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. 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 0.3-1 mg / 100 ml Clinical Jaundice > 3 mg Clinical Jaundice > 3 mg Latent jaundice < 3 mg Latent jaundice < 3 mg Jaundice is described clinically as :- Mild-<6mg\dl Mild-<6mg\dl Moderate- 6-15mg\dl Moderate- 6-15mg\dl Severe->15mg\dl Severe->15mg\dl 1 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. 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. 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. 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. 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. 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. 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. 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. 4 Dr S Chakradhar

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

6. MECHANISMS PRODUCING JAUNDICE 3. Decreased Hepatic conjugation Disturbances of bilirubin conjugation e.g. deficiency of enzymes 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 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 Extra hepatic cholestasis – obstruction of main bile ducts due to common bile duct stone, carcinoma of head of pancreas 6 Dr S Chakradhar

7. Unconjugated bilirubinConjugated Bilirubin It cannot pass in urine as it is not soluble in water It can pass in urine as it is water soluble Soluble in lipids & thus can cause damage to CNS Relatively insoluble. No damage to CNS Van den Bergh reaction is indirect (slowly) positive – indirect reacting bilirubin Van den Bergh reaction is direct (immediate) positive– direct reacting bilirubin Dr S Chakradhar 7

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

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

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

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

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

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

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

15. 2. Extracorpuscular defect Hemolytic disease of newborn Hemolytic disease of newborn Incompatible blood transfusion Incompatible blood transfusion Infections: Malarial parasite Infections: Malarial parasite Physical trauma - Severe burn Physical trauma - Severe burn Chemical trauma: lead poisoning Chemical trauma: lead poisoning Metabolic – uremia Metabolic – uremia Hypersplenism Hypersplenism 15 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 unconjugated bilirubin into the cells and transport of conjugated bilirubin into the canaliculi. Bilirubin transport may be impaired at any point between uptake of unconjugated bilirubin 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 biliary canaliculi. In addition, swelling of cells and oedema resulting from the disease itself may cause obstruction of the biliary canaliculi. In hepatocellular jaundice the concentrations of both unconjugated and conjugated bilirubin in the blood increase In hepatocellular jaundice the concentrations of both unconjugated and conjugated bilirubin in the blood increase 16 Dr S Chakradhar

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

18. Obstructive Jaundice Also called cholestasis i.e. failure of bile flow due to obstruction Also called cholestasis i.e. failure of bile flow due to obstruction Due to the blockage, the conjugated bilirubin enters the circulation. 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 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 Obstruction in the biliary tract distal to bile canaliculi Clinically there is jaundice with the pale stool & dark urine Clinically there is jaundice with the pale stool & dark urine The bilirubin in the serum is conjugated The bilirubin in the serum is conjugated Dr S Chakradhar 18

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

20. PointsHaemolyticHepatocellularObstructive Urine UrobilinogenIncreasedNot so Increased Normal or reduced Stool ColorIncreased darkPalePale or Normal Blood Serum Bilirubin Not very high [> 6 mg] Very High [> 50 mg] Moderately High [30-40mg] BilirubinUnconjugatedMixedConjugated Dr S Chakradhar 20

21. PointsHaemolyticHepatocellularObstructive Common causes Haemolytic anemia Viral hepatitis,Gallstones, carcinoma of head of Pancreas Past H/OFamily H/O or maybe a previous attacks H/O of contact, or of Inj. or of taking hepatotoxic drugs May be previous attacks [STONE] AgeChildhoodAny ageAny Age JaundiceMildMild deepDeep ItchingAbsent Present SpleenEnlargedAbsent LiverEnlargedEnlarged in CarcinomaAbsent Gall Bladder Not Palpable May be Palpable in Carcinoma, not with STONE Dr S Chakradhar 21

22. Dr S Chakradhar 22