Session 4 Stomach and peptic ulcers

• Cells of gastric glands and its secretions ?

  • Mucus neck cells - secretes mucus
  • Chief cells - secrete pespsinogen
  • Parietal/oxyntic cells - secrete intrinsic factor and HCL
  • G cells - secrete gastrin
• Reduced intrinsic factor = reduced Vit B = reduced haematopoiesis.
• Pernicious anaemia = autoimmune disease that results in reduced intrinsic factor release.
• 3 Phases of gastric control?

  • Cephalic
  • Gastric
  • Intestinal
• Intragastric pressure doesn’t increase when large amount of food is ingested?

  receptive relaxation
• Antrum - consists of pyloric antrum and pyloric canal and terminates at pylorus.
• Other secretions of G cells include Ghrelin (from Gr cells) and somatostatin from D cells.
• Cytoplasm of parietal cells has an elaborate series of branches – fuse to form deep canaliculi – increased surface area available for release of HCL.
• Histamine H2 antagonists (cimetidine) prevent acid release.
• Cephalic control?

  • Anticipation of food – sight, smell
  • Can vary with mood and appetite
  • Mediated entirely by the vagus nerves –abolished by vagotomy
  • Vagal activity increases secretion
  • Postganglionic neurons in myenteric plexus release ACh– stimulate parietal cells
  • Vagal stimulation promotes gastrin release from G cells (via gastrin releasing peptide from enteric neurons) – in turn promotes acid release
  • ACh and gastrin stimulate release of histamine from mast cells and enterochromaffin like cells – histamine can trigger acid release.
• Gastric phase?

  • Longest phase – may last for 2-3 hours.
  • Triggered by food in stomach – distension and the presence of amino acids and peptides (EtOH and caffeine also very potent)
  • Distention promotes local myenteric reflexes and longer vasovagal reflexes which result in ACh release and therefore increased secretions.
  • ACh also promotes the release of gastrin – stimulus for acid secretion.
  • Peptides and free aa (esp. tryptophan and phenylalanine) activate vagal chemoreceptors and G-cells.
  • Gastrin is released, which together with ACh promote histamine release.
• Intestinal phase?

  • Chyme in the duodenum
  • As the duodenum expands with chyme a low pH, fat and hypertonic chyme results in Somatostatin release (from D cells) inhibit parietal cells and thus acid secretion.
  • Acid promotes secretin release which in turn inhibits G cells
  • Fatty acids cause the release of GIP, CCK which both inhibit acid secretion.
  • Secretin, GIP, CCK – collectively called enterogastrones
  • Mechanism of hypertonicity unknown, but there is suppression of acid release.
  • Reduced stomach volume/increased duodenal volume may also initiate (via mechanoreceptors) reduced acid secretion.
• • Gastric musculature shows rhythmic changes in membrane potential – Basal Electrical Rhythm (BER), pacesetter potentials, slow waves - Driven by the ICCs (intestinal cells of Cajul).
  • BER coordinates other movements e.g. peristalsis and segmentation.
  • When smooth muscle membrane potential reaches it threshold (at the peak of a slow wave potential – AP and contraction!
• In the absence of eating, gastric contractility occurs episodically about every 90 mins. Sometimes called housekeeping contractions.

  • Bursts of contraction are called Migrating motor complexes (MMCs).
• Migrating motor complexes (MMC)?

  • Stimulated by the hormone motilin
  • Small polypetide (22aa) from enterochromaffin cells
  • Acts via GPCR on enteric neurons to promote smooth muscle contraction.
  • Erythromycin binds to motilin receptors
  • Feeding inhibits MMCs (via vagal activity, gastrin and CCK)
• Gastric motility when we are eating - mixing

  • Waves of contraction originate in the corpus and move towards the antrum pushing stomach contents ahead of them to the pylorus.
  • Pyloric sphincter closes in advance of the wave.
  • The antrum now contracts and contents move back towards the corpus retropulsion.
  • This is sometimes called the gastric mill.
  • Some 3 hrs to reduce contents to a appropriate size to pass through the pyloric sphincter to the duodenum (occurs during retropulsion).
  • Composition of chyme isa significant predictor of the rate of gastric emptying –CHO > Peptides > Fats.
• Regulation of gastric emptying

  • Needs careful control.
  • gastric mucosa is acid resistant but not the duodenal mucosa.
  • Likewise duodenal mucosa is resistant to bile, but not the stomach mucosa.
  • Fatty acids in the duodenum increase contraction of pyloric sphincter.
  • Acidic chyme (pH<3.5) - duodenum slows down emptying
  • Duodenal osmoreceptors detect hyperosmolar chyme and delay emptying.
• Enterogastric reflex

  • Duodenal fatty acids and monoglycerides increase tone of pyloric sphincter – reduces emptying.
  • Prevents fat entering the small intestine at a greater rate than it can be dealt with by bile - Possibly mediated by CCK and GIP.
  • Products of protein digestion also inhibit emptying - Probably mediated by gastrin.
  • Appearance of acid in the duodenum delays gastric emptying - Mediated by secretin (also stimulates alkaline pancreatic juice production) and the vagus nerve (reduced by vagotomy).
• Gastritis is inflammation of the gastric mucosa.
• Causes of gastritis?

  • H. pylori
  • Excessive drinking/smoking
  • Prolonged NSAID use
• Pathophysiology of H.pylori?

  • The bacteria survives in acidic environment of the stomach by creating urease which breaks down urea into CO2 and ammonia.
  • Ammonia neutralizes the stomach acid.
  • The bacterial cells use their flagella and penetrate into the mucus layer (protection).
  • Thinning of mucus layer - decreased mucus production
  • Bacterial toxins and inflammation damage epithelial cells.
  • acid damages exposed tissue causing peptic ulcer.
• H.pylori colonisation

  Antrum predominant: Duodenal ulcer risk

  Body predominant: gastritis/ gastric ulcer and risk of cancer
• Why is a Bacterium that only colonises gastric mucosa implicated in duodenal ulceration?

  • Antral h.pylori colonisation
  • Increased gastrin production
  • Increased parietal cell acid production
  • Damages duodenum, gastric metaplasia of gastric mucosa
  • H.pylori colonisation - duodenitis.
• Zollinger–Ellison syndrome is rare disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers.
• NSAIDS and PUD?

  • The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins.
  • NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential to produce these prostaglandins.
• Treatments for PUD?

  • Smoking cessation
  • Reduce alcohol intake
  • Stop or review use of NSAIDs
  • PPI/H2 receptor antagonists
  • Eradication of h-pylori
• Complications of PUD?

  • perforation of the stomach/abdomen
  • Upper GI bleeds (presenting as haematemesis, malaena)
• Perforations management?

  • ABCDE approach
  • Oxygen
  • Fluid resuscitation
  • Broad spectrum antibiotics
  • NBM (nil by mouth) and NGT (NG tube) placed
  • Analgesia
• Upper GI Bleeding Scoring Systems?

  • Pre-endoscopic Rockall and complete Rockall score
  • Glasgow-Blatchford score (GBS)
  • AIM65 score
• Endoscopic Management of Bleeding Ulcers?

  • Variceal ligation
  • Laser therapy
  • Endoscopic clipping
  • Diathermy
  • Injection sclerotherapy