What does Alkaline Phosphatase (ALP) look at?

Alkaline Phosphatase (ALP): Clinical Significance and Interpretation

Alkaline phosphatase (ALP) is an enzyme that evaluates liver and bone disorders, with elevations indicating potential liver disease, bone disorders, or malignancy. 1

What ALP Measures

ALP is a group of enzymes found in multiple tissues throughout the body, primarily:

• Liver: Particularly in the bile ducts
• Bone: Associated with osteoblast activity
• Intestine: Found in intestinal mucosa
• Placenta: During pregnancy
• Other tissues: Including kidney and white blood cells

Normal Reference Ranges

• Typical adult range: 20-200 nmol/L (5-50 mg/L)
• Values vary by:
  • Age (higher in children/adolescents and elderly)
  • Sex (slightly different ranges for males and females)
  • Laboratory methodology 1

Diagnostic Significance

Liver Disease

• Indicates cholestatic liver disorders (bile flow obstruction)
• Considered significant when ≥2 times the upper limit of normal (ULN) 2
• Particularly important when elevated with gamma-glutamyl transpeptidase (GGT) 2

Bone Disorders

• Elevated in conditions with increased osteoblastic activity
• Common in:
  • Paget's disease
  • Osteomalacia
  • Bone metastases
  • Healing fractures 1

Malignancy

• Often elevated with:
  • Infiltrative intrahepatic malignancy
  • Bony metastases
  • Combined hepatic and bone metastases 3
• An isolated elevated ALP of unclear etiology is frequently associated with metastatic cancer (57% of cases) 3

Patterns of Liver Injury

ALP is used to classify liver injury patterns according to the ratio (R) of ALT/ALP:

• Cholestatic pattern: R ≤2
• Mixed pattern: R >2 and <5
• Hepatocellular pattern: R ≥5 2

Clinical Applications

Distinguishing ALP Source

When ALP is elevated, determining the source is crucial:

• GGT: Elevated with liver-source ALP but normal with bone-source ALP
• Bone-specific ALP isoenzyme: Can confirm bone origin
• Fractionation of ALP: Identifies specific isoenzymes 1

Monitoring Disease

• Liver disease: Monitors cholestasis progression
• Bone disease: Tracks treatment response
• Malignancy: May indicate disease progression or response to therapy 3

Clinical Pitfalls and Caveats

1. Isolated ALP elevation requires thorough investigation - in one study, 47% of patients with isolated elevated ALP of unclear etiology died within an average of 58 months 3

2. Physiologic elevations occur in:

   • Growing children and adolescents
   • Pregnant women (placental isoenzyme)
   • After fatty meals 4

3. Drug-induced elevations may occur with:

   • Glucocorticoids
   • Anticonvulsants
   • Some antibiotics 4

4. GGT elevation alone is not a marker of cellular damage but may indicate enzyme induction 2

5. Inflammation can affect plasma ALP levels 1

Recommended Diagnostic Approach

When elevated ALP is detected:

1. Confirm elevation with repeat testing
2. Check other liver enzymes (ALT, AST, GGT, bilirubin)
3. Consider isoenzyme testing to determine source
4. Imaging studies if clinically indicated:
   • Abdominal ultrasound (first-line)
   • MRCP if biliary obstruction is suspected
   • Bone imaging if bone source suspected 1

Remember that an isolated elevated ALP without obvious etiology should prompt thorough investigation, particularly for underlying malignancy, as this is the most common cause (57%) and associated with significant mortality 3.