hepatic and biliary disorders
Laboratory Tests of the Liver and Gallbladder
Tests for Cholestasis
Bilirubin, the pigment in bile, is produced from the breakdown of heme proteins, mostly from the heme moiety of hemoglobin in senescent red blood cells. Unconjugated (free) bilirubin is insoluble in water and thus cannot be excreted in urine; most unconjugated bilirubin is bound toalbuminin plasma. Bilirubin is conjugated in the liver with glucuronic acid to form the more water-soluble bilirubin diglucuronide. Conjugated bilirubin is then excreted through the biliary tract into the duodenum, where it is metabolized into urobilinogens (some of which are reabsorbed and resecreted into bile), then into orange-colored urobilins (most of which are eliminated in feces). These bile pigments give stool its typical color. Hyperbilirubinemiaresults from one or more of the following: Increased bilirubin production Decreased liver uptake or conjugation Decreased biliary excretion (see Jaundice ) 20 micromol/L). Fractionation measures the proportion of bilirubin that is conjugated (ie, direct, so-called because it is measured directly, without the need for solvents). Fractionation is most helpful for Evaluation and for evaluating elevated bilirubin when other liver test results are normal, suggesting that hepatobiliary dysfunction is not the cause. 85%) reflects increased bilirubin production (eg, in hemolysis) or defective liver uptake or conjugation (eg, in Gilbert Syndrome ). Such increases in unconjugated bilirubin are usually 50%) results from decreased bile formation or excretion (cholestasis). When associated with other liver test abnormalities, a high serum bilirubin indicates hepatocellular and/or biliary tract dysfunction. Serum bilirubin is somewhat insensitive for liver dysfunction. However, the development of severe hyperbilirubinemia in Primary Biliary Cholangitis (PBC) (previously called primary biliary cirrhosis), and so cannot be excreted in urine. Bilirubinuria can be detected at the bedside with commercial urine test strips in Overview of Acute Viral Hepatitis or other hepatobiliary disorders, even before jaundice appears. However, the diagnostic accuracy of such urine tests is limited. Results can be falsely negative when the urine specimen has been stored a long time, vitamin C has been ingested, or urine contains nitrates (eg, due to An increase in levels of this hepatocyte enzyme suggests cholestasis. Results may not be specific because alkaline phosphatase consists of several isoenzymes and has a widespread extrahepatic distribution (eg, in the placenta, the small intestine, white blood cells, kidneys, and particularly bone). Alkaline phosphatase levels increase to≥4 times normal 1 to 2 days after onset of biliary obstruction, regardless of the site of obstruction. Levels may remain elevated for several days after the obstruction resolves because the half-life of alkaline phosphatase is about 7 days. Increases of up to 3 times normal occur in many liver disorders, including Chronic cholestatic liver disorders with hepatitis (ie, Overview of Acute Viral Hepatitis Cirrhosis None Space-occupying lesions (eg, Hepatocellular Carcinoma ) Infiltrative disorders (eg, Symptoms and Signs , Syphilitic hepatitis (alkaline phosphatase may be disproportionately elevated compared with modest changes in other liver tests) Post–liver transplant rejection Isolated elevations (ie, when other liver test results are normal) may accompany Focal liver lesions (eg, abscess, tumor) Partial or intermittent bile duct obstruction (eg, Choledocholithiasis and Cholangitis , Syphilitic hepatitis Infiltrative disorders Chronic cholestatic liver disorders (ie, Primary Biliary Cholangitis (PBC) , Post–liver transplant rejection Isolated elevations also occur in the absence of any apparent liver or biliary disorder, as in the following: Some cancers without apparent liver involvement (eg, Overview of Lung Tumors , After ingestion of fatty meals (because of an enzyme produced in the small intestine) Pregnancy (because of an enzyme produced in the placenta) Children and adolescents who are still growing (because of bone growth) Chronic renal failure (because of an enzyme produced in the intestine and bone) Levels of gamma-glutamyl transpeptidase or 5′-nucleotidase, which are more specific to the liver, can differentiate hepatic from extrahepatic sources of alkaline phosphatase better than fractionation of alkaline phosphatase, which is technically difficult. Also, in otherwise asymptomatic older people, an increase in alkaline phosphatase usually originates in bone (eg, in Paget disease) and may not require further investigation for liver injury. Increases in levels of this enzyme are as sensitive as alkaline phosphatase for detecting cholestasis and biliary obstruction but are more specific, almost always indicating hepatobiliary dysfunction. Because levels of alkaline phosphatase and 5′-nucleotidase do not always correlate, one can be normal while the other is increased. Levels of this enzyme increase in hepatobiliary dysfunction, especially cholestasis, and correlate loosely with levels of alkaline phosphatase and 5′-nucleotidase. Levels do not increase because of bone lesions, during childhood, or during pregnancy. However, alcohol and certain drugs (eg, some antiseizure medications,warfarin), herbs, and foods can induce hepatic microsomal (cytochrome P-450) enzymes, markedly increasing GGT and thus somewhat limiting its specificity. 