Serum Bile Acids

Ø Rarely performed; requires very complex methods:

Ø Extraction with organic solvents, partition chromatography, GCM-S, spectrophotometry,
ultraviolet light absorption, fluorescence, RIA, and EIA
Ø Total concentration is extremely variable, adding no diagnostic value to other tests
of liver function
Ø More relevant information of liver dysfunction may be gained by examining
patterns of individual bile acids and their state of conjugation:
Ø Ratio of the trihydroxy to dihydroxy bile acids in serum: differentiate patients with
obstructive jaundice from those with hepatocellular injury
Ø Ratio of the cholic to chenodeoxycholic acids: diagnosis of primary biliary cirrhosis and
extrahepatic cholestasis
Ø The high cost of these tests, the time required to do them, and the current
controversy concerning their clinical usefulness render this approach
unsatisfactory for routine use.
 Enzyme Tests
PHOSPHATASES: ALKALINE PHOSPHATASE
Ø In the liver, it is localized in the microvilli of the bile canaliculi:
Ø Good marker for extrahepatic biliary obstruction (e.g. common bile duct stone), as well
as intrahepatic cholestasis (e.g. drug cholestasis, primary biliary cirrhosis)
Ø Hepatocellular disorders (e.g. hepatitis, cirrhosis): slight to moderate elevations
Ø Difficult interpretation as it may also elevate in non-liver disorders/conditions:
Ø Bone-related disorders, pregnancy, etc.
5' NUCLEOTIDASE
Ø No bone source, significantly increased in hepatobiliary disease, normal or only
slightly elevated in bone disease; thus, useful in differentiating ALP elevations due
to liver disorders from other conditions
Ø Much more sensitive to metastatic liver disease than ALP
 Enzyme Tests
AMINOTRANSFERASES
Ø Highest levels: Acute conditions (e.g. viral hepatitis, drug- and toxin-induced liver
necrosis, and hepatic ischemia
Ø ALT activity is usually greater than AST activity
Ø Obstructive liver damage: normal to slight increase
Ø Serum transaminases may actually decrease in some patients with severe acute
hepatitis, owing to the exhaustive release of hepatocellular enzymes
Ø conduct of serial determination is helpful when following the course of a patient with
hepatitis
Ø caution should be used in interpreting abnormal levels
 Enzyme Tests
Ү-GLUTAMYLTRANSFERASES
Ø Similar clinical utility as 5NT
Ø A hepatic miscrosomal enzyme; thus, ingestion of alcohol ot certain drugs (e.g.
barbiturates, tricyclic antidepressants, anticonvulsants) causes elevations
Ø Sensitive test for cholestasis caused by chronic alcohol/drug ingestion
Ø Also useful for the confirmation of hepatic neoplasms without jaundice
LACTATE DEHYDROGENASE
• High levels: sometimes found in metastatic carcinoma of the liver
• Moderate increase of total LDH: acute viral hepatitis, cirrhosis
• Slight increase: biliary tract disease
• Due to wide distribution, it provides no additional clinical information
– Fractionation of LDH isoenzymes may give useful information about the origin of LDH elevation
 Enzyme Tests
Liver Enzyme Utility
Increased: Hepatitis
Aldolase
Normal: Cirrhois, obstructive jaundice
B-glucoronidase Increased: liver damage, diabetes, atherosclerosis
Increased: liver cirrhosis, MI
Ceruloplasmin
Decreased: Wilson disease, nephrotic syndrome
Isocitrate Increased: viral hepatitis, hepatic injury, intrahepatic
dehydrogenase obstruction
Sorbitol
Increased: liver damage
dehydrogenase
 Dye Excretion Tests
Ø Served as hepatic function tests, evaluates the ability to:
Ø Uptake
Ø Conjugate (Detoxify)
Ø Excrete (Removal)
Ø Dyes that were used:
Ø Bromsulfopthalein
Ø Evans Blue
Ø Indocyanin Green
Ø Rose Bengal
Ø Vital Red
Ø 131I-albumin
 Metabolic Tests (for Synthetic
Protein Metabolism Function)
Ø Not sensitive to minimal liver damage, they may be useful in quantitating the
severity of hepatic dysfunction
Ø Albumin: correlates well with the severity of functional impairment; decreased
levels found more often in chronic rather than in acute liver disease
Ø A-globulins: tend to decrease in chronic liver disease
Ø low or absent A-globulin suggests A-antitrypsin deficiency as the cause of the chronic
liver disease
Ø Ү-globulin levels: transiently increased in acute liver disease and remain elevated
in chronic liver disease; highest levels found in chronic active hepatitis and post-
necrotic cirrhosis.
Ø IgG and IgM levels: chronic active hepatitis
Ø IgM: primary biliary cirrhosis
Ø IgA: alcoholic cirrhosis.
 Metabolic Tests (for Synthetic
Protein Metabolism Function)
Ø Prothrombin time:
Ø Prolonged in liver disease due to:
Ø disruption of bile flow resulting to inadequate intestinal absorption of vitamin K
Ø inability to manufacture adequate amounts of clotting factor
Ø Vitamin K Response test: differentiates Vitamin K malabsorption/deficienc from loss of
hepatic capacit
Ø Not routinely used to aid in the diagnosis of liver disease: serial measurements maybe
useful in following the progression of disease and the assessment of the risk of bleeding.
Ø A marked prolongation of the prothrombin time indicates severe diffuse liver disease and
a poor prognosis.
 Metabolic Tests (for Synthetic
Function)
Nitrogen Metabolism/Ammonia Detemination
Ø Liver plays a major role in removing ammonia from the bloodstream and
converting it to urea so that it can be removed by the kidneys
Ø Ammonia level: reflection of the liver’s ability to perform mentioned conversion
Ø Liver failure: ammonia and other toxins increase in the bloodstream, ultimately causing
hepatic coma
Ø Correlation between ammonia levels and the severity of the hepatic coma is poor:
ammonia levels are most useful when multiple measurements are made over time.
Ø 2-Oxoglutarate + NH4+ + NADPH⎯ GLDH → glutamate + NADP+ + H2O
Ø Sample of choice: plasma collected in EDTA, heparin, or potassium oxalate;
should be immediately placed on ice
 Metabolic Tests (for Synthetic
Function)
Carbohydrate Metabolism
Ø In liver disease, patients may have: hypoglycemia, decreased carbohydrate
tolerance, impaired glycogen synthesis
Ø Some tests for carbohydrate metabolism:
Ø Glucose tolerance test: cirrhosis
Ø Galactose tolerance test: abnormal results for hepatocellular jaundice, but normal for
obstructive jaundice

Lipid Metabolism
Ø Lipid metabolism abnormalities, usually caused by obstructive liver disease are
manifested by fatty deposits in the liver
Ø Marked increase: bile acids and salts (cholesterol
Ø Also affects fat-soluble vitamins
 Other Tests
1. Hepatitis Tests
2. Hippuric Acid test
3. AFP
4. CEA
5. Ceruloplasmin