Mechanism of elevation of serum alkaline phosphatase activity in biliary obstruction: an experimental study

First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 3-1, Hongo 6-chome, Bunkyoku, Tokyo 113, Japan
Clinica Chimica Acta (Impact Factor: 2.82). 10/1980; 107(1-2):85-96. DOI: 10.1016/0009-8981(80)90417-9


Bile duct ligation in rats increased alkaline phosphatase activity in serum and liver. In the serum, the activity reached a peak 24 h after bile duct ligation, earlier than in the liver. This finding indicates that the elevation of serum alkaline phosphatase activity is not due to simple overspill of this enzyme from the liver into the circulation. An electrophoretic study, employing polyacrylamide gel with Triton X-100, and a gel filtration study disclosed that 24 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphatase in addition to the hepatic and intestinal isoenzymes. The high molecular weight form was also found in bile, indicating that regurgitation of bile contributed to the increase in alkaline phosphatase activity in the serum. The absence of the high molecular weight alkaline phosphatase in the sera of rats with intrahepatic cholestasis induced by α-naphthylisothiocyanate suggests that, in this type of cholestasis, regurgitation of bile alkaline phosphatase does not play an important role in the elevation of serum alkaline phosphatase activity. These findings indicate that the high molecular weight alkaline phosphatase in serum is a useful diagnostic marker of biliary obstruction.

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    • "Nevertheless, several features of much of the cholephilic enzyme activity found in the blood are not entirely answered by either of these pathways. These features include the fact that much of the cholephilic enzyme activity found in the blood is relatively low molecular weight and hydrophilic, while almost all of the activity found in bile is hydrophobic (Inoue et al., 1980; Toda et al., 1980; Tsuji et al., 1980; Selvaraj et al., 1984), and the hydrophobic forms found in blood frequently present within large particles that have biochemical characteristics consistent with their originating from basolateral, not apical, membranes (De Broe et al., 1985; Kihn et al., 1991). These particles are not found in bile and are believed to be membrane fragments shed from the basolateral surfaces of liver cells (Deng et al., 1996b; Van Hoof et al., 1997). "
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