Hepatobiliary - bilirubin, cholestasis, and functional mass Flashcards
What bilirubin tests are sensitive or insensitive to artifact like lipemia or hemolysis?
Total bilirubin = sensitive
Bu - insensitive
Bc - insensitive
What is the more sensitive way of measuring bilirubin?
bilirubin subfractions Bu and Bc
more reliable than Bt
What is another name for unconjugated bilirubin? Why?
Indirect
When we run the assay to measure Bu, we indirectly measure it by adding alcohol to solubalize it
What is another name for conjugated bilirubin? Why?
Direct
We directly measure it with the assay
What is the approximate half life for Bd? Why?
3-10 days
So long because it depends on the half life of the protein it is bound to.
How can you calculate the Bd of a sample with bichem results?
Bt - Bu - Bc = Bd
Although conjugated bilirubin is synonymous with direct bilirubin, what do we mean when we say direct bilirubin in the lab?
Direct bilirubin in the lab = Bc + Bd
What is the disadvantage of a direct bilirubin reading in the lab?
With cholestasis, direct bilirubin values remain elevated longer than Bc because of the influence of Bd – this can mislead clinicians to think that active cholestasis is still present.
Not able to distinguish b/w active and previous cholestasis
What is the extended bilirubin profile?
measures Bt, Bu, Bc, Bd
What are the three types of hyperbilirubinemia?
Pre-hepatic
Hepatic
Post-hepatic
Can cholestasis be pre-hepatic?
NO
hepatic or post hepatic cause!
What is the classic pattern for pre-hepatic hyperbilirubinemia?
increase in Bu and no increase in Bc (or at least proportionately very little Bc)
What are two major mechanisms for pre-hepatic hyperbilirubinemia?
- hemolytic disease
2. decreased uptake of Bu (decreased hepatocytes or decreased functional mass)
What is the mechanism to get increased Bu due to hemolytic disease w/o Bc increase?
Bu uptake by a healthy liver is not easily overwhelmed!
For Bu to increase before Bc – severe hemolysis –> hypoxic injury –> comprise hepatocyte uptake function
How can hemolytic disease lead to both Bu and Bc increase in the blood – suggesting cholestasis?
Uptake of Bu and conjugation may exceed ability to excrete Bc into bile canaliculi –> increase Bc in plasma
Hypoxic injury –> swelling –> physical obstruction of bile outflow
What is the rate limiting step in conjugation/excretion?
ability to excrete Bc into bile canaliculi
What is the pattern seen for intrahepatic hyperbilirubinemia?
Mixture of increased Bc and Bu – Bc will usually predominate in all except horses
What is the mechanism for intrahepatic hyperbilirubinemia?
intraheptaic cholestasis –> backup of Bc into the blood
hepatocytes are compromised in ability to take up Bu –> increase Bu in blood
Why is the pattern for intrahepatic hyperbilirubinemia least specific?
Chronic prehepatic or posthepatic can appear as intraheptic.
If there is no evidence of prehepatic (hemolysis) or posthepatic, call it intrahepatic.
What is the classic pattern of post-hepatic hyperbilirubinemia?
almost exclusively Bc
What is the mechanism for post-hepatic hyperbilirubinemia?
Obstruction of common bile duct (tumor, stone, pancreatitis) –> backup of Bc into blood
If acute – Bc may be elevated before cholestasis induces increase production of ALP or GGT
What happens with post-hepatic hyperbilirubinemia progression?
secondary hepatocellular injury –> may interfere with Bu uptake –> mixed pattern –> can no longer be differentiated from intrahepatic
What are most sensitive for cholestasis in the dog?
ALP > GGT > urine bilirubin > serum bilirubin (Bc)
What are most sensitive for cholestasis in horse and cat?
GGT > ALP > serum Bc > urine bilirubin
