GI Ulceration

• Structure of the GI tract


  • Muscosal layer
  • Submucosal layer
  • Muscularis exerna
  • Serosa
• Mucosa


  • Epithelia layer - single layer of cells that lines the GI tract
  • Lamina propria - cells and structures that hold the GI tract together
  • Muscularis mucosa - thin innermost layer of intestinal SM
• Submucosal layer


  Made mostly of connective tissue - collagen, elastin
• Muscularis externa


  Thick layer of muscle, made of circular and longitudinal muscle, controls peristalsis
• Serosa


  Another connective tissue layer
• Plexus


  Innervate the smooth muscle and the secretory processes of the gut (meissners plexus and auerbacks plexus)
• Plexus are important for CONTRACTION of the gut and SECRETION OF ACID AND MUCUS
• Gastric ulceration


  Occurs due to an imbalance between the protective elements of the mucosa VS the aggressive elements (the acid secreted from stomach)
• Cells in the gland region of the stomach mucosa


  • Mucus neck cells - secrete thick protective mucus
  • Parietal cells - principle acid secreting cells
  • Chief cells - secrete pepsinogens
  • Endocrine cells - e.g. ECL cells that secrete histamine
  • G cells - secrete gastrin
• Pepsinogens


  Get turned into active pepsins (the digestive enzymes that degrade proteins into amino acids)
• Histamine


  Regulates the activity of other cells within the system (e.g the parietal cells)
• Gastrin


  Hormone that helps in the regulation of gastric acid secretion
• Protective factors against gastric ulceration


  • Mucous gel
  • Secretion of bicarbonate to neutralise the acid
  • Ability to regenerate epithelial cells quickly
  • Presence of tight junctions between epithelial cells
  • Blood supply able to protect the integrity of the stomach lining
• pH gradient


  • Gastric lumen = pH 1.5 (strong acidic)
  • Mucus cells of the stomach = pH 7.4
• How the pH gradient is maintained


  1. Mucus gel neutralisation zone decreases H+ concentration

  2. Bicarbonate secreted into mucosal cell layer to buffer acid

  3. Bicarbonate gradient (low in lumen, high near mucosal cells)
• Prostaglandins


  Maintain the protective mechanisms of the GI tract, especially PG-E2 and PG-I2
• Aggressive factors that may promote gastric ulceration


  • H+ protons from acid
  • Pepsins - proteolytic digestive enzymes
  • Helicobacter pylori bacterial infection
  • Some drugs
• Helicobacter pylori


  Lives attached to/just above the Gastric mucosal cells, secretes factors that break up the mucosal layer and secretes urease to neutralise stomach acid
• Aspirin


  Blocks the synthesis of protective prostaglandins by inhibiting COX enzymes
• Adrenaline and NA


  Block the production of protective prostaglandins
• Management of peptic ulcers


  1. Treat H.pylori infection with antibiotics

  2. Control acid secretion and enhance mucus production
• Histamine


  Central regulator, acts on H2 receptors on parietal cells to induce acid secretion
• Gastrin


  Acts on CCK-B receptors on parietal cells
• Acetylcholine


  Acts on Muscarinic receptors of the parietal cells
• Pharmacological interventions


  1. Block muscarinic receptors on parietal cells

  2. Block histamine H2 receptors on parietal cells

  3. Use direct proton pump inhibitors
• H2 receptor antagonists


  e.g. Cimetidine, blocks H2 receptors on parietal cells, reduces basal and food stimulated acid secretion by 90%
• Muscarinic receptor antagonists


  e.g. Pirenzepine, targets M1 receptors on parietal cells, reduces basal and food stimulated acid secretions
• Proton pump inhibitors


  e.g. Omeprazole and Lansoprazole, directly block the H+/K+ ATPase exchanger, irreversibly inhibit the proton pump
• Antacids


  e.g. sodium bicarbonate, directly neutralise gastric acid, but can cause side effects like gas and alkalosis
• Aluminium and magnesium salts


  React with HCl to form an insoluble colloid that is retained in the stomach
• Sucralfate


  Forms a protective gel complex with stomach mucus
• Bismuth chelate


  Coats the ulcer, absorbs pepsin, toxic to H.pylori, stimulates bicarbonate and prostaglandin secretion
• Misoprostol


  Synthetic PG-E1 analogue, decreases acid secretion, increases mucus and bicarbonate secretion, maintains blood supply