Bilirubin Production

Heme proteins
myoglobin, cytochromes
(20 to 25%)
ferritin

Hemoglobin
(70 to 80%)

Erythroid cells

Heme

(250 to 400 mg/day)

3 [O]
Heme oxygenase
3+
Fe + CO

apoferritin

Biliverdin
NADPH + H+
NADP+

Biliverdin reductase

Bilirubin

albumin

indirect
unconjugated
pre-hepatic
Eric Niederhoffer
SIU-SOM

Bilirubin Processing
albumin-Bilirubin
ligandin

albumin
hepatocyte

ligandin-Bilirubin

2 UDP-glucuronate
ER

UDP-Glucuronyl
transferase

2 UDP

Bilirubin diglucuronide
bile (gall bladder)

direct
conjugated
post-hepatic

Bilirubin Excretion
Bilirubin diglucuronide
2 glucuronate

liver

Bacterial enzyme

Intrahepatic
urobilinogen cycle

Bilirubin
8H
intestines

Bacterial enzyme

Urobilinogen

kidneys

Urobilin

urine

Stercobilin

feces

kidneys

Bacterial enzymes

Stercobilinogen

Bilirubin Lab values

Bilirubin form

Normal value

Total (elderly, adult, child)

0.1 to 1.0 mg/dL

(newborn)

1.0 to 12.0 mg/dL

Critical value (adult)

>12 mg/dL

(newborn)
Pre-hepatic, unconjugated, indirect

>15 mg/dL
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 patients inability to process
bilirubin normally?