Interpretation of Protein Patterns

Total protein must be evaluated in relation to hematocrit and hydration status. Significant dehydration increases both hematocrit and total protein, and albumin and globulins are increased equally so the albumin to globulin ratio (A:G) is not affected. This is described as panhyperproteinemia. There is little physiologic reason for the body to produce more albumin than necessary and hyperalbuminemia is often explained by dehydration. In rare cases, hyperalbuminemia may be due to drug treatment or liver neoplasia.

With acute blood loss or overzealous fluid therapy, hematocrit and total protein (both albumin and globulins) are decreased and the A:G is not affected. This is described as panhypoproteinemia. Panhypoproteinemia can also be seen with protein-losing enteropathy, loss into body cavities, and severe exudative skin disease, such as burn injury.

Acute inflammation is often associated with increased synthesis and release of positive APPs (included in the globulins calculation) and decreased synthesis of albumin. Albumin is sometimes referred to as a negative APP because inflammatory cytokines cause decreased production of albumin. This may result in a low A:G due to decreased albumin and increased globulins (as they move in opposite directions) and is described as a selective hyperproteinemia when total protein is increased. Albumin may also be decreased in the face of marked hyperglobulinemia (e.g. due to plasma cell neoplasia); possible explanations for this may relate to inflammatory cytokines, a response to increased colloid oncotic pressure caused by hyperglobulinemia, or consequences of neoplasia such as decreased production due to liver damage or increased loss via the intestines or kidneys. Protein-losing nephropathy may develop secondary to glomerular damage from immunoglobulin and/or immunoglobulin light chain deposition.

Selective hypoproteinemia can also occur. Protein-losing nephropathy causes selective albumin loss so that serum albumin concentration is low, globulins are unaffected, and the A:G is low. Hypoalbuminemia is rarely seen with low protein diets or inappetence, however, both starvation, particularly in wildlife during harsh winters, and cachexia due to neoplasia or chronic infections, may result in severe hypoalbuminemia leading to edema.

The protein pattern seen with hepatic dysfunction or failure is more variable. Typically with hepatic dysfunction one would expect to see hypoalbuminemia, normal globulins, and a low A:G. However, sometimes globulins are also low, probably because many of the α and β globulins are produced in the liver and their synthesis may be impaired along with albumin synthesis. Occasionally liver failure is associated with hyperglobulinemia, likely due to increased immunoglobulin production. The immune system may be responding to the etiologic agent of the hepatic disease, or there may be increased delivery of intestinal-derived antigens to the immune system if the function of the mononuclear phagocyte system of the liver (Kupffer cells) is impaired. Therefore, although hypoalbuminemia is expected in advanced hepatic dysfunction/failure, globulins may be normal, low, or high.

Occasionally, normal albumin with mildly decreased globulins is seen and can result in an increased A:G. This pattern may be present particularly in young animals that have a lack of antigenic stimulation, or when adult reference intervals are used to evaluate young animals. A less commonly seen protein pattern is normal albumin with markedly decreased globulins and a high A:G. This pattern can be seen with both acquired and inherited immunodeficiency states. Failure of passive transfer (FPT) of immunoglobulins is the most common example of an acquired immunodeficiency condition. This condition results from inadequate colostrum intake in neonatal animals that do not receive maternal immunoglobulins in utero (i.e. foals and calves). FPT is confirmed by radial immunodiffusion to quantitate serum IgG in the neonate. Measurement of total protein, globulins, or GGT are not appropriate means for diagnosing FPT in an individual animal but may be used to monitor colostrum management on a herd basis. Inherited combined immunodeficiency, documented most commonly in dogs and horses, consists of both a lack of immunoglobulin production and lymphopenia due to hypoplastic or aplastic lymphoid tissue. Radial immunodiffusion to quantitate IgG, IgM, and IgA may be done when a selective deficiency of one or more of these immunoglobulins is suspected.