Origins of Alkaline Phosphatase (ALP) in the Body
Alkaline phosphatase (ALP) primarily originates from the liver, bones, and in lesser amounts from intestines, placenta, kidneys, and leukocytes. 1, 2
Main Sources of ALP
Tissue-Nonspecific Alkaline Phosphatase (TNALP)
- TNALP is one of four human ALP isozymes and is expressed in three main tissues 3:
- Liver: Produces liver isoform of ALP
- Bone: Produces bone isoforms (B/I, B1, B1x, and B2)
- Kidney: Produces kidney-specific isoform
Other Sources
- Intestinal ALP: Derived from intestinal tissue
- Placental ALP: Present during pregnancy
- Leukocyte ALP: Found in white blood cells
Clinical Significance of Different ALP Sources
Bone-Origin ALP
- Bone-specific alkaline phosphatase (BAP) is a marker of bone turnover 1
- Elevated in conditions such as:
- Paget's disease
- Osteomalacia
- Rickets
- Hyperparathyroidism
- Bone metastases
Liver-Origin ALP
- Elevated in hepatobiliary conditions 1, 4:
- Biliary obstruction
- Infiltrative liver diseases
- Cholangiocarcinoma
- Primary biliary cholangitis
- Primary sclerosing cholangitis
Intestinal ALP
- May be elevated after fatty meals
- Can contribute to total ALP elevation, though rarely solely responsible 2
Distinguishing the Source of Elevated ALP
To determine the origin of elevated ALP, several approaches are recommended:
Measure Gamma-Glutamyl Transferase (GGT) 1:
- Elevated GGT suggests liver origin
- Normal GGT with elevated ALP suggests bone origin
Isoenzyme Testing 2:
- Direct measurement of bone, liver, and intestinal ALP isoenzymes
- More accurate than GGT alone for determining the source
Additional Laboratory Tests 1:
- For suspected liver origin: Complete liver panel (AST, ALT, bilirubin, albumin, PT/INR)
- For suspected bone origin: PTH, vitamin D levels, calcium, phosphate
Clinical Pearls and Pitfalls
Serial measurements of ALP are more valuable than a single reading 1
The R ratio [(ALT/ULN)/(ALP/ULN)] can help classify liver injury patterns 1:
- R ≥5: Hepatocellular pattern
- R ≤2: Cholestatic pattern
- R >2 and <5: Mixed pattern
Pitfall: Relying solely on GGT to determine ALP origin can lead to misidentification in some cases. In one study, this approach incorrectly identified the source in 3 of 28 hemodialysis patients 2
Caveat: ALP levels may be elevated in multiple conditions simultaneously. For example, a patient could have both liver disease and bone pathology contributing to elevated ALP 2