section
12.1
Anatomy and Physiology of the Gl Tract
201
contraction of the gallbladder and relaxation of the sphin-
cter of Oddi, both mediated by cholecystokinin.
Bile contains bile acids, bile pigments, cholesterol,
phosphatidylcholine
(lecithin),
and electrolytes.
Bile
pigments are glucuronide conjugates of bilirubin and
biliverdin derived from the degradation of heme, a pros-
thetic group of many proteins. Most of the bilirubin formed
in the body comes from hemoglobin catabolized in reti-
culoendothelial cells (liver is one of the sites where
these cells are formed). The bilirubin is bound to plasma
albumin and transported to hepatocytes, where it is con-
verted to glucuronide conjugates and secreted into the bile,
giving it a golden yellow color. If bilirubin remains in the
gallbladder, it is oxidized to biliverdin, which is greenish
brown. Bile pigments are toxic metabolites (Chapter 29).
The bile acids are 24-carbon steroid derivatives. The two
primary bile acids, cholic acid and chenodeoxycholic acid,
are synthesized in the hepatocytes from cholesterol by hy-
droxylation, reduction, and side chain oxidation. They are
conjugated by amide linkage to glycine or taurine before
they are secreted into the bile (see cholesterol metabolism,
Chapter 19). The mechanism of secretion of bile acids
across the canalicular membrane is poorly understood.
Bile acids are present as anions at the pH of the bile, and
above a certain concentration (critical micellar concen-
tration) they form polyanionic molecular aggregates, or
micelles (Chapter 11). The critical micellar concentration
for each bile acid and the size of the aggregates are affected
by the concentration of Na+ and other electrolytes and of
cholesterol and lecithin. Thus, bile consists of mixed mi-
celles of conjugated bile acids, cholesterol, and lecithin.
While the excretion of osmotically active bile acids is a
primary determinant of water and solute transport across
the canalicular membrane, in the canaliculi they contribute
relatively little to osmotic activity because their anions
aggregate to form micelles.
Bile is also a vehicle for excretion of other endogenous
(e.g., bilirubin and steroids) and exogenous (e.g., drugs
and dyes) compounds. The dye sulfobromophthalein is re-
moved from the bloodstream by the hepatocytes, excreted
in the bile, and eliminated through the GI tract. Its rate
of removal from the circulation depends on the functional
ability of the hepatocytes and of the hepatic blood flow,
and so it is used to assess hepatic function.
Cholesterol is virtually insoluble in water but is
solubilized through the formation of micelles, which
also contain phosphatidylcholine and bile acid anions in
specific proportions. Cholesterol can be precipitated to
form stones (known as
gallstones)
when the critical con-
centration of micellar components is altered, i.e., when the
concentration ratio of cholesterol to bile acids is increased.
Gallstones may also form because of precipitation of
bilirubin, e.g., with increased production of bile pig-
ments due to hemolysis, associated with infection and
bile
stagnation.
Presumably,
under these
conditions
the bilirubin diglucuronide is converted to free bilirubin
by /3-glucuronidase. Bilirubin is insoluble and forms
calcium-bilirubinate
stones
(called
pigment
stones).
Gallstones occur in 10-20% of the adult population in
Western countries. Cholesterol stones account for 80%
(see Chapter 19).
More than 90% of the bile acids are reabsorbed, mostly
in the ileum. About 5-10% undergoes deconjugation
and dehydroxylation catalyzed by bacterial enzymes
in the colon to form deoxycholic acid and lithocholic
acid. These acids are known as secondary bile acids.
Deoxycholic acid is reabsorbed, but lithocholic acid,
which is relatively insoluble, is poorly absorbed. The
reabsorbed bile acids enter the portal blood circulation,
are reconjugated in the liver, and are secreted into bile.
This cycling is known as the
enterohepatic circulation
and occurs about six to eight times daily. The rate of
cycling increases after meals. The lithocholic acid is
conjugated with either taurine or glycine, sulfated at the
ring hydroxyl group, and again secreted into the bile.
Sulfated lithocholate is not reabsorbed. Free lithocholic
acid is highly toxic to tissues and causes necrosis.
The bile acid pool normally consists of about 2-4 g of
conjugated and unconjugated primary and secondary bile
acids. Daily loss of bile acids in feces, mostly as litho-
cholate, is about 0.2-0.4 g. Hepatic synthesis of bile acids
equals this amount, so that the size of the bile acid pool is
maintained at a constant level.
Exocrine Pancreatic Secretion
The pancreatic gland is 10-15 cm long and resides in the
retroperitoneal space on the posterior wall of the abdomen,
with its broad and flat end (“head”) fitting snugly into the
loop formed by the duodenum. The endocrine function
of the pancreas consists of synthesis, storage, and secre-
tion of the hormones insulin, glucagon, and somatostatin
into the venous circulation that drains the pancreas. These
hormones are essential in the regulation of metabolism
of carbohydrates and other substrates (Chapter 22). The
endocrine cells are located in the
islets o f Langerhans,
distributed throughout the pancreas but separated from
the surrounding exocrine-acinar tissue by collagen fibers.
The exocrine function of the pancreas consists of syn-
thesis, storage, and secretion of digestive enzymes and
bicarbonate-rich fluids.
The acinar cells of the pancreas are arranged in ellip-
soidal structures known as
acini.
Each acinus contains
about a dozen cells arranged around a lumen, which forms
