Monday 23 March 2009
Severe PEM is a disastrous disease. It is far too common in third world countries, where up to 25% of children may be affected; in these countries, it is a major factor in the high death rates among children younger than age 5 years.
PEM refers to a range of clinical syndromes characterized by an inadequate dietary intake of protein and calories to meet the body’s needs. From a functional standpoint, there are two protein compartments in the body: the somatic protein compartment, represented by the skeletal muscles; and the visceral protein compartment, represented by protein stores in the visceral organs, primarily the liver.
These two compartments are regulated differently, and as we shall see, the somatic compartment is affected more severely in marasmus (calorie deficiency), while the visceral compartment is depleted more severely in kwashiorkor (protein deficiency). Before the clinical presentations of the two polar forms of severe malnutrition (marasmus and kwashiorkor) are discussed, some comments are made on the clinical assessment of undernutrition and some of its general metabolic characteristics.
The diagnosis of PEM is obvious in its most severe forms. In mild to moderate forms, the usual approach is to compare the body weight for a given height with standard tables; other parameters are also helpful, including evaluation of fat stores, muscle mass, and serum proteins. With a loss of fat, the major storage form of energy, the thickness of skin folds (which includes skin and subcutaneous tissue) is reduced.
If the somatic protein compartment is catabolized, the resultant reduction in muscle mass is reflected by reduced circumference of the midarm. Measurement of serum proteins (albumin, transferrin, and others) provides a measure of the adequacy of the visceral protein compartment. The most common victims of PEM worldwide are children. A child whose weight falls to less than 80% of normal is considered malnourished.
Malnutrition can present in many forms. Marasmus and kwashiorkor are two ends of a specimen and considerable overlap exists. Marasmus refers to malnutrition caused primarily by severe reduction in caloric intake. It results in greater than 60% reduction in body weight adjusted for height and sex.
A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment. This seems to be an adaptational response that serves to provide the body with amino acids as a source of energy.
Interestingly, the visceral protein compartment, which is presumably more precious and critical for survival, is depleted only marginally, and hence serum albumin levels are either normal or only slightly reduced. In addition to muscle proteins, subcutaneous fat is also mobilized and used as a fuel.
With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity. Hence, concurrent infections are usually present, and they impose an additional stress on an already weakened body.
Kwashiorkor, in contast to marasmus, occurs when protein deprivation is relatively greater than the reduction in total calories. This is the most common form seen in African children who have been weaned (often too early, owing to the arrival of another child) and are subsequently fed an exclusively carbohydrate diet.
The prevalence of kwashiorkor is also high in impoverished countries of Southeast Asia. Less severe forms may occur worldwide in persons with chronic diarrheal states in which protein is not absorbed or in those with conditions in which chronic protein loss occurs (e.g., protein-losing enteropathies, the nephrotic syndrome, or after extensive burns).
Kwashiorkor is a more severe form of malnutrition than marasmus. Unlike marasmus, marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.
The weight of children with severe kwashiorkor is typically 60% to 80% of normal. However, the true loss of weight is masked by the increased fluid retention (edema). In further contrast to marasmus, there is relative sparing of subcutaneous fat and muscle mass. The modest loss of these compartments may also be masked by edema. 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, straightening, line texture, and loss of firm attachment to the scalp. Other features that differentiate kwashiorkor from marasmus include an enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite. As in marasmus, other vitamin deficiencies are likely to be present, as are defects in immunity and secondary infections. The latter add to the catabolic state, thus setting up a vicious circle.
Secondary PEM is not uncommon in chronically ill or hospitalized patients within the United States. Both marasmus-like and kwashiorkor-like syndromes (with intermediate forms) may develop.
Secondary PEM is a common complication in advanced cancer patients and in patients with AIDS. The malnutrition in these settings is sometimes called cachexia. Individuals with chronic gastrointestinal disease and elderly patients who are weak and bedridden may show physical signs of protein and energy malnutrition: (1) depletion of subcutaneous fat in the arms, chest wall, shoulders, or metacarpal regions; (2) wasting of the quadriceps femoris and deltoid muscles; and (3) ankle or sacral edema.
Bedridden or hospitalized malnourished patients have an increased risk of infection, sepsis, impaired wound healing, and death after surgery.68 The biochemical mechanisms responsible for secondary PEM in patients with cachexia are complex. In contrast to patients with anorexia nervosa, described next, patients with cachexia show loss of fat as well as muscle mass, which may occur before a decrease in appetite. Cachectic patients show increased expenditure of resting energy; in contrast, in chronic starvation, the basal metabolic rate is decreased. Cytokines produced by the host during sepsis, for example, or by tumors have been postulated to be involved in cachexia: tumor necrosis factor, interleukin-1, interleukin-6, and interferon-γ. In addition, as discussed in Chapter 7, lipid- and protein-mobilizing factors have been isolated from animals and people with cancer cachexia.
The central anatomic changes in PEM are (1) growth failure; (2) peripheral edema in kwashiorkor; and (3) loss of body fat and atrophy of muscle, more marked in marasmus.
The liver in kwashiorkor, but not in marasmus, is enlarged and fatty; superimposed cirrhosis is rare.
In kwashiorkor (rarely in marasmus), the 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 a full-strength, milk-based diet. With treatment, the mucosal changes are reversible.
The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
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 observers to show cerebral atrophy, a reduced number of neurons, and impaired myelinization of the white matter, but there is no universal agreement on the validity of these findings.
Many other changes may be present, including (1) thymic and lymphoid atrophy (more marked in kwashiorkor than in marasmus); (2) anatomic alterations induced by intercurrent infections, particularly with all manner of endemic worms and other parasites; and (3) deficiencies of other required nutrients, such as iodine and vitamins.