Senescent RBCs are taken up by macrophages in the reticuloendothelial system, where catalytic degradation of hemoglobin leads to release of unconjugated bilirubin (UnBr). As measured by a bilirubin test, the concentration of indirect bilirubin (calculated by subtracting the direct-reacting fraction from the total bilirubin concentration) correlates with the concentration of UnBr. UnBr, bound to albumin, travels in the blood to the liver. Hepatocytes take up UnBr and conjugate it to one or two glucuronic acid residues. Bilirubin travels through the biliary system to the duodenum; most bilirubin in bile is conjugated but some UnBr (up to 4%) in bile or UnBr formed by enteric bacterial deconjugation undergoes enterohepatic recycling. In the terminal ileum and colon, bacterial proteases reduce bilirubin diglucuronide to urobilinogen. Approximately 15% to 20% of urobilinogen is returned to the liver via the portal vein. Urobilinogen remaining in the colon can be converted to stercobilinogen, among other metabolites. Stercobilinogens and urobilins are excreted in feces. Urobilinogen is also excreted in urine.
Courtesy of Dr. Sharon Center.