Bilirubin Production

Eric NiederhofferSIU-SOM

Heme(250 to 400 mg/day)

Heme oxygenase

Biliverdin reductase

Hemoglobin(70 to 80%)

Erythroid cellsHeme proteinsmyoglobin, cytochromes

(20 to 25%)

Biliverdin

Bilirubin

NADPH + H+

NADP+

3 [O]

Fe3+ + CO

apoferritinferritin

indirectunconjugatedpre-hepatic

albumin

Bilirubin Processingalbumin-Bilirubin

ligandin

Bilirubin diglucuronide

ER

hepatocyte

UDP-Glucuronyl transferase

albumin

ligandin-Bilirubin

bile (gall bladder)

directconjugatedpost-hepatic

2 UDP-glucuronate

2 UDP

Bilirubin Excretion

Bilirubin diglucuronide

Intrahepatic urobilinogen cycle

StercobilinogenBacterial enzymes

BilirubinBacterial enzyme2 glucuronate

Bacterial enzyme

Urobilinogen

8H

liver

Urobilinkidneys urine

Stercobilin feces

kidneysintestines

Bilirubin Lab valuesBilirubin form Normal value

Total (elderly, adult, child)(newborn)

Critical value (adult)(newborn)

0.1 to 1.0 mg/dL1.0 to 12.0 mg/dL

>12 mg/dL>15 mg/dL

Pre-hepatic, unconjugated, indirect 0.0 to 0.8 mg/dL

Post-hepatic, conjugated, direct 0.0 to 0.25 mg/dL

Fecal urobilinogen 40 to 280 mg/day

Urine 0.0 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?