Heme Degradation and Jaundice Flashcards Preview

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Flashcards in Heme Degradation and Jaundice Deck (20)
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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


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


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


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


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)


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


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


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


give an overview of heme degradation


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


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


describe prehepatic/hemolytic jaundice


describe the lab findings in prehepatic/hemolytic jaundice


describe hepatic jaundice


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


describe posthepatic/obstructive/cholestatic jaundice


describe lab findings of posthepatic/obstructive/cholestatic jaundice


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 


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


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