Bilirubin

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Bilirubin

  1. 1. What does this blue color reminds you?
  2. 2. Corrigendum-Uric Acid 1. Solubility of Uric acid. 2. Biphasic nature of salicylate. At low doses, salicylate inhibit secretion of uric acid but at high doses, they inhibit tubular reabsorption.
  3. 3. Our beloved Micheal - Case Scenario! Micheal was a 22-year-old tourist from Greece. Two months ago after his arrival in Australia he developed a wound infection and is seen by his GP. His wound is cleaned and is prescribed an antibiotic. Over the next few days he experiences pain and his wound is healing well, but he feels very tired. He comes in again to see the GP because he has developed shortness of breath when he walks a short distance. His GF also notices that his eyes are yellowish in color. Micheal has no fever and his wound is healing well. Further history reveal that he has no history of medical illness or hospitalization but has family history of anaemia. On examination he looks pale. His pulse is 110/min (N=72 to 100/min), blood pressure is 110/70 (N=120/80mmHg), respiratory rate is 20/min(N=12 to 16/min), temperature is 98.2F. The sclerae of his eyes looks yellow and the color of urine is dark yellow. Generate some hypothesis? What is going on with Micheal?
  4. 4. Lets find the connection! BILIRUBIN
  5. 5. R.B.C Bilirubin Metabolism Cells of RE System Cells of Spleen Liver Intestine
  6. 6. Bilirubin Metabolism R.B.C Hb Globin Heme •Cells of the reticular endothelial system. •Cells of the spleen. Purple CO Heme Oxygenase Fe Biliverdin Green Biliverdin Reductase Orange Bilirubin Unconjugated bilirubin Bilirubin in Blood BLOOD
  7. 7. Bilirubin Metabolism (Contd..) Albumin Bilirubin Unconjugated bilirubin. Water-insoluble BLOOD Anti-atherogenic, anti-oxidant (lipid peroxidation prevention), antiinflammatory, anti-apoptotic & anti-proliferative. BIRNH Study (2001) UDP-Glucuronate (2) LIVER •Hemolysis UDP-Glucuronyl transferase •Crigler-Najjar Syndrome (Type I& II) •Gilbert Syndrome (TATAA Sequence) Bilirubin diglucuronide Conjugated bilirubin. Watersoluble P oeh bn t ra lai b •Low levels of conjugation enzymes in newborn. INTESTINE Bilirubin diglucuronide Conditions that increases unconjugated Bilirubin. [Normal Values <1mg/dl] (via gallbladder) •Liver damage i.e Cirrhosis
  8. 8. Bilirubin Metabolism (Contd..) LIVER Active Transport INTESTINE Bilirubin diglucuronide in bile G.I FLORA Conditions that increases conjugated Bilirubin. [Normal Values 0 mg/dl] Urobilinogen •Hepatic Damage Stercobilinogen Feces 250 mg/day Kidney Urobilins in urine •Bile duct obstruction (Clay-colored stool) •Dubin Johnson Syndrome . [cMOAT Protein defect*] 1 mg/day •Rotor Syndrome *canalicular Multispecific Organic Anion Transporter (cMOAT) protein.
  9. 9. Bilirubin Metabolism R.B.C Hb Globin Cells of the reticular endothelial system. Cells of the spleen. Heme CO Heme Oxygenase Fe R.B.C Biliverdin Biliverdin Reductase Hb in the plasma Bilirubin Haptoglobin Extravascular hemolysis Unconjugated bilirubin Bilirubin in Blood BLOOD Intravascular hemolysis
  10. 10. R.B.C Hyperbilirubinemia (>1mg/dl) Pre-hepatic Hepatic Post-hepatic Unconjugated Conjugated/Unconj ugated Conjugated
  11. 11. R.B.C Hyperbilirubinemia Unconjugated hyperbilitubinemia • Hemolysis (Sickle cell disease, PNH) • Neonatal Jaundice • Hypoalbuminemia • Ineffective erythropoiesis (Thalassemia, vitamin B-12 deficiency) Conjugated hyperbilitubinemia • Hepatitis (toxic, viral, etc) • Biliary Obstruction (Stones, tumor, etc) • Right Heart Failure • Primary Biliary Cirrhosis • AFLP • Sclerosing Cholangitis • Heamochromatosis • Drug toxicity
  12. 12. Hyperbilirubinemia (Contd..) • A word about Delta Bilirubin • Fraction that remain covalently bounded to albumin. • Patient will be jaundiced after conjugated bilirubin falls.
  13. 13. Micheal’s problem and the summary 1. Bilirubin is a colored pigment. It is the end product of the hemoglobin catabolism and is able to stain the sclerae and skin when present in excess. 2. Micheal’s tiredness, rapid pulse and shortness of breath occurred after the intake of antibiotics and is due to acute haemolysis (anaemia). 3. Micheal is from Greece (up to 30% males in Mediterranean region has G6PD deficiency)and has family history of anaemia (hereditary). 4. Urine is dark yellow. Increased production of urobilinogen. 5. It is most likely that Micheal developed antibioticassociated heamolysis leading to increase bilirubin and jaundice .
  14. 14. A 4 days-old-newborn presented to the Emergency Medicine with yellowish tinge to the whole body. Not feeding well, lethargic and irritable. Total Bilirubin 30mg/dl.
  15. 15. Thank you very much

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