Pathology of Jaundice

1. Jaundice
Dr. Anurag Yadav
BHMS, MD(Hom)

2. Jaundice
•Hyperbilirubinemia- > 0.3-1.2 mg/dl
•Jaundice- > 2.0-2.5 mg/dl
•Icterus- Yellow discoloration of Sclera
•Cholestasis- All Bile elements

3. Source Of Bilirubin
•Major- (85%) Derived from catabolism of Hb
by RE system (breakdown of senescent red cells. )-
0.2-0.3 mg/dl
•Minor- (15%) Degradation of Heme produced from
other sources (e.g. the P-450 cytochromes) and from
premature destruction of hemoglobin in developing
red cell precursors in the bone marrow.

5. Kernicterus
In hemolytic disease of new born(Erythroblastosis fetalis)
High concentrationof free unconjugated Bilirubin
Cross Blood Brain Barrier, reaches Brain
Cause severe irreversible neurological damage

6. Kernicterus
- Deposition of excess
bilirubin to brain mainly
Basal Ganglia
-C/f – 3 phases
• Decreased alertness,
Hypotonia, poor feeding,
•Hypertonia, Opisthotonus
•Hypotonia.

7. Types Of Bilirubin
•Unconjugated bilirubin-
- Insoluble in water pass.
- Cannot be excreted in the urine even
when Its levels are high in the blood.
- Present in the circulation forming tight
complexes with serum albumin.
•Conjugated bilirubin-
- Water-soluble, nontoxic
- Loosely bound to albumin in the plasma
- Excess conjugated bilirubin in plasma can
be excreted in urine

8. Jaundice
It is defined as Yellowish pigmentation
(discoloration) of Skin, Mucus membrane &
Sclera due to increased levels of bilirubin
(Hyperbilirubinemia) in the blood.
- Normal bilirubin level- 0.3-1.2 mg/dl
- Jaundice- 2.0-2.5 mg/dl
- Latent Jaundice- 1.2-2.0 mg/dl- wthout
clinical menifestation

9. Classification of Jaundice
•Based on the underlying cause -
- Predominantly unconjugated hyperbilirubinemia
- Predominantly conjugated hyperbilirubinemia
• Based on pathological mechanism -
- Hemolytic jaundice.
- Hepatocellular jaundice.
- Obstructive jaundice.

10. Other Classification
•1-
- Pre-hepatic (Haemolytic)
- Hepatic (Toxic)
- Post-hepatic (Obstructive)
• 2-
- Medical
- Surgical

11. Mechanism of Jaundice
1- Predominantly Unconjugated
Hyperbilirubinemia
2- Predominantly Conjugated
Hyperbilirubinemiaz
Eqilibirium between bilirubin production &
clearance is disturbed.

12. Predominantly Unconjugated
1- Excessive Extrahepatic Production of Bilirubin-
- Hemolytic Anemias
- Ineffective erythropoiesis (Thalassemia,
Pernicious anemia )
- Resorption of blood from internal
hemorrhage (GIT bleeding, Hematomas)

13. Predominantly Unconjugated
2- Reduced Hepatic Uptake-
- Drug interference with membrane
carrier systems
- Some cases of Gilbert syndrome
3- Impaired Bilirubin Conjugation-
- Physiological Jaundice of Newborn
- Diffuse hepatocellular disease (Viral or
drug induced hepatitis, cirrhosis) ….

14. ....
- Crigler–Najjar syndrome types I and II
- Gilbert syndrom
Breast Milk Jaundice-
Neonatal jaundice, may be exacerbated by
breastfeeding, due to the presence of bilirubin-
deconjugating enzymes in breast milk.

15. Gilbert Syndrome
- Genetically inherited disorder with no clinical
consequences. (Most commonest)
- It is inherited as Autosomal recessive
- It leads to mutations in the UGT1 gene.
- Affecting 2-5% of population
- Mild, chronic unconjugated hyperbilirubinemia
which is not due to haemolysis.
- Usually jaundice devoloped is asymptomatic,
or mild & intermittent.

16. Crigler-Najjar Syndrome
Two forms of this condition
- Crigler–Najjar Syndrome Type 1
- Crigler–Najjar Syndrome Type 2
Crigler–Najjar syndrome: Basic abnormality
is impaired conjugation of bilirubin

17. Crigler–Najjar Syndrome Type 1-
- Rare, autosomal recessive disorder due to
complete absence of hepatic UGT1A1.
- Characterized by chronic, severe,
unconjugated hyperbilirubinemia produce
severe jaundice, icterus and death secondary
to kernicterus within 18 months of birth.
- Liver is morphologically normal by light and
electron microscopy
- Extreme elevation of Unconjugated bilirubin
(usually more than 20 mg/dl)

18. Crigler–Najjar Syndrome Type 2-
- Autosomal dominant disorder.
- Partial deficiency of UGT1A1 enzyme.
- Less severe, nonfatal disorder
- Unconjugated hyperbilirubinaemia is mild to
moderate (usually less than 20 mg/dl)

19. Predominantly Conjugated
1- Decreased Hepatocellular Excretion-
- Drug-induced canalicular membrane
dysfunction (Oral contraceptives,
Cyclosporine)
- Hepatocellular damage or Toxicity (Viral or
drug induced hepatitis, systemic infection,
Total parenteral nutrition )

20. Predominantly Conjugated
2- Impaired Bile Flow (Intra/Extra Hepatic)-
- Inflammatory destruction of intrahepatic bile
ducts (Primary biliary cirrhosis, Primary
sclerosing cholangitis, liver transplantation
- Gallstones(Most common surgical cause of
obstructive jaundice is- Common bile duct
stones)
- External Compression (carcinoma of pancreas)

22. Clinical Features
Common signs and symptoms seen in individuals
with jaundice include-
- Yellow discoloration of the skin, mucous
membranes, and the whites of the eyes
- Light-colored stools
- Dark-colored urine
- Itching of the skin

23. The underlying disease process may result in
additional signs and symptoms. These may include-
• Nausea and vomiting,
• Abdominal pain,
• Fever,
• Weakness,
• Loss of appetite,
• Headache,
• Confusion,
• Swelling of the legs and abdomen

24. Lab Diagnosis
Laboratory Tests-
•Liver function test (Serum Bilirubin)
•FBC/Peripheral blood film
•Urine for urobilinogen (haemolytic) or
bilirubin (cholestatic)
•Reticulocyte count
•Serology for viral hepatitis
•PT/APTT
The following tests may be performed-

25. Lab Diagnosis
Imaging (Non invasive)-
• Ultrasound hepato-biliary system
• Computerised Tomography (CT) Scan
• Magnetic resonance cholangiopancreatography
(MRCP)/Magnetic resonance imaging (MRI)

26. Lab Diagnosis
Invasive procedure- diagnostic and
therapeutic)-
• Endoscopic retrograde
cholangiopancreatography (ERCP)
• Percutaneous transhepatic cholangiography
(PTC)
• Endoscopic ultrasonography (EUS)

27. Van Den Bergh Test
Test done to determine type of Jaundice-
There are three main reactions
• Direct Reaction
a) Immediate or Prompt
b) Delayed
• Biphasic Reaction
• Indirect Reaction

28. Van Den Bergh Test
Conclusions-
• Vanden Berg test is direct & prompt-Obstructive
• Vanden Berg test is indirect- Haemolytic
• Vanden Berg test is delayed direct/ biphasic-
Toxic jaundice where parenchymatous liver
damage is seen

29. Thank You