Bilirubin Production Eric Niederhoffer SIU-SOM Heme (250 to 400 mg/day) Heme oxygenase Biliverdin reductase Hemoglobin (70 to 80%) Erythroid cellsHeme proteins myoglobin, cytochromes (20 to 25%) Biliverdin Bilirubin NADPH + H + NADP + 3 [O] Fe 3+ + CO apoferritinferritin indirect unconjugated pre-hepatic albumin

Bilirubin Processing albumin-Bilirubin ligandin Bilirubin diglucuronide ER hepatocyte UDP-Glucuronyl transferase albumin ligandin-Bilirubin bile (gall bladder) direct conjugated post-hepatic 2 UDP-glucuronate 2 UDP

Bilirubin Excretion Bilirubin diglucuronide Intrahepatic urobilinogen cycle Stercobilinogen Bacterial enzymes Bilirubin Bacterial enzyme2 glucuronate Bacterial enzyme Urobilinogen 8H liver Urobilin kidneys urine Stercobilinfeces kidneys intestines

Bilirubin Lab values Bilirubin formNormal value Total (elderly, adult, child) (newborn) Critical value (adult) (newborn) 0.1 to 1.0 mg/dL 1.0 to 12.0 mg/dL >12 mg/dL >15 mg/dL Pre-hepatic, unconjugated, indirect0.0 to 0.8 mg/dL Post-hepatic, conjugated, direct0.0 to 0.25 mg/dL Fecal urobilinogen40 to 280 mg/day Urine0.0 to 0.02 mg/dL Conjugated bilirubin - water soluble - direct reaction with dyes Unconjugated bilirubin - water insoluble - alcohol is needed for dye (indirect) reaction Observe the color changes associated with heme degradation by watching the progress of a bruise (dark red to green to yellow).

Review Questions How is bilirubin produced? How is bilirubin transported in the blood? How is bilirubin eliminated from the body? What is the intrahepatic urobilinogen cycle? What clinical observations would you make concerning a patient’s inability to process bilirubin normally?