Liver Function Tests

Tests Based on Detoxification and Excretory Functions

Serum Bilirubin Breakdown product of the porphyrin ring of heme-containing proteins Found in the blood in two fractions: conjugated and unconjugated

Unconjugated Bilirubin – Insoluble in water – Bound to albumin in blood – Elevation is rarely due to liver disease – Elevation- prompt a work up for hemolysis

Conjugated Bilirubin – Water soluble – Almost always implies liver or biliary tract disease. – Rate limiting step in bilirubin metabolism is the transport of conjugated bilirubin into bile canaliculi – Elevation maybe seen in any type of liver disease.

Blood Ammonia Produced in the body during normal protein metabolism and by intestinal bacteria Liver plays a role in the detoxification of ammonia by converting it to urea, which is excreted in the kidneys.

Blood Ammonia Some physicians use blood ammonia for detecting encephalopathy or for monitoring hepatic enzyme functions. Elevated arterial ammonia levels have been shown to correlate with outcome in fulminant hepatic failure.

Enzymes that Reflect Hepatocyte Damage

Aminotransferases AST: Found primarily in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, leukocytes, and erythrocytes. ALT: found primarily in the liver. Normally present in the serum in very low concentrations

Aminotransferases Liver cell membrane damage -> increased permability-> enzymes are released into the blood in great amounts. Striking elevations during viral hepatitis, ischemic liver injury ( prolonged hypotension or acute failure), and toxin/drug induced liver injury

Aminotransferases Acute hepatocellular disorders: ALT higher or equal of AST AST:ALT ration >3:1 highly suggestive of alcoholic liver disease

Enzymes that reflect Cholestasis

Alkaline Phosphatase, 5’-nucleotidase, Y- glutamyl transpeptidase Alkaline Phosphatase and 5’-nucleotidase found in or near the bile canalicular membrane of hepatocytes GGT located in ER and in bile duct epithelial cells, more diffuse localization, therefore elevation reflects a less specificity for cholestasis.

Serum Alkaline Phosphatase has isoenzymes from liver, bone, placenta. Maybe elevated on persons over age 60, blood types O and B after eating a fatty meal, children on rapid bone growth, and in normal pregnancies. Elevation of ALP is not totally specific but elevations greater four times the normal occur primarily in patients with cholestatic disorders and infiltrative liver diseases

Tests that measure biosynthesic function of the liver

Serum Albumin Synthesized exclusively by hepatocytes, levels <3g/dL suggest a chronic liver disease Not a good indicator of acute liver disease due to slow turnover. Hypoalbuminemia is not specific for liver disease, it may occur in protein malnutrition, protein losing enteropathies, nephritic syndrome, and some chronic infections.

Serum Globulin Group of proteins made up of gamma globulins ( immunoglobulins) produced by B lymphocytes and alpha and beta globulins produced in the hepatocytes. Gamma globulins are increased in chronic liver disease, such as chronic hepatitis and cirrhosis. Cirrhosis- increased levels due to increased synthesis of antibodies

Serum Globulin Diffuse polyclonal increases of IgG are common in autoimmune hepatitis Increase IgM levels are common in primary biliary cirrhosis Increase IgA levels occur in alcoholic liver disease.

Coagulation Factors Except F8, are made exclusively in the hepatocytes. Measurement is single best acute measure of hepatic function Helpful in diagnosis and assessment of acute parenchymal liver diseases SERUM PROTHROMBIN is measured

PT elevated in hepatitis, cirrhosis. Marked PT elevation >5s above control and not corrected by parenteral vitamin K  poor prognostic sign in acute viral hepatitis and other liver diseases.