Heme Degradation and Jaundice Flashcards Preview

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Flashcards in Heme Degradation and Jaundice Deck (20)
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1

describe jaundice

  • yellowish discoloratino of the skin, mucus membranes, sclera and nail beds
  • characterized by binding of bilirubin (bile pigment) to the connective tissue
  • occurs when serum bilirubin levels >2 mg/dL

2

describe heme degradation

  • RBCs contain hemoglobin that is broken down to heme and globin (amino acids enter amino acid pool)
  • heme containing proteins like myoglobin and cytochromes also release heme on degradation that also forms bilirubin

3

describe the formation of bilirubin in macrophages/reticular endothelial system

  • heme oxygenase
    • Fe2+ is released
    • porphyrin ring is cleaved
    • CO is formed in the rxn
    • biliverdin is a green pigment
  • biliverdin reductase
    • bilirubin formed has an orange-yellow color

4

describe the transport of bilirubin in the blood to the liver

  • bilirubin formed in macrophages is not water soluble
    • this bilirubin is unconjugated bilirubin
  • it binds in blood to albumin for transport
    • prevents it from being excreted in urine
    • drugs can displace bilirubin from albumin (salicylates, sulfonamides)
      • administratino of these drugs can displace bilirubin from albumin and free uncojugated bilirubin can cross the BBB to cause kernicterus in children

5

describe the uptake of unconjugated bilirubin by the liver

  • unconjugated bilirubin is taken up by the liver by specific transporters on the the hepatocytes
  • within the hepatocyte, bilirubin is bound to ligandin (intracellular protein)

6

describe the conjugation of bilirubin in the liver

  • bilirubin is converted to conjugated biliruin (more water soluble) by the addition of 2 molecules of glucuronic acid
    • this is done my microsomal UDP-glucuronyl transferase
    • the donor of glucuronic acid is UDP-glucuronic acid

7

describe the secretion of conjugated bilirubin into bile

  • conjugated bilirubin is actively transported into the bile canaliculus against a concentration gradient by a specific ABC transporter
  • conjugated bilirubin is a component of bile and is released into the 2nd part of duodenum via the common bile duct

8

describe the formation of urobilinogen and then stercobilin in the large intestine

  • conjugated bilirubin is acted upon by bacterial flora in the large intestine
  • conjugated bilirubin undergoes deconjugation and is next converted to urobilinogen (colorless)
    • lost in urine as urobilin (10%) (light yellow color) 
  • bacterial action on urobilinogen forms stercobilin that is lost in the feces and gives the feces a characteristic brown color

9

give an overview of heme degradation

10

describe the Van den Berg reaction

  • conjugated bilirubin (direct reacting) is water soluble and reacts rapidly with the reagent
  • unconjugated biliruin (indirect reacting) is water insoluble and reacts in the presence of methanol
  • total bilirubin - direct (conjugated) bilirubin = indirect (unconjugated) bilirubin

11

describe the 3 types of jaundice

  • prehepatic (hemolytic): increased breakdown of RBCs
  • hepatic: decreased conjugation capacity of liver and decreased excretion of bilirubin
  • posthepatic (obstructive/cholestatic): decreased excretion of bilirubin via bile

12

describe prehepatic/hemolytic jaundice

13

describe the lab findings in prehepatic/hemolytic jaundice

14

describe hepatic jaundice

15

describe the lab findings of hepatic jaundice

  • serum conjugated bilirubin is elevated since the capacity to excrete conjugated biliruin into the biliary canaliculus is reduced; conjugated bilirubin regurgitates into the plasma (cannot be excreted into the bile)
  • serum unconjugated bilirubin is elevated as hepatocellular damage results in lower uptake of unconjugated bilirubin into liver
    • also liver damage reduces the conjugating capacity of liver

16

describe posthepatic/obstructive/cholestatic jaundice

17

describe lab findings of posthepatic/obstructive/cholestatic jaundice

18

describe jaundice in newborn and phototherapy

  • unconjugated bilirubin crosses the blood brain barrier (since it is lipid soluble and not well developed) and deposits in the basal ganglia of the brain resulting in kernicterus
  • phototherapy: light converts bilirubin to more polar, water soluble isomers that can be excreted in bile without conjugation 

19

describe Crigler-Najjar syndrome I, II and Gilbert's syndrome

all caused by lowered activity of bilirubin glucuronyl transferase

  • Crigler-Najjar syndrome I
    • most severe 
  • Crigler-Najjar syndrome II
    • lowered activity of enzyme
    • children respond to phenobarbital (induces the enzyme)
  • Gilbert's syndrome
    • mild jaundice
    • 50% of normal enzyme activity

20

describe Dubin-Johnson syndrome

  • inherited deficiency of the ABC transporter that transports conjugated bilirubin from the hepatocyte into the biliary canaliculus
  • typically presents in young adults
  • characterized by elevated levels of conjugated (direct) bilirubin in circulation