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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:
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Bile contains bile acids, which are critical
for digestion and absorption of fats and fat-soluble vitamins
in the small intestine.
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Many waste products 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 two stages:
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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.
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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 hydrophilic.
Their amphipathic nature enables bile acids to carry out two
important functions:
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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.
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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
fat-soluble vitamins.
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.
Enterohepatic Recirculation
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 the ileum.
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 digestive phase.
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:
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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.
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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. |
