Protein, Total - Kresser Institute Membership Site

Marker Name: Protein, Total

REFERENCE RANGES FOR TOTAL PROTEIN:

Laboratory reference range: 6–8.5 g/dL

Functional reference range: 6.9–7.4 g/dL

DESCRIPTION:

Total protein is the quantity of circulating proteins per unit volume of serum. Blood contains a variety of circulating proteins, but they can be grouped into two major classes: albumin and globulins.¹ Serum albumin makes up 60 percent of total protein, and serum globulins make up the remaining 40 percent.² Globulins include immunoglobulins (i.e., antibodies), clotting factors, enzymes, and peptide hormones, among other proteins.^1,2 Plasma proteins perform a number of critical functions in blood such as providing osmotic pressure to maintain fluid balance between the vasculature and tissues, carrying small molecules and ions, and acting as an amino acid repository for tissues.²

Albumin and most globulin proteins are synthesized by the liver.³ One notable exception is immunoglobulins, which are synthesized by mononuclear cells in the bone marrow, lymph nodes, and spleen.⁴ The liver is capable of synthesizing all amino acids except for the so-called essential amino acids, which need to be consumed in the diet. This synthesis assumes, however, that the liver has a steady supply of dietary proteins for biosynthesis reactions. In healthy individuals, the rate of protein synthesis roughly equals the rate at which protein is used, catabolized by cells, or excreted. Thus, total protein levels in the serum are relatively stable.²

Total protein measurement is a relatively inexpensive way to quantify albumin and globulins in the blood. Most modern laboratories use a simple colorimetric assay to detect protein levels. Divalent copper reacts with peptide bonds within proteins to form a purple biuret complex.^1,5 Importantly, this reaction detects all peptide linkages, so total protein cannot distinguish between albumin or individual types of globulins.¹ Since albumin comprises roughly 60 percent of total serum protein, a decrease in albumin levels may be sufficient to reduce total protein quantity without altering other serum protein levels.^2,4 Additional testing is required to determine abnormalities in specific serum proteins.

Hyperproteinemia is an abnormally high level of proteins in the blood. Almost all cases of hyperproteinemia can be explained by one of two causes: either total water in the plasma is abnormally low, resulting in hemoconcentration, or the rate of protein synthesis is abnormally high (e.g., inflammation, monoclonal gammopathy).^2,4,6 Elevated total protein levels should be considered in the context of dehydration, either due to a lack of water intake or excessive water loss. In the absence of dehydration, one must consider inflammatory processes or hematological neoplasm. Tests for polyclonal and monoclonal immunoglobulins can help distinguish the former from the latter.

An abnormally low total serum protein level is called hypoproteinemia. Hemodilution or relative abundance of water in the plasma may cause relative hypoproteinemia. Hemodilution commonly occurs subsequent to intravenous fluid administration and in advanced congestive heart failure, but may also occur in polydipsia.^7-9 Aside from hemodilution, hypoproteinemia is either due to decreased protein production or increased protein loss. Decreased protein production may be due to protein malnutrition, which deprives the liver of amino acids and peptides required for biosynthetic pathways. Liver disease may result in decreased protein synthesis even in the context of adequate protein intake. While healthy kidneys do not excrete plasma proteins, people with nephrotic syndrome may experience considerable protein wasting in the urine, which can lead to hypoproteinemia.^3,10

Total protein is virtually always measured as part of a liver panel, which also includes alanine aminotransferase (ALT), acetate aminotransferase (AST), alkaline phosphatase, bilirubin, and albumin.¹¹ Some liver function tests also include gamma-glutamyl transferase (GGT) and lactate dehydrogenase. Since hemodilution and hemoconcentration can directly affect the interpretation of total serum protein, a basic or complete metabolic panel is also ordered to obtain measures of blood urea nitrogen (BUN) and creatinine.²

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^3,4,6

Hemoconcentration
- Inadequate water intake
- Excessive diuresis
Acute inflammation
Acute infection
HIV/AIDS
Amyloidosis
Hematological neoplasm
- Multiple myeloma
- Monoclonal gammopathy
- Lymphoma
- Leukemia
- Macroglobulinemia (e.g., Waldenström macroglobulinemia)

Low in:^3,7-9,12

Hemodilution
- Excessive IV fluid administration
- Advanced congestive heart failure
- Polydipsia
- Protein malnutrition
Protein malnutrition
Advanced liver disease
Renal failure
Nephrotic syndrome
Protein-losing enteropathy
- Primary gastrointestinal mucosal diseases (e.g., ulcerative colitis)
- Increased interstitial pressure or lymphatic obstruction (e.g., sarcoidosis)
- Non-erosive upper gastrointestinal diseases (e.g., celiac sprue)
Hypogammaglobulinemia

FUNCTIONAL RANGE INDICATIONS:

High in:

Hypochlorhydria
Gout

Low in:

Protein malabsorption (due to hypochlorhydria or impaired liver function)

References: