Blood biochemistry: alkaline phosphatase (ALP)

Overview

• Membrane associated enzyme.
• Number of isoenzymes produced in a range of tissues (liver, kidney, intestine, placenta).
• Special procedures are necessary to determine isoenzymes.
• Levamisole inhibition or heat activation commonly used to separate hepatic from steroidal isoenzymes as cause of increased activity.
• May see overlap in steroid and hepatic isoenzymes in many types of disease so not always helpful in separating underlying cause.
• Increased plasma levels are derived from liver and bone.
• Good indicator of liver disease and cholestasis - increases before plasma bilirubin.
• Corticosteroids induce a specific isoenzyme from the liver (steroid-induced alkaline phosphatase - SIAP/sALP).

Uses

Alone

• Identification of cholestasis.

• Screening for bone disease.

In combination

• As part of routine biochemical screening panel.
• Liver disease in conjunction with:
  • Aspartate aminotransferase (AST) .
  • Alanine aminotranferase (ALT) .
  • Gamma-glutamyltransferase (GGT) .
  • Bile salts .
• Investigation of suspected hyperadrenocorticism .

Other points

• High levels of ALP (and GGT) occur in canine colostrum.
• May see <100x increase following colostral ingestion.
• May take approximately 10 days to return to within reference interval for adult dogs.

Result data

Normal (reference) values

• Example of reference interval: 0-120 umol/l.
• No absolute values - individual laboratories should supply normal range for their test.
• <300 IU/L probably not pathological.

Abnormal values

• Cholestasis (up to 150 fold increase).
• Liver damage (infectious hepatitis , toxic hepatitis , chronic active hepatitis , severe trauma, primary neoplasia , cirrhosis , acute pancreatitis ).
• Steroid induced - SIAP (hyperadrenocorticism , glucocorticoid therapy).
• Bone disease:
  • Hyperparathyroidism .
  • Panosteitis .
  • Bone tumors .
  • Bone healing.
  • Craniomandibular osteopathy .
  
  In general elevations in non-hepatic disease are much lower than in liver disease except for glucocorticoid induction which may result in very high ALP levels. Levels >1000 give strong suspicion of exposure to glucocorticoids..
• ALP usually increases within 6 days after glucocorticoid administration, but may not reach peak for 3-4 weeks.
• May require months for ALP to return to within reference interval following steroid withdrawal.

Errors and Artifacts

• Increased in dogs <1 year old due to bone metabolism/growth.
• Anticonvulsants, barbiturates and glucocorticoids induce ALP.
• May also see induction with ketoconazole, phenylbutazone.

Sources

Publications

Refereed papers

• Center S A, Slater M R, ManWarren T et al(1992) Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease - 277 cases (1980-1990). JAVMA 201 , 1258.

Other sources of information

• Ettinger S J & Feldman E C (eds) (2000) Textbook of Veterinary Internal Medicine. 5th edn. Philadelphia: W B Saunders & Co.
• Kaneko J J, Harvey J W & Brass M L (eds) (1997) Clinical Biochemistry of Domestic Animals. 5th edn. Boston: Academic Press.
• Duncan J R, Prasse K W & Mahaffey E A (1994) Veterinary Laboratory Medicine. Clinical Pathology. 3rd edn. Iowa: Iowa University Press.