Background

• Origin of Alkaline Phosphatase
  • Bone
  • Intestine
  • Kidney
  • Liver
  • Third Trimester Placenta
• Determination of Origin
  • Elevated Alkaline Phosphatase Associated with a Normal Gamma-Glutamyl Transpeptidase or 5′-Nucleotidase Suggests a Non-Hepatic Source of the Alkaline Phosphatase
  • Fractionation of Alkaline Phosphatase: may also be used to determine origin
    • Heat-Labile Alkaline Phosphatase: suggests bone origin (“bone burns”)
    • Heat-Stable Alkaline Phosphatase: suggests liver origin
• Alkaline Phosphatase Levels are Age-Dependent
  • Alkaline Phosphatase Levels are Higher (Up to 3x Adult Levels) in Children and Adolescents: due to physiologic osteoblastic activity
  • Normal Alkaline Phosphatase Level Increases from 40 to 65 y/o: especially in women

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Indications

• Evaluation of Liver Function: alkaline phosphatase is a standard component of liver function tests (LFT’s)

• xxx

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Etiology of Elevated Alkaline Phosphatase (see Elevated Liver Function Tests, [[Elevated Liver Function Tests]])

Moderate Alkaline Phosphatase Elevation (<4x Upper Limit of Normal)

Hepatic

• Acute Viral Hepatitis
  • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
  • Epstein-Barr Virus (EBV) (see Epstein-Barr Virus, [[Epstein-Barr Virus]])
  • Hepatitis A Virus (see Hepatitis A Virus, [[Hepatitis A Virus]])
  • Hepatitis B Virus (HBV) (see Hepatitis B Virus, [[Hepatitis B Virus]])
  • Hepatitis C Virus (HCV) (see Hepatitis C Virus, [[Hepatitis C Virus]])
• Alcoholic Hepatitis (see Alcoholic Hepatitis, [[Alcoholic Hepatitis]])
• Chronic Viral Hepatitis
  • Hepatitis B Virus (HBV) (see Hepatitis B Virus, [[Hepatitis B Virus]])
  • Hepatitis C Virus (HCV) (see Hepatitis C Virus, [[Hepatitis C Virus]])
• Cirrhosis (see Cirrhosis, [[Cirrhosis]])
• Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
  • Physiology: hepatic hypoperfusion
• Hepatic Infiltration
  • Amyloidosis (see Amyloidosis, [[Amyloidosis]])
  • Liver Abscess (see Pyogenic Liver Abscess, [[Pyogenic Liver Abscess]])
  • Lymphoma (see Lymphoma, [[Lymphoma]])
  • Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
  • Tuberculosis (see Tuberculosis, [[Tuberculosis]])
• Sepsis (see Sepsis, [[Sepsis]])
  • Physiology: hepatic hypoperfusion

Non-Hepatic

• Benign Familial Elevation of Alkaline Phosphatase
  • Physiology: intestinal source
• High Bone Turnover
  • Bone Metastases
  • Growth
  • Healing Fracture
  • Hyperparathyroidism (see Hyperparathyroidism, [[Hyperparathyroidism]])
  • Hyperthyroidism (see Hyperthyroidism, [[Hyperthyroidism]])
  • Osteosarcoma (see Osteosarcoma, [[Osteosarcoma]])
  • Osteomalacia (see Osteomalacia, [[Osteomalacia]])
  • Paget Disease of Bone (see Paget Disease of Bone, [[Paget Disease of Bone]])
• Influx of Intestinal Alkaline Phosphatase After Eating a Fatty Meal
  • Epidemiology: occurs in patients with blood type O or B
• Malignancy
  • Gastric Cancer (see Gastric Cancer, [[Gastric Cancer]])
  • Head and Neck Cancer (see Head and Neck Cancer, [[Head and Neck Cancer]])
  • Hodgkin’s Disease (see Hodgkin’s Disease, [[Hodgkins Disease]])
  • Lung Cancer (see Lung Cancer, [[Lung Cancer]])
  • Osteosarcoma (see Osteosarcoma, [[Osteosarcoma]])
  • Ovarian Cancer (see Ovarian Cancer, [[Ovarian Cancer]])
  • Renal Cell Carcinoma (see Renal Cancer, [[Renal Cancer]])
  • Uterine Cancer (see Uterine Cancer, [[Uterine Cancer]])
• Physiologic Elevation of Alkaline Phosphatase: occurs in children and adolescents
• Third Trimester of Pregnancy (see Pregnancy, [[Pregnancy]])
• Other
  • Myeloid Metaplasia
  • Peritonitis (see Peritonitis, [[Peritonitis]])
  • Diabetes Mellitus (see Diabetes Mellitus, [[Diabetes Mellitus]])
  • Subacute Thyroiditis (see Subacute Thyroiditis, [[Subacute Thyroiditis]])
  • Gastric Ulcer (see Peptic Ulcer Disease, [[Peptic Ulcer Disease]])

Marked Alkaline Phosphatase Elevation (≥4x Upper Limit of Normal)

Intrahepatic Cholestasis

• Alcoholic Hepatitis (see Alcoholic Hepatitis, [[Alcoholic Hepatitis]])
• Benign Postoperative Cholestasis
• Hepatic Infiltration
  • Amyloidosis (see Amyloidosis, [[Amyloidosis]])
  • Liver Abscess (see Pyogenic Liver Abscess, [[Pyogenic Liver Abscess]])
  • Lymphoma (see Lymphoma, [[Lymphoma]])
  • Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
  • Tuberculosis (see Tuberculosis, [[Tuberculosis]])
• Hepatic Metastases
  • Breast Cancer (see Breast Cancer, [[Breast Cancer]])
  • Lymphoma (see Lymphoma, [[Lymphoma]])
  • Melanoma (see Melanoma, [[Melanoma]])
  • Multiple Myeloma (see Multiple Myeloma, [[Multiple Myeloma]])
  • Small Cell Lung Cancer (see Lung Cancer, [[Lung Cancer]])
• Intrahepatic Cholestasis of Pregnancy (see Pregnancy, [[Pregnancy]])
• Ischemic Cholangiopathy (see Ischemic Cholangiopathy, [[Ischemic Cholangiopathy]])
• Liver Transplant Rejection (see Liver Transplant, [[Liver Transplant]])
• Primary Biliary Cirrhosis (PBC) (see Primary Biliary Cirrhosis, [[Primary Biliary Cirrhosis]])
• Primary Sclerosing Cholangitis (PSC) (see Primary Sclerosing Cholangitis, [[Primary Sclerosing Cholangitis]])
• Sickle Cell Disease (Hepatic Crisis) (see Sickle Cell Disease, [[Sickle Cell Disease]])
• Drugs/Toxins
  • Alkylated Steroids
  • Arsenic (see Arsenic, [[Arsenic]])
  • Chlorpromazine (xxx) (see Chlorpromazine, [[Chlorpromazine]])
  • Jamaican Bush Tea (see Jamaican Bush Tea, [[Jamaican Bush Tea]])
  • Total Parenteral Nutrition (TPN) (see Total Parenteral Nutrition, [[Total Parenteral Nutrition]])

Extrahepatic Cholestasis (Biliary Obstruction)

• Acute Pancreatitis (see xxxx, [[xxxx]])
  • Physiology: xxx
• Biliary Infection
  • AIDS Cholangiopathy (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
  • Ascaris Lumbricoides (see Ascariasis, [[Ascariasis]])
  • Liver Flukes (Trematodes)
    • Clonorchis (see Clonorchiasis, [[Clonorchiasis]])
    • Fasciola (see Fascioliasis, [[Fascioliasis]])
    • Metorchis (see Metorchiasis, [[Metorchiasis]])
    • Opisthorchis (see Opisthorchiasis, [[Opisthorchiasis]])
• Biliary Stricture
  • Chronic Pancreatitis with Stricture of Distal Bile Duct (see Chronic Pancreatitis, [[Chronic Pancreatitis]])
  • Post-Liver Transplant Biliary Anastomotic Stricture (see Liver Transplant, [[Liver Transplant]])
  • Post-Procedure
  • Primary Sclerosing Cholangitis (PSC) with Extrahepatic Bile Duct Stricture (see Primary Sclerosing Cholangitis, [[Primary Sclerosing Cholangitis]])
• Choledocholithiasis (see Cholelithiasis, [[Cholelithiasis]])
  • Epidemiology: most common etiology of extrahepatic biliary obstruction
• Malignant Biliary Obstruction
  • Carcinoma of the Ampulla of Vater (see xxxx, [[xxxx]])
  • Cholangiocarcinoma (see Cholangiocarcinoma, [[Cholangiocarcinoma]])
  • Gallbladder Cancer (see Gallbladder Cancer, [[Gallbladder Cancer]])
  • Pancreatic Cancer (see Pancreatic Cancer, [[Pancreatic Cancer]])

Non-Hepatic

• Transient Hyperphosphatemia of Infancy and Childhood

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References

• Heat stability of human serum alkaline phosphatase in bone and liver diseases. Clin Chim Acta. 1972 Oct;41:329-34 [MEDLINE]