Increases in serum alkaline phosphatase (ALP) activity commonly originate from 1 or both of 2 sources: liver and bone. Consequently, serum ALP measurements are of particular interest in the investigation of 2 groups of conditions: hepatobiliary disease and bone disease associated with increased osteoblastic activity.
Serum ALP was the first enzyme to be used for the investigation of hepatic disease. The response of the liver to any form of biliary tree obstruction induces the synthesis of ALP by hepatocytes. The newly formed coenzyme is released from the cell membrane by the action of bile salts and enters the circulation to increase the enzyme activity in serum. Increase tends to be more notable (greater than 4-fold the upper reference value [URV]) in extrahepatic obstruction (eg, by stone, by cancer of the head of the pancreas) than in intrahepatic obstruction, and is greater the more complete the obstruction. Serum enzyme activities may reach 10 to 12 times the URV and usually return to baseline on surgical removal of the obstruction. A similar increase is seen in patients with advanced primary liver cancer or widespread secondary hepatic metastases. ALP increase (greater than 2-fold the URV) can predict transplant-free survival rates of patients with primary biliary cirrhosis.
Liver diseases that principally affect parenchymal cells, such as infectious hepatitis, typically show only moderately (less than 3-fold) increased or even normal serum ALP activities. Increases may also be seen as a consequence of a reaction to drug therapy, and ALT/ALP-based criteria to discriminate the type of liver injury in drug-induced hepatic toxicity have been recommended. Intestinal ALP isoenzyme, an asialoglycoprotein normally cleared by the hepatic asialoglycoprotein receptors, is often increased in patients with liver cirrhosis.