The stomach has three main functions: it stores a large volume of food, digests it, and controls its emptying into the small intestine.
Filling and emptying
An empty stomach holds about 50 ml, yet it can expand to about 1 litre as food and fluid are swallowed. The pressure inside does not rise in step with the volume, for two reasons: the smooth muscle cells are plastic, so they can be stretched without developing tension, and the stomach undergoes receptive relaxation, controlled mainly by the vagus nerve through the release of VIP and nitric oxide.
Once food is inside, mixing with gastric juice begins, helped by peristaltic contractions that travel toward the antral sphincter. Emptying into the duodenum is then finely regulated. The force of the peristaltic contractions pushes content along, while the pyloric sphincter decides how much passes. The sphincter relaxes mainly under VIP and nitric oxide released from the vagus nerve, and it contracts under cholinergic vagal stimulation, the sympathetic system, gastrin, cholecystokinin, secretin and gastric inhibitory peptide. Two gastric factors also speed emptying: a larger volume inside the stomach, and a more fluid chyme.
The gastric gland
The lining of the stomach is thrown into rugae, visible to the eye, which carry microscopic gastric pits. Each pit branches into four or five gastric glands lined by specialised epithelial cells, and the mix of cells changes with the region of the stomach. The cardia accounts for less than 5% of the mucosa and is made up mostly of mucus-producing and endocrine cells; the rest divides into the oxyntic mucosa of the fundus and body, and the antral mucosa.
About 75% of the gastric glands lie in the fundus and body, the oxyntic area. Alongside mucus-producing cells, the oxyntic glands contain three cell types that matter most.
Parietal cells sit mostly in the neck and isthmus of the glands. At rest they keep a dense network of tubulovesicle membranes whose surface carries the H⁺/K⁺-ATPase, the pump that secretes acid; the tubulovesicles are held on short microtubules. When the cell is stimulated, the microtubules lengthen and the tubulovesicles form the canaliculi of the parietal cell, carrying large amounts of the pump to the surface to create the acidic environment of the stomach. Besides acid, parietal cells make intrinsic factor and IL-11. Their acid secretion is driven mainly through H2 receptors, cholinergic M3 receptors and the gastrin receptor, and is tuned by humoral and neuronal factors including amylin, ANP, cholecystokinin, ghrelin, IL-11, obestatin, secretin and serotonin. Ghrelin, released from Gr cells, raises acid production indirectly by stimulating ECL cells to release histamine.
Chief cells lie mainly in the fundus and produce pepsinogen and gastric lipase. Pepsinogen becomes pepsin at a pH of about 2, and the rate of activation falls sharply at about pH 4.
Endocrine cells include enterochromaffin cells, enterochromaffin-like (ECL) cells, D cells, which release somatostatin, and Gr cells, which produce the appetite hormone ghrelin and lie mainly in the oxyntic glands. Specialised tuft cells in the neck of the gland are thought to sample the gastric contents and help regulate acid production. The pyloric glands of the antrum contain mucus-producing cells and endocrine cells, including the gastrin-producing cells.
Gastric juice composition
The juice changes with the rate of secretion. At a low rate it is hypotonic, and at a higher rate it becomes nearly isotonic, largely because of protons and chloride. As secretion rises, the ions in the juice change in different ways: chloride increases linearly, protons increase, potassium rises only slightly, and sodium falls. During acid production, bicarbonate is released into the bloodstream around the gastric mucosa, a shift called the alkaline tide.
Acid secretion
Acid and pepsinogen are important for digesting protein and for absorbing iron, magnesium, calcium and vitamin B12, and the same acid can also damage the stomach. Acid secretion is best seen in two forms. Basal acid secretion follows a circadian rhythm, peaking at night and reaching its lowest level in the morning, and is controlled mainly by vagal tone and local histaminergic nerves. Stimulated acid secretion occurs in three phases: the cephalic phase, driven by the sight, smell and taste of food acting through the vagus nerve; the gastric phase, after food enters the stomach, in which the G cells of the antrum release gastrin that acts directly on parietal cells, with distension of the stomach adding a further stimulus; and the intestinal phase, after food enters the intestine, when distension and the nature of the food continue to stimulate acid production.