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Presented by Ri 91-5-6
60 y/o male patient: 1. Septic shock 2. Increased of bilirubin, predominantly conjugated form 3. No elevation of liver enzyme, ALP, GGT 4. Abdominal echo and CT: negative finding
Extrahepatic defects
Stones Infection Tumors Hemobilia Primary sclerosing Cholangitis Compression of biliary duct
Bile and bilirubin excretion in relation to hepatic energy status during hemorrhagic shock and hapoxemia in rabbits
Posttraumatic jaundice:
hepatocyte dysfunction due to shock, infection, or drugs
AKBR (arterial ketone body ratio): the ratio of acetoacetate to - hydroxybutyrate reflects the hepatic mitochondrial function Bile flow, total and direct bilirubin excretion, total bile acid excretion Plasma bilirubin ( T/D )
Results (1)
Results (2)
Arterial ketone body concentrations and the arterial ketone body ratio (AKBR)
Control Shock Hypoxemia ANOVA 53 47 100 1.14 34 178 206 0.16 16 85 97 0.23 P<0.005 P<0.005 P<0.005 P<0.005
Results (3)
Result (4)
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
Discussion (2)
The fourth step is rate limiting Bile secretion may be linked to an ATPdependent sodium pump The excretion of conjugated bilirubin from hepatocytes to bile canaliculi consumes energy and limits the rate of bilirubin metabolism.
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)
Discussion (4)
3. In the shock and hypoxemia groups: AKBR 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.
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.
Conjugated hyperbilirubinemia without liver enzyme abnormalities is relatively uncommon but can be seen in 1. Pregnancy 2. Sepsis 3. After recent surgery
~from Harrisons Principles of Internal Medicine