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SECTION V
Gastrointestinal Physiology
The potential danger of the release into the pancreas of a
small amount of trypsin is apparent; the resulting chain reac-
tion would produce active enzymes that could digest the pan-
creas. It is therefore not surprising that the pancreas normally
contains a trypsin inhibitor.
Another enzyme activated by trypsin is phospholipase A
2
.
This enzyme splits a fatty acid off phosphatidylcholine (PC),
forming lyso-PC. Lyso-PC damages cell membranes. It has
been hypothesized that in
acute pancreatitis,
a severe and
sometimes fatal disease, phospholipase A
2
is activated in the
pancreatic ducts, with the formation of lyso-PC from the PC
that is a normal constituent of bile. This causes disruption of
pancreatic tissue and necrosis of surrounding fat.
Small amounts of pancreatic digestive enzymes normally
leak into the circulation, but in acute pancreatitis, the circulat-
ing levels of the digestive enzymes rise markedly. Measure-
ment of the plasma amylase or lipase concentration is
therefore of value in diagnosing the disease.
REGULATION OF THE SECRETION OF
PANCREATIC JUICE
Secretion of pancreatic juice is primarily under hormonal
control. Secretin acts on the pancreatic ducts to cause copious
secretion of a very alkaline pancreatic juice that is rich in
HCO
3
- and poor in enzymes. The effect on duct cells is due to
an increase in intracellular cAMP. Secretin also stimulates bile
secretion. CCK acts on the acinar cells to cause the release of
zymogen granules and production of pancreatic juice rich in
enzymes but low in volume. Its effect is mediated by phospho-
lipase C (see Chapter 2).
The response to intravenous secretin is shown in Figure
26–13. Note that as the volume of pancreatic secretion
increases, its Cl
- concentration falls and its HCO
3- concen-
tration increases. Although HCO
3
- concen-
is secreted in the small
ducts, it is reabsorbed in the large ducts in exchange for Cl
(Figure 26–14). The magnitude of the exchange is inversely
proportionate to the rate of flow.
Like CCK, acetylcholine acts on acinar cells via phospholi-
pase C to cause discharge of zymogen granules, and stimulation
of the vagi causes secretion of a small amount of pancreatic
juice rich in enzymes. There is evidence for vagally mediated
conditioned reflex secretion of pancreatic juice in response to
the sight or smell of food.
BILIARY SECRETION
An additional secretion important for gastrointestinal function,
bile, arises from the liver. The bile acids contained therein are
important in the digestion and absorption of fats. In addition,
bile serves as a critical excretory fluid by which the body dispos-
es of lipid soluble end products of metabolism as well as lipid
soluble xenobiotics. Bile is also the only route by which the body
can dispose of cholesterol—either in its native form, or follow-
ing conversion to bile acids. In this chapter and the next, we will
be concerned with the role of bile as a digestive fluid. In Chapter
29, a more general consideration of the transport and metabolic
functions of the liver will be presented.
FIGURE 26–10
Ion transport proteins of parietal cells.
Protons are generated in the cytoplasm via the action of carbonic anhydrase II
(C.A. II). Bicarbonate ions are exported from the basolateral pole of the cell either by vesicular fusion or via a chloride/bicarbonate exchanger.
(Adapted from Barrett KE:
Gastrointestinal Physiology
. McGraw-Hill, 2006.)
Potassium
channel
Chloride
channel
Lumen Blood Stream
H+, K+ATPase
Na+, K+ATPase
3Na+
2K+
Na+
H+
NHE-1
K+
H+
Cl− Cl−
ClC
Apical Basolateral
Cl−/HCO 3
HCO 3
HCO 3
exchanger
H 2 O+ CO 2
H++ HCO 3
C.A.II
−
−
−
−