NORMAL GASTRIC PHYSIOLOGY



The stomach serves as a reservoir in which in­gested food is churned and fragmented into small particles prior to its timed release into the duo­denum. Beyond these important mechanical func­tions, the stomach also initiates the processes of digestion by the secretion of HC1 and pepsinogen, which in the presence of HC1 is rapidly converted to proteolytic pepsin. Acid-peptic disease occurs when there is an imbalance between the processes of secretion and the normal processes of defense against chemical selfinjury.

tiormal Secretion. HC1 is secreted by the par­ietal cells and pepsinogen by the chief cells, both found in the gastric mucosa, predominantly in the body and fundus of the stomach. These two agents are secreted in parallel; no condition is known in which there is selective secretion of either HC1 or pepsinogen. Three endogenous chemicals stim­ulate the secretion of acid: gastrin, histamine, and acetylcholine (Fig. 39-1). Acetylcholine is re­leased locally from vagal (cholinergic) nerve ter­minals in the stomach, stimulated by stretch reflexes within the stomach or by the cephalic phase of gastric secretion. Gastrin is released from “G cells” in the antrum of the stomach and in the duodenum, stimulated largely by the products of protein digestion and by alkalinization. It circulates as a hormone before acting on the parietal cell. Histamine is found in mastlike cells in the gastric wall in close proximity to the chief cells. The role and control of local histamine release are unknown, but histamine and its structural ana­logues are powerful gastric secretagogues when administered systemically, and the use of H2-re-ceptor antagonists markedly inhibits HC1 (and pepsinogen) secretion by the stomach. There is also evidence of a nongastrin gut-derived secret-agogue stimulated by the products of protein digestion, but its structure has not been defined. The interaction of these various agents at the final common parietal cell pathway for acid secretion is unclear. In brief, gastric secretion seems to re­sult largely from the cephalic phase [via the vagus), the gastric phase (stretch stimulation of the vagus; protein and alkalinization stimulation of gastrin release), and the intestinal phase (fur­ther release of gastrin and of the nongastrin se-cretagogue). Secretion of pepsinogen seems to be controlled through acetylcholine and possibly the other described mechanisms as well.

Basal secretion of acid averages about 1.0 to 2.0 mEq per hour in men but less in women. The nor­mal range, however, varies widely from 0 to 10.5 mEq per hour for men and from 0 to 5.6 mEq per hour for women. When maximally stimulated with a secretagogue—usually betazole (a hista­mine analogue) or pentagastrin—the secretory rate may rise as high as 50 mEq per hour for men and 30 mEq per hour for women. The ratio of basal to maximal acid output (MAO) is sometimes de­termined in the study of patients with suspected abnormal secretory drives.

normal Defense. The stomach and the duo­denum have developed several defense mechanisms to protect the mucosa from the acid-pepsin mix of gastric juice (Fig. 39-2). A thin coating of mucus is continuously formed and spreads out protectively over the mucosal cells. This dimin­ishes the exposure of these cells to luminal gastric juice. The surface apical cells secrete bicarbonate within and under the mucin layer, which serves to neutralize the H+ that diffuses back from the lumen. The epithelial cells are constantly being shed and renewed so that damaged cells are re­placed. Prostaglandins may play a role in stimu­lating all of these repair mechanisms, including an increase in mucosal blood flow. As a result the average individual can secrete more than 100 mmol of HC1 daily throughout life without sig­nificant mucosal injury.