10.1 GORD, Barrett's Oesophagus & Oesophageal Motility Disorders

Upper gastrointestinal pathology forms a core component of the MRCP(UK) Part 1 curriculum. Candidates must master the physiological mechanisms of gastro-oesophageal reflux, endoscopic surveillance criteria in premalignant lesions, manometric classification of motility disorders, the pathophysiology and eradication regimens of Helicobacter pylori, and the biochemical workup of neuroendocrine gastrinomas.

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1. Gastro-Oesophageal Reflux Disease (GORD) & Barrett's Oesophagus

Pathophysiology of GORD

Gastro-oesophageal reflux disease (GORD) develops when the antireflux barrier at the esophagogastric junction is compromised, allowing acidic gastric contents and bile acids to retrograde into the oesophagus. Key pathophysiological drivers include:

1. Transient Lower Oesophageal Sphincter Relaxations (TLESRs): Abrupt, vagally mediated reflex relaxations of the lower oesophageal sphincter (LOS) unassociated with swallowing, accounting for >70% of physiological and pathological reflux episodes.
2. Hiatus Hernia: Herniation of elements of the abdominal cavity through the oesophageal hiatus into the mediastinum. In sliding hiatus hernia (Type I, ~95%), the gastro-oesophageal junction (GOJ) slides upward above the diaphragmatic crus, uncoupling the intrinsic LOS smooth muscle from the extrinsic diaphragmatic sphincter ("pinchcock" mechanism), blunting acid clearance and creating an acid pocket. In rolling / paraoesophageal hernia (Type II/III), the fundus herniates alongside the oesophagus while the GOJ remains anchored; this carries a high risk of strangulation, volvulus, and gastric infarction, frequently demanding elective surgical repair.
3. Impaired Oesophageal Clearance & Delayed Gastric Emptying: Defective secondary peristalsis, hyposecretion of salivary bicarbonate, and gastroparesis exacerbate mucosal contact time with noxious hydrochloric acid, pepsin, and conjugated bile salts.

Clinical Presentation & Diagnostic Strategy

• Typical Symptoms: Retrosternal burning pyrosis (heartburn) radiating toward the neck, acid regurgitation, and water brash (reflex salivary hypersecretion triggered by oesophageal acidification).
• Extra-Oesophageal (Atypical) Manifestations: Chronic dry cough, nocturnal asthma exacerbations (microaspiration or vagally mediated bronchospasm), reflux laryngitis with hoarseness, globus pharyngeus, and severe dental enamel erosion.
• Endoscopy Indications (NICE Guidelines): Upper endoscopy is not required for uncomplicated reflux in young patients responding to empirical proton pump inhibitor (PPI) therapy. Urgent 2-week-wait endoscopy is mandated in the presence of "alarm features": dysphagia (any age), unintentional weight loss, persistent vomiting, epigastric mass, gastrointestinal bleeding, or age >=55 with new-onset unexplained dyspepsia.
• Ambulatory 24-Hour Oesophageal pH and Impedance Monitoring: Regarded as the diagnostic gold standard for confirming pathological acid reflux in patients with endoscopy-negative reflux disease (NERD) or those considered for antireflux surgery (laparoscopic Nissen fundoplication). A DeMeester score >14.72 or acid exposure time (AET) >6% establishes pathological acid exposure.

Barrett's Oesophagus

Barrett's oesophagus is defined histopathologically by the replacement of the normal stratified squamous epithelium of the distal oesophagus by specialized columnar epithelium containing mucin-secreting goblet cells (intestinal metaplasia), extending >=1 cm proximal to the anatomical gastro-oesophageal junction.

• Malignant Risk: Barrett's oesophagus represents the single recognized precursor lesion for oesophageal adenocarcinoma (OAC). The baseline risk of malignant progression in non-dysplastic Barrett's is approximately 0.1–0.3% per patient-year, escalating dramatically when dysplasia develops.
• Endoscopic Staging — The Prague Classification: Evaluates the extent of Barrett's mucosa above the proximal margins of the gastric folds:
  • C Criteria: Circumferential extent of columnar epithelium in centimetres.
  • M Criteria: Maximum extent of columnar epithelium (including tongues/islands) in centimetres (e.g., C3M5 indicates 3 cm circumferential involvement with a maximum tongue length of 5 cm).
• Surveillance & Management (British Society of Gastroenterology [BSG] Guidelines):
  • Non-Dysplastic Barrett's Oesophagus: Surveillance gastroscopy utilizes high-definition white-light endoscopy with the Seattle protocol (targeted biopsies of mucosal irregularities plus four-quadrant random biopsies taken every 2 cm throughout the Barrett's segment):
    • Segment length <3 cm (short-segment): Surveillance gastroscopy every 3–5 years.
    • Segment length >=3 cm (long-segment): Surveillance gastroscopy every 2–3 years.
  • Indefinite for Dysplasia: Optimize acid suppression (high-dose PPI BD) for 3–6 months to resolve active mucosal inflammation, followed by repeat endoscopy with Seattle protocol biopsies.
  • Low-Grade Dysplasia (LGD): Must be independently confirmed by two gastrointestinal expert pathologists. Options comprise either endoscopic radiofrequency ablation (RFA) or intensive 6-monthly endoscopic surveillance.
  • High-Grade Dysplasia (HGD) & Intramucosal Carcinoma (T1a): High risk of progression to invasive adenocarcinoma (>10% per year). Managed via endoscopic mucosal resection (EMR) for any visible discrete nodule or elevated lesion to ensure accurate histological staging, followed by radiofrequency ablation (RFA) to eradicate the residual flat Barrett's mucosa. Oesophagectomy is now reserved for submucosal invasive adenocarcinoma (T1b) or refractory multifocal disease.

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2. Oesophageal Motility Disorders

Achalasia

Achalasia is a primary neurodegenerative motility disorder characterized by failure of the lower oesophageal sphincter (LOS) to relax upon deglutition, accompanied by loss of coordinated propulsive peristalsis within the tubular oesophagus.

• Pathophysiology: Chronic inflammation and autoimmune-mediated destruction of postganglionic inhibitory parasympathetic ganglion cells in the myenteric (Auerbach) plexus of the oesophageal muscularis propria. Loss of inhibitory neurotransmitters (nitric oxide [NO] and vasoactive intestinal peptide [VIP]) leads to unopposed cholinergic stimulation, elevating basal LOS tone and abolishing receptive sphincter relaxation.
• Clinical Features: Insidious, slowly progressive dysphagia to both solids and liquids from onset (unlike mechanical obstruction where solid dysphagia precedes liquids), effortless regurgitation of undigested, non-acidic food and saliva, nocturnal aspiration, retrosternal chest discomfort, and progressive weight loss.
• Diagnostic Evaluation:
  • Chest Radiograph: May show an absent gastric air bubble, a dilated fluid-filled mediastinum, and a widened mediastinal contour with an air-fluid level.
  • Barium Swallow: Smooth, tapered, conical symmetric narrowing at the gastro-oesophageal junction with massive dilatation and tortuosity of the proximal oesophagus—the classic "bird's beak" or "rat-tail" sign.
  • Upper GI Endoscopy: Essential to exclude pseudoachalasia (secondary achalasia), in which gastric cardia or gastro-oesophageal junction adenocarcinoma, lymphoma, or metastatic disease infiltrates the myenteric plexus, mimicking achalasia. Red-flag clues for pseudoachalasia include age >60 years, abrupt symptom duration (<6 months), and profound, rapid weight loss.
  • High-Resolution Manometry (HRM): Gold standard diagnostic investigation. Characterized per the Chicago Classification into three distinct subtypes, all requiring an elevated Integrated Relaxation Pressure (IRP >15 mmHg) and 100% failed peristalsis:

• Therapeutic Interventions:
  • Pneumatic Balloon Dilatation: Forceful disruption of the LOS circular muscle fibres using graded large-diameter balloons (30, 35, 40 mm). High initial clinical success (~80–90%), but carries a 2–3% risk of oesophageal perforation.
  • Laparoscopic Heller Myotomy: Surgical division of the circular muscle fibres of the distal oesophagus and proximal stomach, coupled with an antireflux partial fundoplication (Dor or Toupet procedure) to prevent postoperative reflux.
  • Peroral Endoscopic Myotomy (POEM): Advanced, minimally invasive endoscopic submucosal technique that creates a submucosal tunnel to dissect the inner circular muscular layer. Particularly effective in Type III spastic achalasia where a long myotomy is required.
  • Botulinum Toxin A Injection: Endoscopic injection into the four quadrants of the LOS blocks presynaptic acetylcholine release. Reserved strictly for frail, elderly individuals or patients unfit for definitive surgical or balloon interventions due to transient efficacy (symptoms recur in >50% within 6–12 months).
  • Pharmacological Therapy: Oral calcium channel blockers (nifedipine) or sublingual isosorbide dinitrate relax smooth muscle, serving solely as temporary bridges before intervention.

Diffuse Oesophageal Spasm & Other Motility Disorders

• Diffuse Oesophageal Spasm (Distal Oesophageal Spasm): Uncoordinated, simultaneous, non-propulsive contractions of the distal smooth-muscle oesophagus with normal lower oesophageal sphincter relaxation. Manifests with severe, episodic, gripping retrosternal chest pain (often provoked by hot or cold liquids, mimicking acute coronary syndrome) and intermittent dysphagia. Barium swallow classically shows a "corkscrew" or "rosary bead" oesophagus. High-resolution manometry reveals normal IRP with >=20% premature contractions (distal latency <4.5 seconds). Managed with calcium channel blockers (diltiazem), nitrates, tricyclic antidepressants (neuropathic pain modulation), or sildenafil.
• Systemic Sclerosis (Scleroderma Oesophagus): Progressive smooth muscle atrophy, collagen deposition, and fibrous replacement of the muscularis propria in the lower two-thirds of the oesophagus. Leads to complete aperistalsis and profound hypotonia of the lower oesophageal sphincter (a wide-open, patulous sphincter). Results in severe, intractable gastro-oesophageal reflux, recurrent peptic strictures, and high risk of Barrett's oesophagus. High-resolution manometry shows normal or low resting IRP with completely absent peristalsis.

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