Bilirubin Metabolism(simplified)

Lumhs Online Clinical Discussion Forum

The breakdown of heme produces bilirubin (an insoluble waste product) and other
bile pigments. Bilirubin must be made water-soluble to be excreted. This transfo
rmation occurs in five steps: formation, plasma transport, liver uptake, conjuga
tion, and biliary excretion.
Formation
About 250 to 350 mg of unconjugated bilirubin forms daily; 70 to 80% derives fro
m the breakdown of degenerating RBCs, and 20 to 30% (early-labeled bilirubin) de
rives primarily from other heme proteins in the bone marrow and liver. Hb is deg
raded to iron and biliverdin, which is converted to bilirubin.
Plasma transport
Unconjugated (indirect-reacting) bilirubin is not water-soluble and so is transp
orted in the plasma bound to albumin. It cannot pass through the glomerular memb
rane into the urine. Albumin binding weakens under certain conditions (eg, acido
sis), 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 serum alb
umin.
Conjugation
Unconjugated bilirubin in the liver is conjugated to form mainly bilirubin diglu
curonide, or conjugated (direct-reacting) bilirubin. This reaction, catalyzed by
the microsomal enzyme glucuronyl transferase, renders the bilirubin water-solub
le.
Biliary excretion
Tiny canaliculi formed by adjacent hepatocytes progressively coalesce into ductu
les, interlobular bile ducts, and larger hepatic ducts. Outside the porta hepati
s, 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 const
ituents. In the intestine, bacteria metabolize bilirubin to form urobilinogen, m
uch of which is further metabolized to stercobilins, which render the stool brow
n. In complete biliary obstruction, stools lose their normal color and become li
ght gray (clay-colored stool). Some urobilinogen is reabsorbed, extracted by hep
atocytes, and re-excreted in the bile (enterohepatic circulation).
A small amount is excreted in the urine.
Because conjugated bilirubin is excreted in urine and unconjugated bilirubin is
not, only conjugated hyperbilirubinemia (eg, due to hepatocellular or cholestati
c jaundice) causes bilirubinuria.