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1420 PART XIII Hematology
CHAPTER 89
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Hyperproteinemia
The plasma protein fraction is composed mainly of albumin, hyperglobulinemia indicates the presence of dehydration or
globulins, and fibrinogen; fibrinogen is absent in serum as a a preanalytic issue. Rehydration results in resolution of rela-
result of clotting and conversion into fibrin. In some breeds, tive hyperproteinemia.
such as the Greyhound, serum protein concentrations are When exposed to an electrical field (i.e., protein electro-
below the reference ranges for most laboratories (Fayos et al., phoresis), the protein molecules migrate according to their
2005). The term hyperproteinemia is given to an absolute shape, charge, and molecular weight. Staining of the electro-
or relative increase in the serum or plasma protein con- phoresis gel after migration usually reveals six distinct
centration. Before further evaluation of a cat or dog with protein bands—albumin (closer to the anode or negative
hyperproteinemia, the clinician should make sure that the electrode), α 1 -globulin, α 2 -globulin, β 1 -globulin, β 2 -globulin,
condition is not attributable to a preanalytic issue (e.g., inter- and γ-globulin (closer to the cathode or positive electrode;
ference of other substances in protein determination), which Fig. 89.1, A). The albumin fraction is responsible for confer-
constitutes one of the most common causes of hyperprotein- ring oncotic properties on body fluids. Acute-phase reac-
emia. Lipemia and, to a lesser degree, hemolysis typically tants (APRs), also termed acute-phase proteins, migrate in
result in artifactual increases in the plasma or serum protein the α 2 and α 1 regions, whereas immunoglobulins (Igs) and
concentration. complement usually migrate in the β and γ regions. APRs in
Once true hyperproteinemia has been established, the dogs and cats include C-reactive protein (CRP), serum
clinician should determine whether it is relative or abso- amyloid A (SAA), haptoglobin (Hp), α 1 -acid glycoprotein
lute. Relative hyperproteinemia is usually accompanied by (AGP), and ceruloplasmin (Cp). Most of these APRs can be
erythrocytosis and is caused by hemoconcentration (i.e., measured in serum, plasma, or fluids in commercial diag-
dehydration). However, in an anemic cat or dog, relative nostic laboratories; in-house diagnostic kits for CRP are
hyperproteinemia may be present in association with a commercially available worldwide. Igs migrate in the follow-
normal packed cell volume (PCV); that is, the PCV is low, ing order (from anode to cathode and beginning in the α 2
but hemoconcentration results in an artifactual increase. The region): IgA, IgM, and IgG. By evaluating a protein electro-
relative proportions (ratio) of albumin and globulin provide phoretogram, the clinician can gain insight into the patho-
considerable information regarding the pathogenesis of genesis of the hyperglobulinemia.
hyperproteinemia. This information is usually contained in Increased production of globulins occurs in a variety of
reports of serum biochemistry profiles from most referral clinical situations but mainly in two groups of disorders:
diagnostic laboratories and in-house analyzers. Occasionally inflammatory-infectious and neoplastic. In inflammation
only the total serum protein and serum albumin concen- and infection, the hepatocytes elaborate a variety of globu-
trations are reported. In this case, the total globulin con- lins, collectively termed APRs, which result in increases in
centration is determined simply by subtracting the albumin the α 2 - and α 1 -globulin fractions. Because the hepatocytes
concentration from the total protein concentration. are reprogrammed to produce APRs, the albumin produc-
In dogs and cats with relative hyperproteinemia (i.e., tion is switched off, resulting in hypoalbuminemia; albumin
hemoconcentration), both the albumin and globulin con- is considered a negative APR. In conjunction with these
centrations are increased above the reference values, whereas changes, the immune system produces a variety of immune
in those with absolute hyperproteinemia, only the globu- proteins (mainly Igs), which results in increases in the α 2 , β,
lin concentration is increased, usually in association with or γ regions or a combination of these.
a mild or marked hypoalbuminemia. Hyperalbuminemia Because the immune system reacts against an organism
does not occur because the liver is already at its maximal (e.g., a bacterium) by producing antibodies against each
synthetic capacity. The finding of hyperalbuminemia and somatic antigen, several clones of lymphocyte–plasma cells
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