Gastric acid secretion

• Describe the composition of gastric juice

  There is around 1.5 litres produced per day

  • HCl: kills microbes and activates pepsinogen, which is converted to pepsin, which is an active protease.
  • Gastric lipase is secreted by chief cells
  • Intrinsic factor is a glycoprotein produced by the parietal cells and supports the absorption of vitamin B12 in the small intestine
  • Mucus is secreted from the mucus gland to protect the stomach lining and lubricate the food
• Describe the mechanism of HCl secretion in the stomach

  HCl is secreted by the parietal cells:

  1. Protons are released intracellularly via the dissolution of carbonic acid, which is catalysed by carbonic anhydrase.
  2. These free H+ are actively transported out of the cell via the ATP-driven proton pump in exchange for K+ ions.
  3. The free bicarbonate ions then diffuse out of the cells into the blood in exchange for Cl- ions, leading to a higher pH of blood leaving the stomach.
  4. Cl- ions are secreted into the lumen where they combine with H+ to form HCl.

  
• Describe the cephalic phase of gastric acid secretion

  This phase is stimulated by the sight, smell or sound of food and occurs when the brain signals via two main pathways:

  • ACh binds to M3 receptors in parietal cells to induce secretion of HCl
  • Gastrin releasing peptide (GRP) is released by the vagus nerve and stimulates G cells to secrete gastrin. Gastrin travels to the parietal cells to stimulate acid secretion.

  
• Describe the gastric phase of gastric acid secretion

  This is when food in the stomach leads to stretching of the stomach, which sends vagal impulses to act directly on parietal cells to secrete acid. The vagus nerve also stimulates the G cells to secrete gastrin and partially digested proteins, especially aromatic amino acids, stimulate gastrin release.
• Describe the insestinal phase of gastric acid secretion

  This is initiated when chyme enters the duodenum, initiating the enterogastric reflex. This sends signals to the enteric nervous system to inhibit the vagus nerve and stimulate sympathetic nerves, which inhibit gastric secretion. Secretin is produced by S cells in the duodenal mucosa and inhibits both gastrin and gastric acid release. CCk binds to CCk-1 receptors on somatostatin cells and somatostatin is released. Enteroendocrine cells secrete gastric inhibitory peptide which has a weakly inhibits gastric acid release.
• Describe how the intestinal phase is inhibited?

  Food in the stomach acts as a buffer to the secreted acid and therefore increases the pH, which prevents negative feedback on acid secretion.
• Describe the negative feedback on gastric acid secretion

  Gastric acid release is controlled by negative feedback:

  • Reduction in pH is detected by somatostain cells and leads to somatostatin secretion, which reduces gastric acid secretion.
• Describe the role of gastrin releasing peptide in gastric control

  GRP is a neurotransmitter that stimulates G cells to release gastrin. Gastrin then enters the bloodstream and travels to the gastric glands, where it binds to receptors on parietal and chief cells to stimulate acid and pepsinogen secretion respectively.
• Describe the role of the dorsal vagal complex in gastric control

  During the cephalic phase, the dorsal vagal complex sends impulses to the stomach via the vagus nerve. The vagus nerve releases GRP and ACh, which also stimulates the parietal cells to increase acid secretion. Gastrin and ACh also act on the enterochromaffin-like cells to secrete histamine, which acts directly on the parietal cells to secrete HCl. Gastrin also binds to CCK-B receptors which stimulates an increase in intracellular calcium.
• Describe the action of histamine in gastric control

  Histamine binds to H2 receptors to initiate an increase in cAMP in parietal cells. This leads to an increase in gastric acid secretion
• Describe the mechanisms of mucosal protection

  The main mechanism is by controlling the secretion of protons. Mucus is also secreted in two layers; inner layer and an outer unattached loose layer. The mucus contains glycoproteins and water formed from gel-forming mucus called MUC6, which is produced by mucous cells within the gastric glands. HCO3- is secreted by the epithelium in the stomach and the Brunner’s gland in the duodenum, which neutralises the acid.
• Describe the formation of ulcers

  These are open sores in the gastric mucosa, which occur due to digestion of the lining of the GI tract due to increased gastric acid secretion or lack of mucus protection. As the ulcer develops it can erode into a blood vessel and cause bleeding into the GI tract. Perforation occurs when the ulcer erodes through the gastric mucosa and allows bacteria from the stomach to leak into the peritoneum, which is known as peritonitis.
• Describe the treatment of perforated ulcers

  Perforated ulcers can be achieved by covering the hole with a patch of omentum (fatty tissue covering th stomach and intestines) or partial gastrectomy (removing a small part of the stomach). Vagotomy can be performed to treat ulcers, by cutting one or more branches of the vagus nerve to reduce gastric acid secretion. More often drugs are prescribed such as histamine receptor antagonists or H+ K+ ATPase inhibitors.
• Describe how Helicobacter pylori can cause gastric ulcers


  This bacteria causes inflammation of the stomach lining as the bacteria are able to tolerate the low pH in the stomach. This is by metabolising urea to produce NH3, which increases the local pH. Bacteria can penetrate the mucus and live attached to the epithelial cells. The resulting inflammation impairs somatostatin release which leads to increased gastrin and increased acid secretion
• Describe H2 receptor antagonists

  These are compounds with similar motifs to histamine that reduce gastric acid secretion as histamine is the predominant modulator of acid secretion. Examples include cimetidine and randtidine which are used for indigestion relief and pain relief.
• Describe omeprazole

  This is a proton pump inhibitor that enters and accumulates in acid spaces without crossing cell membranes. It is activated in acid and chemically altered by H+ to an active sulphenamide form. This forms an irreversible S-S bond with H+ K+ ATPase in parietal cells. It is given in an enchanted formulation to avoid breakdown by the stomach acid and is absorbed in the small intestine and travels to the parietal cells in the blood.
• Describe the triple therapy to eradicate H. pylori for ulcers

  The use of 2 antibiotics alongside a proton pump inhibitor and Bismuth compounds, which are bacteriocidal. PPI and bismuth enhance antibiotic action as antibiotics work best on dividing bacteria. PPI raises ambient pH and bismuth slows further acidification of bacterial interior, to increase bacterial division.
• Describe the actions of bismuth on bacteria

  Bismuth has direct bacetricidal actions:

  • forms complexes in cell wall, which inhibits bacterial enzymes and ATP synthesis
  • Reduces adherence of bacteria to gastric mucosa and increases mucosal protection via PGs and HCO3 secretion, thus raising the pH. This increases bacterial division as H. pylori grows quickly at ph6-8
• Describe the link between NSAIDs and ulcers

  These are Non-steroidal anti-inflammatory drugs that inhibit the cyclo-oxygenase enzyme. They are non-selective so inhibit COX1 which is important in the production of PGE2 in the gastric and duodenal mucosa. PGE2 acts on EP3 receptors on parietal cells to reduce acid production and stimulates mucus and bicarbonate secretion to protect the mucosa. This promotes the formation of ulcers.