Albumin Albumin is a globular protein with a MW of 69,000 daltons. It is synthesized in the liver and catabolized by all metabolically active tissues. Albumin makes a large contribution to plasma colloid osmotic pressure due to its small size and abundance (35-50% of total plasma proteins by weight). It also serves as a carrier protein for many insoluble organic substances (e.g., unconjugated bilirubin). Albumin is measured by its ability to bind to bromcresol green. Bromcresol purple is another dye that is used extensively in laboratories testing human samples, however this technique produces artefactually low values in animal sera and should not be used for measuring albumin in samples from animals. There are also species pecularities in the amount of bromcresol green that binds to albumin. Falsely high albumin values are seen in samples from new world monkeys (e.g. lemurs) and rabbits, whereas low values are seen with birds. The falsely high values in rabbits can be overcome by the use of rabbit serum as a calibrator for the reaction (normally a human-based calibrator is used), however this is not routinely done by veterinary laboratories. Serum is the preferred sample for albumin measurement. The stability of albumin is about 7-10 days at room temperature, 1 month at 4 C (refrigerated) and indefinitely when frozen. Hyperalbuminemia Overproduction of albumin is not known to occur. Relative: Hyperalbuminemia is a relative change seen with dehydration. Globulins will also increase in this situation, resulting in hyperproteinemia with no change in A:G ratio. Drugs: Increases in albumin are reported in experimental studies in dogs administered corticosteroids. It is not clear if this is due to increased production of corticosteroids or dehydration secondary to free water losses from corticosteroid-induced polyuria. Laboratory error: Albumin values can be artifactually elevated in severely lipemic or hemolyzed samples, but this is analyzer- and method-dependent. Albumin is also higher in heparinized plasma than serum (due to non-specificity of bromcresol green which also binds to globulins, including fibrinogen), however newer procedures have been developed to minimize this phenomenon. Hypoalbuminemia Physiologic: Excessive fluid administration (overdilution). Decreased production 1) Decreased production can occur if there are insufficient amino acids available for hepatic production of albumin. This occurs in cases of chronic severe malnutrition due to dietary deficiency) or starvation. 2) The liver is the main site of albumin production. Chronic hepatic disease will result in hypoalbuminemia when there is a > 80% reduction in functional mass. 3) Acute phase reactions stimulate downregulation of albumin production. An acute phase reactant response is initiated in response to trauma, inflammation, neoplasia, etc and involves release of cytokines (IL-1, IL-6, TNF) from macrophages. These cytokines act on regulatory elements in hepatocyte genes, resulting in upregulation of transcription of acute phase reactant proteins (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin) and downregulation of transcription of other proteins, including albumin and transferrin (so-called "negative acute phase reactants"). Increased degradation of albumin may also play a role in the hypoalbuminemia in this reaction. In this case, the A:G is decreased due to the combination of low albumin and high globulins. Note that an acute phase reactant response is typically associated with an increase in alpha2 globulins on serum electrophoresis. Increased loss of albumin This occurs with the following: 1) Protein-losing glomerulopathy: This can result in nephrotic syndrome which is characterized by proteinuria, hypoalbuminemia, hypercholestorelemia and edema. In these conditions, albumin is lost, but globulin levels are usually maintained, resulting in a low A:G. 2) Severe hemorrhage: Both albumin and globulins are lost, resulting in a normal A:G. 3) Protein-losing enteropathies. In these conditions, albumin and globulins are usually lost concurrently, thereby maintaining a normal A:G. There are exceptions to this, e.g. Basenjis with immunoproliferative bowel disease have hyperglobulinemia. 4) Severe exudative dermatopathies. This may also associated with concommitant albumin and globulin loss (A:G tends to remain normal). Sequestration: Hypoalbuminemia can be due to sequestration of albumin within body cavities, e.g. peritonitis. Catabolism: This is not a well-characterized mechanism for low albumin. Increased albumin catabolism may occur with negative energy balance or protein malnutrition (e.g. chronic infections, neoplasia, trauma) and, potentially, as part of an acute phase response (see decreased production above).