Clinical and Interpretive

Alkaline phosphatase (ALP) is present in a number of tissues including liver, bone, intestine, and
placenta. Serum ALP is of interest in the diagnosis of 2 main groups of conditions-hepatobiliary disease and bone disease associated with increased osteoblastic activity. A rise in ALP activity occurs with all forms of cholestasis, particularly with obstructive jaundice. The response of the liver to any form of biliary tree obstruction is to synthesize more ALP. The main site of new enzyme synthesis is the hepatocytes adjacent to the biliary canaliculi.

ALP also is elevated in disorders of the skeletal system that involve osteoblast hyperactivity and bone remodeling, such as Paget’s disease, hyperparathyroidism, rickets and osteomalacia, fractures, and malignant tumors. A considerable rise in alkaline phosphatase activity caused by increased osteoblast activity following accelerated bone growth is sometimes seen in children and juveniles.

The elevation in alkaline phosphatase (ALP) tends to be more marked (more than 3 fold) in extrahepatic biliary obstruction (eg, by stone or 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 upper limit of normal, returning to normal on surgical removal of the obstruction.

The ALP response to cholestatic liver disease is similar to the response of gamma-glutamyltransferase (GGT), but more blunted. If both GGT and ALP are elevated, a liver source of the ALP is likely. Among bone diseases, the highest level of ALP activity is encountered in Paget disease as a result of the action of the osteoblastic cells as they try to rebuild bone that is being resorbed by the uncontrolled activity of osteoclasts. Values from 10 to 25 times the upper limit of the reference interval are not unusual. Only moderate rises are observed in osteomalacia, while levels are generally normal in osteoporosis. In rickets, levels 2 to 4 times normal may be observed. Primary and secondary hyperparathyroidism are associated with slight to moderate elevations of ALP; the existence and degree of elevation reflects the presence and extent of skeletal involvement. Very high enzyme levels are present in patients with osteogenic bone cancer.

A considerable rise in ALP is seen in children following accelerated bone growth. In addition, an increase of 2 to 3 times normal may be observed in women in the third trimester of pregnancy, although the interval is very wide and levels may not exceed the upper limit of the reference interval in some cases. The additional enzyme is of placental origin.