Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (170 page)

   Uptake phase: Unconjugated bilirubin is bound to albumin and is presented to the hepatocyte, where the complex dissociates and bilirubin enters the cell either by diffusion or by transport across the membrane.

   Conjugation phase: Bilirubin is then conjugated in a two-step process. This occurs in the endoplasmic reticulum and is catalyzed by glucuronyl transferase. Bilirubin glucuronide is generated.

   Excretion phase: In an energy-dependent process occurring in the biliary canaliculi, conjugated bilirubin is excreted into the bile. It is important to remember that this is the rate-limiting step. When this phase is impaired, either through obstruction or through excretory defects, the conjugated bilirubin is presumed to reflux through the hepatic sinusoids into the bloodstream.

   Intestinal phase: After excretion into the bile, conjugated bile is transported into the duodenum. It is not reabsorbed by intestinal mucosa. In the intestine, it is either excreted in the feces unchanged or metabolized by intestinal bacteria to urobilinogen. Urobilinogen is then reabsorbed, where a small portion is metabolized in the liver, and the remainder bypasses the liver and is excreted by the kidney.

   Differential Diagnosis of Jaundice (Table
5-6
)

   Extrahepatic biliary obstruction

   The history, physical examination, and initial laboratory assessment have a sensitivity of 90–95%. The specificity, however, is only 76%. When radiologic imaging is factored in, the specificity rises to 98%.

   Approximately 40% of patients with this diagnosis present with jaundice.

   In the setting of complete obstruction, alcoholic stools are seen and no urobilinogen is detected in the urine (see Cancer Head of the Pancreas, Acute Abdomen).

   In patients with extrahepatic biliary obstruction, ALP would be expected to rise to levels 2–3 times normal. A normal level would be uncommon. Serum transaminases would generally be <300 U/L.

   Intrahepatic cholestasis: Consider intrahepatic etiologies in the differential diagnosis because high levels may be seen in patients with primary biliary cirrhosis and granulomatous hepatitis.

   This group of disorders is defined by the lack of evidence of mechanical obstruction and cannot be explained on the basis of hepatocellular injury alone. Among these disorders are those characterized by disordered enzyme function (intrinsic/acquired), infiltrative disorders, and drugs.