|Bile is a complex fluid containing water, electrolytes and a battery of organic
molecules including bile acids, cholesterol, phospholipids and bilirubin that flows
through the biliary tract into the small intestine. There are two fundamentally
important functions of bile in all species:
- Bile contains bile acids, which are critical for digestion and
absorption of fats and fat-soluble vitamins in the small intestine.
- Many waste products, including bilirubin, are eliminated from the
body by secretion into bile and elimination in feces.
Adult humans produce 400 to 800 ml of bile daily, and other animals
proportionately similar amounts. The secretion of bile can be considered to occur in
- Initially, hepatocytes secrete bile into canaliculi, from which it
flows into bile ducts. This hepatic bile contains large quantities of bile
acids, cholesterol and other organic molecules.
- As bile flows through the bile ducts it is modified by addition of a
watery, bicarbonate-rich secretion from ductal epithelial cells.
In species with a gallbladder (man and most domestic animals except horses and
rats), further modification of bile occurs in that organ. The gall bladder stores
and concentrates bile during the fasting state. Typically, bile is concentrated
five-fold in the gall bladder by absorption of water and small electrolytes -
virtually all of the the organic molecules are retained.
Secretion into bile is a major route for eliminating cholesterol. Free
cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made
soluble by bile acids and lipids like lethicin.
Gallstones, most of which are composed predominantly of cholesterol, result from
processes that allow cholesterol to precipitate from solution in bile.
Role of Bile Acids in Fat Digestion and Absorption
Bile acids are derivatives of cholesterol synthesized in the hepatocyte.
Cholesterol, ingested as part of the diet or derived from hepatic synthesis is
converted into the bile acids cholic and chenodeoxycholic acids, which are then
conjugated to an amino acid (glycine or taurine) to yield the conjugated form that
is actively secreted into cannaliculi.
Bile acids are facial amphipathic, that is, they contain both hydrophobic (lipid
soluble) and polar (hydrophilic) faces. The cholesterol-derived portion of a bile
acid has one face that is hydrophobic (that with methyl groups) and one that is
hydrophilic (that with the hydroxyl groups); the amino acid conjugate is polar and
Their amphipathic nature enables bile acids to carry out two important functions:
- Emulsification of lipid aggregates: Bile acids have detergent action
on particles of dietary fat which causes fat globules to break down or be
emulsified into minute, microscopic droplets. Emulsification is not digestion
per se, but is of importance because it greatly increases the surface area of
fat, making it available for digestion by lipases, which cannot access the
inside of lipid droplets.
- Solubilization and transport of lipids in an aqueous environment:
Bile acids are lipid carriers and are able to solubilize many lipids by forming
micelles - aggregates of lipids such as fatty acids, cholesterol and
monoglycerides - that remain suspended in water. Bile acids are also critical
for transport and absorption of the
Role of Bile Acids in Cholesterol Homeostasis
Hepatic synthesis of bile acids accounts for the majority of cholesterol
breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to
bile acids and eliminated in bile every day. This route for elimination of excess
cholesterol is probably important in all animals, but particularly in situations of
massive cholesterol ingestion.
Interestingly, it has recently been demonstrated that
bile acids participate in cholesterol metabolism by functioning as hormones that
alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.
Large amounts of bile acids are secreted into the intestine every day, but only
relatively small quantities are lost from the body. This is because approximately
95% of the bile acids delivered to the duodenum are absorbed back into blood within
Venous blood from the ileum goes straight into the portal vein, and hence through
the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from
sinusoidal blood, and little escapes the healthy liver into systemic circulation.
Bile acids are then transported across the hepatocytes to be resecreted into
canaliculi. The net effect of this enterohepatic recirculation is that each bile
salt molecule is reused about 20 times, often two or three times during a single
It should be noted that liver disease can dramatically alter this pattern of
recirculation - for instance, sick hepatocytes have decreased ability to extract
bile acids from portal blood and damage to the canalicular system can result in
escape of bile acids into the systemic circulation. Assay of systemic levels of bile
acids is used clinically as a sensitive indicator of hepatic disease.
Pattern and Control of Bile Secretion
The flow of bile is lowest during fasting, and a majority of that is diverted
into the gallbladder for concentration. When chyme from an ingested meal enters the
small intestine, acid and partially digested fats and proteins stimulate secretion
of cholecystokinin and secretin. As discussed previously, these
enteric hormones have important effects on pancreatic exocrine secretion. They
are both also important for secretion and flow of bile:
- Cholecystokinin: The name of this hormone describes its effect on the
biliary system - cholecysto = gallbladder and kinin = movement. The most potent
stimulus for release of cholecystokinin is the presence of fat in the duodenum.
Once released, it stimulates contractions of the gallbladder and common bile
duct, resulting in delivery of bile into the gut.
- Secretin: This hormone is secreted in response to acid in the
duodenum. Its effect on the biliary system is very similar to what was seen in
the pancreas - it simulates biliary duct cells to secrete bicarbonate and water,
which expands the volume of bile and increases its flow out into the intestine.
The processes of gallbladder filling and emptying described here
can be visualized using an imaging technique called scintography. This procedure
is utilized as a diagnostic aid in certain types of hepatobiliary disease.