Secretions of the Stomach

SECRET IONS OF T HE ST OMACH Main secretions of gastric mucosa • • • Body and fundus o Hydrochloric acid (0.15M HCl as it leaves the glands) → as it leaves glands it is isotonic with plasma o Pepsinogen (proteolytic enzyme) – activates pepsinogen into pepsin o Intrinsic factor (essential for vitamin B12 absorption) produced by parietal cells o Some peptide hormones Antrum o Gastrin (peptide hormone) – principal signal to secrete acid Surface and upper pit cells in all parts of stomach secrete: o Mucus – every cell produces mucus o Some HCO3- (bicarbonate) from surface cells – small amount Function of gastric acid • Has been preserved throughout vertebrate evolution and increased from ancient times (survival value) • Only a small role in modern humans since people on strong acid inhibitors for years have few or no problems • Best guess: gastric acid partly protected ancestors from micro-organisms in contaminated food Problem of strong gastric acid • • • If gastric acid stays in the stomach and the gastric mucosa is healthy, there is no problem If gastric juice refluxes back into oesophagus too often it can cause gastroesophageal reflux disease If gastric or duodenal mucosal defences are impaired it can cause gastric or duodenal peptic ulcers Histology of gastric body mucosa Gastric parietal cell • Packed with mitochondria to produce energy to produce HCl Parietal cells • • Tubulovesicles move cell membrane to increase secretory surface area H/K ATPase (enzyme) is machinery for producing HCl and are taken to luminal membrane of cell Control of acid secretion at a cellular level • pH of 7 is maintained in the cell and 0.7 in the lumen – tremendous pH shift requires ATP • Sodium bicarbonate is pumped out of the cell to remove base (otherwise pumping out acid would result in highly basic conditions) • Assumptions of old model don’t fit experimental data • ECLs (enterochromaffin-like cell) are endocrine cells that produces histamine deep in gastric glands – it is loaded with gastrin receptors and responds to vagal stimulation o Delivers histamine to the downstream parietal cells via mucosal capillaries Side effects of proton pump inhibitors • • • • Very few (usually none in short-term use) Slightly increased incidence of bacterial intestinal infections e.g. traveller’s diarrhoea, Clostridium difficile colitis Possibly an increase in bone fractures with long-term use (but data is from case-control studies where confounding factors are possible or likely) Possibly an increase in chronic kidney disease with long-term use (also confounding factors) Molecules that stimulate acid secretion by parietal cells • • Gastrin – peptide hormone produced in endocrine cells in gastric antrum Histamine – released from endocrine cells in body mucosa (close to parietal cells) when stimulated by gastrin • Acetylcholine – released from branches of the vagus nerve Stimulus to acid secretion • • Main stimulus = arrival of food in the stomach Food stimulates release of gastrin from the antral endocrine cells (G cells) by: o Chemical stimulation – the G cells sample the luminal contents to detect nutrients o Distension of antrum – probably signals gastrin release via nerve stretch receptors • • • Distension also directly stimulates parietal cells via short nerve reflexes, releasing acetylcholine on the parietal cells The main signal to tell the stomach to stop secreting acid is low pH (high acidity) in the stomach This is mediated by inhibition of gastrin secretion when stomach contents are highly acidic Control of acid secretion (at stomach level) • Stimulation of acid secretion starts before food reaches the stomach via: thinking of food, scent, taste → have a common efferent pathway via the vagus nerve with terminals ending on parietal cells (AChRs) o These pathways were classically called the cephalic phase of gastric secretion Operations to reduce gastric acid • • • Divide the vagus nerves (vagotomy) Resect (remove) the antrum (antrectomy) → can’t secrete gastrin Resect the body mucosa – won’t be any parietal cells