I.

Severe Protein-Energy Malnutrition (PEM)

A. General Considerations on PEM

it occurs as a result of a relative or absolute deficiency of energy and protein. It
may be primary, due to inadequate food intake, or secondary, as a result of other
illness.
Caused either by decreased intake of energy and protein, increased nutrient
losses, or increased nutrient requirements dictated by the underlying illness.
o E.g. diminished oral intake may result from poor dentition or various GI
disorders
o Loss of nutrients results from malabsorption and diarrhea as well as
from glycosuria
o Nutrient requirements are increased by fever, surgery, neoplasia, and
burns.
is a serious, often lethal disease affecting children. It is common in low-income
countries, where up to 25% of children may be affected, and where it is a major
factor in the high death rates among children younger than 5 years. Decreased
food intake can also occur due to sharp increases in prices.
In severe cases, virtually all organ systems are affected
Proteins loss correlates with weight loss: 35-40% total body weight loss is usually
fatal
In developed countries, PEM is most often secondary to other diseases. PEM occurs
in elderly and debilitated patients in nursing homes and hospitals.
o Kwashiorkor-like secondary protein-energy malnutrition occurs
primarily in association with hypermetabolic acute illnesses such as
trauma, burns, and sepsis.
o Marasmus-like secondary protein-energy malnutrition typically results
from chronic diseases such as COPD, CHF, Cancer, or AIDS.

In malnourished children, PEM presents as a range of clinical syndromes, all

characterized by a dietary intake of protein and calories inadequate to meet the
body's needs.

From a functional standpoint, there are two differentially regulated protein

compartments in the body: the somatic compartment, represented by proteins in
skeletal muscles, and the visceral compartment, represented by protein stores in
the visceral organs, primarily the liver.

Marasmus and Kwashiorkor are two ends of a spectrum, and considerable overlap
exists between those conditions.

Kwashiorkor-caused by protein deficiency; marasmus-caused by combined protein

and energy deficiency

B. Pathophysiology of PEM

5-10% weight loss - tolerated without loss of physiologic function

35-40% of body weight - death

Loss of protein from skeletal muscle and internal organs is usually proportionate to
weight loss. Protein mass is lost from the live, GI tract, kidneys, and heart
PEM progresses = Organ dysfunction develops
o Hepatic synthesis of serum proteins decreases, depressed levels of
circulating proteins
o Cardiac output and contractility proteins are decreased
o ECG may show decreased voltage and a rightward axis shift
o Autopsies of patients who die with severe undernutrition show
myofibrillar atrophy and interstitial edema of the heart
o Respiratory function is affected primarily by weakness and atrophy of
the muscles of respiration.
Vital capacity and tidal volume decreased
Mucociliary clearance is abnormal
o GI tract is affected by mucosal atrophy and loss of villi of small
intestine = malabsorption
o Intestinal disaccharidase deficiency and mild pancreatic insufficiency
o Changes in immunologic function
T-lymphocyte number and function depressed
B-cell function are more variable
Impaired complement activity, granulocyte function, and
anatomic barriers to infection are noted, and wound
healing is poor

C. Clinical Findings of PEM

Malnutrition is determined according to the body mass index (BMI, weight in

kilograms divided by height in meters squared). Bmi<16 kg/m2 is considered
malnutrition (normal= 18.5-25 kg/m2). In more practical ways, a child whose
weight falls less than 80% of normal is considered malnourished
The bone marrow in both kwashiorkor and marasmus may be hypoplastic
(Pathology. abnormal deficiency of cells or structural elements; inability to mature
properly owing to a disease or inadequate supply of nutrients.), mainly as a result
of decreased numbers of red cell precursors. The peripheral blood commonly
reveals mild to moderate anemia, which often has a multifactorial origin;
nutritional deficiencies of iron, folate, and protein, as well as suppressive effects of
infection (anemia of chronic disease) may all contribute. Depending on the
predominant factor, the red cells may be microcytic, normocytic, or macrocytic.

The brain in infants who are born to malnourished mothers and who suffer PEM
during the first 1 or 2 years of life has been reported by some to show cerebral
atrophy, a reduced number of neurons, and impaired myelinization of white matter.

Many other changes may be present, including:

o thymic and lymphoid atrophy (more marked in kwashiorkor than in
marasmus)
o anatomic alterations induced by inercurrent infections, particularly with
all manner of endemic worms and other parasites
o -deficiencies of other required nutrients such as iodine and vitamins.

Other helpful parameters are the evaluation of fat stores (thickness of skin folds),
muscle mass (reduced circumference of mid arm), and serum proteins (albumin
and transferrin-measure of adequacy of visceral protein compartment).

D. Treatment of PEM

Treatment is a slow process requiring great care.

1. Initial efforts should be directed at correcting fluid and electrolyte
abnormalities and infections. Of particular concern are depletion of K, Mg,
and Ca, and acid-base abnormalities.
2. Second phase of treatment is directed at repletion of protein, energy, and
micronutrients.
a) Treatment is started with modest quantities of protein and calories
calculated according to the patient's actual body weight. Adult patients
are given 1 g/kg of protein and 30 kcal/kg of calories.
b) Concomitant administration of vitamins and minerals is obligatory.
Either the enteral or parenteral route can be used, although the former
is preferable. Enteral fat and lactose are withheld initially.
c) Patients with less severe protein-calorie undernutrition can be given
calories and protein simultaneously with the correction of fluid and
electrolyte abnormalities. Similar quantities of protein and calories are
recommended for initial treatment.
d) Treatment requires close follow-up. In adults, both calories and protein
are advanced as tolerated, adults to 1.5g/kg/d of protein and
40kcal/kg/d of calories.
e) Treatment also includes elevation of the dependent area, and modest
sodium restriction. Diuretics are usually ineffective, may aggravate
electrolyte deficiencies, and should not be used.

E. Indications

Patients who are re-fed too rapidly may develop a number of untoward clinical
sequelae. During refeeding, circulating K, Mg, P, and Glucose move intracellularly
and can result in low serum levels of each.
The administration of water and sodium with carbohydrate refeeding can result in
CHF inpersons with depressed cardiac function.
Enteral refeeding can lead to malabsorption and diarrhea due to abnormalities in
the GI tract.
Refeeding edema is a benign condition to be differentiated from CHF. Changes in
renal sodium reabsorption and poor skin and blood vessel without other signs of
heart disease

F. Two Ends of Spectrum of PEM

1. Kwashiorkor
2. Marasmus
1. KWASHIORKOR

a. General Considerations of Kwashiorkor

The visceral compartment is depleted more severely

o Visceral protein compartment, which is presumably more precious and
critical for survival, is only marginally depleted, and hence serum
albumin levels are either normal or only slightly reduced.
Occurs when protein deprivation is relatively greater than the reduction in total
calories.
the name kwashiorkor is form the Ga language in Ghana describing a disease of a
baby due to the arrival of another child
Most common form of PEM seen in African. Prevalence is also high in impoverished
countries of SEA.
Less severe forms may occur worldwide in persons with chronic diarrheal states in
which protein is not absorbed or in those with chronic protein loss due to
conditions such as protein-losing enteropathies, the nephrotic syndrome, or after
extensive burns
May cause secondary lactase deficiency

b. Causes of Kwashiorkor

children who have been weaned (accustom (an infant or other young mammal) to
food other than its mother's milk) too early and subsequently fed, almost
exclusively, a carbohydrate diet.
Cases of kwashiorkor resulting from fad diets or replacement of milk by rice-based
beverages have been reported in the US.
Caused by a deficiency of protein in a diet that is adequate in calories.

c. Clinical Findings/ Manifestations of Kwashiorkor

Initially present as vague manifestations that include lethargy, apathy, and/or

irritability.
When advanced, there is lack of growth, lack of stamina, loss of muscle tissue,
increased susceptibility to infections, vomiting, diarrhea, anorexia, flabby
subcutaneous tissues, dermatitis with darkening of the skin in irritated areas, but in
contrast to pellagra, not in areas exposed to sunlight.
Marked protein deprivation is associated with severe loss of the visceral protein
compartment. The concentration of the plasma proteins decreases. Fluid is not
drawn back to the blood and the resultant hypoalbuminemia will increase in
interstitial fluid and gives rise to generalized or dependent edema
o seen as ascites-accumulation of fluid in the peritoneal cavity (serous
membrane lining the cavity of the abdomen and covering the
abdominal organs), causing abdominal swelling, "plump"
o and puffiness of the face, hands, and legs).
o The loss of weight is masked by the increased fluid retention

There is relative sparing of subcutaneous fat and muscle mass.

Muscle wasting is caused by the lack of essential amino acids in the diet; existing
proteins must be broken down to produce these amino acids for new protein
synthesis. These problems may be compounded by a decreased ability to produce
digestive enzymes and new intestinal epithelial cells because of a decreased
availability of amino acids for the synthesis of new proteins.
Children with kwashiorkor have characteristic skin lesions, with alternating zones
of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a
"flaky paint" appearance.
Hair changes include overall loss of color or alternating bands of pale and darker
hair. The hair is sparse and thin, and in dark-haired children, it may become
streaky red or gray.
Enlarged, fatty liver (resulting from reduced synthesis of the carrier protein
component of lipoproteins), superimposed cirrhosis is rare. The liver is not able to
synthesize new proteins as a result of the deficiency of essential amino acids.
Development of apathy, loss of appetite
Defects in immunity and secondary infection (an infection that occurs during or
after treatment of another pre-existing infection. It may result from the treatment
itself or from changes in the immune system. For example, a vaginal
yeast infection that occurs after antibiotic treatment of a bacterial infection is
a secondary infection.)
Small bowel shows a decrease in the mitotic index in the crypts of the glands,
associated with mucosal atrophy and loss of villi and microvilli. In such cases,
concurrent loss of small intestinal enzymes occurs, most often manifested as
disaccharidase deficiency. Hence, infants with kwashiorkor initially may not
respond well to full-strength, milk-based diets. With treatment, the mucosal
changes are reversible.
Eventually, there is stupor, coma, and death.

d. Other Nutritional Deficiencies that may be presented by children with

Kwashiorkor

Vitamin deficiencies are likely to be present

micronutrients

2. Marasmus

The somatic compartment is affected more severely

When weight falls to 60% of normal for sex, height, and age
Marasmic child suffers growth retardation and loss of muscle
o loss of muscle results from catabolism and depletion of the somatic
protein compartment.
o An adaptive response that provided the body with AA as a source of
energy

Subcutaneous fat is also mobilized and used as fuel. The production of leptin is
low, which may stimulate the hypothalamic-pituitary-adrenal axis to produce high
levels of cortisol that contribute to lipolysis. With such losses of muscle and
subcutaneous fat, the extremities are emaciated, the head appears too large for
the body.
Anemia and manifestations of multiple vitamin deficiencies are present, and there
is evidence of immune deficiency, particularly T-cell mediated immunity. Hence,
concurrent infections are usually present, which impose additional nutritional
demands

References:

Robbins and Cotran Pathologic basis of disease, 2010,

Current Medical Diagnosis and Treatment, 51st ed., 2012
Marks' Essentials of Medical Biochemistry, A Clinical Approach, 2nd ed.
Nelson Textbook of Pediatrics, 18th ed.