PROTEIN ENERGY

MALNUTRITION(PEM)
DR THOMAS B. NYAMBO
DEPARTMENT OF BIOCHEMISTRY
SCHOOL OF MEDICINE MUCHS
3 November 2004
 Protein energy malnutrition(PEM)
OBJECTIVES:
1. Describe proteinenergy malnutrition (PEM) and discuss
the concepts of marasmus and kwashiorkor.
2. Describe the pathogenesis of the syndrome of P.E.M.
3. Describe the complications associated with proteinenergy
malnutrition.
4. Identify important associated nutritional deficiencies and
the clinical syndromes associated with them.
 Definition of malnutrition
Malnutrition is defined by the World
Health Organization (WHO)as the
cellular imbalance between supply of
nutrients and energy and the bodys
demand for them to ensure normal
growth, maintenance, and specific
tissue functions.
 Causes of Inadequate Nutrient Intake (Quantity or Quality)

Aging
Mental illness
Alcoholism
Drug addiction
Avoidance of specified food groups (meat, eggs, milk, fruits
and vegetables, grains)
Poor dentition
Food idiosyncrasies
Poverty
Isolation
Anorexia (from disease process, drugs, emotional problems)
Inappropriate food choices from lack of information
 PEM
Although it can affect all age groups,
malnutrition is implicated in more than
50% of all child deaths in developing
countries, particularly in children younger
than 5 years.
Malnourished children have lowered
resistance to infection, they are more
likely to die from common childhood
disorders like diarrhoeal diseases and
respiratory tract infections
 Starvation.
Starvation is the pathologic process whereby there is
inadequate nutrient intake to meet demands.
If prolonged, starvation will result in malnutrition.
Normal humans can adapt to inadequate intake by
readjusting nutrient use. Therefore, the deleterious
effects on metabolism, healing, and organ function
may not be evident for several weeks.
The most important adaptive response is
maintaining optimum "protein and energy
partitioning," where the majority of energy comes
from fat metabolism (90% to 95%) and only 5%
from protein
 Stress response.
The host response to illness, injury, or infection is an
amplification of the flight or fight reaction.
The initial insult leads to local and generalized
inflammation and to the activation of an abnormal hormonal
response, characterized by a marked increase in
catecholamines and other stress hormones. This response
produces a hypermetabolic-catabolic state .
The degree of hypermetabolism and catabolism is
dependent on both the degree of injury and the host
response to injury.
The hormonally induced metabolic response produces a
marked increase in energy demands and change in nutrient
use, with 50% coming from fat, 30% from carbohydrates,
and 20% (or more) from protein
 Lean mass.
The body's protein is contained in lean body mass,
mostly as skeletal muscle.
Lean body mass is 50% to 60% muscle mass by
weight and the rest is bone and tendon. Protein
makes up the critical cell structure in muscle,
viscera, red cells, and connective tissue.
This includes Enzymes and antibodies
It is the loss of body protein, not fat loss, that
produces the complications of malnutrition .Protein
synthesis is essential for harnessing energy, tissue
repair, growth and defense.
 Lean mass

.
 Methods of Measuring Body Composition
Body mass index (BMI).BMI determines the body
mass according to the relationship of weight to
height and compares it to a normal range. The
formula for BMI is weight in kilograms divided by
height in square meters (kg/m2). Accuracy depends
on how close the individual is to the "normal"
population.
Skinfold thickness. This measurement estimates fat
mass based on the thickness of a skin fold at a
number of precisely defined areas on the body.
Circumference measurements. Circumference
measurements are taken for specific body areas and
then added to the skinfold measure.
Nutrient partitioning
 Stress response to Injury and infection

.
 Adaptation to starvation
0-24 hrs:Glycogenolysis
24-76 hrs Proteolysis
>76 hrs Lipolysis followed by proteolysis
 Glucose-Alanine cycle is at maximum in the 24-76 hrs.

.
PEM and infection
 Kwashiorkor and Marasmus

Two forms of PEM have been described

kwashiorkor and marasmusand they are
distinguished based on the presence(kwashiorkor)
or absence (marasmus) of oedema.
Marasmus involves inadequate intake of protein
and calories, but a child with kwashiorkor has a fair
to normal calorie intake, but inadequate protein
intake.
Furthermore,whereas marasmus affects children
and adults, kwashiorkor is commonly found in
children
A mixed form (marasmic kwashiorkor) also occurs
 Kwashiorkor
The name for the wet form (kwashiorkor),
originate from West African tribe Ga literally
meaning the disease which the first child gets
when the second child is born.
It refers to the observation that the first child
develops protein-energy malnutrition when the
second child is born and replaces the first child at
the breast of the mother.
 Wellcomes classification of
malnutrition
Underweight80% of expected ody
weight with no oedema
Kwashiorkor60-80% of expected body
weight, plus oedema
Marasmusless than 60% of expected
body weight, with no oedema
Marasmic kwashiorkorless than 60% of
expected body weight,plus oedema
 Kwashiorkor and marasmus
Marasmus Kwashiorkor

Onset is later, after the breast-feeding

1.The onset is earlier, usually in is stopped.
the first year of life
Not very Pronounced.
1.Growth failure is more
pronounced.
Edema is present.
1.There is no edema

Blood protein concentration is reduced

1.Blood protein concentration is very much.
reduced less markedly.
Red boils and patches are classic
1.Skin changes are seen less symptoms.
frequently.
Fatty liver is seen.
1.Liver is not infiltrated with fat

Recovery period is short.

1.Recovery is much longer.
 Micronutrient deficiencies
In addition to PEM, individuals may also
be affected by micronutrient deficiencies,
which have a detrimental effect on
growth and development.
The most common and clinically
significant micronutrient deficiencies in
children and childbearing women are
deficiencies of iron, zinc,folate, vitamin D,
vitamin A,and iodine.
Other trace elements are also deficient in
most cases
 How does the body respond
to malnutrition?

The bodys protein is contained in lean body

mass, mostly as skeletal muscle. Lean body mass
is made up of 50-60% muscle mass by
weight,and the rest is bone and tendon.
Protein makes up the critical cell structure in
muscle, viscera, red cells, and connective tissue.
Enzymes and antibodies that maintain immune
functions, are also proteins.
It is the loss of body protein that produces the
complications
of malnutrition, and protein synthesis is essential
for any tissue
repair.
 Depletion of body proteins
In severe malnutrition,as adipose tissue
reserves
are depleted, there is a net increase in the
rate of protein catabolism to provide
amino acids, not only as substrates for
gluconeogenesis but also as the main
metabolic fuel of the tissues.
Death results when essential tissue
proteins are catabolised beyond the point
at which the tissues can sustain this
metabolic drain
 Metabolic changes
Liver glycogen is exhausted within a few
hours18-26 hrs), and skeletal muscle protein is
then used via gluconeogenesis to maintain
adequate amounts of blood glucose in the
bloodstream.
At the same time, triglycerides in fat depots are
broken down into free fatty acids, which
provide some energy for most tissues, but not
for the nervous system, especially neurons in
the brain, who rely on pure carbohydrates for
energy.
 Metabolic Changes
When near starvation is prolonged, fatty acids
are incompletely oxidized to ketone bodies,
which can be used by the brain and other organs
for energy.
Thus, in the severe energy deficiency of
marasmus, adaptation is facilitated by high
cortisol and growth hormone levels, in order
to alert cells in the body that there is a state of
high stress.
 Metabolic changes
Further adapation is faciliated by depression of
insulin and thyroid hormone secretion,
because these hormones decreases blood sugar
and increases energy consumption respectively.
Because amino acids are mobilized from muscle
to provide the liver with substrate for protein
synthesis, plasma protein levels decrease less in
marasmus than in kwashiorkor.
 Immune response changes
In addition to the impairment of physical growth and
of cognitive and other physiological functions
Immune response changes occur early in the course
of significant malnutrition.These immune response
changes correlate with poor outcomes,and mimic the
changes
observed in people with AIDS.
Loss of delayed hypersensitivity, fewer T
lymphocytes, impaired lymphocyte response,
impaired phagocytosis secondary to decreased
complement and cytokine levels, as well as
decreased secretory immunoglobulin A (IgA) levels
are some changes that may occur.
 Hypoalbuminemia and fatty liver
In kwashiorkor, relatively increased carbohydrate intake
with decreased protein intake leads to decreased visceral
protein synthesis.
The resulting hypoalbuminemia causes dependent edema
Impaired -lipoprotein synthesis causes fatty liver.
Insulin secretion is initially stimulated but is reduced later
in the disease. Fat mobilization and amino acid release from
muscle are reduced, so that less amino acid substrate is
available to the liver.
In marasmus and kwashiorkor, the insulin response to a
glucose load is poor, possibly due to chromium deficiency
Chromium
 Protein requirement
Total body protein synthesis is about 300 g/day or 5
g/kg/day in the average adult male. The daily
obligatory loss is only about 60 to 75 g (9 to 12 g
nitrogen), because 75 to 80% is reused.
The RDA of protein for an adult is about 0.8 g/kg;
Infants and children require 1 to 2 g/kg/day: Thus,
infants require a higher proportion of essential
amino acids in their diet than do adults
 Essential amino acids
Eight amino acids are generally regarded as essential for
humans:
1. Tryptophan
2. Lysine
3. Methionine
4. Phenylalanine
5. Threonine
6. Valine
7. Leucine
8. Isoleucine.
9. Two others, histidine and arginine are essential only
in children.
 Nitrogen Balance
6g protein1g Nitrogen
To be in nitrogen balance intake=output
Normal loss 14g
+ve nitrogen balance intake> loss (growth)
-ve nitrogen balance intake<loss (PEM,burns)
 Metabolic adaptation
In protein deficiency, adaptive enzyme changes occur in the
liver, amino acid synthetases increase, and urea formation
diminishes, thus conserving nitrogen and reducing its loss in
urine.
Homeostatic mechanisms initially operate to maintain the
level of plasma albumin and other transport proteins.
The rates of albumin synthesis eventually decrease, and
plasma levels fall, leading to reduced oncotic pressure and
edema.
Growth, immune response, repair, and production of some
enzymes and hormones are impaired in severe protein
deficiency

Why is infection so important in proteinenergy malnutrition
Globulins and acute phase proteins are synthesized
diverting amino acid from synthesis of albumin and other
visceral proteins.
Increase in acute phase proteins, like alpha1antitrypsin
and other antiproteinases, may decrease muscle protein
turnover by preventing muscle breakdown.
Impaired ketone production and use of ketones as energy
source during infection may increase use of amino acid for
energy.
Infections increase protein catabolism and nitrogen loss via
epinephrine and cortisol increases
 Zinc deficiency acquired acrodermatitis enteropathica

An important associated deficiency, since it can result

in:
Severe growth retardation;
Diarrhea and malabsorption;
Acrodermatitis (bullous red scaling skin rash) and
alopecia (loss of hair);
Immunodeficiency (mainly affects T lymphocyte
system);
Sepsis
 Vitamin A deficiency
Eye:night blindness, xerosis, or xerophthalmia,
(drying of cornea and conjunctiva), Bitot's spots
(keratinized desquamated epithelial cells),
keratomalacia liquefaction and ulceration of
cornea. 250,000 children per year go blind from
Vitamin A deficiency
Skin:follicular hyperkeratosis roughened
keratinized epithelial cells heaped up around hair
follicles;
Mucosa:squamous metaplasia of gastrointestinal,
genitourinary and respiratory tract.

 Laboratory findings(Hormonal changes)

Changes in endocrine functions initially regulates

adaptive processes.
Low plasma glucose and free amino acid levels
decreases insulin and increases epinephrine.
Growth hormone increases. Corticosteroids
increase.
T3 and T4 decrease and reverse T3 increases
decrease basal metabolic rate (BMR).
 Laboratory findings
Mild or moderately severe PEM may cause a slight
depression of plasma albumin and a decrease in the urinary
excretion of urea, due to decreased protein intake, and in
hydroxyproline, reflecting impaired growth.
Increased urinary 3-methylhistidine reflects muscle
breakdown. In marasmus and kwashiorkor, the percentage
of body water and extracellular water is increased.
Electrolytes, especially potassium and magnesium, are
depleted; levels of some enzymes and circulating lipids are
low, and blood urea decreases.
Anemia, usually due to iron deficiency, and metabolic
acidosis are also present.
Diarrhea is common and is sometimes aggravated by
intestinal disaccharidase deficiency, especially of lactase.
 Laboratory findings
Kwashiorkor is characterized by low plasma levels
of albumin (10 to 25 g/L), transferrin, essential
amino acids (especially branched-chain),
-lipoprotein, and glucose.
Plasma cortisol and growth hormone levels are high,
but insulin secretion and insulin-like growth factor
are depressed.
 Laboratory findings:Anemia in PEM

 Electrolyte imbalance and acidosis

Dehydrationdifficulttoassessbyphysicalappearancelow
urineoutput,weakthreadypulse,lowbloodpressure.
Electrolytedisturbances
i. hyponatremia,withexcessintracellularsodium
ii. intracellularpotassiumdepletion,butacidosismaymask
hypokalemia
iii. hypocalcemia,butmaynotbesymptomaticbecause
hypoalbuminemiaionizedcalciumfractionincreased,also
acidosisincreasesionizedfraction;
iv. hypomagnesemia.
v. AcidBasedisorders:metabolicacidosis.