Elevated ALP

ALKALINE PHOSPHATASE

The term alkaline phosphatase applies generally to a group of isoenzymes distributed widely throughout the body. The isoenzymes of greatest clinical importance in adults are in the liver and bone because these organs are the major sources of serum alkaline phosphatase. Other isoenzymes originate from the placenta, small intestine, and kidneys. In the liver, alkaline phosphatase is found on the canalicular membrane of hepatocytes; its precise function is undefined. Alkaline phosphatase has a serum half-life of approximately seven days, and although the sites of degradation are unknown, clearance of alkaline phosphatase from serum is independent of either patency of the biliary tract or functional capacity of the liver. Hepatobiliary disease leads to increased serum alkaline phosphatase levels through induced synthesis of the enzyme and leakage into the serum, a process mediated by bile acids.

A number of individual physiologic variations in serum alkaline phosphatase levels have been identified. Patients with blood groups O and B have elevations in serum alkaline phosphatase levels caused by release of intestinal alkaline phosphatase after a fatty meal.[23] This observation is the basis for the recommendation by some authorities that the serum alkaline phosphatase level be checked in the fasting state. An increased serum alkaline phosphatase level of intestinal origin is seen in a benign familial elevation of serum alkaline phosphatase. Serum alkaline phosphatase values vary with age. Male and female adolescents have serum alkaline phosphatase levels twice the level seen in adults; the level correlates with bone growth, and the increase in serum is in bone alkaline phosphatase. Although the level of serum alkaline phosphatase increases after age 30 years in both men and women, the increase is more pronounced in women than in men; a healthy 65-year-old woman has a serum alkaline phosphatase level 50% higher than that of a healthy 30-year-old woman.[24] The reason for this difference is not known. In a person with isolated elevation of the serum alkaline phosphatase level, the serum GGTP or 5′NT are used to distinguish a liver origin from bone origin of the alkaline phosphatase elevation.

A low serum alkaline phosphatase level may occur in patients with Wilson disease, especially those presenting with fulminant hepatitis and hemolysis, possibly because of reduced activity of the enzyme owing to displacement of the co-factor zinc by copper.

Evaluation of an isolated elevation of the serum alkaline phosphatase level. ACE, angiotensin-converting enzyme; ALP, alkaline phosphatase; AMA, antimitochondrial antibodies; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; GGTP, gamma glutamyl transpeptidase; MRCP, magnetic resonance cholangiopancreatography; 5′NT, 5′ nucleotidase; RUQ US, right upper quadrant ultrasound. 

Evaluation of cholestatic liver enzyme elevations. ACE, angiotensin-converting enzyme; AMA, antimitochondrial antibodies; CMV, cytomegalovirus; CT, computed tomography; EBV, Epstein-Barr virus; ERCP, endoscopic retrograde cholangiopancreatography; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; MRCP, magnetic resonance cholangiopancreatography; RUQ US, right upper quadrant ultrasound. 


 Intrahepatic Causes of Cholestatic Liver Enzyme Elevations in Adults

Drugs*

Bland cholestasis    Anabolic steroids    Estrogens    Cholestatic hepatitis    Angiotensin-converting enzyme inhibitors: captopril, enalapril    Antimicrobials: amoxicillin-clavulanic acid, ketoconazole    Azathioprine    Chlorpromazine    Nonsteroidal anti-inflammatory drugs: sulindac, piroxicam    Granulomatous hepatitis    Allopurinol    Antibiotics: sulfonamides    Antiepileptics: carbamazepine, phenytoin    Cardiovascular agents: hydralazine, procainamide, quinidine    Phenylbutazone    Vanishing bile duct syndrome    Amoxicillin-clavulanic acid    Chlorpromazine    Dicloxacillin    Erythromycins    Flucloxacillin

Primary Biliary Cirrhosis

Primary Sclerosing Cholangitis

Granulomatous Liver Disease

Infections    Brucellosis    Fungal: histoplasmosis, coccidioidomycosis    Leprosy    Q fever    Schistosomiasis    Tuberculosis, Mycobacterium avium complex, bacillus Calmette-Gu?rin    Sarcoidosis    Idiopathic granulomatous hepatitis    Other    Crohn's disease    Heavy metal exposure: beryllium, copper    Hodgkin's disease

Viral Hepatitis

Hepatitis A    Hepatitis B and C, including fibrosing cholestatic hepatitis    Epstein-Barr virus    Cytomegalovirus

Idiopathic Adult Ductopenia

Genetic Conditions

Progressive familial intrahepatic cholestasis    Type 1 (Byler's disease)    Type 2    Type 3    Benign recurrent intrahepatic cholestasis    Type 1    Type 2    Cystic fibrosis

Malignancy

Hepatocellular carcinoma    Metastatic disease    Paraneoplastic syndrome    Non-Hodgkin's lymphoma    Prostate cancer    Renal cell cancer

Infiltrative Liver Disease

Amyloidosis    Lymphoma

Intrahepatic Cholestasis of Pregnancy

Total Parenteral Nutrition

Graft-versus-Host Disease

Sepsis

*	Categorized by histologic pattern. Drug lists are not meant to be comprehensive.

Table 73-4   -- Extrahepatic Causes of Cholestatic Liver Enzymes in Adults

Intrinsic

Choledocholithiasis

Immune-Mediated Duct Injury

Autoimmune pancreatitis    Primary sclerosing cholangitis

Malignancy

Ampullary cancer    Cholangiocarcinoma

Infections

AIDS cholangiopathy    Cytomegalovirus    Cryptosporidiosis    Microsporidiosis    Parasitic infections    Ascariasis

Extrinsic

Malignancy

Gallbladder cancer    Metastases, including portal adenopathy from metastases    Pancreatic cancer

Mirizzi's syndrome*

Pancreatitis

Pancreatic pseudocyst

AIDS, acquired immunodeficiency syndrome.

*	Compression of the common hepatic duct by a stone in the neck of the gallbladder.