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bilirubin own class.ppt
- 1. 1 Presented by: KRJ Lumbini medicalcollege Pravas, Tansen, Palpa BILIRUBIN METABOLISM
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- 6. globin globin globinglobin Hemoglobin heme heme heme heme
- 7. Bilirubin Metabolism Bilirubinformation Transport of bilirubin in plasma Hepatic bilirubin transport Hepatic uptake Conjugation Biliary excretion Enterohepatic circulation
- 11. 3 Steps ofBiliverdin Metabolism 1) Hepatic Uptake -Unconjugated bilirubin is presented in the liver cell -The albumin associated with it is dissociated -Ligandin is delivered to prevent efflux of bilirubin back to plasma
- 12. 2) Conjugation:- Uncojugated bilirubin( H2O insoluble ) is converted to bilirubin diglucuronides ( H2O soluble). Takes place in the smooth endoplasmic reticulum of the liver. Catalysed by glucoronyl transferase. 3) Excretion:- Bilirubin which is now H2O soluble can now be excreted from the liver cells to the biliary system.
- 13. Role of BloodProteins in the Metabolism of Bilirubin 1. Albumin Dissolved in Blood Sparingly soluble in Blood
- 14. Blood Liver Ligandin (-) charge Ligandin (-) charge LigandinPrevents bilirubin from going back to plasma own class
- 15. Fate of ConjugatedBilirubin in intestine Intestinal bacteria deconjugate the conjugated bilirubin This free bilirubin is further reduced to a colorless tetrapyrrole urobilinogen (UBG) Further reduction of the vinyl substituent groups of UBG leads to formation of mesobilinogen and stercobilinogen (SBG) Stercobilinogen is mostly excreted through feces (250-300mg/day)
- 16. Enterohepatic Circulation 20% ofthe UBG is reabsorbed from the intestine and returned to the liver by portal blood The UBG is again re-excreted Since it is passed through blood, a small fraction is excreted in urine (<4mg/day)
- 17. Final Excretion UBGand SBG are both colorless compounds but are oxidized to colored products, urobilin and stercobilin respectively by atmospheric oxidation Both urobilin and stercobilin are present in urine as well as in feces
- 18. Plasma bilirubin Normalplasma bilirubin level ranges from 0.2 – 0.8 mg/dl Unconjugated bilirubin = 0.2 – 0.6 mg/dl Conjugated bilirubin = 0 -0.2 mg/dl Hyperbilirubinemia = >1 mg/dl Latent jaundice = 1 – 2 mg/dl Jaundice = > 2 mg/dl
- 19. Vanden Berg Reaction: Direct Indirect Biophagic > Conjugated > unconjugated > both > Purple colour produced > Immediate Purple > Colour Produced after immediately and colour Colour appear addition of alcohol only. intensified after addition of alcohol. 19
- 20. Jaundice:- Jaundice is alsok/a Icterus. Defination: It is yellow colour pigmentation present in skin, conjuctiva, mucous membrane and clinically it becomes apperent when serum bilirubin conc. Excess more than 2 mg/dl.
- 23. Pathophysiology of jaundice Disturbance in bilirubin production or clearance. It is characterized by yellow color of white of the eyes (sclera) and skin Serum bilirubin levels rise above 2.0 to 2.5 mg/dL; level as high as 30-40mg/dL can occur with severe disease ↑ also called as hyperbilirubinemia.
- 24. Mechanism of jaundice Excessive production of bilirubin Reduced hepatic uptake Impaired conjugation Decreased hepato-cellular excretion Impaired bile flow (both intrahepatic and extrahepatic)
- 25. Types of jaundice Jaundice Pre-hepaticPost-hepatic Hepatic
- 26. Classification of jaundice 1)Hemolytic / pre-hepatic jaundice Excessive production of bilirubin due to excessive destruction of red blood cells. It is associated with increased hemolysis of erythrocytes (e.g incompatible blood transfusion, malaria, sickle cell anemia). This results in overproduction of bilirubin beyond the capacity of the liver to conjugate and excrete bilirubin.
- 27. Causes of haemolyticjaundice:- a) Inside RBC.( thalessimia, sickle cell anaemia) b) RBC cell wall( elliptocytosis,spherocytosis) c) Outside the RBC (Acquired haemolytic anaemia).
- 28. Hemolytic Jaundice Symptoms weakness, Darkurine, anemia, Icterus, splenomegaly Lab UB without bilirubinuria fecal and urine urobilinogen hemolytic anemia hemoglobinuria (in acute intravascular hemolysis) Reticulocyte counts
- 29. 2) Hepatocellular /Hepatic jaundice Defective hepatic uptake Abnormal conjugation Hepatocellular damage
- 30. Defective hepatic uptake Unconjugated bilirubin in the plasma is carried into the liver by intracellular transport proteins. Absences of these proteins result in failure of bilirubin uptake, leading to unconjugated hyperbilirubinemia (e.g Gilbert Syndrome). Defective of blood supply to the liver also can cause abnormality of bilirubin metabolism These problems happen in congestive heart failure, pathway shunt due to surgery and adverse effect from drug intake.
- 31. Abnormal conjugation -Partial deficiency of glucoronyl transferase - drugs may interfere with this enzyme system e.g Novobiocin Hepatocellular damage - Acute or chronic hepatocellular injury
- 32. Hepatic Jaundice Symptoms weakness, lossappetite, hepatomegaly, palmar erythema Lab Findings • liver function tests are abnormal • both CB and UCB • Bilirubinuria
- 34. Gross specimen ofcirrhosis of the liver
- 36. 3) Obstructive Jaundice: >Also k/a post-hepatic jaundice. Pathogenesis it is due to intra- and extra hepatic obstruction of bile ducts intrahepatic Jaundice: Hepatitis, Drugs Extra Hepatic Biliary Obstruction: Stones, Stricture, Inflammation, Tumors.
- 37. Intrahepatic:- Liver cellDamage/Blockage of Bile Canaliculi. Drugs or chemical toxins Dubin-Johnson syndrome Intrahepatic biliary hypoplasia or atresia Primary biliary cirrhosis Extrahepatic:- Obstructive of bile Ducts Compression obstruction from tumors Extrahepatic biliary atresia Intraluminal gallstones
- 39. Acholuric Vs. Choluricjaundice CHOLURIC – presence of bile derivatives in the urine – Occurs in regurgitation hyperbilirubinemia – Obstructive type ACHOLURIC – absence of bile in urine – Retention hyperbilirubinemia – Hemolytic type
- 40. Jaundice- Differential diagnosis DifferentialDiagnosis UCB or CB Exclude UCB (e.g. hemolysis or Gilbert Synd.) Distinguish hepatocellular from obstructive Distinguish intrahepatic from extra hepatic cholestasis
- 42. Hyperbilirubinemia 1. Gilbert’s Syndrome 2.Dubin’s johnson’s syndrome. 3. Rotor syndrome. 4. Crigler-Najjar Syndrome (Type I) 5. Crigler-Najjar Syndrome (Type II)
- 43. 1) Gilbert’s syndrome:- It is ihherited as an autosomal dominent trait. Defect in uptake of bilirubin by the liver. Bilirubin level is usually 3mg/dl and patient is asymptomatic except for the presence of mild jaundice. Defficiency of UDP-glucoronyl transferase resulting increased unconjugated bilirubin. No treatment is necessary
- 44. 2) Dubin’s johnson’ssyndrome:- It is a autosomal recessive trait. Leading to defective excretion of conjugation bilirubin and increased conjugation bilirubin in blood. The bilirubin gets deposited in the liver and the liver appears black ( black liver jaundice). The patient is asymptomatic except for mild intermittent jaundice. No treatment is required.
- 45. 3) Rotor syndrome:- Bilirubin excretion is defective but there is no deposit in liver. 4) Crigler-Najjar Syndrome (Type I):- Severe deficiency of UDP-glucuronyl transferase. The disease is often fatal and the children die before the age of 2 yr. Jaundic e usually appear within the first 24hrs of life. Since unconjugated bilirubin level increases to high levels >20mg/dl lead to kernicterus.
- 46. 5) Crigler-Najjar Syndrome(Type II):- Serum bilirubin raises above 15mg/dl. Hence kernicterus doesnot occurs. In the bile bilirubin monoglucuronides is present. 2nd stage of conjugation is deficient. When barbiturates are given some response is seen and jaundice improves.
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