Alkaline Phosphatase Pathophysiology with Emphasis on the Seldom-Discussed Role of Defective Elimination in Unexplained Elevations of Serum ALP - A Case Report and Literature Review

Abstract

While serum alkaline phosphatase activity has become a routine clinical measurement, we have found that physicians' knowledge of the pathophysiology of this enzyme is almost solely limited to the concept that an elevated serum alkaline phosphatase suggests disease of liver or bone. For example, physicians at all levels of training had no understanding of such basic physiological information as the function of alkaline phosphatase in the liver or how this enzyme is eliminated from the serum. Based on a patient with an enormously elevated alkaline phosphatase, this report provides a review of existing clinically relevant information concerning the pathophysiology of alkaline phosphatase with emphasis on the mechanisms involved in the homeostasis of this enzyme. A novel aspect of this paper is the discussion of the previously neglected concept that defective enzyme elimination could play a major role in the pathogenesis of serum alkaline phosphatase elevations.

Keywords: alkaline phosphatase catabolism; alkaline phosphatase isoforms; galactomannan; galactose receptor.

Figure 1

Chronology of serum ALP measurement during the course of the patient’s illness. Electrophoretic analysis of a serum sample obtained near the time of the peak level showed that the ALP was comprised of 51% liver, 23% bone and 26% macrohepatic isoforms, with no detectable placental or intestinal ALP isoforms. The arrow indicates the time that voriconazole treatment was initiated.