Symptom Finder - Elevated Alkaline Phosphatase
ALKALINE PHOSPHATASE ELEVATION
Developing a list of diagnostic possibilities for an elevated alkaline phosphatase level involves the use of biochemistry and physiology. As with other laboratory values, we need to know where alkaline phosphatase is produced, how it is transported, and how it is degraded or excreted.
Alkaline phosphatase is produced in many tissues but in terms of pathophysiology, only the osteoblasts of the bone need be recalled. Thus, disorders that increase osteoblastic activity such as metastatic tumors of the bone, osteogenic sarcoma, Paget disease, and primary and secondary hyperparathyroidism may cause the alkaline phosphatase level to increase and must be considered in the differential. Transport of blood alkaline phosphatase does not seem to be affected by disease. However, the excretion of alkaline phosphatase seems to take place in the liver by an undetermined pathway, but anything that blocks the cholangioles or biliary tree will usually cause an elevation of alkaline phosphatase.
Consequently, carcinoma of the head of the pancreas, common duct stones, carcinoma of the ampulla of Vater, and drugs that produce cholestasis (such as chlorpromazine) may cause an elevated alkaline phosphatase. Metastatic carcinoma of the liver probably produces an elevated alkaline phosphatase by blocking individual cholangioles. In addition to the above diagnostic possibilities, there are disorders that cause an elevated alkaline phosphatase level by an unknown mechanism such as pregnancy, sepsis,
and gynecologic malignancies that must be included in the differential.
Approach to the Diagnosis
If the elevated alkaline phosphatase level is related to liver disease, the clinical examination will often show jaundice or hepatomegaly. If it is related to bone disease, the clinical examination will show bone pain, pathologic fracture, or bone mass. A liver profile will also help diagnose a liver disorder, but a CT scan of the abdomen may be necessary. A skeletal survey will usually reveal bony metastasis and other disorders of the bone, but a bone scan may be necessary to show early metastasis to the bone. A serum parathyroid hormone (PTH) level will help diagnose primary hyperparathyroidism, whereas secondary hyperparathyroidism (rickets, etc.) will require the specialized tests listed below.
Other Useful Tests
1. CBC
2. Chemistry profile (liver disease)
3. Sedimentation rate (hepatitis)
4. Urinalysis (renal tubular acidosis)
5. 24-hour urine calcium (hyperparathyroidism, malignancy)
6. Gallbladder ultrasound (common duct stone)
7. ERCP (obstructive jaundice)
8. Transhepatic cholangiogram (obstructive jaundice)
9. Liver biopsy (cirrhosis, hepatitis)
10. Bone biopsy (metastatic malignancy)
11. D-xylose absorption test (malabsorption syndrome)
12. Acid phosphatase (metastatic cancer of the prostate)
13. PSA (metastatic cancer of the prostate)
14. Vitamin D metabolites (25-hydroxycholecalciferol) (rickets,
osteomalacia)
15. Exploratory laparotomy
Developing a list of diagnostic possibilities for an elevated alkaline phosphatase level involves the use of biochemistry and physiology. As with other laboratory values, we need to know where alkaline phosphatase is produced, how it is transported, and how it is degraded or excreted.
Alkaline phosphatase is produced in many tissues but in terms of pathophysiology, only the osteoblasts of the bone need be recalled. Thus, disorders that increase osteoblastic activity such as metastatic tumors of the bone, osteogenic sarcoma, Paget disease, and primary and secondary hyperparathyroidism may cause the alkaline phosphatase level to increase and must be considered in the differential. Transport of blood alkaline phosphatase does not seem to be affected by disease. However, the excretion of alkaline phosphatase seems to take place in the liver by an undetermined pathway, but anything that blocks the cholangioles or biliary tree will usually cause an elevation of alkaline phosphatase.
Consequently, carcinoma of the head of the pancreas, common duct stones, carcinoma of the ampulla of Vater, and drugs that produce cholestasis (such as chlorpromazine) may cause an elevated alkaline phosphatase. Metastatic carcinoma of the liver probably produces an elevated alkaline phosphatase by blocking individual cholangioles. In addition to the above diagnostic possibilities, there are disorders that cause an elevated alkaline phosphatase level by an unknown mechanism such as pregnancy, sepsis,
and gynecologic malignancies that must be included in the differential.
Approach to the Diagnosis
If the elevated alkaline phosphatase level is related to liver disease, the clinical examination will often show jaundice or hepatomegaly. If it is related to bone disease, the clinical examination will show bone pain, pathologic fracture, or bone mass. A liver profile will also help diagnose a liver disorder, but a CT scan of the abdomen may be necessary. A skeletal survey will usually reveal bony metastasis and other disorders of the bone, but a bone scan may be necessary to show early metastasis to the bone. A serum parathyroid hormone (PTH) level will help diagnose primary hyperparathyroidism, whereas secondary hyperparathyroidism (rickets, etc.) will require the specialized tests listed below.
Other Useful Tests
1. CBC
2. Chemistry profile (liver disease)
3. Sedimentation rate (hepatitis)
4. Urinalysis (renal tubular acidosis)
5. 24-hour urine calcium (hyperparathyroidism, malignancy)
6. Gallbladder ultrasound (common duct stone)
7. ERCP (obstructive jaundice)
8. Transhepatic cholangiogram (obstructive jaundice)
9. Liver biopsy (cirrhosis, hepatitis)
10. Bone biopsy (metastatic malignancy)
11. D-xylose absorption test (malabsorption syndrome)
12. Acid phosphatase (metastatic cancer of the prostate)
13. PSA (metastatic cancer of the prostate)
14. Vitamin D metabolites (25-hydroxycholecalciferol) (rickets,
osteomalacia)
15. Exploratory laparotomy