A 45-year-old man presents with a 3-year history of progressive dysphagia to both solids and liquids, regurgitation of undigested food at night, and a 12 kg weight loss. Upper endoscopy reveals a dilated esophagus with retained food debris and a tight lower esophageal sphincter (LES) that yields to gentle endoscope pressure, as shown in the structure marked **A** in the diagram. High-resolution manometry confirms absent esophageal contractility with elevated integrated relaxation pressure (IRP 18 mmHg). Which of the following pathophysiological mechanisms best explains the findings in structure **A**?

Explanation

## Why option 1 is correct The structure marked **A** represents primary achalasia, a primary esophageal motility disorder defined by impaired LES relaxation and absent esophageal peristalsis. The pathophysiological basis is selective and progressive loss of inhibitory ganglion cells (containing nitric oxide and vasoactive intestinal peptide) in the myenteric (Auerbach) plexus. This loss of inhibition leaves unopposed cholinergic excitation, causing high LES resting pressure, failed LES relaxation, and aperistalsis. The clinical presentation (dysphagia to both solids and liquids, regurgitation, weight loss) and the endoscopic finding of a tight LES that yields to gentle pressure are hallmark features of primary achalasia. The manometric finding of elevated IRP with absent contractility confirms this diagnosis. (Sleisenger & Fordtran 11e Ch 43; Chicago Classification v4.0) ## Why each distractor is wrong - **Option 2 (Pseudoachalasia)**: While pseudoachalasia due to malignancy can mimic achalasia, the endoscopic finding of a tight LES that **yields** to gentle endoscope pressure is characteristic of primary achalasia. A malignant stricture would NOT yield to pressure and would show resistance to endoscope passage. This finding excludes pseudoachalasia. - **Option 3 (Diffuse esophageal spasm)**: Diffuse esophageal spasm presents with intermittent simultaneous contractions on manometry and a normal, relaxing LES. The patient's manometry shows absent contractility and elevated IRP, not simultaneous contractions. Additionally, DES typically presents with chest pain rather than dysphagia to both solids and liquids. - **Option 4 (Scleroderma esophagus)**: Scleroderma causes a patulous (open) LES with severe reflux esophagitis, not a tight non-relaxing LES. The patient's tight LES that yields to pressure is incompatible with scleroderma, which presents with heartburn and reflux symptoms rather than dysphagia from LES obstruction. **High-Yield:** Achalasia = loss of inhibitory neurons in myenteric plexus → unopposed cholinergic excitation → tight, non-relaxing LES + aperistalsis. Dysphagia to BOTH solids AND liquids from onset is the key clinical clue. [cite: Sleisenger & Fordtran 11e Ch 43; Chicago Classification v4.0 Neurogastroenterol Motil 2021]