Regulation and Disorders of Gastric Secretion Pt.2

• What are the main anatomical regions of the stomach?

  The stomach is divided into four main regions:

  1. Cardia – The entry region near the lower esophageal sphincter
  2. Fundus – Dome-shaped superior portion that stores undigested food and gases
  3. Body – Largest central portion involved in digestion
  4. Pylorus – Terminal region leading to the pyloric sphincter and duodenum
• What are the curvatures of the stomach, and what attaches to them?

  • Greater curvature: The larger convex border; attached to the greater omentum
  • Lesser curvature: The smaller concave border; attached to the lesser omentum

  
• What are the layers of the stomach wall from outermost to innermost?

  1. Serosa – Outer protective layer
  2. Muscularis externa – Three layers of smooth muscle (longitudinal, circular, oblique)
  3. Submucosa – Connective tissue with blood vessels, nerves, and lymphatics
  4. Mucosa – Innermost layer, with gastric pits and glands

  
• What are the main cell types in the gastric mucosa and their functions?

  1. Mucous cells – Secrete mucus to protect the stomach lining
  2. Parietal cells – Secrete hydrochloric acid (HCl) and intrinsic factor
  3. Chief cells – Secrete pepsinogen (inactive form of pepsin)
  4. G cells – Secrete gastrin, a hormone that stimulates acid secretion
• How does the structure of the stomach lining aid its function?

  • The stomach mucosa has deep gastric pits leading to gastric glands that secrete digestive substances
  • The surface is covered in mucus, which protects against acidic pH
  • The presence of rugae (folds) allows the stomach to expand when food enters
• What neurotransmitters and hormones regulate gastric secretion?

  • Acetylcholine (ACh) – Stimulates secretion of HCl and pepsinogen
  • Gastrin – Increases HCl secretion from parietal cells
  • Histamine – Binds to H₂ receptors on parietal cells to enhance acid secretion
  • Somatostatin – Inhibits gastrin release and acid secretion
• What is the anatomical location of the stomach?

  The stomach is located in the left upper quadrant of the abdomen, mainly in the epigastric and left hypochondriac regions. It lies between the oesophagus and the duodenum.

  
•  What is the function of rugae in the stomach?

  Rugae are folds in the stomach lining that allow for expansion when the stomach fills with food, increasing its surface area for secretion and digestion.
•  What is the blood supply of the stomach?

   The stomach receives blood from the celiac trunk, mainly via:

  • Left gastric artery
  • Right gastric artery
  • Left gastroepiploic artery
  • Right gastroepiploic artery
•  How is venous drainage of the stomach linked to the portal system?

   Venous drainage occurs via the left and right gastric veins (to the portal vein) and short gastric/gastroepiploic veins (to the splenic vein). This connection makes the stomach prone to portal hypertension complications (e.g., gastric varices).
• What is the function of intrinsic factor?

  Intrinsic factor, secreted by parietal cells, is essential for vitamin B12 absorption in the ileum. Deficiency can lead to pernicious anaemia.
• What are the main protective factors that prevent the stomach from being digested by its own secretions?

  1. Mucus-bicarbonate barrier
  2. Tight junctions between epithelial cells
  3. Rapid epithelial cell renewal
  4. Alkaline tide
  5. Prostaglandins (PGs) and blood supply
• How does the mucus-bicarbonate barrier protect the stomach?

  • Mucus (produced by surface mucous cells) forms a gel-like protective layer.
  • Bicarbonate (HCO₃⁻) (secreted by epithelial cells) neutralizes HCl near the epithelial surface.
  • Maintains a pH gradient (neutral pH near cells, acidic in the lumen).
  • Prevents HCl and pepsin from contacting and damaging epithelial cells.
• What role do tight junctions play in protecting the stomach lining?

  • Tight junctions between gastric epithelial cells prevent HCl and pepsin from penetrating between cells.
  • Ensures that gastric acid remains in the lumen and does not damage underlying tissue.
• Why is rapid epithelial cell renewal important for gastric protection?

  • The gastric epithelium has a high turnover rate (~3-7 days).
  • Damaged cells are rapidly replaced by new cells derived from stem cells in the gastric pits.
  • This prevents long-term damage from acid and proteolytic enzymes.
• What is the alkaline tide, and how does it contribute to gastric protection?

  • Definition: The temporary rise in blood pH after eating due to HCO₃⁻ secretion from parietal cells into the bloodstream.
  • Helps buffer systemic acid-base balance and may contribute to maintaining mucosal integrity.
• How do prostaglandins (PGs) protect the stomach?

  • Prostaglandins (especially PGE₂ and PGI₂) increase mucus and bicarbonate secretion.
  • They inhibit acid secretion from parietal cells.
  • Enhance mucosal blood flow, ensuring cell survival and repair.
  • NSAIDs (non-steroidal anti-inflammatory drugs) inhibit PGs, increasing the risk of gastric ulcers.
• What are the consequences of protective factor failure in the stomach?

  Failure of these mechanisms can lead to:

  • Peptic ulcers (due to excessive acid or inadequate protection).
  • Gastritis (inflammation of the stomach lining).
  • Gastric bleeding (from erosion of blood vessels).
  • Helicobacter pylori infection can further impair mucosal protection by decreasing mucus production
• How does Helicobacter pylori contribute to gastric ulcers?

  • H. pylori produces urease, which converts urea to ammonia, neutralising stomach acid.
  • This allows bacterial survival and mucosal damage.
  • It also triggers inflammation, reducing mucus production and increasing acid secretion.
  • Leads to gastric and duodenal ulcers.
• How do NSAIDs contribute to gastric mucosal injury?

  • NSAIDs inhibit prostaglandin synthesis (via COX-1 inhibition).
  • Leads to reduced mucus and bicarbonate secretion → Weakened mucosal barrier.
  • Increased gastric acid secretion → Higher risk of erosion
  • Decreased mucosal blood flow, impairing repair mechanisms → Impaired healing.
  • Increased epithelial damage → Increased risk of gastric ulcers and bleeding
• What are the two types of cyclooxygenase (COX) enzymes, and how do they differ?

  • COX-1: Constitutive enzyme, protects the gastric mucosa, regulates platelet function, and maintains renal blood flow.
  • COX-2: Inducible enzyme, involved in inflammation and pain response.

  Traditional NSAIDs (e.g., ibuprofen, aspirin) inhibit both COX-1 and COX-2, leading to gastric side effects.
• What are the clinical consequences of NSAID-induced gastric damage?

  1. Gastritis – Inflammation of the gastric mucosa.
  2. Peptic ulcers – Ulceration in the stomach (gastric ulcer) or duodenum (duodenal ulcer).
  3. Gastrointestinal bleeding – Due to weakened blood vessel integrity.
  4. Perforation – Severe cases may lead to perforation and peritonitis.
• What risk factors increase NSAID-induced gastric damage?

  • High doses or prolonged NSAID use
  • Elderly patients (reduced mucosal defense)
  • History of peptic ulcer disease
  • Use of corticosteroids or anticoagulants (increased bleeding risk)
  • Helicobacter pylori infection (compounds mucosal injury)
  • Smoking and alcohol consumption (weaken mucosal defences)
• What strategies can be used to reduce NSAID-induced gastric damage?

  • Use of COX-2 selective NSAIDs (e.g., celecoxib) instead of non-selective NSAIDs.
  • Proton pump inhibitors (PPIs) (e.g., omeprazole) to reduce acid secretion.
  • Misoprostol (a prostaglandin analog) to replace lost prostaglandins.
  • H2 receptor antagonists (e.g., ranitidine) to lower acid production.
  • Taking NSAIDs with food to reduce direct irritation.
  • Eradication of H. pylori if present.
• What is a duodenal ulcer?

  A duodenal ulcer is a break in the mucosal lining of the duodenum caused by an imbalance between gastric acid secretion and mucosal protection.