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Liver - Anatomy & Physiology (view source)
Revision as of 18:35, 15 March 2022
, 18:35, 15 March 2022→Bile Acids
==Bile Acids==
==Bile Acids==
Bile acids are composed of cholesterol, bile acids and steroids. The main bile acid is '''cholic acid''' (C24). Conjugated to taurine or glycine in the liver to reduce pKa so they exist in an ionised form as bile salts. Bile salts conjugate with cholesterol and phospholipids and are then secreted into the bile. 95% are recycled in enterohepatic circulation. They emulsify fats which helps absorb fat soluble vitamins. In aqueous solution, they form micelles which are amphiphilic and can transport free fatty acids across the brush border.
Bile acids are synthesised in the liver from cholesterol and are conjugated with taurine or glycine before excretion as bile salts into the bile. Once fat absorption in the small intestine has been completed bile acids are re-absorbed in the ileum. Bacterial action in the intestine deconjugates some to bile acids and converts the rest to secondary bile salts. Around 95% of bile acids and salts are re-absorbed, these products enter the portal circulation and are extracted and recycled by the hepatocytes (enterohepatic circulation). This is normally a highly efficient process but when there is reduced hepatic function some of these bile acids are not extracted and can be measured in the peripheral blood. References: [[NationWide Laboratories]]
Bile acids are composed of cholesterol, bile acids and steroids. The main bile acid is '''cholic acid''' (C24). Conjugated to taurine or glycine in the liver to reduce pKa so they exist in an ionised form as bile salts. Bile salts conjugate with cholesterol and phospholipids and are then secreted into the bile. They emulsify fats which helps absorb fat soluble vitamins. In aqueous solution, they form micelles which are amphiphilic and can transport free fatty acids across the brush border.
=== Small animals ===
The measurement of fasting bile acid levels is at least as sensitive as either the bromsulphthalein clearance test or the ammonia tolerance test as a measure of hepatic function. Pre and post feeding bile acids are measured on a 8-12 hour fasted sample and a sample taken 2 hours post feeding. This is more sensitive than a single fasted sample. However, it can be difficult to balance the quantity of food required to stimulate gallbladder contraction with the presence of postprandial lipaemia which interferes with the assay, and is noted if a large amount of food is given. Feeding a normal meal is recommended, but this approach may need to be tailored for individual patients. A fatty meal or oil supplementation is not required to stimulate gallbladder contraction.
The measurement of bile acids is useful in the investigation of hepatic disease, but the interpretation can be complex and a number of factors should be considered
* The bile acid result does not provide specific information regarding the nature or reversibility of hepatic changes
* The degree of increase does not correlate well with the severity of disease
* Increases are noted with extrahepatic disease for example, intestinal disease, etc. Commonly the increase in bile acids is only mild, but increases up to 100μmol/l have been noted occasionally
* Concentrations above 30μmol/l correlate with the presence of histological changes in the liver but these could be associated with primary or secondary hepatopathies
* Some authors suggest that increases above 40μmol/l correlate well with the presence of primary hepatic disease, but the cut-off is a matter of controversy
* It is not necessary to measure bile acids where there is hyperbilirubinaemia secondary to cholestasis
* A postprandial result lower than the one on the fasted sample is seen in some cases. The cause is not always clear (for example, failure of stomach to empty or gall bladder to contract, too fast or too slow intestinal transit, SIBO) but it is recommended to interpret the higher of the results.
===== Causes of increased bile acids =====
* Congenital or acquired portosystemic shunt
* Reduced hepatocellular function (decreased hepatocellular mass)
* Cholestasis
===== Complementary tests =====
Tests for cholestasis (ALP, GGT and bilirubin) and hepatic function (albumin, urea, glucose, cholesterol) are indicated along with tests for hepatocellular damage (ALT, AST and GLDH).
=== Equine ===
As in the dog and cat, bile acids are conjugated largely with taurine. The rate of enterohepatic circulation is fairly constant and horses do not possess a gall bladder, therefore fasting and stimulation testing is not required.
===== Causes of increased bile acids =====
* Hepatic insufficiency
* Cholestasis
* Portosystemic shunt
===== Complementary tests =====
Tests for cholestasis (ALP, GGT and bilirubin) and hepatocellular damage (AST and GLDH). Albumin is less useful as an indicator of hepatic insufficiency in the horse than in small animals due to its long half life (hypoalbuminaemia is only seen in advanced liver failure). Liver biopsy and ultrasound examination may be required to confirm the aetiology and provide prognostic information.
Small animal and Equine references: [[NationWide Laboratories]]
==Species Differences==
==Species Differences==
**Zone 3 - centrilobular (periacinar), bordering the hepatic venules
**Zone 3 - centrilobular (periacinar), bordering the hepatic venules
NB: blood enters from Zone 1 to Zone 3 and thus becomes less and less oxygenated
NB: blood enters from Zone 1 to Zone 3 and thus becomes less and less oxygenated
== References ==
Text referenced 'Nationwide Laboratories': [[NationWide Laboratories]]
==Links==
==Links==