Alkaline Phosphatase Isoenzymes

Alkaline phosphatase (ALP) is present in a number of tissues including liver, bone, intestine and placenta.^1,2 The activity of ALP found in serum is a composite of isoenzymes from those sites and in some circumstances, placental or Regan isoenzymes. Serum ALP is of interest in the diagnosis of two 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 is also elevated in disorders of the skeletal system that involve osteoblast hyperactivity and bone remodeling, such as Paget disease, rickets, osteomalacia, fractures and malignant tumors. Moderate elevation of ALP may be seen in other disorders such as Hodgkin disease, congestive heart failure, ulcerative colitis, regional enteritis and intra-abdominal bacterial infections.

Liver is the isoenzyme most frequently elevated when total ALP levels are elevated. Liver ALP increases in the blood early in liver disease before most other liver function tests show abnormalities. The wide group of conditions leading to increased liver ALP include acute hepatitis, cirrhosis, fatty liver, drug-induced liver disease, obstruction of biliary flow by carcinoma at the head of the pancreas, bile duct stricture, primary biliary cirrhosis and metastatic carcinoma of the liver.

Bone isoenzyme is elevated as a result of increased osteoblastic activity. This isoenzyme is normally elevated in growing children and adults above age 50. The highest total ALP values have been attributed to an increased bone isoenzyme level due to Paget disease or renal rickets. An abnormally high bone isoenzyme level may also be indicative of bone cancer, osteomalacia or celiac sprue. A decreased bone ALP in children may be attributed to cretinism or to hypophosphatasia.

Intestinal alkaline phosphatase is seen normally in the serum of subjects who have B or O blood types, especially after a fatty meal. Pathologically, the band may be present in perforation of the bowel, ulcerative disease of the intestine and faintly in liver cirrhosis. Acute infarction of the intestine will cause a release of intestinal ALP from the mucosa. Large erosive or ulcerative lesions of the stomach, duodenum or other small intestinal areas or colon may result in an elevation of the serum ALP level. The small intestinal lesions associated with malabsorption are associated with an elevation of the serum intestinal ALP level only if there is an erosive or ulcerative mucosal lesion.