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SECTION V
Gastrointestinal Physiology
solution, the micelles simply become larger, and since osmo-
larity is a colligative property, bile remains isotonic. However,
bile becomes slightly acidic as sodium ions are exchanged for
protons (although the overall concentration of sodium ions
rises with a concomitant loss of chloride and bicarbonate as
the bile is concentrated).
When the bile duct and cystic duct are clamped, the intra-
biliary pressure rises to about 320 mm of bile in 30 min, and
bile secretion stops. However, when the bile duct is clamped
and the cystic duct is left open, water is reabsorbed in the gall-
bladder, and the intrabiliary pressure rises only to about 100
mm of bile in several hours.
REGULATION OF BILIARY SECRETION
When food enters the mouth, the resistance of the sphincter of
Oddi decreases under both neural and hormonal influences
(Figure 29–9). Fatty acids and amino acids in the duodenum
release CCK, which causes gallbladder contraction.
The production of bile is increased by stimulation of the
vagus nerves and by the hormone secretin, which increases
the water and HCO
3
- content of bile. Substances that increase
the secretion of bile are known as
choleretics.
Bile acids them-
selves are among the most important physiologic choleretics.
EFFECTS OF CHOLECYSTECTOMY
The periodic discharge of bile from the gallbladder aids diges-
tion but is not essential for it. Cholecystectomized patients
maintain good health and nutrition with a constant slow dis-
charge of bile into the duodenum, although eventually the bile
duct becomes somewhat dilated, and more bile tends to enter
the duodenum after meals than at other times. Cholecystecto-
mized patients can even tolerate fried foods, although they gen-
erally must avoid foods that are particularly high in fat content.
VISUALIZING THE GALLBLADDER
Exploration of the right upper quadrant with an ultrasonic
beam
(ultrasonography)
and computed tomography (CT)
have become the most widely used methods for visualizing the
gallbladder and detecting gallstones. A third method of diag-
nosing gallbladder disease is
nuclear cholescintigraphy.
When administered intravenously, technetium-99m-labeled
derivatives of iminodiacetic acid are excreted in the bile and
provide excellent gamma camera images of the gallbladder
and bile ducts. The response of the gallbladder to CCK can
then be observed following intravenous administration of the
hormone. The biliary tree can also be visualized by injecting
contrast media from an endoscope channel maneuvered into
the sphincter of Oddi, in a procedure known as endoscopic
retrograde cholangiopancreatography (ERCP). It is even pos-
sible to insert small instruments with which to remove gall-
stone fragments that may be obstructing the flow of bile, the
flow of pancreatic juice, or both (Clinical Box 29–2).
FIGURE 29–9
Neurohumoral control of gallbladder
contraction and biliary secretion.
Dorsal
vagal
Vagal complex
efferentsAChCCKVagal
ACh and CCK afferent
cause smooth
muscle contraction
CCKCCKSphincter
of OddiGall-
bladderVia
bloodstreamDuodenum
NutrientsNO
VIPCLINICAL BOX 29–2
Gallstones
Cholelithiasis,
that is, the presence of gallstones, is a com-
mon condition. Its incidence increases with age, so that in
the United States, for example, 20% of the women and 5%
of the men between the ages of 50 and 65 have gallstones.
The stones are of two types: calcium bilirubinate stones
and cholesterol stones. In the United States and Europe,
85% of the stones are cholesterol stones. Three factors ap-
pear to be involved in the formation of cholesterol stones.
One is bile stasis; stones form in the bile that is seques-
trated in the gallbladder rather than the bile that is flowing
in the bile ducts. A second is supersaturation of the bile
with cholesterol. Cholesterol is very insoluble in bile, and it
is maintained in solution in micelles only at certain concen-
trations of bile salts and lecithin. At concentrations above
line ABC in Figure 29–8, the bile is supersaturated and con-
tains small crystals of cholesterol in addition to micelles.
However, many normal individuals who do not develop
gallstones also have supersaturated bile. The third factor is
a mix of nucleation factors that favors formation of stones
from the supersaturated bile. Outside the body, bile from
patients with cholelithiasis forms stones in 2 to 3 d,
whereas it takes more than 2 wk for stones to form in bile
from normal individuals. The exact nature of the nucleation
factors is unsettled, although glycoproteins in gallbladder
mucus have been implicated. In addition, it is unsettled
whether stones form as a result of excess production of
components that favor nucleation or decreased production
of antinucleation components that prevent stones from
forming in normal individuals.