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Alkaline Phosphatase (ALP)
(Tissue Non-Specific Alkaline Phosphatase – Liver/Bone Enzyme)
Synonyms
- ALP
- Alkaline phosphatase
- Alk Phos
- Tissue nonspecific alkaline phosphatase (TNSALP)
- Serum ALP
- Bone ALP (B-ALP)
- Liver ALP (L-ALP)
Units of Measurement
nkat/L, µkat/L, nmol/(s•L), µmol/(s•L), U/L, IU/L, µmol/(min•L), µmol/(h•L), µmol/(h•mL)
Description
Alkaline Phosphatase (ALP) is a hydrolytic enzyme that removes phosphate groups from proteins and other molecules at an alkaline pH (~10).
Major isoenzymes arise from:
- Liver (hepatobiliary system)
- Bone (osteoblasts)
- Intestine
- Placenta
- Kidney (minor contribution)
Serum ALP is commonly used to evaluate:
- Cholestasis (bile duct obstruction)
- Bone turnover
- Metabolic bone disease
- Liver disease
- Pediatric growth assessment
Physiological Role
- Bone mineralization (osteoblast function)
- Biliary canalicular transport
- Hydrolysis of phosphate esters
- Marker of osteoblastic activity
- Increases during bone growth, healing, pregnancy
Clinical Significance
Elevated ALP
1. Hepatobiliary Diseases
- Cholestasis (intrahepatic or extrahepatic)
- Gallstones
- Primary biliary cholangitis (PBC)
- Primary sclerosing cholangitis (PSC)
- Liver metastases
- Drug-induced cholestasis
- Infiltrative diseases (sarcoidosis)
Pattern: ALP ↑, GGT ↑ → hepatic/cholestatic origin
2. Bone Diseases
- Paget disease
- Osteomalacia / Rickets
- Hyperparathyroidism
- Bone metastases
- Healing fractures
- High bone turnover states
Pattern: ALP ↑, GGT normal → bone origin
3. Physiological Causes
- Adolescents during growth spurts
- Pregnancy (placental ALP)
- Elderly adults
- Blood type O and B after fatty meals (intestinal ALP)
Low ALP
Seen in:
- Hypophosphatasia (ALPL gene mutations)
- Severe malnutrition
- Zinc deficiency
- Hypothyroidism
- Vitamin C deficiency
- Post-cardiac bypass
- Anemia
- Magnesium deficiency
Low ALP is uncommon but clinically significant when present.
Reference Intervals
Adults
- Male: 40 – 129 U/L
- Female: 35 – 104 U/L
Children & Adolescents (High due to bone growth)
- 150 – 500 U/L (pubertal peak)
- Age-specific ranges required in pediatrics.
SI Units
- 1 U/L = 16.67 nkat/L
- Thus typical adult range in SI:
- ~580 – 2150 nkat/L (method dependent)
- ~580 – 2150 nkat/L (method dependent)
Always interpret ALP with GGT to differentiate liver vs bone origin.
Isoenzymes of ALP
| Isoenzyme | Source | Clinical Relevance |
| Liver ALP | Hepatobiliary | Cholestasis, obstruction |
| Bone ALP (B-ALP) | Osteoblasts | Paget disease, rickets, high turnover |
| Placental ALP | Placenta | Pregnancy (physiologic) |
| Intestinal ALP | Gut | Blood group O/B after meals |
| Regan/ Nagao isoenzymes | Tumors | Rare cancer markers |
Unit Meanings
| Unit | Meaning |
| nkat/L | nanokatal per liter |
| µkat/L | microkatal per liter |
| nmol/(s•L) | nanomole per second per liter |
| µmol/(s•L) | micromole per second per liter |
| U/L or IU/L | enzyme units per liter |
| µmol/(min•L) | micromole per minute per liter |
| µmol/(h•L) | micromole per hour per liter |
| µmol/(h•mL) | micromole per hour per milliliter |
IFCC Enzyme Conversions
- 1 U/L = 16.67 nkat/L
- 1 nkat/L = 0.06 U/L
- 1 µkat/L = 60 U/L
Time conversions:
- µmol/(min•L) × 60 = µmol/(h•L)
- µmol/(h•L) ÷ 1000 = µmol/(h•mL)
Analytical Notes
- Measured by kinetic IFCC method at 37°C.
- Hemolysis typically does not significantly affect ALP.
- Use age-specific pediatric ranges.
- High ALP → confirm with GGT to assess liver origin.
Clinical Pearls
- ALP ↑ + GGT ↑ = cholestatic liver disease
- ALP ↑ + normal GGT = bone disease
- Children have physiologically high ALP due to growth plate activity
- ALP > 1000 U/L → think cholestasis, Paget disease, metastases
- Low ALP is a red flag for hypophosphatasia
Interesting Fact
Placental ALP rises sharply during pregnancy and was historically used as a crude marker of placental health before modern imaging techniques.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Enzymes & Liver Function.
- IFCC Enzyme Standardization Guidelines.
- Mayo Clinic Laboratories - ALP Interpretation.
- ARUP Consult - ALP and Isoenzyme Testing.
- NIH MedlinePlus - ALP Blood Test.
- Paget Disease / Rickets Biochemical Pathways - Clinical Reviews.