Conjugated Hyperbilirubinemia

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Conjugated Hyperbilirubinemia

• Presented by Ri ???
• 91-5-6

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• 60 y/o male patient1. Septic shock2. Increased
  of bilirubin, predominantly conjugated form
  3. No elevation of liver enzyme, ALP, GGT4.
  Abdominal echo and CT negative finding

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Production and metabolism of bilirubin
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The transport system of hepatocyte
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Causes of conjugated hyperbilirubinemia
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Bile and bilirubin excretion in relation to
hepatic energy status during hemorrhagic shock
and hapoxemia in rabbitsJournal of Trauma.
39(4) 665-670, October 1995
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• Posttraumatic jaundice hepatocyte dysfunction
  due to shock, infection, or drugs
• Trauma- induced disturbance of the hepatic energy
  status? influence bilirubin metabolism? esp.
  excretion of conjugated bilirubin from hepatocyte

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Materials and Methods (1)
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Materials and Methods (2)

• AKBR (arterial ketone body ratio) the ratio of
  acetoacetate to ß- hydroxybutyrate? reflects the
  hepatic mitochondrial function
• Bile flow, total and direct bilirubin excretion,
  total bile acid excretion
• Plasma bilirubin ( T/D )

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Results (1)

• Blood gas analysis

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Results (2)

• Arterial ketone body concentrations and the
  arterial ketone body ratio (AKBR)

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Results (3)
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Result (4)
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Discussion (1)

• Four main steps in bilirubin metabolism
• 1. Uptake of unconjugated bilirubin from the
  bloodstream into hepatocytes
• 2. Transport to the endoplasmic reticullum in
  hepatocytes
• 3. Conjugation with glucuronic acids
• 4. Excretion of conjugated bilirubin into the
  bile canaliculi

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Discussion (2)

• The fourth step is rate limiting? Bile secretion
  may be linked to an ATP-dependent sodium pump?
  The excretion of conjugated bilirubin from
  hepatocytes to bile canaliculi consumes energy
  and limits the rate of bilirubin metabolism.

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Discussion (3)

• 1. The hepatic energy status can be estimated in
  vivo by measuring the AKBR.
• 2. The bile flow and the excretion of bilirubin
  and total bile acids into bile were significantly
  decreased during the hepatic energy crisis.(
  clearly in hypoxia model)

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Discussion (4)

• 3. In the shock and hypoxemia groupsAKBR and
  the hepatic energy decreased? decreased bile
  flow and excretion of direct bilirubin into the
  bile duct
• 4. The increase in the plasma bilirubin results
  from back diffusion of water-soluble conjugated
  bilirubin in hepatocytes.

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Discussion (5)

• 5. Rabbits only 1/3 of the hemoglobin metabolite
  is excreted as bilirubin.Human most of the
  hemoglobin metabolite as bilirubin.? Disturbed
  bilirubin excretion may be more pronounced in
  humans.

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• Conjugated hyperbilirubinemia without liver
  enzyme abnormalities is relatively uncommon but
  can be seen in 1. Pregnancy2. Sepsis3. After
  recent surgery from Harrisons
  Principles of Internal Medicine

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