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1. the skin and other tissues (Biìirubin)

2. JAUNDICE Dr.T.Prathyusha Assistant professor Dept of gen medicine AIIMS,Mangalagiri

3. Bilirubin formation Transport of bilirubin in plasma Hepatic bilirubin transport ‹ Hepatic uptake .. Conjugation ‹ Biliary excretion Enterohepatic circulation

4. Büirubin formation

5. Molar Albumin + UB UB - Albumin Complex H affinity binding sites Plasma protein

6. UCB-Albumin Complex Separated Bilirubin CB be) taken up MTA (receptor ?) Transfer across Microvillar membrane Plasma membrane of the liver Bile canaliculus

7. CB B and I be degraded Bacterial Enzymes 4 mg/d urine urobilinogen •The serum of normal adults contains ñ1 mg of bilirubin per 100 ml. Urobilinogens (col‹›ress) •In healthy adults The direct fraction is usually <0.2 mg/100 ml The indirect fraction is usually <0.8 mg/100 ml

8. Hemolytic Jaundice Hepatic Jaundice Obstructive Jaundice(Cholestasis) Congenital Jaundice

9. •’predominantly unconjugated hyperbilirubinaemia • ^ predominantl y conjugated hyperbilirubinaemia

10. Pathogenesis Hemolysis (intra and extra vascular) inherited or genetic disorders acquired immune hemolytic anemia (Autoimmune hemolytic anemia) nonimmune hemolytic anemia (paroxysmal nocturna Hemoglobinruia) .• Ineffective erythropoiesis fJverproduction may overload the liver with UB

11. Symptoms weakness, Dark urine, anemia, Icterus, splenomegaly Lab UB1 without bilirubinuria fecal and urine urobilinogenl hemolytic anemia hemoglobinuria (in acute intravascular hemolysis) Reticulocyte counts†

12. Hemolytic Jaundice (pre- hepatic) ’» Serum / blood: bilirubin (micormoIes/I) 50- 150; normal range 3- 17 AST I.U. < 35; normal range <35 ALP I.U. <250; normal range <250 gamma GT I.U. 15- 40; normal range 15- 40 albumin g/I 40- 50; normal range 40- 50 reticuIocytes(%) 10- 30; normal range < 1 prothrombin time (seconds) 13- 15; normal range 13- 15

13. (pre- hepatic) n urinary changes: bilirubin : absent urobilinogen: increased or normal »faecaI changes: stercobilinogen: normal

14. Pathogenesis I it is due to intra- and extra hepatic obstruction of bile ducts intrahepatic Jaundice: I-Hepatitis, PBC, Drugs Extra Hepatic Biliary Obstruction: Stones, Stricture, In3ammation, Tumors, (Ampulla of Vater)

15. Intrahepatic- Liver cell Damage/Blockage of Bile Canaliculi Drugs or chemical toxins Dubin- Johnson syndrome Estrogens or Pregnancy Hepatitis- viral,chemical Infiltrative tumors Intrahepatic biliary hypoplasia or atresia Primary biliary cirrhosis

16. Congenital choledochal cyst Extrahepatic biliary atresia Intraluminal gallstones Stenosis- postoperative or inñammary

17. pain, due to gallbladder disease, malignancy, or stretching of the liver capsule fever, due to ascending cholangitis palpable and / or tender gallbladder enlarged liver, usually smooth

18. General signs of cholestasis xanthomas: palmar creases, below the breast, on the neck. They indicate raised serum cholesterol of several months. Xanthomas on the tendon sheaths are uncommonly associated with cholestasis. xanthelasma on the eyelids scratch marks: excoriation finger clubbing loose, pale, bulky, offensive stools dark orange urine

19. Serum Bilirubinl Feceal urobilinogen)• (incomplete obstruction) Feceal urobilinogen absence (complete obstruction) urobilinogenuria is absent in complete obstructive jaundice bilirubinuria ALP cholesterol

20. Obstructive Jaundice extrahepatic a serum / blood bilirubin (micromoIes/I) 100- 500; normal range 3- 17 AST I.U. 35- 400; normal range <35 ALP I.U. >500; normal range <250 gamma GT I.U. 30- 50; normal range 15- 40 albumin g/I 30- 50; normal range 40- 50 reticuIocytes( o /o)</1; normal range <1 prothrombin time (secs) 15- 45; normal range 13- 15 ( ” + parenteral vitamin K) falls

21. extrahepatic a urinary changes bilirubin: increased urobilinogen: reduced or absent afaecal changes stercobilinogen: reduced or absent

22. Due to a disease affective hepatic tissue either congenital or acquired diffuse hepatocellular injury

23. H epatic ,jaundice Pathogenesis Impaired or absent hepatic conjugation of bilirubin decreased GT activity (Gilbert‘s syndrome) hereditary absence or deficiency of UDPGT (Grigler-Na}Jar Syndrome) Familiar or hereditary disorders Dubin-Johnson Syndrome Rotor syndrome Acquired disorders hepatocellular necrosis intrahepatic cholestasis (Hepatitis, Cirrhosis, Drug- related)

24. ChronŃ hepatśtiø

25. the liver

26. Syinpt‹inis weakness, loss appetite, hepatomegaly, palmar erythema, spider Lab Findings liver function tests are abnormal both CB and UCB† Bilirubinuria †

27. ‹c› 200Z Dr Petra Htisa

28. Hepatic Jaundice ’a serum / blood bilirubin (micromoIes/I) 50- 250; normal range 3- 17 AST I.U. 300- 3000; normal range <35 ALP I.U. <250- 700; normal range <250 gamma GT I.U. 15- 200; normal range 15- 40 albumin g/I 20- 50; normal range 40- 50 reticuIocytes ( o /o ) • X 1; normal range <1 prothrombin time (secs) 15- 45; normal range 13- 15 ( " + parenteral vit. K) 15- 45

29. » urinary changes bilirubin: normal or increased urobilinogen: normal or reduced a faecal changes stercobilinogen: normal or reduced

30. history and exam ination Ourine, stools Oserum biochemistry bilirubin transaminases - AST, ALT albumin alkaline phosphatase

31. Jaundice III haematology haemoglobin WCC platelets prothrombin time +/- parenteral vitamin K CI abdominal ultrasound and chest X- ray El further investigations - determined by the basis of the jaundice, e.g. pre- hepatic, hepatic, extra- hepatic

32. conjugated hyperbilirubinaemia the liver is able to conjugate bilirubin, but the excretion is impaired. failure of bilirubin excretion by hepatocytes: Dubin- Johnson syndrome Rotor's syndrome O obstruction to biliary flow i.e. cholestasis, both intra- hepatic and extra- hepatic

33. The proportion of conjugated bilirubin to the total raised bilirubin 20- 40 /o of total: more suggestive of hepatic than posthepatic jaundice 40- 60 o /o of total: occurs in either hepatic or posthepatic causes 3• 50 o /o of total: more suggestive of posthepatic than hepatic jaundice less than 20 o /o :secondary to haemolysis or constitutional e.g. Gilbert's disease, Crigler- Najjar syndrome

34. unconjugated hyperbilirubinaemia increased bilirubin formation 1•haemoIysis 1•ineffective erythropoiesis: megaloblastic anaemia iron deficiency haemoglobinopathies

35. needle insgf t9d into tic liver and tUfhof

36. Primary sclerosing cholangitis in childhood

37. Jaundice- Differential diagnosis Once Jaundice is recognized, it is important to determine whether hyperbilirubinemia is predominantly CB or UCB? DiGerentiation of hemolitic from other type of Jaundice is usually not diYicult. The laboratory findings are in constant in partial biliary obstruction and differentiation from intrahepatic cholestesis is particularly difl"icult.

38. UCB or CB Exclude UCB (e.g. hemolysis or Gilbert Synd.) Distinguish hepatocellular from obstructive Distinguish intrahepatic from extra hepatic cholestasis

39. Have the patient had an isolated elevation of serum bilirubin?

40. Is the bilirubin elevation due to an increased unconjucated or conjucated fraction?

41. Is the hyperbilirubinemia hepatocellular or cholestatic?

42. If cholestatic,is it intra-or extrahepatic?