Plasma proteins are synthesized predominantly in the liver; immunoglobulins are synthesized by mononuclear cells of lymph nodes, spleen and bone marrow. The 2 general causes of alterations of serum total protein are a change in the volume of plasma water and a change in the concentration of 1 or more of the specific proteins in the plasma. Of the individual serum proteins, albumin is present in such high concentrations that low levels of this protein alone may cause hypoproteinemia.

Hemoconcentration (decrease in the volume of plasma water) results in relative hyperproteinemia; hemodilution results in relative hypoproteinemia. In both situations, concentrations of all the individual plasma proteins are affected to the same degree.

Hyperproteinemia may be seen in dehydration due to inadequate water intake or to excessive water loss (eg, severe vomiting, diarrhea, Addison disease, and diabetic acidosis) or as a result of increased production of proteins. Increased polyclonal protein production is seen in reactive, inflammatory processes; increased monoclonal protein production is seen in some hematopoietic neoplasms (eg, multiple myeloma, Waldenstrom macroglobulinemia, monoclonal gammopathy of undetermined significance).

ild hyperproteinemia may be caused by an increase in the concentration of specific proteins normally present in relatively low concentration, eg, increases in acute phase reactants and polyclonalimmunoglobulins produced in inflammatory states, late-stage liver disease, and infections. Moderate-to-marked hyperproteinemia may also be due to multiple myeloma and other malignant paraproteinemias, although normal total protein levels do not rule out these disorders. A serum protein electrophoresis should be performed to evaluate the cause of the elevated serum total protein.

Hypoproteinemia may be due to decreased production (eg, hypogammaglobulinemia) or increased protein loss (eg, nephrotic syndrome, protein-losing enteropathy). A serum protein electrophoresis should be performed to evaluate the cause of the decreased serum total protein. If a nephrotic pattern is identified, urine protein electrophoresis should also be performed.