---

Gastric Secretion: Sources, Composition, and Regulation

Anatomy of Secretory Regions

• Body/Fundus (proximal ~80%) - contains oxyntic (gastric) glands that secrete HCl, pepsinogen, intrinsic factor, and mucus
• Antrum/Pylorus (distal ~20%) - contains pyloric glands that secrete mucus and the hormone gastrin

---

Cell Types and Their Secretory Products

---

Composition of Gastric Juice

---

Cellular Mechanism of HCl Secretion

1. CO2 + H2O → H2CO3 (catalyzed by carbonic anhydrase inside the parietal cell)
2. H2CO3 dissociates → H+ + HCO3-
3. H+ is actively pumped into the lumen via the apical H+/K+-ATPase (proton pump), exchanging H+ for K+
4. K+ recycles back via apical K+ channels; Cl- enters from blood via a basolateral Cl-/HCO3- exchanger and exits into the lumen via apical Cl- channels
5. HCO3- exits into the blood (causing "alkaline tide" in gastric venous blood during acid secretion)
6. Final canalicular secretion: HCl ~150-160 mEq/L + KCl ~15 mEq/L + trace NaCl

---

Pepsinogen Secretion and Activation

• Chief cells secrete pepsinogen (MW ~42,500), an inactive zymogen
• At luminal pH < 5, HCl cleaves pepsinogen to active pepsin (MW ~35,000); autocatalytic at pH < 3.5
• Pepsin is a protease active at pH 1.8-3.5; it begins protein digestion
• Stimuli: ACh (most potent direct stimulus), gastrin, secretin (minor)
• At pH > 5, pepsin is irreversibly inactivated (Guyton & Hall)

---

Mucus and the Gastric Mucosal Barrier

• A viscid gel of mucopolysaccharides (glycoproteins) forms a 0.5-1 mm layer over the epithelium
• HCO3- secreted by surface cells is trapped in mucus, creating a pH gradient (pH ~7 at cell surface, pH ~2 in lumen)
• Trefoil peptides stabilize the mucus layer
• Prostaglandin E2 maintains the barrier, stimulates HCO3- secretion, and promotes mucosal blood flow
• Barrier is damaged by aspirin, NSAIDs, alcohol, and H. pylori (Bailey & Love's Surgery, 28th ed.; Costanzo)

---

Regulation of Gastric Secretion

Three Primary Stimulants

---

Three Phases of Gastric Secretion

1. Cephalic Phase (~30% of total acid output)

• Triggered by sight, smell, taste, and thought of food - conditioned reflex (first demonstrated by Pavlov)
• Mediated entirely by the vagus nerve (dorsal vagal complex)
• Vagal output releases:
  • GRP (gastrin-releasing peptide) → stimulates G cells → gastrin
  • ACh → directly stimulates parietal cells (M3), chief cells, ECL cells
• Abolished by vagotomy

2. Gastric Phase (~60% of total acid output - quantitatively most important)

• Triggered by food entering the stomach
• Mechanisms:
  • Gastric distension → local myenteric reflexes + vago-vagal reflexes → ACh release
  • Protein breakdown products (oligopeptides, amino acids) → directly stimulate G cells → gastrin
  • Meal also buffers luminal acidity, relieving somatostatin inhibition and allowing gastrin to rise
• Gastrin travels via the bloodstream to stimulate ECL cells and parietal cells

3. Intestinal Phase (~10% of total acid output)

• Stimulatory early component: amino acids absorbed in the small intestine → enteric G cells release a small amount of gastrin
• Inhibitory (dominant): chyme entering the duodenum triggers powerful brakes on gastric secretion

---

Inhibitory Mechanisms

1. Somatostatin (D cells) - Primary "Off Switch"

• Released by antral and fundal D cells in response to luminal acid (pH < 3)
• Acts paracrine on G cells (inhibits gastrin release), ECL cells (inhibits histamine release), and parietal cells directly
• This creates the key negative feedback loop: HCl → somatostatin → inhibits G/ECL cells → less gastrin/histamine → less HCl
• When a meal is present, buffering of luminal pH releases this inhibition, allowing gastrin to rise (Ganong's, Costanzo)

2. Enterogastric Reflexes (Intestinal Phase)

• Distension of the duodenum
• Acid in the duodenum
• Protein breakdown products
• Hyperosmolar or hypo-osmolar fluids → Reverse enterogastric reflex via myenteric plexus + sympathetic nerves → inhibits gastric secretion and motility (Guyton & Hall)

3. Intestinal Hormones

---

Interdigestive (Basal) Secretion

• Only a few mL/hour during fasting - predominantly mucus, minimal pepsinogen, almost no acid
• Emotional stimuli can raise this to >50 mL/hour (highly acidic and peptic) - contributing to stress ulcers (Guyton & Hall)

---

Intrinsic Factor

• Secreted by parietal cells in parallel with HCl
• A glycoprotein that binds vitamin B12 in the stomach and protects it from digestion
• The B12-IF complex is absorbed by specific receptors in the terminal ileum
• After total gastrectomy or parietal cell destruction (autoimmune gastritis), intrinsic factor loss leads to pernicious anemia

---

Clinical Correlations

---

• Guyton and Hall Textbook of Medical Physiology
• Ganong's Review of Medical Physiology, 26th Edition
• Costanzo Physiology, 7th Edition
• Bailey and Love's Short Practice of Surgery, 28th Edition