Regulation and Disorders of Gastric Secretion Pt. 1

• What are the main functions of the stomach?

  1. Mechanical digestion – Churns food via peristalsis.
  2. Chemical digestion – Secretes gastric juice containing acid and enzymes.
  3. Storage – Temporarily holds food before passing it to the small intestine.
  4. Regulation – Controls the rate of food passage into the duodenum.
• What are the major secretions of the stomach?

  • Hydrochloric acid (HCl) – Produced by parietal cells to aid digestion and kill pathogens.
  • Pepsinogen – Secreted by chief cells, converted to pepsin, a protein-digesting enzyme.
  • Mucus – Secreted by mucous cells to protect the stomach lining from acid.
  • Intrinsic factor – Produced by parietal cells for vitamin B12 absorption in the ileum.
  • Gastrin – A hormone secreted by G cells that stimulates acid production.
• What are the three phases of gastric secretion regulation?

  1. Cephalic phase (Prepares stomach for food)

  • Triggered by sight, smell, taste, or thought of food.
  • Stimulated by the vagus nerve (CN X), leading to gastrin release.

  1. Gastric phase (Major secretion phase)

  • Begins when food enters the stomach.
  • Stretch receptors and chemoreceptors detect food, triggering gastrin release.
  • Gastrin stimulates HCl and pepsinogen secretion.

  1. Intestinal phase (Regulates gastric emptying)

  • Begins when chyme enters the duodenum.
  • Enterogastric reflex and hormones (secretin, cholecystokinin, GIP) inhibit acid secretion.
• What are the functions of HCl in the stomach?

  • Activates pepsinogen into pepsin.
  • Denatures proteins for easier digestion.
  • Kills most ingested bacteria.
  • Provides the acidic environment needed for enzyme activity.
• What is pepsin, and how is it activated?

  Pepsin is a proteolytic enzyme that digests proteins.

  • It is secreted as inactive pepsinogen by chief cells.
  • HCl converts pepsinogen into active pepsin.
  • Pepsin breaks proteins into smaller peptides for further digestion.
• How does the stomach protect itself from self-digestion?

  • Mucus layer – Provides a barrier between acid and stomach lining.
  • Bicarbonate secretion – Neutralises acid near the epithelium.
  • Tight junctions – Prevent acid from leaking between epithelial cells.
  • Rapid cell turnover – Damaged epithelial cells are replaced quickly.
• What is gastroesophageal reflux disease (GERD)?

  GERD is chronic acid reflux, where stomach acid enters the esophagus, causing irritation and symptoms like heartburn.

  • Caused by lower esophageal sphincter dysfunction.
  • Risk factors: Obesity, pregnancy, spicy foods, smoking.
  • Treatment: Lifestyle changes, antacids, proton pump inhibitors (PPIs).
• What is peptic ulcer disease (PUD), and what causes it?

  PUD is the formation of ulcers in the stomach or duodenum due to excessive acid or weakened mucosal protection.

  • Causes:
  • Helicobacter pylori infection (most common).
  • Long-term NSAID use (e.g., aspirin, ibuprofen).
  • Excessive acid production (Zollinger-Ellison syndrome).
• What are the symptoms and treatment options of peptic ulcer disease (PUD)?

  • Symptoms: Burning stomach pain, nausea, vomiting, weight loss.
  • Treatment: PPIs, antibiotics (for H. pylori), avoiding NSAIDs.
• What is Zollinger-Ellison syndrome (ZES)?

  ZES is a rare condition caused by a gastrin-secreting tumour (gastrinoma), leading to excessive acid production and severe ulcers.
• Describe the symptoms, diagnosis, and treatment options of Zollinger-Ellison Syndrome (ZES)?

  • Symptoms: Severe peptic ulcers, diarrhea, acid reflux.
  • Diagnosis: Elevated gastrin levels in blood tests.
  • Treatment: PPIs, surgery to remove tumour.
• What is achlorhydria, and what are its consequences?

  Achlorhydria is the absence of stomach acid (HCl), leading to:

  • Poor digestion of proteins.
  • Bacterial overgrowth in the stomach.
  • Vitamin B12 deficiency (due to lack of intrinsic factor).
  • Increased risk of infections.
• What is the primary component of gastric acid?

  Hydrochloric acid (HCl)
•  Which cells in the stomach secrete hydrochloric acid (HCl)?

  Parietal cells (also called oxyntic cells) in the gastric glands of the stomach
• What is the main enzyme involved in the production of gastric acid?

   Carbonic anhydrase
• What is the equation catalysed by carbonic anhydrase in parietal cells?

  CO₂ + H₂O ⇌ H₂CO₃ (carbonic acid) ⇌ H⁺ + HCO₃⁻
• How is H⁺ (proton) secreted into the stomach lumen?

  Via the H⁺/K⁺ ATPase (proton pump), which exchanges H⁺ for K⁺
• What happens to the bicarbonate (HCO₃⁻) produced in parietal cells?

   It is exchanged for Cl⁻ in the blood via the chloride-bicarbonate exchanger (alkaline tide)
• How does Cl⁻ reach the stomach lumen to form HCl?

  Cl⁻ diffuses through chloride channels into the gastric lumen and combines with H⁺ to form HCl
•  How does histamine stimulate gastric acid production?

   It binds to H₂ receptors on parietal cells, activating adenylate cyclase → increased cAMP → activation of H⁺/K⁺ ATPase → H⁺ secretion
• What hormone inhibits gastric acid secretion?

  Somatostatin, released from D cells in response to low pH, inhibits gastrin, histamine, and parietal cells
• What are the two main phases of gastric acid secretion in response to a meal?

  1. Cephalic phase – Initiated by the sight, smell, taste, or thought of food, triggering vagal stimulation.
  2. Gastric phase – Activated when food enters the stomach, leading to gastric distension and chemical stimulation of acid secretion.
• How does the cephalic phase stimulate gastric acid secretion?

  • The vagus nerve (CN X) is activated by sensory stimuli related to food.
  • Vagal efferents release acetylcholine (ACh), which:
  • Directly stimulates parietal cells to secrete HCl.
  • Stimulates G cells to release gastrin, which enhances acid secretion.
  • Inhibits D cells, reducing somatostatin release (which normally inhibits acid secretion).
• What triggers the gastric phase of gastric acid secretion?

  • Gastric distension (stretching of the stomach) → Activates mechanoreceptors → Vagal stimulation.
  • Chemical stimulation by peptides and amino acids → Stimulates G cells to release gastrin → Gastrin promotes acid secretion.
  • Vagal stimulation → Directly activates parietal cells via ACh and indirectly via gastrin and histamine.
• What role does the vagus nerve play in gastric acid secretion?

  • The vagus nerve releases ACh, which:
  • Directly stimulates parietal cells → HCl secretion.
  • Stimulates G cells → Gastrin release → Indirectly promotes HCl secretion.
  • Inhibits D cells → Reduced somatostatin → Allows greater acid secretion.
  • The vagus nerve is most active during the cephalic and gastric phases.
• How does gastrin regulate gastric acid secretion?

  • Released by G cells in the antrum of the stomach in response to:
  • Peptides & amino acids in the stomach.
  • Vagal stimulation via gastrin-releasing peptide (GRP).
  • Stomach distension.
  • Effects:
  • Stimulates parietal cells → Increased HCl secretion.
  • Stimulates ECL cells → Histamine release, further enhancing HCl secretion.
• How does histamine influence gastric acid secretion?

  • Produced by enterochromaffin-like (ECL) cells in response to gastrin and ACh.
  • Binds to H₂ receptors on parietal cells, activating adenylate cyclase → Increased H⁺/K⁺ ATPase activity → HCl secretion.
  • Potentiates the effects of gastrin and ACh on acid secretion.
• How does somatostatin regulate gastric acid secretion?

  • Produced by D cells in the stomach and pancreas.
  • Inhibits gastric acid secretion by:
  • Directly inhibiting parietal cells.
  • Inhibiting G cells → Decreasing gastrin release.
  • Inhibiting ECL cells → Reducing histamine release.
  • Stimulated by high H⁺ concentration (low pH) → Provides negative feedback to prevent excessive acid secretion.
• What are the main inputs regulating acid secretion by parietal cells in the stomach?

  • Neural Input
  • Gastrin-releasing peptide (GRP)
  • Hormonal Input
  • Paracrine Regulation
• How is acid secretion by parietal cells regulated by neural input?

  • Vagus nerve stimulation: The vagus nerve releases acetylcholine (ACh) that binds to M3 receptors on parietal cells, stimulating acid secretion.
  • Gastrin-releasing peptide (GRP): Released by vagal fibres, it stimulates the release of gastrin from G cells.
• How is acid secretion by parietal cells regulated by hormonal input?

  • Gastrin: Released from G cells in the antrum in response to food (especially proteins) or neural signals, gastrin binds to CCK-B receptors on parietal cells, leading to acid secretion.
  • Histamine: Released by enterochromaffin-like (ECL) cells, histamine binds to H2 receptors on parietal cells, amplifying acid secretion.
  • Somatostatin: Inhibits gastric acid secretion by acting on parietal cells and inhibiting gastrin release from G cells.
• How is acid secretion by parietal cells regulated by paracrine regulation?

  Prostaglandins: They can inhibit acid secretion by parietal cells through a cyclic AMP-dependent mechanism.
• How does the vagus nerve regulate acid secretion by parietal cells?

  • releases acetylcholine (ACh) onto parietal cells.
  • ACh binds to M3 muscarinic receptors on parietal cells, triggering intracellular signalling pathways.
  • Activation leads to the fusion of H+/K+ ATPase pumps with the apical membrane of parietal cells, increasing acid secretion.
• How does vagal stimulation affect gastrin release?

  Induces the release of gastrin-releasing peptide (GRP). GRP stimulates G cells to release gastrin, which further enhances acid secretion by parietal cells.
• Where is gastrin produced, and what stimulates its release?

  Gastrin is a peptide hormone secreted by G cells in the antrum of the stomach. Its release is stimulated by:

  • The presence of food, especially proteins.
  • Vagal stimulation, which releases gastrin-releasing peptide (GRP).
  • Stomach distension.
  • Increased pH in the stomach (due to food buffering acid).
• How does gastrin stimulate acid secretion?

  Gastrin stimulates acid secretion in two ways:

  1. Directly: It binds to CCK-B receptors on parietal cells, leading to increased HCl secretion.
  2. Indirectly: It stimulates enterochromaffin-like (ECL) cells to release histamine, which then binds to H2 receptors on parietal cells, further amplifying acid secretion.
• Where is histamine released from in the stomach?

  Histamine is released from enterochromaffin-like (ECL) cells in response to gastrin or vagal stimulation.
• How does histamine stimulate acid secretion in the stomach?

  • Binds to H2 receptors on parietal cells, activating adenylyl cyclase, which increases cyclic AMP (cAMP) levels.
  • Activates protein kinase A (PKA), which enhances the H+/K+ ATPase pump activity, increasing proton (H+) secretion into the stomach lumen.
• How does histamine interact with other regulators of acid secretion?

  Histamine potentiates acid secretion by working alongside gastrin and acetylcholine, amplifying the overall stimulation of parietal cells.
• What is the role of somatostatin in regulating gastric acid secretion?

  Somatostatin is a hormone that inhibits gastric acid secretion. It is released from D cells located in the stomach and pancreatic islets. Somatostatin inhibits acid secretion in two ways:

  1. Direct inhibition on parietal cells, reducing their acid production.
  2. Inhibition of gastrin release from G cells, thus reducing the stimulatory signal for acid secretion.Somatostatin’s inhibitory effects are crucial for maintaining the balance of gastric acid production.