Protein-energy malnutrition may result from a number of causes. These are shown in Table 2 Intake or assimilation may be impaired or, alternatively, losses may be increased, as occurs with excessive enteric protein loss in protein-losing enteropathies. In some disorders, multiple causes may be present. Moreover, requirements may be significantly increased in some patients as a result of growth, pregnancy, tissue injury or a superimposed disease process. In some patients with chronic debilitating diseases, multiple factors may be responsible.

Attempts have been made to classify malnutrition into a predominantly protein-depleted (i.e., kwashiorkor) or calorie- (energy-) starved (i.e., marasmus) state. In kwashiorkor, the subject ingests a moderate number of calories, usually as complex carbohydrate (e.g., rice), but very little protein. The carbohydrate is absorbed as glucose, causing rises in plasma glucose and insulin, and leading to decreased lipolysis and proteolysis. The liver is therefore supplied with inadequate amino acids, with little oral intake and little peripheral mobilization from skeletal muscle stores. Transport of triglyceride made from ingested glucose is impaired since there is inadequate production of apoprotein, which is needed for the formation of VLDL. The liver becomes fatty and enlarged. Furthermore, other proteins, including albumin, are inadequately produced by the liver in kwashiorkor, and serum albumin falls, with resulting peripheral edema. With marasmus the subject takes inadequate amounts of protein and calories. The low caloric intake means that only small amounts of carbohydrate are taken; plasma glucose and insulin are low. Hence, lipolysis and proteolysis occur, with adequate delivery of amino acids from muscle to the liver for protein production. Fatty liver does not occur, and serum albumin levels tend to be normal, with no peripheral edema. Often patients fall between these two extremes of nutritional states, but there are examples of kwashiorkor and marasmus in Western clinical practice. Anorexia nervosa is a classic example of marasmus. Marked muscle wasting and loss of subcutaneous tissue (adipose tissue) occur with normal-sized nonfatty livers and no peripheral edema. In contrast, the intensive care unit patient who has received intravenous dextrose (glucose) without amino acids for a prolonged period will often show a fatty liver and marked hypoalbuminemia and edema.

Clinical features of protein-energy malnutrition vary depending on the severity and duration of nutrient deficiency, age at onset and the presence or absence of other contributing or conditioning factors. With minimal deficiency, abnormalities may be subtle - particularly in adults, in whom there are no growth requirements. In these patients muscle wasting and loss of subcutaneous fat may be present. Weakness and minimal changes in psychomotor function may develop. Nontender parotid enlargement may occur, sometimes bilaterally. Patchy brown pigmentation, particularly over the malar eminences of the face, may occur. A lackluster appearance with thinning and increased shedding of hair from the sides of the head, particularly on combing or brushing, may develop. Bradycardia may occur. Variable degrees of hepatomegaly may result, sometimes with steatosis. In patients with protein-energy malnutrition following jejunoileal bypass a wide spectrum of histopathologic change has been observed, similar to findings frequently associated with alcoholic liver disease. Other changes in the liver that may occur in nutritional disorders are listed in Table 3.

In adults with severe protein-energy malnutrition and in growing children, clinical features may be even more significant. Muscle wasting, subcutaneous fat loss, dependent edema and weight loss may be marked. Severe mental apathy and reduced physical activity may occur. Abnormalities in the hair, particularly of children, may be striking. Severe dyspigmentation may develop, especially distally; rarely, alternating strands of light and dark hair are observed. Hair may be removed without pain. Nails may become brittle, with horizontal grooves. An asymmetrical confluent pattern of skin hyperpigmentation may be seen, particularly over perineal and exposed areas, such as the face. Extensive desquamation may occur, leaving depigmented areas of superficial ulcers, particularly on the buttocks and backs of the thighs. Gastrointestinal symptoms are common but variable. These include marked constipation, diarrhea, anorexia or hyperphagia, nausea, vomiting and dehydration. Laboratory features are also variable. Serum proteins may be substantially reduced, including serum albumin and some higher-molecular-weight transfer proteins, such as transferrin, ceruloplasmin, lipoproteins, thyroxin and cortisol binding proteins. Serum amino acid analysis may show a decrease in essential amino acids (i.e., leucine, isoleucine, valine, methionine), and either normal or depressed levels of nonessentials (i.e., glycine, serine, glutamine). The urinary excretion of urea, creatinine and hydroxyproline may decrease. Severe electrolyte abnormalities develop, although serum levels may be normal.

Clinical vitamin deficiencies are listed in Table 4. Except for cheilosis and glossitis, which are seen with multiple vitamin B deficiencies, physical findings of single or isolated vitamin deficiencies are seldom observed in protein-calorie malnourished patients in developed countries. Trace elements are elements that are required in small quantities (mg amounts or less) for normal growth and/or function. Essential trace elements for humans include iron, iodine, zinc, chromium, copper, selenium and cobalt, and possibly molybdenum, manganese and vanadium. Except for iron deficiency due to blood loss and/or poor intake, deficiency states of trace elements are rare in subjects with some oral intake, since only minute amounts are required.