hepatic and biliary disorders
Liver Structure and Function
Overview of bilirubin metabolism
The breakdown of hemoglobin produces bilirubin (an insoluble waste product) and other bile pigments. Bilirubin must be made water soluble to be excreted. This transformation occurs in 5 steps: formation, plasma transport, liver uptake, conjugation, and biliary excretion. Formation:About 250 to 350 mg of unconjugated bilirubin forms daily; 70 to 80% derives from the breakdown of degenerating red blood cells, and 20 to 30% (early-labeled bilirubin) derives primarily from other heme proteins in the bone marrow and liver. Hemoglobin is degraded to iron and biliverdin, which is converted to bilirubin. Plasma transport:Unconjugated (indirect-reacting) bilirubin is not water soluble and so is transported in the plasma bound toalbumin. It cannot pass through the glomerular membrane into the urine.Albuminbinding weakens under certain conditions (eg, acidosis), and some substances (eg, salicylates, certain antibiotics) compete for the binding sites. Liver uptake:The liver takes up bilirubin rapidly but does not take up the attached serumalbumin. Conjugation:Unconjugated bilirubin in the liver is conjugated to form mainly bilirubin diglucuronide (conjugated [direct-reacting] bilirubin). This reaction, catalyzed by the microsomal enzyme glucuronyl transferase, renders the bilirubin water soluble. Biliary excretion:Tiny canaliculi formed by adjacent hepatocytes progressively coalesce into ductules, interlobular bile ducts, and larger hepatic ducts. Outside the porta hepatis, the main hepatic duct joins the cystic duct from the gallbladder to form the common bile duct, which drains into the duodenum at the ampulla of Vater. Conjugated bilirubin is secreted into the bile canaliculus with other bile constituents. In the intestine, bacteria metabolize bilirubin to form urobilinogen, much of which is further metabolized to stercobilins, which render the stool brown. In complete biliary obstruction, stools lose their normal color and become light gray (clay-colored stool). Some urobilinogen is reabsorbed, extracted by hepatocytes, and re-excreted in bile (enterohepatic circulation). A small amount is excreted in urine. Because conjugated bilirubin is excreted in urine and unconjugated bilirubin is not, only conjugated hyperbilirubinemia (eg, due to hepatocellular or cholestatic jaundice) causes bilirubinuria. 