JAUNDICE.pptx

Seminar on jaundice for medical students . Post graduation students . DNB medicine students

1. JAUNDICE

2. Introduction Jaundice/ icterus, is a condition characterized by yellow discoloration of skin, conjunctivae, and mucus membranes as a result of widespread tissue deposition of the pigmented metabolite bilirubin. Normal total bilirubin level <1-1.5mg/dl Jaundice seen if Value exceeds 3mg/dl Bilirubin have high affinity for elastin rich tissues eg sclera, frenulum of tongue,so jaundice appear first here .

3. Bilirubin metabolism bilirubin is the end product of heme Degradation

4. Bilirubin uptake to be mediated by liver specific bilirubin transporter (BT) by facilitating diffusion process and by simple diffusion process Intracelluar binding to S- glutathion transferase to keep bilirubin in solution Conjugation with uridine diphosphate (UDP)-glucuronic acid done by the enzyme bilirubin UDP- glucuronosyl transferase(B-UGT1A1) into monoglucuronide,diglucuronide Conjugated bilirubin transported into the bile canaliculu s by an ATP-dependant export pump eg.MRP-2,ABCC2

5. Conjugated bilirubin in intestine converted to Urobilinogen by bacterial action which undergo hepatic reuptake and partly renal elimination. Small amount secreted across sinusoidal membrane by MRP-3,that undergo renal elimination and reuptake to hepatocyte by OAP1B1,OATP1B3

6. Differential diagnosis of jaundice Isolated disorders of bilirubin metabolism- Unconjugated hyperbilirubinemia - • Increased bilirubin production - Haemolysis Ineffective erythropoiesis Blood transfusion Resorption of hematomas • Decreased hepatocellular uptake - Drugs such as rifampicin Various cholecystography contrast agents

7. • Decreased conjugation – Gilbert’s syndrome, Crigler-Nazzer syndrome type1 and type2 Physiological jaundice of newborn Drugs such as indinavir, atazanavir Conjugated or mixed Hyperbilirubinemi a- Dubin johnson syndrome, Rotor’s syndrome

8. 2. Liver diseases- a. Hepatocellular dysfunction – Acute or subacute hepatocellular injury – Viral hepatitis Hepatotoxins such as ethanol, acetaminophen ,isoniazid , phenytoin Ischaemia such as in hypotension , vascular outflow obstruction Metabolic disorders such as Wilson’s ds, Reye’s syndrome

9. Chronic hepatocellular disease - Viral hepatitis Alcoholic liver disease Hepatotoxins such as ethanol , vinyl chloride , vitamin A Autoimmune hepatitis Metabolic disorders such as Hemochromatosis , Wilson's ds, NAFLD, a1-antitrypsin deficiency

10. b . Cholangiocytic injury- Primary biliary cirrhosis Graft-versus-host disease Drugs such as erythromycin, trimetholrim-sulfamethxazole , Cystic fibrosis

11. 3. Obstruction of the bile ducts Choledocholithiasis Primary sclerosing cholangitis Post surgical strictures Cholangiocarcinoma Pancreatic cancer Metastatic lymphadenopathy Ampullary carcinoma Pancreatitis

12. Diagnostic approach to jaundice When clues are evaluated in the context of the physical findings and routine laboratory tests , jaundice can be characterized correctly as obstructive or nonobstructive.

13. History H/O biliary surgery , fever, abdominal pain in right upper quadrant= Biliary obstruction with cholangitis C/O anorexia, malaise, myalgia With H/O a known infectious exposure, injection drug use ,prior transfusions of blood products= suggestive of viral hepatitis Family H/O jaundice or liver disease= suggest hereditary hyperbilirubinaemia or genetic liver disease

14. Physical Examination High fever and abdominal tenderness in RUQ= suggests cholangitis Palpable abdominal mass= Neoplastic cause of obstructive jaundice Silver coloured stool= Suggests ampullary neoplasms Ascites , splenomegaly and prominent abdominal veins= Suggests cirrhosis Abdominal scar in midline or RUQ= Prior biliary surgery

15. Essential laboratory studies in patient with jaundice Serum total bilirubin, Direct bilirubin Alkaline phosphatase (ALP) AST/SGOT ALT/SGPT Complete blood count Prothrombin time

16. Serum bilirubin Bilirubin is found in two fractions- Unconjugated or indirect- Insoluble in water, bound to albumin Conjugated bilirubin – water soluble ,excreted by kidney Normal value of total serum bilirubin -1-1.5 mg/dl If the direct acting fraction is <15% of total ,the bilirubin can be considered to all be indirect.

17. Alkaline phosphatase (ALP) Increases in biliary obstruction and intrahepatic cholestasis Not a specific marker Elevation more than 4 times of normal is significant More specific markers for cholestasis are gamma glutamyl transpeptidase[GGT], 5’ Nucleotidase

18. Aminotransferase (ALT,AST) ALT, Cytosolic enzyme found predominantly in hepatocytes AST, Found in cytosol and mitochondria of parenchymal cells of liver Normal serum concentrations –10-40 IU/L Levels of upto 300 IU/L are nonspecific and may be found in any liver disorder Level >1000 IU/L occur almost exclusively in disorders associated with extensive hepatocellular injury such as in viral hepatitis, ischaemic liver injury, toxins or drug induced liver injury.

19. Predominantly elevation of serum aminotransferase activity in comparison with alkaline phosphatase activity suggests that jaundice is the result of intrinsic hepatocellular disease Pattern of the aminotransferase elevation can be helpful diagnostically AST:ALT Ratio <1 is suggestive of chronic viral hepatitis and NAFLD AST:ALT Ratio >2 is highly suggestive of alcoholic liver disease

20. Complete blood count Leucocytosis = Suggests Biliary tract obstruction or other inflammatory disorders Anaemia = Suggests haemolysis is the cause of bilirubin overload Thrombocytopenia =. Characteristic finding in cirrhosis results from reduced platelet production from decrease hepatocyte synthesis of thrombopoietin or from increase of platelet consumption from splenic sequestration

21. Prothrombin time Measure the plasma activities of coagulation factor 1,2,5,7,10 each of which is synthesized by hepatocytes Prolongation of PT(and an associated increase in INR) can result from impaired hepatic synthesis of these proteins and from deficiency of vitamin K which is required as a cofactor for essential posttranslational modification of factor 2,7,9,10.

22. Efficient absorption of vitamin K by the small intestine requires an intact enterohepatic circulation of bile salts(hence ,an unobstructed biliary tree). Exogenous administration of vitamin K will generally normalize a prolonged PT in patients with Obstructive jaundice and intrahepatic cholestasis but not in patients with liver disease caused by hepatocellular injury.

23. Algorithm for evaluation and management

24. References 1.Harrison’s principles of internal medicine 2.Sleisenger and fordtran’s gastrointestinal and liver disease

25. Thank you