Acid Secretion and Peptic Ulcer Disease

Gastric regions and major cell types

Fundus/Body: mucous neck cells, parietal cells, chief cells, ECL cells; Gastric Antrum: mucous cells, G cells.

Function of parietal cells

Secrete HCl (kills microbes, activates pepsin) and intrinsic factor (B12 absorption).

Function of chief cells

Secrete pepsinogen → activated to pepsin by HCl; proteolysis.

Function of ECL cells

Release histamine → stimulates parietal cells to secrete HCl.

Function of G cells

Release gastrin → ↑ acid, ↑ pepsinogen, ↑ ECL histamine, trophic effect on parietal/ECL cells.

Function of D cells

Release somatostatin → inhibits gastrin, histamine, and parietal cell acid secretion.

Mechanism of acid secretion (parietal cell)

Carbonic anhydrase forms H+; H+/K+ ATPase pumps H+ into lumen; Cl– follows; HCO3– enters blood (“alkaline tide”).

Stimulators of acid secretion

Histamine (H2 receptor), gastrin, acetylcholine (vagus).

Inhibitors of acid secretion

Somatostatin, prostaglandins, secretin, low gastric pH.

Cephalic phase of acid secretion

Sight/smell/taste → vagus → ↑ ACh, ↑ gastrin, ↑ histamine; inhibits D cells.

Gastric phase of acid secretion

Gastric distention (vagovagal reflex) + peptides → ↑ gastrin.

Intestinal phase of acid secretion

Peptides stimulate duodenal G cells; acid/fat inhibit via secretin + CCK → ↑ somatostatin.

Mucosal protective factors

Mucus, bicarbonate, epithelial barrier, prostaglandins, mucosal blood flow.

Damaging factors of mucosal lining

Acid, pepsin, H. pylori, NSAIDs, smoking, alcohol, stress, bile reflux.

Pathogenesis of Peptic Ulcer Disease

Imbalance between acid/pepsin and mucosal defenses → ulceration.

Major causes of Peptic Ulcer Disease

H. pylori (#1), NSAIDs, stress (critical illness), gastrinoma (ZE syndrome).

H. pylori characteristics

Gram‑negative rod; urease‑producing(produces ammonia which neutralizes acid); lives in mucus layer; causes chronic gastritis.

H. pylori complications

Peptic ulcers, gastric adenocarcinoma, MALT lymphoma.

Meds to treat H Pylori

Bismuth Subsalicylate, Metronidazole, Tetracycline, Omepraziole = Quadrupule regimen

NSAID mechanism of injury in Peptic Ulcer Disease

COX‑1 inhibition → ↓ prostaglandins → ↓ mucus, ↓ bicarbonate, ↓ blood flow → ↑ acid injury.

Prostaglandin protective effects

↑ mucus, ↑ bicarbonate, ↑ blood flow, ↑ epithelial repair, ↓ acid secretion.

Stress ulcers

Seen in critically ill (trauma, burns, head injury, ventilated); due to ↓ mucosal blood flow.

Complications of Peptic Ulcer Disease

Bleeding, perforation, gastric outlet obstruction, pain.

Treatment principle for Peptic Ulcer Disease

NO ACID = NO ULCER; eliminate H. pylori; stop NSAIDs; reduce acid; enhance mucosal protection.

H2 blockers mechanism + Example

Block H2 receptors on parietal cells → ↓ histamine‑stimulated acid secretion. Famotidine(Pepcid)

Famotidine (Pepcid) moa

H2 Receptor Antagonist on parietal cells»decreases histamine stimulated acid secretion

PPI mechanism

Irreversibly inhibit H+/K+ ATPase → block final step of acid secretion.

Examples of PPIs

Omeprazole(Prilosec), esomeprazole, pantoprazole(Protonix), lansoprazole, rabeprazole, dexlansoprazole.

Long‑term PPI risks

Low‑quality evidence: kidney disease, fractures, infections, B12 deficiency; absolute risk very low.

Mucosal protectants: sucralfate (Carafate)

Forms protective coating on ulcers; binds proteins; inhibits pepsin.

Mucosal protectants: misoprostol (Cytotec)

prostaglandin analog → ↑ mucus/bicarbonate, ↓ acid; contraindicated in pregnancy (abortifacient).

Acid reduction interventions

Anticholinergics, vagotomy, H2 blockers, antrectomy, PPIs.