbalance in free radical production
and their disposal leading to cell damage and their leakiness, and the deterioration of metabolic
pathways in the liver, where a very high free radical production is a continuous procedure, leading to
fatty infiltration. Deficiencies of vitamins and minerals through their protective roles in free radical
scavenging fit into this theory.
Conclusion
There is no real consensus on the pathophysiology neither on whether marasmus and kwashiorkor are
two ends of a spectrum with common causes, as in the protein/energy theory, or of two entirely different
aetiologies as in the free radical theory. What is however clear, is that both theories accent a
multicausality and that they do not look for one explaining mechanism. The practical conclusion is that
severely malnourished children are high risk children with a multitude of deficiencies where great
caution has be taken in their treatment. They very easily
-
go in hypothermia (rains!)
are immuno suppressed and prone to infections which can take a generalised character
have a fluid overload
go in hypoglycaemia
Recommended reading
Chapter 4 Page 8
Beghin I, Cap M, Dujardin B. A guide to Nutrition assessment. WHO Geneva, 1988.
Waterlow, JC. Kwashiorkor revisited: the pathogenesis of oedema in kwashiorkor and its significance.
Trans. Roy.Soc.Trop.Med.Hyg.1984;78:436-441.
Golden MHN. The effects of malnutrition
Roy.Soc.Trop.Med.Hyg. 1988; 82: 3-6.
in
the
metabolism
of
children.
Golden MHN. Free radicals in the pathogenesis of kwashiorkor. Proc. Nutr.Soc. 1987; 46: 53-68.
Trans.