Serum markers of malnutrition

Biochemical assessment of the protein component of the trophic nutritional status includes determination of the concentration of various proteins in the patient's blood serum. The main organ for synthesizing serum protein markers is the liver, which is also the first organ affected by malnutrition syndrome. All these proteins perform transport functions.

An ideal marker for assessing short-term changes in protein status should have a small serum pool, a high rate of synthesis, a short half-life, a specific response to protein deficiency, and no response to non-nutritional factors.

Serum proteins used for nutritional assessment

Serum marker	Half-life	Reference range	Place of synthesis
Albumen	21 days	36-50 g/l	Liver
Prealbumin	2 days	150-400 mg/l	Liver
Transferrin	8 days	2-3.2 g/l	Liver
Somatomedin C	24 h	135-449 ng/ml	Mainly liver, to a lesser extent in other tissues
Fibronectin	15 h	200-400 mcg/ml	Endothelial cells, fibroblasts, macrophages and liver
Vitamin A-binding protein	12 h	30-60 mg/l	Liver

Albumin is the first biochemical marker of malnutrition, the determination of which has been used in clinical practice for a long time. The human body has a relatively large pool of albumin, more than half of which is outside the vascular bed. The concentration of albumin in the blood serum reflects changes occurring within the vascular bed. Due to a fairly long half-life (21 days), albumin is not a sensitive indicator of short-term protein deficiency in the body or a marker of the effectiveness of nutritional correction. Redistribution of albumin from the extravascular to the intravascular space also reduces its indicator capabilities. Albumin helps to identify patients with chronic protein deficiency leading to hypoalbuminemia, provided that they consume adequate non-protein calories.

Serum albumin concentrations are affected by liver and kidney disease and by the patient's hydration status. Age also affects albumin concentrations, which decrease with increasing age, probably due to a decrease in the rate of synthesis.

Transferrin is a β-globulin, which, in contrast to albumin, is almost entirely located in the intravascular bed, where it performs the function of iron transport. Transferrin has a short half-life (8 days) and a significantly smaller pool compared to albumin, which improves its capabilities as an indicator of protein status. However, the concentration of transferrin in the blood serum is affected by iron deficiency in the body, pregnancy, diseases of the gastrointestinal tract, liver, kidneys, oral contraceptives, antibiotics in high doses, neoplastic processes.

Vitamin A-binding protein has a very short half-life (12 h) and a low pool, so its concentration decreases rapidly with protein and calorie deficiency and responds quickly to dietary correction. However, serum vitamin A-binding protein concentrations are altered in liver disease, vitamin A deficiency, acute catabolic states, after surgery, and hyperthyroidism.

Prealbumin, or transthyretin, has a half-life of 2 days and a slightly higher serum pool than vitamin A-binding protein; however, it is equally sensitive to protein deficiency and nutritional modification. Patients with acute renal failure may have elevated serum prealbumin levels due to the role of the kidneys in its catabolism. Prealbumin is a negative acute phase protein (its serum concentration decreases during inflammation). Therefore, in order to differentiate inflammatory prealbumin reduction from nutritional status disorders, another acute phase protein (e.g., CRP or orosomucoid) must be measured simultaneously. If CRP is normal, low prealbumin is most likely due to protein deficiency. Conversely, if CRP is elevated, low prealbumin should not be considered a sign of malnutrition. During monitoring of ongoing nutritional correction, patients with decreasing CRP and increasing prealbumin levels can be assessed as likely to have a tendency to improve protein-energy status. Once the CRP concentration returns to normal, prealbumin becomes an objective indicator of the patient's nutritional status. Determination of prealbumin concentration is especially useful in critically ill intensive care patients at the initiation of parenteral artificial nutrition and in monitoring the response to such therapy. Serum prealbumin concentrations above 110 mg/L are considered an indicator indicating the possibility of transferring the patient from parenteral to enteral nutrition. If prealbumin concentrations during parenteral nutrition do not increase or remain below 110 mg/L, it is necessary to review the feeding method, the amount of nutrients, or to look for complications of the underlying disease.

Fibronectin is a glycoprotein found in lymph, blood, basement membranes, and on the surface of many cells that perform structural and protective functions. Determining the concentration of fibronectin in blood plasma in combination with other nutritional indicators is important because it is one of the few markers synthesized not only in the liver. With adequate enteral/parenteral nutrition, the concentration of fibronectin in blood plasma increases 1-4 days after the start of therapy.

Somatomedin C, or insulin-like growth factor (IGF) I, has a structure similar to insulin and has a pronounced anabolic effect. Somatomedin C circulates in the blood bound to carrier proteins; its half-life is several hours. Due to such a short half-life and sensitivity to nutritional status, somatomedin C is considered the most sensitive and specific marker of nutritional status. A decrease in its concentration is possible in patients with insufficient thyroid function (hypothyroidism) and with the introduction of estrogens.

Although fibronectin and somatomedin C measurements have advantages over other markers in assessing nutritional status, their use in clinical practice is currently limited due to the high cost of these tests.

To assess subclinical forms of protein deficiency and quickly monitor the effectiveness of therapy, methods for determining the ratio of certain amino acids in plasma, as well as the activity of serum cholinesterase, can also be used.

Along with the listed indicators that allow assessing the severity of protein deficiency, simple and informative indicators include determining the absolute number of lymphocytes in the blood. Their content can be used to generally characterize the state of the immune system, the severity of suppression of which correlates with the degree of protein deficiency. With insufficient protein-calorie nutrition, the number of lymphocytes in the blood often decreases to less than 2.5×10 ⁹ /l. The lymphocyte content of 0.8-1.2×10 ⁹ /l indicates moderate nutritional deficiency, and less than 0.8×10 ⁹ /l indicates severe deficiency. Obvious absolute lymphopenia in the absence of other causes of immunodeficiency allows the clinician to assume malnutrition.

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