JAUNDICE Definition :-

1. JAUNDICE Definition:- • Jaundice refers to the yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentration in the body fluids. Normal values • 0.3-1 mg / 100 ml • Clinical Jaundice > 3 mg • Latent jaundice < 3 mg Jaundice is described clinically as :- • Mild-<6mg\dl • Moderate- 6-15mg\dl • Severe->15mg\dl Dr S Chakradhar

2. Dr S Chakradhar

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4. BILIRUBIN METABOLISM • Unconjugated bilirubin is produced from the catabolism of haem after removal of its iron component. • Bilirubin in blood is normally almost all unconjugated and it is not water soluble, it is bound to albumin and does not pass into urine. • Unconjugated bilrubin is conjugated by the endoplasmic reticulum enzyme, glucuronyl transferase, into mono and diglucuronide. • These bilirubin conjugates are water soluble and exported into the bile via specific carriers on the haepatocyte membrane. • Conjugated bilirubin is metabolised by colonic bacteria to form stercobilinogen,which may be further oxdised to stercobilin. • Both stercobilin and stercobilinogen are then excreted in the stool. • A small amount of stercobilinogen is absorbed from the bowel,passes through the liver and is excreted in the urine ,where it is known as urobilinogen,or following further oxidation, urobilin. Dr S Chakradhar

5. MECHANISMS PRODUCING JAUNDICE 1. Increased production of bilirubin • Haemolysis 2. Decreased Hepatic uptake • Defect in the process of bilirubin diffusion into the cells from the sinusoids Dr S Chakradhar

6. MECHANISMS PRODUCING JAUNDICE 3. Decreased Hepatic conjugation • Disturbances of bilirubin conjugation e.g. deficiency of enzymes 4. Impaired excretion of bilirubin • Intrahepatic chelestasis – defect in transport of bile from microsome to main bile duct e.g. viral hepatitis, drugs • Extra hepatic cholestasis – obstruction of main bile ducts due to common bile duct stone, carcinoma of head of pancreas Dr S Chakradhar

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8. 1. Pathophysiological Classification of Jaundice Predominantly unconjugated hyperbilirubinaemia 1. Excessive production of bilirubin • Haemolytic anemia • Resorption of blood from internal haemorrhage ( hematoma, GI bleeding) 2.Reduced hepatic uptake • Drugs interferance with membrane carrier protein • Glibert’s syndrome (some) Dr S Chakradhar

9. Predominantly unconjugated hyperbilirubinaemia 3. Impaired bilirubin conjugation • Gilbert’s syndrome- hereditary disorder - reduced activity of the enzyme glucuronyltransferase • Physiological jaundice of newborn as glucuronyltransferase is low at birth • Breast milk jaundice • Diffuse hepatocellular disease e.g. viral hepatitis, cirrhosis Dr S Chakradhar

10. Predominantly conjugated hyperbilirubinaemia Decreased intrahepatic excretion of bile • Hepatocellular damage e.g. viral hepatitis, drug induced hepatitis • Deficiency of canalicular membrane transport (Dubin johnson syndrome, rotor’s syndrome) • Oral contraceptives • Intrahepatic bile duct disease e.g. primary biliary cirrhosis Extrahepatic biliary obstruction • Obstruction by gallstone • Ca. of head of Pancreas, ampulla of vater or extrahepatic bile duct • Others like atresia , cyst in biliary tree, liver flukes Dr S Chakradhar

11. 2. Clinical classification 1. Haemolytic jaundice [pre Hepatic] • Due to increased RBC Breakdown 2. Hepatocellular jaundice [hepatic] • Due to Hepatocellular damage 3. Cholestatic or Obstructive jaundice [post hepatic] • Due to obstruction of Bile flow & its cause may lie anywhere between the Hepatocytes & Duodenum • a) intrahepatic (medical) • b) extrahepatic (surgical) Dr S Chakradhar

12. 1)HAEMOLYTIC JAUNDICE • Results from increased destruction of red blood cells, or their precursors in the marrow, causing increased bilirubin production. Dr S Chakradhar

13. 1. Intracorpuscular Defect a. Cell membrane Defect • Spherocytosis • elliptocytosis b. Enzyme deficiency • Glucose 6 phosphate dehydrogenase deficiency • Hexokinase deficiency Dr Chakradhar

14. c. Disorders of hemoglobin synthesis • Thalassemia - Deficient α or β chain of globin synthesis • Hemoglobinopathies - Structurally abnormal globin synthesis e.g sickle cell anemia Dr Chakradhar

15. 2. Extracorpuscular defect • Hemolytic disease of newborn • Incompatible blood transfusion • Infections: Malarial parasite • Physical trauma - Severe burn • Chemical trauma: lead poisoning • Metabolic – uremia • Hypersplenism Dr Chakradhar

16. 2)HEPATOCELLULAR JAUNDICE It results from an inability of the liver to transport bilirubin into the bile occuring as a consequences of parenchymal liver disease. • Bilirubin transport may be impaired at any point between uptake of unconjugatedbilirubin into the cells and transport of conjugated bilirubin into the canaliculi. • In addition, swelling of cells and oedema resulting from the disease itself may cause obstruction of the biliarycanaliculi. • In hepatocellular jaundice the concentrations of both unconjugated and conjugated bilirubin in the blood increase Dr S Chakradhar

17. CAUSES • Acute Hepatitis • Chronic hepatitis or Cirrhosis • Toxic Injury to Liver by • Drugs - rifampicin, INH , • Alcohol Dr S Chakradhar

18. Obstructive Jaundice • Also called cholestasis i.e. failure of bile flow due to obstruction • Due to the blockage, the conjugated bilirubin enters the circulation. Intrahepatic • Due to parenchymal liver damage or excretory dysfunction of bile canaliculi at a cellular level Extra hepatic • Obstruction in the biliary tract distal to bile canaliculi • Clinically there is jaundice with the pale stool & dark urine • The bilirubin in the serum is conjugated Dr S Chakradhar

19. CAUSES OF CHOLESTATIC JAUNDICE Intrahepatic • Viral hepatitis • Drugs • Alcohol • Primary biliary cirrhosis • Pregnancy Extrahepatic • Choledocholithiasis • Carcinoma of • Ampullary • head of Pancreatic • Bile duct (cholangiocarcinoma) • Parasitic infection • Biliary strictures Dr S Chakradhar

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