An interpretation of the elevation of serum alkaline phosphatase in disease.

Evidence is presented in this paper which supports the hepatogenic theory for the mechanism by which the level of serum alkaline phosphatase is raised in liver disease and provides additional evidence that serum phosphatase is not excreted in the bile. By starch gel and paper electrophoresis the normal serum alkaline phosphatase isoenzyme is shown to be rarely present in hepatic bile. The action of neuraminidase demonstrates that beta-globulin isoenzymes of liver and bone are not identical. From these results a theory which clarifies the rationale of the elevation of alkaline phosphatase in bone and liver disease is postulated. The proposed mechanism may be summarized as follows. The normal serum level is the result of two factors, the rate of release of the enzyme from the tissues, principally liver and bone, and the rate of inactivation of the enzymes in the serum and body protein pool. In osteoblastic bone disease the elevated level is due to the rate of release of the enzyme exceeding the rate of inactivation. The raised level does not indicate an inability of the liver to excrete the enzyme via the biliary tract. In liver disease the increase in serum levels is a result of increased liberation of the enzyme from the sinusoidal surface of the liver cell and of regurgitation of the biliary isoenzyme back into the serum.