Jaundice Pathology

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.

4. 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

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

6. 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

7. 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

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

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

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

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

12. 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) ….

13. .... - 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.

14. 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.

15. 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

16. 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)

17. 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)

18. 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 )

19. 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)

20. Clinical Features Common signs and symptoms seen in individuals with jaundice include- - Y ellow discoloration of the skin, mucous membranes , and the whites of the eyes - Li ght- colored stools - D ark- colored urine - Itching of the skin

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

22. 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-

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

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

25. 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

26. 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

27. Thank You