Secretion rate

Figure 5.6 Variation in composition of gastric juice with secretion rate

Figure 5.7 Mechanism of acid production by the parietal cell

released when stimuli descend the vagus nerve in response to the sight, smell and taste of food and to the physical effects of chewing and swallowing. It is likely that acetylcholine and gastrin may operate by activating the mast cells which then release histamine, so that histamine is the final common pathway by which the parietal cell is activated.

The process of gastric secretion has been divided into three phases: cephalic, gastric and intestinal, which have different primary mechanisms. The phases of gastric secretion overlap, and there is an interrelation and some interdependence between the neural and humoral pathways.

The cephalic phase of gastric secretion occurs in response to stimuli received by the senses; that is, taste, smell, sight, and sound. This phase is entirely reflex in origin and is mediated by the vagus nerves. The gastric juice that is secreted in response to vagal stimulation is rich in enzymes and is highly acidic.

The gastric phase is mediated both by the vagus nerves and by the release of gastrin. Acid continues to be secreted during the gastric phase in response to distension, and to the peptides and amino acids liberated from food as protein digestion proceeds. The free amino acids and peptides liberate gastrin from the antrum into the circulation. When the pH of the antral contents falls below 2.5, a feedback mechanism inhibits the release of gastrin, thus the system is self-limiting. The gastric phase continues until the food leaves the stomach.

During the intestinal phase the chyme in the small intestine continues to elicit acid secretion for many hours, although the amount of acid released diminishes progressively during the digestion and absorption processes in the small intestine. Some of the actions of the intestinal phase are due to gastrin released from the duodenum, but there is evidence that another hormone-like substance not yet characterised may be responsible. Finally, as certain amino acids and small peptides are infused into the circulation during this phase, they also promote gastric acid secretion. It is possible, therefore, that the absorption of the products of protein digestion also may have a role in the intestinal phase.

Once food reaches the small intestine, it stimulates the pancreas to release fluid containing a high concentration of bicarbonate. This neutralizes the highly acidic gastric juice, which would otherwise destroy the intestinal epithelium, resulting in a duodenal ulcer. Other secretions from the pancreas, gallbladder, liver, and glands in the intestinal wall add to the total volume of chyme.


Pepsinogen is converted to the active enzyme, pepsin, by hydrolysis of the precursor by hydrochloric acid. The hydrochloric acid present in the stomach provides the correct pH for the pepsins to act, i.e. between 1.8 and 3.5; above pH 5 they are denatured. Human pepsins are endopeptidases which hydrolyse several peptide bonds within the interior of ingested protein molecules to form polypeptides, but little free amino acid. The susceptible bonds involve the aromatic amino acids tyrosine or phenylalanine. The polypeptides produced have N-terminal amino acids with lipophilic side chains which facilitate absorption.

Other enzymes

Some other enzymes, including gastric lipase and gastric amylase and gelatinase can be found in gastric juice. Gastric lipase is highly specific tributyrase acting solely on butterfat which is largely tributyrin. It is not capable of digesting medium- and long-chain fatty acids, but since there is only a small proportion of short-chain fatty acids in food, little fat digestion proceeds in the stomach. Gastric amylase plays a minor role in the digestion of starches and the enzyme gelatinase helps liquefy some of the proteoglycans in meats.

Intrinsic factor of Castle

Parietal cells also secrete a glycoprotein known as intrinsic factor of Castle (m. w. 1350 Dalton) which is required for the absorption of vitamin B12. It is continuously secreted, even in the absence of any gastric secretory stimulus in man. Its basal secretion greatly exceeds the minimum amount required for normal vitamin B12 absorption.


Prostaglandins are hormone-like substances which are derived from dietary lipids. They are present in virtually all animal tissues and body fluids, and are involved in the contraction and dilatation of blood vessels, the aggregation of platelets (clotting), and the contraction and relaxation of the smooth muscle of the gastrointestinal tract. Prostaglandins also inhibit the secretion of hydrochloric acid by the stomach in response to food, histamine, and gastrin. They also protect the mucosa from damage by various chemical agents. This protection is not related to their ability to influence acid secretion. Prostaglandins increase the secretion of mucus and bicarbonate from the mucosa, and they stimulate the migration of cells to the surface for repair and replacement of the mucosal lining.

Digestion and absorption

Salivary amylase acts on food starch while the acidity of the mixture is low, around pH 6, but ceases when the acidity of the mixture increases with greater acid secretion. Gastric pepsins account for only about 10 to 15 percent of the digestion of protein and are most active in the first hour of digestion. The stomach is primarily a processing organ and not an absorptive one and is not essential to life. It is possible, for example, after total gastrectomy (the complete removal of the stomach) for a person to remain, or to become, obese because most of the digestion and absorption of food takes place in the intestine. The stomach can absorb some substances, including glucose and other simple sugars, amino acids, and some fat-soluble substances. A number of alcohols, including ethanol, are readily absorbed from the stomach. The pH of the gastric contents controls the absorption of certain ionizable materials such as aspirin, which is readily absorbed in its unionized form when the stomach is acidic, but more slowly when the gastric contents are neutral. The absorption of water and alcohol can be slowed if the stomach contains food, especially fat, probably because gastric emptying is delayed and most water in any situation is absorbed from the jejunum.

Water moves freely from the gastric contents across the gastric mucosa into the blood. The net absorption of water from the stomach is small, however, because water moves just as easily from the blood across the gastric mucosa to the lumen of the stomach. In tracer experiments using deuterium oxide, about 60 percent of the (isotopic) water placed in the stomach is absorbed into the blood in 30 minutes.

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