GERD

Gastroesophageal reflux disease (GERD) results from the pathological retrograde movement of gastric contents (acid, pepsin, bile acids) into the esophagus, causing symptoms and/or mucosal injury. The primary anti-reflux barrier is the lower esophageal sphincter (LES), a 3-4 cm zone of tonically contracted smooth muscle at the gastroesophageal junction (GEJ), normally maintaining a resting pressure of 10-30 mmHg above intragastric pressure. The dominant mechanism of GERD is transient LES relaxations (TLESRs) — vagally mediated, non-swallow-related relaxations lasting 10-60 seconds that occur independently of esophageal peristalsis, accounting for >70% of reflux episodes in GERD patients. Additional mechanisms include a hypotensive LES (basal pressure <10 mmHg, allowing free reflux), hiatal hernia (which disrupts the extrinsic crural diaphragm reinforcement of the LES and creates an acid pocket above the diaphragm), and impaired esophageal clearance (reduced peristaltic amplitude and salivary bicarbonate buffering). At the mucosal level, refluxed hydrochloric acid (pH <4) and activated pepsin cause epithelial injury by disrupting intercellular tight junctions, allowing acid penetration into the submucosa where it activates nociceptors (producing heartburn) and triggers an inflammatory cascade. Chronic acid exposure induces adaptive metaplasia — replacement of the normal stratified squamous esophageal epithelium with intestinal-type columnar epithelium containing goblet cells (Barrett esophagus), which represents a premalignant condition with progression risk through low-grade dysplasia, high-grade dysplasia, to esophageal adenocarcinoma (~0.5%/year progression rate). Proton pump inhibitors (PPIs) target the H+/K+ ATPase proton pump on the apical membrane of gastric parietal cells, irreversibly inhibiting the final common pathway of acid secretion. PPIs are prodrugs requiring acid activation in the parietal cell canaliculus — this explains the critical importance of dosing 30-60 minutes before meals (meal-stimulated acid secretion activates the proton pumps, which the drug then irreversibly binds). The NP applies a step-up management approach (lifestyle modifications → H2RAs → PPI → double-dose PPI → surgical evaluation), screens for Barrett esophagus in high-risk patients (chronic GERD >5 years, male, age >50, obesity, smoking), and manages the omeprazole-clopidogrel interaction (omeprazole inhibits CYP2C19-mediated clopidogrel activation — use pantoprazole instead in patients on dual antiplatelet therapy).