Don’t make me come up there and steal your google...
Transcript of Don’t make me come up there and steal your google...
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Bilirubin Physiology – WYNTKFTB
• Bilirubin metabolism– Unconjugated– Conjugation– Excretion
• Enterohepatic circulation• Implication of bilirubin metabolism– Urine– Stool
• Understand the metabolic pathway as related to the disease state of JAUNDICE
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Don’t make me come up there and steal your google machines!
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BR - Alb
the Bilirubinan overview
by howard sachs
BGThank you.
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Slo-Motion Instant Replay…
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Heme oxygenase Biliverdin Reductase
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Heme oxygenase Biliverdin Reductase
Bilirubin(unconjugated)
Albumin
…not water soluble…
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Unconjugated Bilirubin (‘Indirect’)
Key points:• ‘Attached to albumin’: too big to pass through glomerular filtration barrier.
• Intravascular: Hemoglobin ® urine• Unconjugated: not water soluble.
How can we get too much unconjugated bilirubin in the serum?1. Hemolysis
• Elevated indirect bilirubin is used as a diagnostic marker (with LDH, ¯ haptoglobin)
2. Conjugation defect: inherited (Gilbert’s, Crigler-Najjar)
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Bilirubin binds to cytosolic binding protein, glutathione s-transferase (GST) for transport to ER
Conjugation of bilirubin is catalyzed by bilirubin-uridinediphosphate (UDP)- glucuronosyltransferase(UGT1A1). Product is bilirubin diglucuronide.
UDPGA is the donor sugar
Multidrug resistance associated protein
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Bilirubin binds to cytosolic binding protein, glutathione s-transferase (GST) for transport to ER
Conjugation of bilirubin is catalyzed by bilirubin-uridinediphosphate (UDP)- glucuronosyltransferase(UGT1A1). Product is bilirubin diglucuronide.
UDPGA is the donor sugar
Multidrug resistance associated proteinEndoplasmic reticulum
Bilirubin diglucuronideConjugated (direct)
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Multidrug resistance associated proteinEndoplasmic reticulum
Transport into biliary canniculus is rate-limiting step in bilirubin excretion
We’ll return later to review all the steps that can malfunction.
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Cholesterol
Bile Salts
BG
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Stercobilin
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Urobilinogen: 10%
This is normal and healthy
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Based on the enterohepatic circulation of bilirubin:
What disease does this patient suffer from?
What can you deduce about the enterohepatic circulation of bilirubin from this test?
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Based on the enterohepatic circulation of bilirubin:
What disease does this patient suffer from: no disease
What can you deduce about the enterohepatic circulation of bilirubin from this test: Intact
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Urine Bilirubin:
Measures the presence of conjugated bilirubin (water soluble).
Conjugated bilirubin gets in urine through reflux into the sinusoids
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Positive
Patient presents with jaundice. Which disorder is least likely based soley on this urinalysis?
1. Cirrhosis2. Acute infection, HBV3. Adenocarcinoma in pancreatic head4. Wilson’s disease5. Dubin-Johnson syndrome
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Positive
Patient presents with jaundice. Which disorder is least likely based soley on this urinalysis?
1. Cirrhosis2. Acute infection, HBV3. Adenocarcinoma in pancreatic head: obstruction; no urobilinogen4. Wilson’s disease5. Dubin-Johnson syndrome: slow excretion but intact enterohepatic circ
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BG
Conjugated bilirubin refluxes into the sinusoids and is
excreted in the urine
Obstruction: no urobilinogen
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Conjugated Hyperbilirubinemia
Extrahepatic duct
Intrahepatic duct
Hepatocellular injury Failure of transport
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Feces and Bilirubin
Bonus Thoughts!
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Acholicplus blood
Acholic(clay)
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BG
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Bilirubin Physiology – WYNTKFTB • Bilirubin metabolism
– Unconjugated: hemoglobin breakdown product– Conjugation: UDP-glucuronosyltransferase– Excretion: bile canniculi
• Enterohepatic circulation:– Bacterial protease convert to urobilinogen, majority in stool;
minority reabsorbed and excreted in urine
• Implication of bilirubin metabolism– Urine: urobilinogen implies no obstruction– Stool: pale/acholic obstruction; silver implies blood.
• Understand the metabolic pathway as related to the disease state of JAUNDICE– Major players include hemolysis, conjugation defects,
hepatocyte dysfunction, duct disease/obstruction.