DIGESTIVE ACTIVITY
OF STOMACH
The main role of the stomach is to prepare food for digestion and absorption by the intestine. The parietal cells produce hydrochloric acid in gastric secretions. Various neural and hormonal mediators contribute to gastric function. The acid secretory process requires functional receptors, signaling pathways, channels, transporters, and acid-secreting pumps (H+/K+- ATPase). The level of acidity depends upon the relative proportions of parietal and nonparietal secretions; hence, the more rapid the rate of secretion, the higher the level of acidity.
Rebound acid hypersecretion occurs
after therapy with proton pump inhibitors or H2 receptor antagonists has
ceased. Increased HCl secretion has been seen at night and with the acid
secretory response to a meal. The alkaline tide (decrease in urinary
acidity after a meal) is generally attributed to increased alkalinity of the
blood resulting from the secretion of HCl. Its occurrence is influenced by the
rate of formation of HCl and its absorption from the gut. Additional
influencing factors include alkaline digestive secretions (mainly pancreatic),
the neutralizing capacity of the food eaten, respiratory adjustments after a
meal, and the diuretic effect of a meal.
Pepsin, the principal enzyme of gastric juice, is
stored in the chief cells as pepsinogen. At a pH below 6.0, pepsinogen
is converted to pepsin. The free pepsin activates the continued transformation
of pepsinogen to pepsin. The chief cells are the most common cells in the
gastric mucosa, found in the body, fundus, and antrum of the stomach, as well as
in the duodenum. Pepsinogen is stimulated by acetylcholine, histamine, and CCK2
and inhibited by somatostatin.
Powerful stimuli for gastrin
secretion include gastric juice rich in pepsin, hypoglycemia (vagal stimulus),
or direct electrical stimulation of the vagus nerves. The pepsinogen of the
gastric chief cells is also secreted internally into the bloodstream and
appears in the urine as uropepsinogen.
As mentioned previously, gastric
acid secretion is divided into cephalic, gastric, and intestinal phases. Mucus
is excreted from neck cells and surface mucus cells in the stomach and
Brunner glands after stimulation with acetylcholine, secretin, and
prostaglandins. Its function is to provide a protective layer over the gastric
and duodenal mucosa. Mucus slows the diffusion of acid from the lumen to the
mucosa, provides lubrication for the passage of food, and maintains a
near-normal pH at the mucosal surface because of its content of bicarbonate. It
is dissolved by pepsin and N-acetylcysteine and easily penetrated by bile
salts, ethanol, and nonsteroidal anti inflammatory drugs (NSAIDs), leading to
mucosal damage. Mucosal repair is very quick and occurs through the movement of
already established mature mucosal cells over the basal lamina.
Acetylcholine, histamine,
endogenous nitric oxide, and PGE2 cause vasodilation and increased gastric blood
flow; sympathetic stimulation, exogenous epinephrine, norepinephrine, and
vasopressin cause vasoconstriction and decreased gastric blood flow.
Parietal cells synthesize and
secrete intrinsic factor, which plays a key role in absorption of vitamin B12
in the terminal ileum. NSAIDs inhibit the cyclooxygenase (COX) enzyme in the
prostaglandin production pathway and cause damage to the gastric mucosa.
Currently there are two isoforms, COX-1 and COX-2. The COX-1 pathway results in
production of PGE2, and the COX-2 pathway is involved mainly in inflammatory
events. The selective COX-2 inhibitors decrease inflammation without affecting
PGE2 production. Mucosal efenses can also be affected by H. pylori infection.
