Physiology of the stomach including motility, gastric secretion, mucosal resistance in the stomach and integration of gastric physiologic function.
Motility of the stomach
Storage, mixing, trituration, and regulated emptying are accomplished by the muscular apparatus of the stomach. Peristaltic waves originate in the body and pass toward the pylorus. The thickness of the muscle increases in the antrum and corresponds to the stronger contractions that can be measured in the distal stomach. The pylorus behaves as a sphincter, though it normally allows a little to-and-fro movement of chyme across the junction.
An electrical pacemaker situated in the fundal musculature near the greater curvature gives rise to regular (3/min) electrical impulses (pacesetter potential, basic electrical rhythm) that pass toward the pylorus in the outer longitudinal layer. Every impulse is not always followed by a peristaltic muscular contraction, but the impulses determine the maximal peristaltic rate. The frequency of peristalsis is governed by a variety of stimuli mentioned below. Each contraction follows sequential depolarization of the underlying circular muscle resulting from arrival of the pacesetter potential.
Peristaltic contractions are more forceful in the antrum than the body and travel faster as they progress distally. Gastric chyme is forced into the funnel-shaped antral chamber by peristalsis; the volume of contents delivered into the duodenum by each peristaltic wave depends on the strength of the advancing wave and the extent to which the pylorus closes. Most of the gastric contents that are pushed into the antral funnel are propelled backward as the pylorus closes and pressure within the antral lumen rises. Five to 15 mL enter the duodenum with each gastric peristaltic wave.
The volume of the empty gastric lumen is only 50 mL. By a process called receptive relaxation, the stomach can accommodate about 1000 mL before intraluminal pressure begins to rise. Receptive relaxation is an active process mediated by vagal reflexes and abolished by vagotomy. Peristalsis is initiated by the stimulus of distention after eating. Various other factors have influences on the rate and strength of contractions and rate of gastric emptying. Vagal reflexes from the stomach have a facilitating influence on peristalsis. The texture and volume of the meal both play a role in the regulation of emptying; small particles are emptied more rapidly than large ones, which the organ attempts to reduce in size (trituration). The osmolality of gastric chyme and its chemical makeup are monitored by duodenal receptors. If osmolality is greater than 200 mosm/L, a long vagal reflex (the enterogastric reflex) is activated, delaying emptying. Gastrin causes delay in emptying. Gastrin is the only circulating gastrointestinal hormone to have a physiologic effect on emptying.
The output of gastric juice in a fasting subject varies between 500 and 1500 mL/d. After each meal, about 1000 mL are secreted by the stomach.
The components of gastric juice are as follows:
Mucus is a heterogeneous mixture of glycoproteins manufactured in the mucous cells of the oxyntic and pyloric gland areas. Mucus provides a weak barrier to the diffusion of H+ and probably protects the mucosa. It also acts as a lubricant and impedes diffusion of pepsin.
Pepsinogens are stored as visible granules. Cholinergic stimuli, either vagal or intramural, are the most potent pepsigogues, though gastrin and secretin are also effective. The precursor zymogen is activated when pH falls below 5.00, a process that entails severance of a polypeptide fragment from the larger molecule. Pepsin cleaves peptide bonds, especially those containing phenylalanine, tyrosine, or leucine. Its optimal pH is about 2.00. Pepsin activity is abolished at pH greater than 5.00, and the molecule is irreversibly denatured at pH greater than 8.00.
Intrinsic factor, a mucoprotein secreted by the parietal cells, binds with vitamin B12 of dietary origin and greatly enhances absorption of the vitamin. Absorption occurs by an active process in the terminal ileum.
Intrinsic factor secretion is enhanced by stimuli that evoke H+ output from parietal cells. Pernicious anemia is characterized by atrophy of the parietal mucosa, deficiency in intrinsic factor, and anemia. Subclinical deficiencies in vitamin B12 have been described after operations that reduce gastric secretion, and abnormal Schilling tests in these patients can be corrected by the administration of intrinsic factor. Total gastrectomy creates a dependence on parenteral administration of vitamin B12.
The unique characteristic of gastric secretion is its high concentration of hydrochloric acid. As the concentration of H+ rises during secretion, that of Na+ drops in a reciprocal fashion. K+ remains relatively constant at 5–10 meq/L. Chloride concentration remains near 150 meq/L, and gastric juice maintains its isotonicity at varying secretory rates.
The Parietal Cell & Acid Secretion
The onset of secretion is accompanied by striking morphologic changes in the apical membranes. Multiple membrane-bound tubulovesicles and mitochondria are present in the cytoplasm. With stimulation, the secretory canaliculus expands, the microvilli become long and narrow and filled with microfilaments, and the cytoplasmic tubulovesicles disappear.
The basal lateral membrane contains the receptors for secretory stimulants and transfers HCO3– out of the cell to balance the H+ output at the apical membrane. Active uptake of Cl– and K+ conduction also occur at the basal lateral membrane. Separate membrane-bound receptors exist for histamine (H2 receptor), gastrin, and acetylcholine. The intracellular second messengers are thought to be cAMP for histamine and Ca2+ for gastrin and acetylcholine.
Mucosal Resistance in the Stomach & Duodenum
The healthy mucosa of the stomach is provided with mechanisms that allow it to withstand the potentially injurious effects of high concentrations of luminal acid. Disruption of these mechanisms may contribute to acute ulceration.
The surface of the mucosa is coated with mucus and secretes HCO3– in addition to H+. Protected by the blanket of mucus, the surface pH is much higher than the luminal pH. HCO3– secretion is stimulated by cAMP, prostaglandins, cholinomimetics, glucagon, CCK, and by as yet unidentified paracrine hormones. Inhibitors of HCO3– secretion include nonsteroidal anti-inflammatory agents, alpha-adrenergic agonists, bile acids, ethanol, and acetazolamide. Increases in luminal H+ result in increased HCO3– secretion, probably mediated by tissue prostaglandins.
Gastric mucus is a gel composed of high-molecular glycoproteins and 95% water. Since it forms an unstirred layer, it helps the underlying mucosa to maintain a higher pH. At the surface of mucus, peptic digestion continuously degrades mucus, while below it is continuously being replenished by mucous cells. Gastric acid is thought to enter the lumen through thin spots in the mucus overlying the gastric glands. Secretion of mucus is stimulated by luminal acid and perhaps by cholinergic stimuli. mucus is damaged by exposure to nonsteroidal anti-inflammatory agents and is enhanced by topical prostaglandin E2.
Mucosal defects produced by mechanical or chemical trauma are rapidly repaired by adjacent normal cells that spread to cover the defect, a process that can be enhanced experimentally by adding HCO3– to the nutrient side of the mucosa. This important phenomenon has not yet been thoroughly studied.
Phases of the gastric secretion
Stimuli that act upon the brain lead to increased vagal efferent activity. The sight, smell, taste, or even thought of appetizing food may elicit this response. The effect is entirely vagally mediated and is abolished by vagotomy.
Food in the stomach (principally protein hydrolysates and hydrophobic amino acids) stimulates gastrin release from the antrum. Gastric distention has a similar but less intense effect. It excites long vagal reflexes, impulses that pass to the nervous system via vagal afferents and return to stimulate the parietal cells.
A third aspect of the gastric phase involves the sensitizing effect of distention of the parietal cell area to gastrin that is probably mediated through local intramural cholinergic reflexes.
The role of the intestinal in the stimulation of gastric secretion has been incompletely investigated.
Inhibition of Acid Secretion
Without systems to limit secretion, unchecked acid production could become a serious clinical problem. Examples can be found (eg, Billroth II gastrectomy with retained antrum) where acid production rose after surgical procedures that interfered with these inhibitory mechanisms.
pH below 2.50 in the antrum inhibits the release of gastrin regardless of the stimulus. When the pH reaches 1.20, gastrin release is almost completely blocked. If the normal relationship of parietal cell mucosa to antral mucosa is changed so that acid does not flow past the site of gastrin production, serum gastrin may increase to high levels, with marked acid stimulation. Somatostatin in gastric antral cells serves a physiologic role as an inhibitor of gastrin release (a paracrine function).
The intestine participates in controlling acid secretion by liberating hormones. Secretin blocks acid secretion under experimental conditions but not as a physiologic action. Neither somatostatin nor GIP, both released by food in the intestine, seems able to account for the inhibition, and the term enterogastrone is used to denote the still unidentified hormone presumably responsible.
Integration of Gastric Physiologic Function
Ingested food is mixed with salivary amylase before it reaches the stomach. The mechanisms stimulating gastric secretion are activated. Serum gastrin levels increase from a mean fasting concentration of about 50 pg/mL to 200 pg/mL, the peak occurring about 30 minutes after the meal. Food settles in layers determined by sequence of arrival, but fat tends to float to the top. The greatest mixing occurs in the antrum. Antral contents therefore become more uniformly acidic than those in the body, where the central portion of the meal tends to remain alkaline for a considerable time, allowing continued activity of the amylase.
Peptic digestion of protein is only about 5–10% complete. Carbohydrate digestion may reach 30–40%. A lipase originating from the tongue initiates the first stages of lipolysis in the stomach.