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raised alkaline phosphatase

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Possible causes of increased levels of plasma alkaline phosphatase include:

  • hepatobiliary disease including:
    • cholestasis: increased synthesis of hepatocyte ALP and increased secretion of high molecular weight form into plasma; elevations of ALP of up to 10 times normal levels
    • hepatocyte disease, such as viral hepatitis which cause moderate elevations in ALP
  • bone disease - bone isoenzyme of alkaline phosphatase, reflecting increased osteoblastic activity, may be raised in:
    • Paget's disease
    • osteomalacia and rickets
      • vitamin D deficiency
        • profiles of serum calcium, phosphate and alkaline phosphatase may sometimes be helpful in the diagnosis of vitamin D deficiency
          • note though that serum calcium and phosphate concentrations only fall in longstanding, symptomatic, vitamin D deficiency; there is an increase in levels of alkaline phosphatase (total and bone-specific) increase early in vitamin D deficiency
            • this is a non-specific finding, but may be helpful in diagnosing individuals with otherwise unexplained elevations in alkaline phosphatase
    • renal osteodystrophy
    • bone metastases
    • primary bone tumour e.g. sarcoma
    • recent fracture
    • growing child - especially at puberty
  • during pregnancy the placenta secretes its own isoenzyme which raises total alkaline phosphatase concentration
  • malignancies resulting in expression of ALP-like gene e.g. seminomas

In determining whether a raised ALP is of hepatic or bony origin e.g. in metastasis of breast cancer, the following may be useful:

  • other test of hepatic function e.g. GGT
  • electrophoresis separation of isoenzymes
  • bone scan
  • ultrasound scan of liver

Sometimes it is useful to look at the relationship of ALP to bilirubin and lactate dehydrogenase (LD) levels (1)

Pathology Alkaline Phosphatase Bilirubin LD
Intra or extrahepatic cholestasis Increased Increased Normal
Focal benign cholestasis Increased Normal Normal
Focal malignant cholestasis Increased Normal Increased

Notes:

  • If alkaline phosphatase is raised in an asymptomatic patient and serum bilirubin, liver transaminases, creatinine, adjusted calcium, thyroid function, and blood count are normal (2):

    • consider growth spurts in adolescents, pregnancy in women, drugs, and age related increases
    • as most likely sources are either bone or liver, differentiate by measuring GGT (raised in liver) and investigate accordingly
    • for liver cases investigate with abdominal ultrasound scan (cholestasis and hepatic space occupying lesion) and antimitochondrial antibodies (primary biliary cirrhosis)
    • for bone cases investigate vitamin D

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