Various studies have shown that a significant degree of malnutrition is frequent in hospitalized persons, ranging from 25%-50% of patients (depending on whether the population screened was a general or specialty group). In one report, 97% of surgical patients had at least one abnormal result on tests for nutritional status.

Classification of protein-calorie malnutrition

Although protein or caloric deficiency exists in grades of severity, a classification of patients according to pathophysiology and laboratory abnormalities requires analysis of late-stage deprivation. At a late stage, three basic patient types have been described: kwashiorkor, marasmus, and a mixed picture.

Kwashiorkor results from protein deficiency without total calorie deficiency. This condition is produced by a diet with adequate calories that are obtained almost exclusively from carbohydrate. This may result from a nonhospital diet that is low in protein or may be seen in hospitalized patients who are maintained primarily on IV dextrose. Severe stress, major illness, or surgery results in greatly increased utilization of body protein and may rapidly lead to protein depletion if there is not adequate replacement. These patients externally seem to be of normal weight or even overweight and may have edema. Kwashiorkor involves depletion of primarily visceral (nonmuscle) protein.

Marasmus is produced by prolonged deficiency of both protein and carbohydrates. Examples are starvation due to inability to eat and anorexia nervosa. These patients lose both fat and muscle mass and appear emaciated. Marasmus involves loss of primarily somatic (fat and muscle) protein rather than visceral protein.

The mixed category combines various degrees of protein deprivation with various degrees of carbohydrate and total calorie deficiency. It may also result from end-state marasmus (when both somatic and visceral protein are consumed) or may occur in a patient with moderate marasmus who undergoes severe stress, thus accelerating visceral protein loss.

Besides classic end-state cases there are far greater numbers of patients with malnutrition of lesser severity. In general, the greater the degree of deficiency, the greater the chance of unwanted consequences. These include increased postoperative morbidity and mortality and certain defined complications such as increased tendency toward infection, poor wound healing, and extended hospitalization.

Tests useful in patients with malnutrition

Functional categories of tests (i.e., information that tests can supply) in protein-calorie malnutrition include the following:

1. Tests that screen patients for protein-calorie deficiency
2. Tests that assess degree of deficiency
3. Tests that differentiate the various types of deficiency
4. Tests used to guide therapy

Procedures or tests available

1. Anthropometric measurements: triceps skinfold thickness; midarm circumference
2. Calculation of undernourishment based on body height and weight (percent of ideal weight or percent of preillness weight)
3. Biochemical tests reflecting visceral (nonmuscle) protein status: serum albumin and serum transferrin (also, serum iron-binding capacity, retinol-binding protein, serum prealbumin)
4. Metabolic indices: creatinine-height index (somatic protein or muscle mass) and urinary nitrogen excretion (protein catabolism)
5. Tests of immune status: skin tests with various antigens, total lymphocyte count

Anthropometric measurements

These procedures are designed to estimate fat and muscle wasting, which reflects somatic protein depletion. Triceps skin fold measurement is performed with special calipers and measures fat reserves. Midarm circumference is used to estimate lean body mass. Patient measurements are compared with values in standard tables.

Weight deficiency (weight loss)

Weight deficiency may be calculated either as a percentage of preillness weight (current weight/preillness weight) or as a percentage of ideal weight (current weight/ideal weight). Ideal weight requires measurement of height and use of ideal weight tables. Percent weight loss after hospitalization is also useful. In all the various measurements, a 10% weight loss is considered suspicious for protein-calorie deficiency. If this occurred before admission, it probably developed over a relatively extended period of time (there is no standard time period, but at least 4 weeks has been suggested and seems reasonable) rather than over a short period of time, which is more likely to be a fluid problem. After hospitalization, there is no time limit if the weight loss is not due to diuretics, fluid removal, or some other obvious cause. Edema and obesity may produce error in nutritional assessment by these methods.

Tests for visceral protein status

Serum albumin. Albumin is the major force maintaining plasma oncotic pressure. It is synthesized by the liver from amino acids. Decreased serum albumin levels result from decreased production, either from defective synthesis because of liver cell damage, deficient intake of amino acids (absolute protein intake deficit); or from disease- or stress-induced catabolism of body protein, which increases the need for dietary protein without a corresponding increase in dietary protein intake (relative protein intake deficit). The serum albumin level is thus considered an indicator of visceral (nonmuscle) protein status. Other serum proteins that have been used for the same purpose include transferrin, prealbumin, and retinol-binding protein.

Serum albumin has a serum half-life of about 20 days and begins to decrease about 2 weeks after onset of protein depletion. Mild protein deficiency is said to correlate with albumin levels of 3.0-3.5 gm/100 ml (30-35 g/L); moderate deficiency, 2.1-3.0 gm/100 ml (21-30 g/L); and severe deficiency, less than 2.1 gm/100 ml (21 g/L). Other etiologies for albumin decrease besides deficient protein intake include disorders of liver synthesis (cirrhosis, severe acute liver disease), extravascular protein loss (nephrotic syndrome, acute or chronic protein-losing enteropathy, extensive burns), and hemodilution (congestive heart failure). Albumin decrease, whether within or below reference limits, is seen in many severe acute and chronic illnesses. The exact mechanism is frequently uncertain or is sometimes due to more than one cause. Overhydration and dehydration also may change apparent albumin levels.

Serum transferrin. Transferrin has a serum half-life of about 9 days and begins to decrease about 1 week after onset of protein depletion. However, chronic iron deficiency, therapy with estrogen or estrogen-containing contraceptives, and the same severe acute and chronic illnesses that decrease albumin levels tend to elevate serum transferrin levels and could mask early change due to nutritional depletion. Transferrin can be measured directly in a variety of ways, usually by immunologic (antitransferrin antibody) techniques, or can be estimated using serum total iron-binding capacity (TIBC). TIBC is easier and less expensive for most laboratories. The formula most commonly used is: transferrin = (0.8 Ч TIBC) – 43. Mild protein deficiency correlates with transferrin levels of 150-175 mg/100 ml (1.5-1.7 g/L); moderate deficiency, 100-150 mg/100 ml (1.0-1.5 g/L); and severe deficiency, less than 100 mg/100 ml (1.0 g/L).

Serum prealbumin. Prealbumin is a carrier protein for retinol-binding protein and for a small part of serum thyroxine. Its serum half-life is about 2 days. Its serum concentration decreases in many severe illnesses. It is measured by immunologic techniques, most commonly by radial immunodiffusion or immunonephelometry. Prealbumin levels begin to decrease within 48-72 hours in response to protein malnutrition. However, like albumin, it is decreased by severe liver disease or as a temporary short- or long-term result of many severe acute or chronic illnesses.

Retinol-binding protein. Retinol-binding protein is the specific binding protein for vitamin A. Its serum half-life is only about 10 hours. It begins to decrease within 48-72 hours after onset of protein malnutrition and otherwise behaves like prealbumin. However, in addition, retinol-binding protein may decrease when renal function decreases (as frequently occurs in severely ill persons).

Most investigators have accepted serum albumin as the most practical marker for visceral protein depletion. When serial measurements of visceral protein indices are necessary, transferrin may be substituted because it responds faster than albumin to change in nutrition status. Transferrin can also be used if albumin measurement is invalidated by therapeutic administration of albumin. Comparisons of serum albumin with other parameters of malnutrition have generally shown that serum albumin levels have the best single-test correlation with patient outcome.

Metabolic indices

Creatinine height index (CHI). This calculated value is thought to provide an estimate of lean body mass, based on the theory that urinary creatinine (UC) output is related to body muscle mass. Height is used to relate patient data to data of normal (“ideal”) persons. The creatinine height index (CHI) has the advantage that it relates to skeletal muscle mass (somatic protein) rather than to liver production of serum protein (visceral protein). In classic marasmus, the CHI is markedly decreased, whereas the serum albumin concentration may be either within reference range or close to it. Another advantage is that edema does not greatly affect the CHI, whereas it might affect arm circumference measurement. The major disadvantage is need for accurate 24-hour urine collection. Also, urine ketone bodies can interfere with creatinine assay. Data for ideal urine creatinine excretion are presented in Table 37-11.

Nitrogen balance estimates. Nitrogen balance (NB), as measured by urine urea nitrogen (UUN), may be helpful in assessing the quantitative and compositional adequacy of nutritional therapy. The formula most often used is:

NB = (Protein intake / 6.25) – (UUN + 4)

when nitrogen balance is in terms of net gain (+) or loss (–) in grams of nitrogen per day and both protein intake and urine urea output are in grams per day. Reference limits are +4 to –20 gm of nitrogen/day. Protein intake (in grams/day) is usually estimated but can be measured if feeding is entirely through nasogastric tube or hyperalimentation. If the patient has oral food intake, only the food actually eaten rather than food provided should be used in the calculation. The 4-gm correction factor is supposed to compensate for urine non-urea nitrogen loss additional to the urea nitrogen. If additional loss occurs from the GI tract, fistulas, and so forth, such loss must be estimated and incorporated into the correction factor. The 24-hour urine collection must be complete, because incomplete collection results in a falsely higher value.

Tests of immune status

Moderate or severe protein-calorie malnutrition of any type often results in depression of the body immune system. This is reflected in decreased immune response (especially, delayed hypersensitivity response) to various stimuli.

Total lymphocyte count. There is a rough correlation of total lymphocyte count with degree of malnutrition. The correlation is closest in kwashiorkor (visceral protein depletion). Total lymphocyte counts of 1,200-2,000/mm3 (1.2-2.0 x 109/L) are said to be associated with mild protein depletion; counts of 800-1,200/mm3 with moderate depletion, and counts of less than 800/mm3 with severe depletion. However, there is considerable overlap between immunologic impairment and nonimpairment with counts higher than 1,000/mm3. Values less than 1,000/mm3 (1.0 x 109/L) are generally considered evidence of definite significant immunologic impairment. Total lymphocyte count is easy to obtain (WBC count x percent lymphocytes in the peripheral smear WBC differential result). Most investigators have found less correlation with eventual patient outcome than with serum albumin levels. One reason is that various other conditions may cause a decrease in total lymphocytes. Best correlation of total lymphocyte count to patient well-being seems to be associated with infection and with cancer therapy. When both albumin and total lymphocyte counts are significantly decreased, there is some reinforcement of significance compared with abnormality in either test alone.

Skin tests. Skin test response to various intradermally injected delayed hypersensitivity antigens such as Candida, mumps, and streptokinase-streptodornase provides an in vivo method to evaluate immune response. Reactions are measured at 24 and 48 hours. Various studies have shown a substantial correlation between lack of skin test reactivity to multiple antigens and an increased incidence of sepsis or postoperative complications and mortality. There is some disagreement in the literature on the predictive value of skin tests versus serum albumin levels, with the majority opinion favoring albumin. The major drawbacks to skin testing are the time interval required and the necessity for good injection technique.

Current status of tests for protein-calorie malnutrition

Patient screening for protein-calorie malnutrition. Although various institutions have different protocols, the most common practice that is emerging is to determine the percent of weight loss and the serum albumin level, either one alone or in combination, and to take into consideration the type of illness or therapy involved. Total lymphocyte count also seems to be widely used as an adjunctive test. The CHI is helpful if marasmus is suspected; serum albumin levels could be misleading if albumin were the sole criterion for possible malnutrition.

Tests to assess degree of deficiency. Serum albumin level is the most widely used single test. The CHI is also widely employed if marasmus is present.

Nutritional Deficiency Syndromes and Screening Tests
Overall nutritional status
1. Percent weight loss (at least 10% nondiuretic loss)
Marasmus (somatic protein and fat deficit due to total calorie deficiency; somatic protein = skeletal muscle lean body mass)
1. Somatic protein estimation
Creatinine-height index
Midarm circumference
2. Fat
Triceps skin fold thickness
Kwashiorkor (visceral protein deficit due to protein intake deficiency; visceral protein = liver-produced protein, including plasma proteins)
1. Serum albumin (or transferrin, prealbumin, retinol-binding protein)
2. Total lymphocyte count
3. Cell-mediated immunity
Mixed kwashiorkor and marasmus (deficit in both protein intake and total calories)
1. Tests abnormal in both deficiency groups.

Anthropometric measurements, serum transferrin determination, and tests of immune function are available but seem to be ordered more in university or research centers.

Tests to differentiate categories of malnutrition. In classic kwashiorkor, anthropometric measurements and CHI values are relatively normal, whereas serum albumin levels and other tests of visceral protein status are decreased. In classic marasmus, anthropometric measurements and the CHI are decreased, whereas results of visceral protein adequacy tests may be normal. Although immune status test results are depressed in severe marasmus, over the broad spectrum of marasmus severity they are not as severely affected as in kwashiorkor. It must be emphasized that patients may have some combination of overall protein-calorie deficiency and of severe protein loss and therefore may not have clear-cut differential test patterns.

Tests to guide nutritional therapy. Serum albumin levels and total lymphocyte count are still the most commonly used parameters of therapeutic response. Because serum albumin has a relatively long half-life and changes relatively slowly in response to renourishment, and also because fluid shifts influence albumin levels, an increasing number of investigators use serum transferrin or prealbumin levels rather than albumin levels to monitor therapy. Some find that urinary nitrogen excretion data are very helpful in determining when a positive nitrogen balance has been achieved, but others do not believe that it is necessary.