2. 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
5. Causes of conjugatedCauses of conjugated
hyperbilirubinemiahyperbilirubinemia
Intrahepatic defects Extrahepatic defects
1. Familial/ herediatary disorders
2. Hepatocellular disease
3. Drug
4. Sepsis
5. Post-operation state
6. Parenteral nutrition
7. Biliary cirrhosis
8. Neoplasms
1. Stones
2. Infection
3. Tumors
4. Hemobilia
5. Primary sclerosing
Cholangitis
6. Compression of biliary
duct
6. Bile and bilirubin excretion inBile and bilirubin excretion in
relation to hepatic energy statusrelation to hepatic energy status
during hemorrhagic shock andduring hemorrhagic shock and
hapoxemia in rabbitshapoxemia in rabbits
Journal of Trauma. 39(4): 665-670, October 1995Journal of Trauma. 39(4): 665-670, October 1995
7. 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
8. Materials and Methods (1)Materials and Methods (1)
1. Control group
( n = 7 )
2. Hemorrhagic
shock group
( n = 10 )
3. Hypoxia
group
( n = 8 )
Biliary fistula BP: 120 mmHg
50 mmHg
Biliary fistula
PaO2: 87 mmHg
35 mmHg
Biliary fistula
9. Materials and Methods (2)Materials and Methods (2)
AKBR (arterial ketone body ratio):
the ratio of acetoacetate to β- hydroxybutyrate
reflects the hepatic mitochondrial function
Bile flow, total and direct bilirubin excretion,
total bile acid excretion
Plasma bilirubin ( T/D )
14. Discussion (1)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
15. Discussion (2)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.
16. Discussion (3)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)
17. Discussion (4)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.
18. Discussion (5)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.
19. Conjugated hyperbilirubinemia without
liver enzyme abnormalities is relatively
uncommon but can be seen in
1. Pregnancy
2. Sepsis
3. After recent surgery
~from Harrison’s Principles of Internal Medicine