1. Bilirubin Metabolism & Jaundice

2. Formation of Bilirubin from Heme
Heme is degraded in RE system (esp. liver & spleen)
85% from RBCs
15% from turnover of immature RBCs & cytochromes
Heme
heme oxygenase
biliverdin (green)
bilirubin (red-orange)
bile pigments
In Blood with albumin
UNCONJUGATED BILIRUBIN
(or INDIRECT BILITUBIN)
Salicylates & sulfonamides can displace
bilirubin from albumin & so bilirubin enters CNS causing neural damage

3. Bilirubin Metabolism in the Liver
Uptake of Bilirubin by hepatocytes:
Bilirubin dissociates from its carrier albumin & enters hepatocytes
Conjugation of Bilirubin:
In hepatocytes, bilirubin is conjugated with two molecules of glucuronic
acid by the enzyme glucuronyl transferase
Excretion of bilirubin into bile:
Conjugated bilirubin (bilirubin diglucuronide) is transported into bile canalculi
& then into bile.
Process is energy dependent & is impaired in liver diseases

4. Bilirubin Metabolism in the Intestine
Conjugated bilirubin bacteria in the intestine Urobilinogen Stercobilin Reabsorbed in stool (brown) Kidney Urine Urobilin (yellow)

5. OVERVIEW OF BILIRUBIN METABOLISM

6. JAUNDICE IS NOT A DISEASE
Yellow color of skin, nail beds & sclera caused by deposition of bilirubin secondary to increased bilirubin levels in blood (hyperbilirubinemia)
JAUNDICE IS NOT A DISEASE
HOWEVER,
IT IS A SIGN OF
AN UNDERLYING DISEASE

7. Types of Jaundice
1- Hemolytic Jaundice 2- Obstructive Jaundice 3- Hepatocellular Jaundice

8. Hemolytic Jaundice Massive lysis of RBCs in hemolytic anemia
e.g. sickle cell anemia
Bilirubin is produced in a rate faster than rate of
conjugation by the liver
Blood:
Increased blood unconjugated (indirect) bilirubin
Urine:
Urobilinogen is increased
No bilirubin in urine (Color of urine is normal)
as it is bound to albumin
Stool
Dark color
Increased stercobilin (produced from increased urobilinogen)

9. Obstructive Jaundice
In bile duct obstruction: Conjugated bilirubin is prevented from passing to the intestine. Thus, it is regurged to blood increasing conjugated (direct) bilirubin in blood Excessive conjugated bilirubin is excreted in urine giving the yellowish brown color of urine Blood: Increased conjugated (direct) bilirubin GGT & ALP are markedly elevated (ALT is normal or mildly elevated) Urine: Bilirubin appears in urine Thus, color is yellowish brown Urobilinogen is reduced Stool Pale (low stercobilin)

10. Hepatocellular Jaundice
First Liver damage (by hepatitis or hepatitis) causes low conjugation efficiency leading to increased unconjugated (indirect) bilirubin in blood Second Conjugated bilirubin is not efficiently secreted into bile. Instead, diffuses to blood increasing conjugated (direct) bilirubin in blood Blood Increased BOTH unconjugated (indirect) & conjugated (direct) bilirubin ALT & AST levels are markedly elevated Urine: Bilirubin is present in urine So, urine color is yellowish brown Stool Pale (low stercobilin)

11. LABORATORY INVESTIGATIONS IN TYPES OF JAUNDICE
BLOOD
URINE
GGT & ALP
ALT & AST
CONJUGATED
BILIRUBIN
UNCONJUGATED
UROBILINOGEN
NORMAL
N: mg/dl
N: 0.2 – 1 mg/dl
NIL
TRACE
INCREASED
INCREASD
HEMOLYTIC
JAUNDICE
MARKED
INCREASE
Normal or
mild increase
PRESENT
Decreased or absent
OBSTRUCT.
HEPATOCEL. JAUNDICE

12. Jaundice in Newborns In newborns (especially premature),
Bilirubin accumulates as the liver enzyme bilirubin glucuronyl transferase
(responsible for conjugation of bilirubin) is low at birth. (The enzymes reaches
adult levels in about 4 weeks)
Accordingly, unconjugated bilirubin is increased in blood.
Elevated bilirubin in excess of the binding capacity of albumin can diffuse
into basal ganglia & cause toxic encephalopathy (kernicterus)
Treatment
Exposure of the newborn skin to blue fluorescent light which converts
bilirubin to more polar & hence water-soluble isomers
These isomers can be excreted into bile without conjugation to glucuronic
acid.

14. Congenital hyperbilirubinemia
Bilirubin is elevated in blood due to inherited defects in the bilirubin metabolic pathway
Crigler-Najjar syndrome
Low activity of glucoronyltransferase (conjugating enzyme)
Rare Inherited l disease
Severe hyperbilirubinemia in neonates (unconjugated bilirubin)
Complicated by kernicterus & early death
Gilbert`s syndrome
Decreased production (expression) of glucoronyltransferase
Rare autosomal dominant trait
More common men
Occurs in 2-3 % of men
Usually asymptomatic hyperbilirubinemia
Liver function tests are normal
Dubin-Johnson syndrome
Defect in transfer of conjugated bilirubin into the biliary canalculi
Conjugated hyperbilirubinemia.