GERD 1: Pathogenesis — It's Not Just Acid Burns

Episode keywords: GERD pathogenesis, cytokine-mediated esophageal injury, transient LES relaxation TLESR, GABA-B baclofen reflux, LES pressure GERD, nucleus tractus solitarius reflux, ACG GERD definition 2022

Episode Summary

The "acid burn" model of reflux esophagitis has been replaced. This episode covers the Dunbar JAMA 2016 paradigm shift showing that acid triggers a cytokine-mediated inflammatory response that builds from deep to superficial, not from the surface inward. It then establishes the two-component antireflux barrier, the neural control of transient LES relaxations, and one of the most consistently board-tested misconceptions: that most GERD patients have normal resting LES pressure.

Key Topics

• ACG 2022 GERD definition: Reflux of stomach contents causing troublesome symptoms and/or complications, objectively documented by endoscopy or ambulatory pH monitoring. Approximately 20% of Western adults report weekly heartburn.
• The cytokine-mediated injury model: Acid contacts esophageal epithelial cells, which secrete pro-inflammatory cytokines that recruit T lymphocytes. The damage is inflammatory, not chemical. Histologic consequence: basal cell hyperplasia and elongated papillae appear before surface erosions. Injury builds from inside out. This explains why symptom severity does not correlate with endoscopic severity.
• The two-component LES: The intrinsic LES is smooth muscle providing tonic contraction. The extrinsic LES is the crural diaphragm, skeletal muscle that dynamically augments pressure during inspiration and straining. Both components must be understood to explain hiatal hernia and fundoplication mechanics.
• TLESRs as the dominant reflux mechanism: Transient LES relaxations are sudden, prolonged relaxations not triggered by swallowing, lasting more than 10 seconds, representing the normal belch reflex. Controlled by the nucleus tractus solitarius in the medulla. Inhibited by GABA-B neurons, which is why baclofen (a GABA-B agonist) reduces TLESR frequency. CCK-1 receptors mediate intrinsic sphincter relaxation during TLESRs, connecting fatty meals to reflux through a defined pathway.
• The TLESR misconception: GERD patients do not have more TLESRs than normal people. The frequency is the same. What differs is that a higher proportion of TLESRs in GERD are associated with acid reflux rather than just gas venting. The problem is content, not frequency.
• LES pressure in GERD: Most GERD patients have normal resting LES pressure. Only patients with severe erosive esophagitis consistently have abnormally low LES pressure, generally below 10 mmHg. GERD is not simply a "weak sphincter" disease for the majority of patients.

Board Pearls

High-yield: The Dunbar model means histologic changes precede endoscopic findings. Basal cell hyperplasia and T-cell infiltration on biopsy can represent early reflux injury even with a normal-looking mucosal surface.
Board trap: A question states a GERD patient has normal LES pressure and asks if this rules out GERD. It does not. Normal resting LES pressure is the expected finding in most reflux patients.
High-yield: Baclofen reduces TLESRs via GABA-B agonism at the nucleus tractus solitarius. This is a high-frequency board mechanism question.