Basic description on Jaundice Pathology.

1. AMAR RAUT CHHETRI,
KATHMANDU MEDICAL COLLEGE
AND TEACHING HOSPITAL, NEPAL
JAUNDICE (Pathology)

2.  Jaundice or icterus refers to the yellow pigmentation
of skin or sclera by bilirubin.
Jaundice is the result of elevated levels of bilirubin in
the blood termed hyperbilirubinaemia.
Normal serum bilirubin concentration 0.3-1.2mg/dl
( 80% of which is unconjugated).
Jaundice becomes clinically evident when the total
serum bilirubin is >2mg/dl.

3. Bilirubin metabolism and elimination

4. • Sources of unconjugated bilirubin :
Hemoglobin breakdown
Catabolism of other haem containing protein
e.g. :myoglobin & cytochrome containing enzyme.
Ineffective erythropoiesis

5. • Rate of production of unconjugated
bilirubin 250 to 350 mg/day from
catabolism of haem after removal of its
iron component.
• Bilirubin in the blood is normally almost
all unconjugated.
It is not water soluble.
It is bound to albumin.
It does not pass into urine.

6. • In the endoplasmic reticulum :
Unconjugated bilirubin by glucoronyl
trasferase  bilirubin mono and di
glucoronide which are : water soluble
exported into bile.
• In the colon :
Conjugated bilirubin is metabolized by
colonic bacteria forming stercobilinogen
which is further oxidized into stercobilin.
Both stercobilinogen and stercobilin are
excreted in the stools.

7. Small amount of stercobilinogen (4 mg/dl) is
absorbed from the bowel, pass through the liver and
excreted in urine (urobilinogen) which is further
oxidized into urobilin.

8. Classification
Pre-hepatic (haemolytic) jaundice
Hepatic jaundice
Post-hepatic (obstructive) jaundice

9. Causes of Jaundice
Predominantly unconjugated
hyperbilirubinemia
Excess production of bilirubin
Hemolytic anemias
Resorption of blood from internal hemorrhage
(e.g., alimentary tract bleeding, hematomas)
Ineffective erythropoiesis (e.g., pernicious
anemia, thalassemia)

10. Reduced hepatic uptake
 Drug interference with membrane carrier systems
Some cases of Gilbert syndrome
Impaired bilirubin conjugation
Physiologic jaundice of the newborn (decreased
UGT1A1 activity, decreased excretion)
Breast milk jaundice (β-glucuronidases in milk)
Genetic deficiency of UGT1A1 activity (Crigler-Najjar
syndrome types I and II)

11. Gilbert syndrome
Diffuse hepatocellular disease (e.g., viral or drug-
induced hepatitis, cirrhosis)
Predominantly conjugated
hyperbilirubinemia
Deficiency of canalicular membrane transporters
(Dubin-Johnson syndrome, Rotor syndrome)
Impaired bile flow

12. Hemolytic jaundice
Etiology:
• Increased destruction of RBCs or their precursors
leading to increased bilirubin production.
• It is usually mild.
• Healthy liver can excrete a bilirubin load six times
greater than normal before unconjugated bilirubin
accumulates in the plasma.

13. In haemolytic jaundice:
Increased unconjugated bilirubin, urobilinogen,
stercobilinogen

14. Clinical features
• Pallor due to anemia.
• Increaed excretion of bilirubin and stercobilinogen
 normal coloured stool or dark stool.
• Increased urobilinogen excretion  urine darkens
on standing.
• Splenomegaly due to excess RE activity.
• Pigment stones.
• Leg ulcers.

15. Investigations
Biochemical tests:
-Unconjugated bilirubin is high.
-Liver function tests otherwise
normal.
 Blood count : anemia
 Blood film : evidence of hemolysis

16. Hepatocellular jaundice
Etiology:
• Inability of the liver to transport bilirubin into the
bile as a result of parenchymal liver disease.
• Bilirubin transport across the hepatocytes may be
impaired at any point between the uptake of
unconjugated bilirubin into the cells and transport of
conjugated bilirubin into canaliculi.

17. • In addition, swelling of the cells and
oedema resulting from the disease itself
may cause obstruction of biliary canaliculi.
• Hepatocellular jaundice:
Increaesd conjugated bilirubin,
unconjugated bilirubin, stercobilinogen,
urobilinogen

18. Clinical manifestations
• Lemon yellow jaundice.
• Dark urine.
• +/- manifestations of chronic liver disease:
- Ascites
-Circulatory changes: palmar eryth., spider naevi.
-Endocrine: hair loss, gynecomastia.
-Haemorrahgic tendency.
-Manifestations of hepatic encephalopathy.
-Manifestations of portal hypertension.
-Others: pigmentations, clubbing, low grade fever.

19. Investigations
Biochemical tests:
Plasma bilirubin : biphasic increase both
conjugated & unconjugated.
Greater elevation of enzymes.
Evidence of chronic liver disease: decrease plasma
protein, increased prothrombin time.

20. Cholestatic jaundice
Etiology & pathogenesis:
• Conjugated bilirubin is unable to enter the bile
canaliculi and passes back into blood.
• Failure of clearance of unconjugated bilirubin arriving
at the liver cells.
• Causes:
-Failure of hepatocytes to generate bile flow.
-Obstruction to the bile flow in bile ducts in the portal
tracts.
-Obstruction to bile flow in the extrahepatic bile ducts
between porta-hepatis and papillae of Vater.

21. Causes of intrahepatic obstruction
• 1 ry biliary cirrhosis
• Auto-immune hepatitis
• 1 ry sclerosing cholangitis
• Alcohol
• Drugs
• Pregnancy
• Viral hepatitis
• Severe bacterial infection

22. Causes of extrahepatic obstruction
Choledocholithiasis
Carcinoma
Parasitic infection
Traumatic: biliary stricture

23. In cholestatic jaundice:
-Increased S. bilirubin mainly conjugated.
-Decreased stercobilinogen and stercobilin.

24. Clinical features
Early: jaundice, pale stools, pruritis.
Late: xanthelasma & xanthomata,
malabsorption, weight loss, steatorrhea,
osteomalacia, bleeding tendency.
In addition to clinical picture of cholangitis
underlying chronic liver disease.

25. Investigations
Biochemical tests:
-Increased bilirubin mainly conjugated.
-Increased serum bile acids, alk. Phosphatase and
hyperlipidaemia.
Ultrasound to differentiate intra from extra- hepatic
biliary obstruction.

26. THANKS, Cheers 
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