Alkaline Phosphatase (ALP)

ALP comprises a group of related enzymes found in high concentration in liver & biliary tract, bone, intestinal mucosa and placenta

Cholestasis stimulates increased synthesis of hepatic ALP and leakage of the enzyme into blood

Circulating ALP levels are very sensitive to cholestasis of any cause, including localized intrahepatic cholestasis that may not be otherwise apparent

Hepatic causes of elevated ALP include:

• Extra- and intrahepatic biliary obstruction
• Hepatocyte injury of various causes (produces local cholestasis), including viral hepatitis
• Space-occupying lesions (tumors, abcesses, granulomas)
• Sepsis
• Drugs (phenytoin)
• Primary biliary cirrhosis

Circulating ALP may also come from non-hepatic sources, and in those cases it doens not indicate hepatic disease:

• Bone ALP is elevated when bone turnover is increased: Paget’s disease of bone, hyperparathyroidism, osteoporosis, tumor metastatic to bone, and fracture healing. Bone ALP is also substantially elevated in childhood and adolescence due to bone growth. Enlarged reference ranges must be used at those times, and ALP is correspondingly less sensitive for hepatic disease in those age groups.
• Placental ALP and bone ALP are elevated during pregnancy
• ALP may also be elevated during active healing (granulation tissue formation) because it is present in relatively high levels in growing endothelial cells and fibroblasts
• Benign transient elevations can occur in a variety of diseases; may be strikingly high (most common in young), but are self-limited, resolving over a month or two

Elevated ALP is typically confirmed as hepatic using a second test that is also sensitive to cholestasis Gammaglutamyltransferase (GGT))

If additional information is needed, tissue-specific ALP isoenzymes can be determined by electrophoresis (reference laboratories) and will specifically identify the tissue source of an elevation in ALP.