Interpreting protein concentrations takes investigative work

Q How does one interpret serum protein concentrations in dogs and cats?

A Alterations in serum protein concentrations are commonly observed in a large number of diseases in dogs and cats. The key types of proteins present in the serum are albumin and globulins. Albumin is the smallest of these proteins, produced only by the liver, and the concentration of albumin molecules in the blood is greater than the concentration of globulin molecules.

As a result, albumin accounts for about 80 percent of the oncotic pressure of the blood. This oncotic pressure prevents water from diffusing from the blood into the tissues. Albumin is also an important carrier protein. Globulins are a heterogeneous group of proteins that are large, but variable in size. Globulins include various types of antibody molecules, other proteins active in the immune system (e.g., complement), clotting factors, many different enzymes and a variety of carrier proteins. Globulins are typically classified as alpha, beta or gamma based on their electrophoretic mobility.

Both increased and decreased total protein concentrations are commonly detected abnormalities in dogs and cats. Decreases or increases result from alterations in serum albumin and/or globulin concentrations. In plasma, increased concentration of fibrinogen, a globulin, can occasionally result in increased protein concentration. Interpretation of altered protein concentrations depends on determining which major protein constituents of the serum or plasma (i.e. albumin, globulin, and, in plasma, fibrinogen) are abnormal. Decreased or increased albumin or globulin concentrations do not always result in detectable alterations in the total protein concentration. Thus, albumin and globulin concentrations, as well as total protein concentrations, should be assessed when interpreting alterations.

Causes of decreased or increased total protein, albumin, globulin and fibrinogen concentrations are summarized here.

Investigate the cause

• Hypoalbuminemia with hypoglobulinemia: Concurrent hypoalbuminemia and hypoglobulinemia can result from overhydration (excessive fluid therapy or excessive water intake) or from proportional loss of both of these protein fractions. The latter occur in the following protein-losing disorders:
• Blood loss results in proportional loss of all blood constituents. Albumin and globulin are, therefore, lost in concentrations equal to their concentrations in the blood.
• Protein-losing enteropathy results from various intestinal lesions including inflammatory infiltrates in the lamina propria and submucosa and blockage of lymphatic drainage leading to dilation of lymphatics (lymphangiectasia). Regardless of the underlying cause, both albumin and globulin leak from the intestinal wall into the intestinal lumen and are then digested or excreted. In some types of protein-losing enteropathies, a concurrent immune response results in increased, rather than decreased, serum globulin concentrations. This occurs in Basenji and Chinese Shar-pei dogs but also can occur in other breeds of dogs.
• Severe exudative skin disease.
• Severe burns.
• Effusive disease.
• Hypoalbuminemia with normal to increased globulin concentration: Decreased albumin concentrations that are not accompanied by decreased globulin concentrations can be caused by either decreased production or increased loss of albumin. If globulin concentration is concurrently increased, decreased albumin concentration may not result in decreased total protein concentration.

Decreased production of albumin can occur in the disorders highlighted here.

• Hepatic failure: The liver is the only site of albumin production. Because of the liver's reserve capacity, most types of liver damage do not result in decreased albumin production. If more than 80 percent of the functional liver mass is lost, decreased albumin production can occur.
• Gastrointestinal parasitism can cause hypoalbuminemia. If the parasites absorb significant amounts of nutrients, including amino acids, the animal is deprived of the amino acids needed to produce albumin. If gastrointestinal parasites attach to the gastric or intestinal wall and consume the host's blood, albumin and globulin are lost.
• Intestinal malabsorption. Decreased albumin production can occur if intestinal malabsorption results in deficient absorption of amino acids.
• Exocrine pancreatic insufficiency. Inadequate digestion of dietary proteins can result from exocrine pancreatic insufficiency.

Increased loss of albumin can occur in the following protein-losing disorders:

1) Glomerular disease. Because albumin molecules are smaller than globulin molecules, they leak more readily through damaged glomerular membranes (the net negative charge of albumin molecules as compared to globulin molecules also plays a part in this selective leakage). Severe glomerular disease can result in hypoalbuminemia with a normal to increased serum globulin concentration. Urine protein concentrations and urine protein/creatinine ratios should both be increased with glomerular disease.

2) Diseases previously listed as possible causes of decreased albumin and decreased globulin. Although loss of both albumin and globulin typically occurs with these diseases, a concurrent immune response may cause increased production of globulins and result in normal to increased globulin concentrations. These diseases should also be considered when hypoalbuminemia and normal to increased globulin concentrations are detected.

• Hypoglobulinemia with normal to increased albumin concentration: Hypoglobulinemia in the absence of hypoalbuminemia is generally the result of decreased beta or gamma globulin concentration. Decreased alpha globulin concentration alone does not result in decreased total globulin concentration. Decreased beta or gamma globulin concentration in the absence of hypoalbuminemia is almost always the result of decreased immunoglobulin concentration. Such decreases can occur in the following disorders:
• Failure of passive transfer. Ingestion of colostrums and absorption of immunoglobulins from colostrums is referred to as passive transfer. Since most animals are born with minimal immunoglobulin concentrations, this process plays an important role in transferring resistance to infection during the neonatal period. Failure to ingest colostrum and/or to absorb immunoglobulins from colostrum is referred to as failure of passive transfer and is well documented in domestic animals.
• Inherited or acquired immune deficiency. Immune deficiency involving B-lymphocytes and/or plasma cells can result in low concentrations of immunoglobulins and, in some cases, low concentrations of total globulins. Immune deficiencies resulting in low globulin concentrations occur in puppies (combined immune deficiency and selective IgA deficiency).

What’s your question? Send your pediatric/geriatric related questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500 Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr. Hoskins in upcoming columns.