Harpers

284 / CHAPTER 32Table 32–3. Laboratory results in normal patients and patients with three different causes of jaundice.Condition Serum Bilirubin Urine Urobilinogen Urine Bilirubin Fecal UrobilinogenNormal Direct: 0.1–0.4 mg/dL 0–4 mg/24 h Absent 40–280 mg/24 hIndirect: 0.2–0.7 mg/dLHemolytic anemia ↑ Indirect Increased Absent IncreasedHepatitis ↑ Direct and indirect Decreased if micro- Present if micro- Decreasedobstruction is obstruction occurspresentObstructive jaundice 1 ↑ Direct Absent Present Trace to absent1 The commonest causes of obstructive (posthepatic) jaundice are cancer of the head of the pancreas and a gallstone lodged in the commonbile duct. The presence of bilirubin in the urine is sometimes referred to as choluria—therefore, hepatitis and obstruction of thecommon bile duct cause choluric jaundice, whereas the jaundice of hemolytic anemia is referred to as acholuric. The laboratory results inpatients with hepatitis are variable, depending on the extent of damage to parenchymal cells and the extent of micro-obstruction to bileductules. Serum levels of ALT and AST are usually markedly elevated in hepatitis, whereas serum levels of alkaline phosphatase are elevatedin obstructive liver disease.Urobilinogen & Bilirubin in UrineAre Clinical IndicatorsNormally, there are mere traces of urobilinogen in theurine. In complete obstruction of the bile duct, nourobilinogen is found in the urine, since bilirubin hasno access to the intestine, where it can be converted tourobilinogen. In this case, the presence of bilirubin(conjugated) in the urine without urobilinogen suggestsobstructive jaundice, either intrahepatic or posthepatic.In jaundice secondary to hemolysis, the increasedproduction of bilirubin leads to increased production ofurobilinogen, which appears in the urine in largeamounts. Bilirubin is not usually found in the urine inhemolytic jaundice (because unconjugated bilirubindoes not pass into the urine), so that the combinationof increased urobilinogen and absence of bilirubin issuggestive of hemolytic jaundice. Increased blood destructionfrom any cause brings about an increase inurine urobilinogen.Table 32–3 summarizes laboratory results obtainedon patients with three different causes of jaundice—hemolyticanemia (a prehepatic cause), hepatitis (a hepaticcause), and obstruction of the common bile duct (aposthepatic cause). Laboratory tests on blood (evaluationof the possibility of a hemolytic anemia and measurementof prothrombin time) and on serum (eg, electrophoresisof proteins; activities of the enzymes ALT,AST, and alkaline phosphatase) are also important inhelping to distinguish between prehepatic, hepatic, andposthepatic causes of jaundice.SUMMARY• Hemoproteins, such as hemoglobin and the cytochromes,contain heme. Heme is an iron-porphyrincompound (Fe 2+ -protoporphyrin IX) inwhich four pyrrole rings are joined by methenylbridges. The eight side groups (methyl, vinyl, andpropionyl substituents) on the four pyrrole rings ofheme are arranged in a specific sequence.• Biosynthesis of the heme ring occurs in mitochondriaand cytosol via eight enzymatic steps. It commenceswith formation of δ-aminolevulinate (ALA) fromsuccinyl-CoA and glycine in a reaction catalyzed byALA synthase, the regulatory enzyme of the pathway.• Genetically determined abnormalities of seven of theeight enzymes involved in heme biosynthesis result inthe inherited porphyrias. Red blood cells and liverare the major sites of metabolic expression of the porphyrias.Photosensitivity and neurologic problemsare common complaints. Intake of certain compounds(such as lead) can cause acquired porphyrias.Increased amounts of porphyrins or their precursorscan be detected in blood and urine, facilitating diagnosis.• Catabolism of the heme ring is initiated by the enzymeheme oxygenase, producing a linear tetrapyrrole.• Biliverdin is an early product of catabolism and onreduction yields bilirubin. The latter is transportedby albumin from peripheral tissues to the liver, whereit is taken up by hepatocytes. The iron of heme andthe amino acids of globin are conserved and reutilized.• In the liver, bilirubin is made water-soluble by conjugationwith two molecules of glucuronic acid and issecreted into the bile. The action of bacterial enzymesin the gut produces urobilinogen and urobilin,which are excreted in the feces and urine.• Jaundice is due to elevation of the level of bilirubinin the blood. The causes of jaundice can be classified