Bile Acids


Bile acids aid in fat absorption and modulate cholesterol levels. They are produced from cholesterol in the liver and are stored in the gall bladder. Gall bladder contraction with feeding releases bile acids into the intestine. Bile acids undergo enterohepatic circulation, i.e. they are absorbed in the intestine and taken up by hepatocytes for re-excretion into bile. Measurement of bile acid concentrations is, therefore, a good indicator of hepatobiliary function, but is not specific for the type of underlying liver disease and diseases that secondarily affect the liver (e.g. metabolic diseases like hyperadrenocorticism) can also increase bile acid concentrations.

The concentration of bile acids in serum from fasting patients tends to be abnormally high when one or more of the following occurs:

Bile Acids The normal enterohepatic recirculation of bile acids.
  • Cholestasis: This causes "regurgitation" of bile acids back into blood (along with conjugated bilirubin). Since cholestasis alone may increase bile acid concentrations, high concentrations may not indicate any changes to portal blood flow or hepatic mass in a cholestatic animal. Measurement of bile acids is thus of questionable utility if there is evidence of cholestasis in a given patient.
  • Reduced functional hepatic mass: This impairs extraction of bile acids from portal blood.
  • Congenital and acquired vascular shunts: These allow an increased proportion of portal blood to bypass the liver, such that the bile acids normally in the portal blood do not get extracted.

Small animals
Measurement of both fasting and 2 hour post-prandial bile acids can be useful. Feeding stimulates gall bladder contraction which releases bile acids into the intestine and portal circulation (after intestinal absorption). This increases the load of bile acids that must be extracted from blood by the liver and increases the sensitivity of the procedure to hepatobiliary or vascular defects. Young dogs of breeds predisposed to congenital portosystemic shunts should be tested when greater than 16 weeks of age, because bile acid concentrations may be falsely lower in animals younger than this. For stimulation testing, animals should be fed at their routine meal times (e.g. morning) and should be given their regular meal (amount and type).

Interpretation

  • Bile acid concentrations >25-30 umol/L in dogs and > 25 umol/L in cats are suggestive of hepatobiliary disease, i.e. decreased functional mass, alterations in portal circulation, or cholestasis. These guidelines are valid for pre-prandial (fasting), post-prandial and random (unrelated to eating) samples.
  • Based on studies done by Dr. Center at Cornell University, dogs with bile acid concentrations < 15 umol/L do not have evidence of hepatic pathology on biopsy, whereas dogs with values > 25 umol/L usually have hepatic pathology. Dogs with bile acid values between 15-25 umol/L are in an equivocal zone (i.e. may or may not have hepatic pathology).
  • Postprandial > preprandial: Most animals have higher post-prandial than fasting bile acid concentrations, however some animals (up to 20% of dogs) may have higher fasting than post-prandial bile acid concentrations, due to a recent meal, gall bladder contraction during fasting, or delayed gastric emptying. In this scenario, if both results are < 25 umol/L (especially < 15 umol/L), hepatobiliary disease is unlikely.
  • Most animals with congenital or acquired portosystemic shunting have markedly increased post-prandial bile acids concentrations. This is likely due to a combination of portal blood bypassing the liver and decreased functional mass, a frequent concurrent finding in affected animals.

Variables affecting test results

  • Prolonged fasting, intestinal malabsorption, or rapid gastrointestinal transit may lower bile acid concentrations and decrease the sensitivity of bile acid testing for hepatobiliary disease.
  • Lipemia (falsely increases) and hemolysis (falsely decreases) do interfere with bile acid measurement, so efforts should be undertaken to minimize these (by not feeding too large a meal and by separating serum from cells as soon as possible). Our laboratory provides guidelines indicating when the bile acid concentrations may have been affected by these interferences and recommending retesting in such cases.
  • Bile acid testing should not be done in an animal that is clinically icteric or has an increased direct (conjugated) bilirubin, since this test does not give any indication of hepatic function or portosystemic shunting in the presence of cholestasis.

Horses
Horses lack gall bladders and only random bile acid concentrations are measured in these species.

Interpretation

  • Bile acid concentrations above the reference interval can be the result of hepatobiliary disease.
  • Slightly increased concentration (up to approximately 20 umol/L) can result from decreased feed intake for a period of several days or longer.
  • Most horses with hepatobiliary disease have markedly increased bile acids concentration.
  • Note that young foals under 2 weeks of age can have higher bile acid concentrations than adults. Bile acid concentrations approximate adults by about 6 weeks of age in foals.

Variables affecting test results

  • Bile acid testing should not be done in a horse that has an increased direct (conjugated) bilirubin, since this test does not give any indication of hepatic function or portosystemic shunting in the presence of cholestasis.

Cows
These
have extremely variable serum bile acids concentration in health, rendering the test ineffective in detection of disease.

Camelids
Since camelids are constant grazers, only random bile acid measurements are performed.

Interpretation

  • Bile acid concentrations increase with hepatic lipidosis in llamas. This may be a consequence of cholestasis or may reflect hepatocellular dysfunction in non-cholestatic animals.
  • Bile acid concentrations are greater in llamas < 1 year of age versus those older than 1 year of age.
  • Fasting does not appear to affect bile acid concentrations.

 

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