The acid-peptic diseases are those disorders in which gastric acid and pepsin are necessary, but usually not sufficient, pathogenic factors. While inherently caustic, acid and pepsin in the stomach normally do not produce damage or symptoms because of intrinsic defence mechanisms. Barriers to the reflux of gastric contents into the esophagus comprise the primary oesophageal defence. If these protective barriers fail and reflux occurs, dyspepsia and/or erosive esophagitis may result. Therapies are directed at decreasing gastric acidity, enhancing the lower oesophageal sphincter, or stimulating oesophageal motility. In the stomach, mucus and bicarbonate, stimulated by the local generation of prostaglandins, protect the gastric mucosa. If these defences are disrupted, a gastric or duodenal ulcer may form. The treatment and prevention of these acid-related disorders are accomplished either by decreasing the level of gastric acidity or by enhancing mucosal protection. The appreciation that an infectious agent, Helicobacter pylori, plays a key role in the pathogenesis of acid-peptic diseases has stimulated new approaches to prevention and therapy. Gastric acid secretion is a complex, continuous process in which multiple central and peripheral factors contribute to a common endpoint: the secretion of H+ by parietal cells. Neuronal (acetylcholine), paracrine (histamine), and endocrine (gastrin) factors all regulate acid secretion .Their specific receptors (M3, H2, and CCK2 receptors, respectively) are on the basolateral membrane of parietal cells in the body and fundus of the stomach. The H2 receptor is a GPCR that activates the Gs-adenylylcyclase-cyclic AMP-PKA pathway. Acetylcholine and gastrin signal through GPCRs that couple to the Gq-PLC-IP3-Ca2+ pathway in parietal cells. In parietal cells, the cyclic AMP and the Ca2+-dependent pathways activate H+,K+-ATPase (the proton pump), which exchanges hydrogen and potassium ions across the parietal cell membrane. This pump generates the largest known ion gradient in vertebrates, with an intracellular pH of about 7.3 and an intracanalicular pH of about 0.8. The most important structures for CNS stimulation of gastric acid secretion are the dorsal motor nucleus of the vagal nerve, the hypothalamus, and the solitary tract nucleus. Efferent fibres originating in the dorsal motor nuclei descend to the stomach via the vagus nerve and synapse with ganglion cells of the enteric nervous system. Acetylcholine release from postganglionic vagal fibres directly stimulates gastric acid secretion through muscarinic M3 receptors on the basolateral membrane of parietal cells. The CNS predominantly modulates the activity of the enteric nervous system via
acetylcholine, stimulating gastric acid secretion in response to the sight, smell, taste, or anticipation of food (the “cephalic” phase of acid secretion). ACh also indirectly affects parietal cells by increasing the release of histamine from the enterochromaffin-like (ECL) cells in the fundus of the stomach and of gastrin from G cells in the gastric antrum. ECL cells, the source of gastric histamine secretion, usually are in close proximity to parietal cells. Histamine acts as a paracrine mediator, diffusing from its site of release to nearby parietal cells, where it activates H2 receptors. The critical role of histamine in gastric acid secretion is dramatically demonstrated by the efficacy of H2-receptor antagonists in decreasing gastric acid secretion. Gastrin, which is produced by antral G cells, is the most potent inducer of acid secretion. Multiple pathways stimulate gastrin release, including CNS activation, local distention, and chemical components of the gastric contents. Gastrin stimulates acid secretion indirectly by inducing the release of histamine by ECL cells; a direct effect on parietal cells also plays a lesser role. Somatostatin (SST), which is produced by antral D cells, inhibits gastric acid secretion. Acidification of the gastric luminal pH to ❤ stimulates SST release, which in turn suppresses gastrin release in a negative feedback loop. SST-producing cells are decreased in patients with H. pylori infection, and the consequent reduction of SST’s inhibitory effect may contribute to excess gastrin production. The extremely high concentration of H+ in the gastric lumen requires robust defence mechanisms to protect the esophagus and the stomach. The primary oesophageal defence is the lower oesophageal sphincter, which prevents reflux of acidic gastric contents into the esophagus. The stomach protects itself from acid damage by a number of mechanisms that require adequate mucosal blood flow, perhaps because of the high metabolic activity and oxygen requirements of the gastric mucosa. One key defence is the secretion of a mucus layer that protects gastric epithelial cells. Gastric mucus is soluble when secreted but quickly forms an insoluble gel that coats the mucosal surface of the stomach, slows ion diffusion, and prevents mucosal damage by macromolecules such as pepsin. Mucus production is stimulated by prostaglandins E2 and I2, which also directly inhibit gastric acid secretion by parietal cells. Thus, alcohol, aspirin, and other drugs that inhibit prostaglandin formation decrease mucus secretion and predispose to the development of acid-peptic disease. A second important part of the normal mucosal defence is the secretion of bicarbonate ions by superficial gastric epithelial cells. Bicarbonate neutralizes the acid in the region of the mucosal cells, thereby raising pH and preventing acid-mediated damage.
Inspite of healthy life style that includes daily brisk walk for at least half an hour, low fats intake, avoidance from spicy food, regular dietary intake of bulk making food such as green leafy vegetables and ispaghola husk, regular intake of dietary antacids such as milk and yogurt, sometimes a person feel heart burn, indigestion flatulence and pain either in stomach or in intestine due to hyperacidity and this is the time when he needs urgent medication to rectify the situation. Usually medicines are used in the order of most used medicine as the proton pump inhibitors most commonly, followed by the histamine H2-receptor antagonists. Another group of medicines that act locally in gastrointestinal system is antacids; for example salts of aluminium and magnesium are used widely, that may be helpful to reduce acidity in gastric lumen by increasing PH of present medium. Sometimes gastro protective agents like itopride, simethicone and levopraid are also used to prevent the lining of gastric cavity from corrosive action of acid and pepsin.