Gastro-Oesophageal Reflux Disease (GORD)

1. Clinical Overview

Summary

Gastro-Oesophageal Reflux Disease (GORD) is a chronic condition characterized by troublesome symptoms and/or complications resulting from the reflux of gastric contents into the oesophagus. [1,2] The fundamental defect involves failure of the Lower Oesophageal Sphincter (LOS) anti-reflux barrier mechanism, allowing retrograde flow of acidic gastric contents, pepsin, and bile into the oesophageal lumen.

GORD represents one of the most common gastrointestinal disorders in Western populations, with significant impact on quality of life and healthcare costs. [3] The condition exists on a spectrum from Non-Erosive Reflux Disease (NERD) to Erosive Oesophagitis to the pre-malignant condition Barrett's Oesophagus. [4]

While most cases are effectively managed in primary care with lifestyle modification and acid suppression therapy, GORD carries significant long-term sequelae including stricture formation, chronic respiratory disease, and progression to oesophageal adenocarcinoma in a subset of patients with Barrett's metaplasia. [5]

Clinical Pearls

The "Cardiac Mimic": GORD is the leading cause of non-cardiac chest pain, accounting for up to 50% of cases presenting with normal coronary angiography. [6] Retrosternal pain from GORD can be indistinguishable from angina pectoris. Key distinguishing features include postprandial timing, improvement with antacids, exacerbation when supine, and absence of exertional triggers. Always exclude cardiac ischaemia first - "treat the heart, not the heartburn until the heart is ruled out."

The H. pylori Paradox: Helicobacter pylori infection, the principal cause of peptic ulcer disease, paradoxically protects against GORD. [7] H. pylori colonization, particularly when involving the gastric corpus, leads to atrophic gastritis and reduced acid secretion. Eradication therapy can unmask or worsen reflux symptoms in predisposed individuals by restoring normal acid output. This creates a therapeutic dilemma: cure the ulcer disease but potentially worsen reflux.

Silent Reflux (LPR): Laryngopharyngeal Reflux (LPR) presents without classic heartburn in up to 75% of cases. [8] Patients typically present to ENT services with chronic cough, hoarseness, throat clearing, globus sensation, or recurrent laryngitis. GORD is one of the "big three" causes of chronic cough (alongside asthma and upper airway cough syndrome). The mechanism involves both direct acid injury to laryngeal structures and vagally-mediated reflex bronchoconstriction.

PPI Timing Matters: Proton pump inhibitors (PPIs) are prodrugs requiring active H+/K+ ATPase pumps for covalent binding. [9] Maximum efficacy is achieved when taken 30-60 minutes before meals (typically before breakfast), when parietal cells are maximally stimulated. Taking PPIs at bedtime or on an empty stomach significantly reduces bioactivation and therapeutic efficacy. Non-compliance with timing is a major cause of apparent "PPI failure."

NERD Dominates: Approximately 60-70% of GORD patients have Non-Erosive Reflux Disease (NERD) - genuine acid reflux with typical symptoms but entirely normal endoscopy. [10] These patients often have more severe symptoms and poorer response to PPI therapy than those with erosive disease, yet frequently have their symptoms dismissed as "functional" or psychological. Diagnosis requires objective pH/impedance monitoring.

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2. Epidemiology

Prevalence and Demographics

GORD is one of the most prevalent gastrointestinal conditions in developed nations:

Demographic Patterns

• Gender Distribution: While symptom prevalence is equal between sexes, severe complications (Barrett's oesophagus, erosive oesophagitis, adenocarcinoma) show marked male predominance (3-4:1 ratio). [12] This may reflect hormonal protective effects of oestrogen on oesophageal mucosa and differences in visceral obesity patterns.

• Age-Related Changes: Prevalence increases with advancing age due to progressive LOS dysfunction, increased hiatus hernia prevalence, decreased oesophageal clearance, reduced saliva production, and greater medication use (NSAIDs, calcium channel blockers, nitrates). [11]

• Geographical Variation: GORD is predominantly a disease of Western, industrialized nations. [13] Prevalence in Asia and Africa is significantly lower, though recent data suggest increasing prevalence with economic development and adoption of Western dietary patterns.

Risk Factors

Non-Modifiable Risk Factors

Modifiable Risk Factors

Obesity: The strongest modifiable risk factor. [14]

• BMI \u003e30 kg/m²: OR 2.8 for GORD symptoms
• BMI \u003e35 kg/m²: OR 4.7 for GORD symptoms
• Central adiposity (waist circumference, waist-to-hip ratio) shows stronger association than BMI alone
• Mechanisms: Increased intra-abdominal pressure, increased intragastric pressure, mechanical disruption of LOS, increased transient LOS relaxations (TLOSRs), altered gastric hormonal milieu (adipokines)
• Weight loss demonstrates dose-response improvement in symptoms

Hiatus Hernia: Present in 50-94% of GORD patients (depending on diagnostic criteria). [15]

• Type I (Sliding) hernias are most relevant to GORD
• Herniation disrupts the crural diaphragm's extrinsic compression of LOS
• Creates an "acid pocket" above the diaphragm
• Impairs oesophageal clearance
• Hernia size correlates with symptom severity and complication risk

Dietary Factors: Multiple dietary triggers mediated through LOS relaxation:

• Alcohol: Direct LOS relaxant effect
• Caffeine: Stimulates gastric acid secretion and relaxes LOS
• Chocolate: Contains methylxanthines (theobromine) causing LOS relaxation
• Fatty foods: Delay gastric emptying, stimulate cholecystokinin (CCK) release causing LOS relaxation
• Peppermint: Direct smooth muscle relaxant
• Citrus and tomatoes: High acid content, direct mucosal irritation
• Carbonated beverages: Gastric distension

Smoking: Multiple deleterious effects [16]

• Reduces LOS pressure
• Reduces salivary bicarbonate secretion (impaired buffering)
• Stimulates gastric acid secretion
• Impairs oesophageal clearance
• Increases risk of Barrett's progression to dysplasia/cancer
• Smoking cessation demonstrates symptom improvement within weeks

Medications: Important iatrogenic cause

Pregnancy: Occurs in 40-85% of pregnant women [17]

• Mechanical: Uterine enlargement increases intra-abdominal pressure
• Hormonal: Progesterone-mediated LOS relaxation
• Typically resolves postpartum
• Safe management: Lifestyle modification, alginates; PPIs if severe (generally safe, particularly omeprazole/lansoprazole)

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3. Pathophysiology

GORD results from an imbalance between factors promoting reflux (offensive factors) and mechanisms protecting the oesophageal mucosa (defensive factors).

Anti-Reflux Barrier Mechanisms

The Lower Oesophageal Sphincter (LOS) represents the primary anti-reflux barrier, consisting of:

1. Intrinsic LOS

• 3-4 cm zone of tonically contracted smooth muscle
• Normal resting pressure: 15-30 mmHg (measured manometrically)
• Asymmetric thickening of circular muscle layer
• Maintains closure except during swallowing
• Hypotensive LOS (pressure \u003c10 mmHg) predisposes to reflux

2. Extrinsic Compression

• Crural diaphragm: Right crus forms muscular sling around oesophagus
• Functions as "external sphincter" augmenting LOS during inspiration
• Synergistic contraction with intrinsic LOS
• Disrupted by hiatus hernia

3. Anatomical Factors

• Angle of His: Acute angle of gastro-oesophageal junction creates flap-valve
• Mucosal rosette: Folds at gastro-oesophageal junction provide mechanical closure
• Intra-abdominal LOS segment: Positive abdominal pressure compresses this segment
• Phreno-oesophageal ligament: Anchors oesophagus to diaphragmatic hiatus

Mechanisms of Reflux

Transient Lower Oesophageal Sphincter Relaxations (TLOSRs)

The most common mechanism accounting for \u003e70% of reflux episodes in both healthy individuals and GORD patients. [18]

• Physiological venting mechanism allowing belching (gas release)
• In GORD: Inappropriate frequency, duration, or temporal clustering
• Triggered by gastric distension → vagal afferents → brainstem reflexes
• Characterized by:
  • Complete LOS relaxation (to intragastric pressure)
  • Absence of pharyngeal swallow
  • Duration \u003e10 seconds (vs. 6-10s for swallow-induced relaxation)
  • Inhibition of crural diaphragm contraction
• Mechanisms promoting pathological TLOSRs:
  • Gastric distension (large meals, carbonation)
  • High-fat meals (delayed gastric emptying, CCK release)
  • Supine position
  • Certain medications (baclofen reduces TLOSRs; used experimentally)

Hypotensive LOS

• Sustained reduction in basal LOS pressure (\u003c10 mmHg)
• Represents structural/functional LOS incompetence
• Associated with:
  • Severe erosive oesophagitis
  • Scleroderma (smooth muscle atrophy, fibrosis)
  • Post-surgical (myotomy, fundoplication failure)
  • Severe obesity
  • Chronic gastric distension
• Allows reflux during any rise in intra-abdominal pressure

Anatomical Disruption: Hiatus Hernia

Type I (Sliding) Hiatus Hernia: Proximal stomach herniates through oesophageal hiatus into posterior mediastinum.

Pathophysiological consequences:

1. Loss of crural compression: LOS moves from positive-pressure abdomen to negative-pressure thorax
2. Shortened intra-abdominal LOS: Reduces pressure gradient
3. Impaired oesophageal clearance: Reduced oesophageal shortening, ineffective peristalsis
4. Acid pocket: Unbuffered acid layer at gastro-oesophageal junction above hernia sac - first material to reflux
5. Increased TLOSRs: Hernia sac distension triggers vagal reflexes
6. Reduced LOS pressure: Mechanical stretching

Delayed Gastric Emptying (Gastroparesis)

• Prolongs gastric distension → increased TLOSRs
• Maintains high gastric volume available for reflux
• Causes: Diabetes mellitus, post-vagotomy, medications (opiates, anticholinergics), idiopathic
• May explain PPI-refractory symptoms (continued volume reflux despite acid suppression)

Increased Intra-Abdominal Pressure

• Obesity: Central adiposity most significant
• Pregnancy: Gravid uterus
• Ascites
• Chronic cough/straining: Creates repetitive pressure spikes
• Tight clothing/abdominal binders

Impaired Oesophageal Clearance

Normally, refluxed material is rapidly cleared by:

1. Primary peristalsis: Clears volume
2. Secondary peristalsis: Triggered by oesophageal distension
3. Salivary bicarbonate: Neutralizes residual acid (produces ~1.5L saliva/day with HCO₃⁻)

In GORD, clearance is impaired by:

• Ineffective oesophageal motility (absent/low-amplitude contractions)
• Hiatus hernia
• Supine position (loss of gravity)
• Reduced salivation (smoking, Sjögren's, medications, sleep)
• Increased saliva viscosity

The "Acid Pocket"

A distinct, unbuffered pool of gastric acid that forms on top of the meal (chyme) in the proximal stomach immediately postprandially. [19]

• Positioned at gastro-oesophageal junction
• Represents highly acidic (pH \u003c2) secretion not yet mixed with food
• In hiatus hernia: Pocket extends above diaphragm → immediate reflux risk
• Targeted by:
  • Alginates (form raft displacing acid pocket downward)
  • Post-meal ambulation (gravity)

Mucosal Defence Mechanisms

Pre-epithelial Defence

• Mucus layer: Viscous gel traps bicarbonate
• Bicarbonate secretion: From submucosal glands, creates pH gradient
• Unstirred water layer: Physical barrier

Epithelial Defence

• Tight junctions: Limit paracellular H⁺ diffusion
• Cell membranes: Lipid bilayer resistant to acid
• Intracellular buffers: Neutralize H⁺ entering cells
• Na⁺/H⁺ exchangers: Active extrusion of H⁺

Post-epithelial Defence

• Blood flow: Removes H⁺, delivers HCO₃⁻ and nutrients
• Tissue repair: Rapid epithelial restitution and proliferation

Breakdown in GORD:

• Prolonged acid exposure overwhelms defences
• Increased epithelial permeability → inflammatory mediators
• Dilated intercellular spaces (DIS) - histological hallmark of NERD
• Chronic inflammation → fibrosis → stricture

Molecular Pathophysiology

Reflux-Induced Epithelial Injury:

• Acid activates TRPV1 receptors (capsaicin receptors) on sensory neurons → pain
• Acid + pepsin + bile synergistically damage epithelium
• Cytokine release: IL-8, IL-1β → neutrophil recruitment
• Oxidative stress: Reactive oxygen species (ROS) damage DNA
• Impaired tight junctions: Claudin proteins disrupted

Progression to Barrett's Metaplasia:

• Chronic injury → Squamous epithelium replaced by columnar (intestinal-type) epithelium
• CDX2 transcription factor drives intestinal metaplasia
• Goblet cells appear (intestinal phenotype)
• Dysplasia → Adenocarcinoma sequence (minority of patients)
• Risk factors for progression: Male, smoking, long-segment Barrett's (\u003e3cm), dysplasia

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4. Clinical Presentation

Typical Oesophageal Symptoms ("The Classic Duo")

1. Heartburn (Pyrosis)

• Burning retrosternal discomfort
• Radiates from epigastrium upward toward throat/neck
• Timing: Postprandial (especially after large/fatty meals), worse when supine/bending forward
• Relief: Antacids, upright posture, water
• Description: "Burning," "hot sensation," "fire in chest"
• Sensitivity/Specificity: High sensitivity (~75%) for GORD but relatively low specificity (other causes: oesophagitis from other causes, functional heartburn)

2. Regurgitation

• Effortless return of gastric contents into pharynx/mouth
• Sour or bitter taste ("acid brash") from gastric acid
• Occurs without nausea or retching (vs. vomiting)
• Worse when supine, bending forward, straining
• May cause nocturnal choking/coughing
• Volume regurgitation suggests:
  • Large hiatus hernia
  • Achalasia (if undigested food)
  • Rumination syndrome (if voluntary/semi-voluntary)

3. Water Brash

• Sudden filling of mouth with clear, salty saliva (not acid)
• Reflex salivary hypersecretion triggered by oesophageal acidification
• Protective mechanism: Bicarbonate-rich saliva neutralizes acid
• Occurs in paroxysms
• Distinguishes from regurgitation (which is gastric content)

Atypical Oesophageal Symptoms

Dysphagia 🚩

• Difficulty swallowing
• Critical Red Flag - requires urgent investigation
• Causes in GORD:
  • "Peptic stricture: Progressive fibrosis → luminal narrowing"
    • Dysphagia to solids initially, then liquids
    • Associated with chronic severe reflux
  • "Oesophageal adenocarcinoma: ALARM symptom"
    • Progressive, relentless dysphagia
    • Associated weight loss
  • "Severe oesophagitis: Mucosal oedema, deep ulceration"
  • "Eosinophilic oesophagitis: Food bolus obstruction"
• 2-Week-Wait referral mandatory for new dysphagia

Odynophagia

• Painful swallowing (pain on swallowing)
• Suggests severe ulcerative oesophagitis
• Differential:
  • Infectious oesophagitis (Candida, CMV, HSV in immunocompromised)
  • Pill oesophagitis (bisphosphonates, doxycycline, potassium)
  • Eosinophilic oesophagitis

Chest Pain 🚩

• Non-cardiac chest pain (NCCP): GORD is leading cause (~50% of cases with normal coronaries) [6]
• Can be indistinguishable from angina: Retrosternal, squeezing, radiating to arm/jaw
• Distinguishing features favouring GORD:
  • Postprandial timing
  • Prolonged duration (\u003e30 minutes)
  • Positional (worse supine)
  • Relief with antacids
  • No relationship to exertion
  • Associated heartburn/regurgitation
• CRITICAL: Always exclude cardiac aetiology first (ECG, troponin, cardiology assessment)
• "PPI test": Symptom response to high-dose PPI (e.g., omeprazole 40mg BD x 2 weeks) has moderate sensitivity/specificity for oesophageal origin

Extraoesophageal (Atypical) Manifestations

Respiratory Symptoms

Chronic Cough

• Defined as cough lasting \u003e8 weeks
• GORD accounts for 10-40% of chronic cough cases [20]
• Mechanisms:
  1. Microaspiration: Direct acid injury to airways
  2. Vagal reflex: Oesophageal acid → vagal afferents → bronchial efferents → cough
• Features suggesting GORD:
  • Non-productive cough
  • Worse after meals, supine, at night
  • Associated heartburn (though may be absent in "silent reflux")
• Diagnosis challenging: May require pH-impedance monitoring with cough correlation
• Response to PPI therapy variable (30-70%); may require 2-3 months trial

Asthma

• Bidirectional relationship:
  • "GORD → Asthma: Acid triggers bronchoconstriction (vagal reflex, microaspiration)"
  • "Asthma → GORD: Increased negative intrathoracic pressure, β-agonists reduce LOS tone, cough increases intra-abdominal pressure"
• Up to 75% of asthmatics have abnormal acid exposure on pH monitoring [21]
• However, PPI treatment does not improve asthma control in most studies (suggests association, not causation)
• Consider GORD in:
  • Nocturnal asthma symptoms
  • Adult-onset asthma
  • Asthma refractory to standard therapy

Recurrent Pneumonia/Aspiration

• Nocturnal aspiration of refluxed material
• Particularly in elderly, supine position, neurological disease
• Recurrent right lower lobe pneumonia (position-dependent aspiration)

ENT Manifestations (Laryngopharyngeal Reflux - LPR)

LPR differs from classic GORD:

• Heartburn often absent (75% have no typical reflux symptoms) [8]
• Laryngopharyngeal mucosa more sensitive to acid/pepsin injury
• Upright reflux pattern (vs. supine in classic GORD)
• Diagnosis challenging: pH probe less sensitive (proximal oesophageal monitoring needed)

LPR Symptoms:

• Hoarseness: Vocal cord inflammation/oedema
• Chronic throat clearing
• Globus pharyngeus: Sensation of lump in throat
• Sore throat (chronic pharyngitis/laryngitis)
• Post-nasal drip sensation
• Excessive throat mucus

Laryngoscopy findings:

• Posterior laryngeal erythema/oedema
• Vocal cord granulomas/polyps
• Posterior commissure hypertrophy
• Subglottic stenosis (rare, severe)

Dental Erosion

• Erosion of palatal surface of teeth (distinguishes from erosion from acidic foods/drinks which affects labial surface)
• Enamel demineralization from chronic acid exposure
• Occurs with chronic regurgitation
• Dentist may be first to identify GORD

Alarm Symptoms ("Red Flags") 🚩

Indicate need for urgent investigation (2-Week-Wait OGD referral):

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5. Differential Diagnosis

Oesophageal Disorders

Gastric/Duodenal Disorders

Cardiac Disorders 🚩

Other Causes of Chest Pain

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6. Investigations

Diagnostic Strategy

NICE CG184 advocates a stratified approach based on age and red flags: [1]

Young patients (\u003c55-60 years), typical symptoms, NO red flags:

• Clinical diagnosis (no investigations required)
• Empirical PPI trial (4-8 weeks)
• Response to therapy confirms diagnosis

ANY red flag present OR Age \u003e55 with new-onset symptoms:

• Urgent OGD (2-Week-Wait)

Refractory symptoms despite PPI:

• OGD (rule out complications, alternative diagnoses)
• Consider pH-impedance monitoring (confirm acid reflux)
• Consider manometry (rule out motility disorder)

Upper GI Endoscopy (Oesophago-Gastro-Duodenoscopy - OGD)

Indications:

Urgent (2-Week-Wait):

• Dysphagia (any age)
• Age \u003e55 years with weight loss AND any of:
  • Upper abdominal pain
  • Reflux
  • Dyspepsia
• Upper abdominal mass
• Iron deficiency anaemia
• Persistent vomiting

Routine:

• Symptoms refractory to PPI therapy
• Relapse on stopping PPI
• Barrett's surveillance
• Pre-surgical assessment

Findings:

Normal Endoscopy (60-70% of GORD patients)

• Non-Erosive Reflux Disease (NERD): Normal macroscopic appearance despite genuine reflux
• Diagnosis requires pH/impedance monitoring
• Microscopic changes: Dilated intercellular spaces, basal cell hyperplasia, papillary elongation

Los Angeles Classification of Erosive Oesophagitis:

Barrett's Oesophagus:

• Salmon-pink columnar mucosa extending proximally from gastro-oesophageal junction
• Prague C\u0026M criteria:
  • "C: Circumferential extent"
  • "M: Maximum extent"
• Requires histological confirmation: Intestinal metaplasia with goblet cells
• Prague Classification: e.g., C2M5 = 2cm circumferential, 5cm maximum extent

Stricture:

• Luminal narrowing (typically \u003c13mm diameter = dysphagia)
• Proximal oesophageal dilation
• Requires dilation therapy

Hiatus Hernia:

• Displacement of gastro-oesophageal junction \u003e2cm above diaphragmatic hiatus
• Gastric folds visible above diaphragm

Malignancy:

• Mass, ulceration, stricture
• Biopsy for histology

pH Monitoring

24-Hour Ambulatory pH Monitoring - "Gold Standard" for diagnosing acid reflux [22]

Indications:

• Typical symptoms with normal endoscopy (NERD diagnosis)
• Refractory symptoms on PPI (confirm genuine reflux vs. functional)
• Pre-operative assessment for anti-reflux surgery
• Atypical symptoms (chest pain, cough) where GORD suspected

Technique:

• Nasally-inserted catheter with pH sensor positioned 5cm above LOS (manometry-guided)
• OR wireless capsule (Bravo) attached to oesophageal mucosa (48-96h recording)
• Off PPI for 7 days before test (to assess acid exposure)
• Patient records symptoms and meals
• Ambulatory monitoring during normal activities

Parameters Measured:

Lyon Consensus 2018 Diagnostic Criteria: [22]

• Proven GORD: AET \u003e6% OR AET 4-6% + Proven reflux-symptom association
• Borderline: AET 4-6%
• Normal: AET \u003c4%

Combined Multichannel Intraluminal Impedance-pH Monitoring (MII-pH)

Advantage over pH monitoring alone: Detects all reflux episodes (acid AND non-acid/weakly acidic/gas/liquid) [23]

Indications:

• PPI-refractory symptoms: Determines if symptoms due to:
  • Persistent acid reflux (inadequate acid suppression)
  • Non-acid reflux (pH \u003e4, e.g., bile, weakly acidic)
  • No reflux (functional symptoms, alternative diagnosis)
• Distinguishes liquid vs. gas reflux (important for belching/bloating symptoms)

Parameters:

• Total reflux episodes (acid + non-acid)
• Reflux type (liquid, gas, mixed)
• Proximal extent of reflux
• Bolus clearance time
• Symptom-reflux correlation

Interpretation on PPI:

• Normal acid exposure (pH \u003e4 most of time) + Symptom-reflux correlation with non-acid reflux = Non-acid reflux (may respond to surgery or anti-reflux agents, NOT more PPI)
• Normal acid exposure + No symptom-reflux correlation = Functional heartburn (consider neuromodulators)

High-Resolution Manometry (HRM)

NOT a primary diagnostic test for GORD (GORD is primarily a pH/endoscopic diagnosis)

Indications:

• Pre-operative assessment (MANDATORY before anti-reflux surgery)
  • Rule out achalasia (fundoplication on achalastic oesophagus = disaster)
  • Rule out severe dysmotility (scleroderma, aperistalsis - relative contraindication to surgery)
• Atypical symptoms with normal pH testing
• Dysphagia evaluation

Findings in GORD:

• Hypotensive LOS (\u003c10 mmHg) in some patients
• Ineffective Oesophageal Motility (IOM): \u003e50% ineffective swallows
• Fragmented peristalsis
• Increased TLOSRs (research setting, not clinical)

Chicago Classification v4.0: Categorizes oesophageal motility disorders

Additional Investigations

Barium Swallow (Contrast Oesophagram)

• Largely superseded by endoscopy
• Indications:
  • Suspected perforation (water-soluble contrast)
  • Dysphagia with failed OGD intubation
  • Motility assessment (timed barium swallow for achalasia)
• Findings: Hiatus hernia, stricture, spontaneous reflux (positional imaging)

Wireless Capsule Endoscopy

• NOT indicated for GORD
• May visualize oesophagitis in patients unable to tolerate OGD

Proton Pump Inhibitor (PPI) Trial

• "Therapeutic trial" as diagnostic test
• Omeprazole 20-40mg BD (or equivalent) x 2 weeks
• Sensitivity: ~70-80% for GORD (many false negatives, especially NERD)
• Specificity: Moderate (~60-70%) (placebo response ~20-40%)
• Used for:
  • Non-cardiac chest pain (after cardiac exclusion)
  • Suspected extraoesophageal GORD (cough, laryngitis)
• Limitations: Not definitive, cannot exclude complications, not substitute for OGD when indicated

Blood Tests

• FBC: Iron deficiency anaemia (chronic bleeding from oesophagitis/malignancy)
• H. pylori serology/stool antigen/urea breath test: If peptic ulcer disease suspected
• Generally not required for straightforward GORD

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7. Management

Management Algorithm

┌─────────────────────────────────────────┐
│     SYMPTOMATIC GORD SUSPECTED          │
└────────────────┬────────────────────────┘
                 │
         ┌───────▼──────────┐
         │  RED FLAGS?      │
         │  Age \u003e55?        │
         └─────┬──────┬─────┘
               │      │
         YES ┌─┘      └─┐ NO
             │          │
    ┌────────▼───┐   ┌─▼──────────────────────┐
    │ URGENT OGD │   │ LIFESTYLE MODIFICATION │
    └────────────┘   │ + PPI 4-8 WEEKS        │
                     │ (e.g., Omeprazole 20mg │
                     │ OD before breakfast)   │
                     └──────┬─────────────────┘
                            │
              ┌─────────────▼─────────────┐
              │    SYMPTOM RESPONSE?      │
              └─────┬────────────────┬────┘
                    │                │
          ┌─────────▼──┐          ┌──▼─────────────┐
          │  RESOLVED  │          │   PERSISTENT   │
          └─────┬──────┘          └────┬───────────┘
                │                      │
       ┌────────▼────────┐     ┌───────▼──────────┐
       │ STEP DOWN       │     │ CHECK ADHERENCE  │
       │ - PRN/On-Demand │     │ - Timing (30min  │
       │ - Low dose      │     │   before food)   │
       │ - H2RA at night │     │ - Triggers       │
       │ (for nocturnal) │     └────┬─────────────┘
       └─────────────────┘          │
                            ┌────────▼──────────┐
                            │ DOUBLE-DOSE PPI   │
                            │ (20mg BD)         │
                            │ x 4-8 weeks       │
                            └─────┬─────────────┘
                                  │
                     ┌────────────▼────────────┐
                     │   STILL REFRACTORY?     │
                     └─────┬─────────────┬─────┘
                           │             │
                     ┌─────▼───┐     ┌───▼────────────┐
                     │   OGD   │     │ ADD H2RA       │
                     │         │     │ (Famotidine    │
                     └─────┬───┘     │ 20mg at night) │
                           │         └────────────────┘
              ┌────────────▼────────────┐
              │ pH/IMPEDANCE MONITORING │
              │ (confirm reflux vs.     │
              │  functional)            │
              └─────────┬───────────────┘
                        │
         ┌──────────────▼──────────────┐
         │ CONSIDER SURGICAL REFERRAL  │
         │ - High-volume regurgitation │
         │ - Proven reflux, PPI failure│
         │ - Patient preference        │
         │ (PRE-OP: Manometry + pH)    │
         └─────────────────────────────┘

1. Lifestyle Modifications

Evidence-Based Lifestyle Interventions:

Weight Loss - MOST EFFECTIVE non-pharmacological intervention [14]

• Magnitude of effect: Each 5-unit BMI increase → 1.5x odds of GORD symptoms
• Weight loss of \u003e10% body weight significantly improves symptoms
• Benefits ALL GORD patients, especially those with BMI \u003e25
• Mechanisms: Reduced intra-abdominal pressure, reduced intragastric pressure, decreased TLOSRs, improved gastric emptying
• Recommendation: Target BMI \u003c25 kg/m²

Dietary Modifications

Smoking Cessation [16]

• Strong recommendation
• Improves LOS pressure, reduces acid secretion, improves salivary function
• Reduces progression to Barrett's dysplasia/cancer

Alcohol Reduction

• Moderate evidence for symptom improvement
• Particularly relevant for evening/night-time symptoms

Positional Therapy

Medication Review

• Stop/reduce aggravating medications where possible:
  • NSAIDs → COX-2 inhibitors or paracetamol
  • Calcium channel blockers → Alternative antihypertensive
  • Nitrates → Consider alternatives for angina
  • Bisphosphonates → Consider timing, liquid formulations, IV alternatives

Clothing

• Avoid tight-fitting garments around abdomen (increases intra-abdominal pressure)

2. Pharmacological Management

Proton Pump Inhibitors (PPIs) - First-Line Therapy

Mechanism of Action:

• Irreversible inhibition of H⁺/K⁺ ATPase (proton pump) on gastric parietal cells
• Prodrugs requiring acid activation in parietal cell canaliculus
• Covalent binding → pump permanently inactivated
• Requires new protein synthesis for recovery (~24-48h)

Available PPIs:

Dosing Principles:

• CRITICAL: Take 30-60 minutes BEFORE breakfast (or largest meal) [9]
  • "Rationale: PPIs require active proton pumps for binding; food stimulates pump activation"
  • "Common error: Taking at bedtime or with food → significantly reduced efficacy"
• For twice-daily dosing: Before breakfast and before evening meal
• Duration: Minimum 4-8 weeks for symptom control and healing

Efficacy:

• Symptom relief: 70-80% at 4-8 weeks
• Healing erosive oesophagitis: 80-90% at 8 weeks [24]
• NERD: Response rates lower (~50-60%) than erosive disease

Step-Down Therapy:

• After symptom control achieved, attempt:
  1. On-demand therapy: PPI only when symptomatic (effective in ~60% of mild GORD)
  2. Lowest effective dose: Halve dose or alternate-day dosing
  3. Switch to H2RA: Less effective but may suffice for mild disease

PPI-Refractory GORD (Failure to respond to standard-dose PPI):

Approach:

1. Confirm adherence and timing: Most common cause of failure
2. Optimize dosing:
   • Increase to twice-daily dosing (before breakfast and dinner)
   • Switch PPI (variable metabolism: some respond better to different agents)
3. Add bedtime H2RA (addresses nocturnal acid breakthrough)
4. Perform OGD (rule out alternative diagnosis, complications)
5. pH/impedance monitoring (on therapy):
   • Persistent acid reflux → Increase PPI dose, check compliance
   • Non-acid reflux → Consider surgery, alginates, prokinetics
   • No reflux → Functional heartburn (consider neuromodulators)

Long-Term PPI Safety - Controversial but generally reassuring for genuine GORD [25]

Established Small Risks:

Uncertain/Refuted Risks:

• Chronic kidney disease: Association in observational studies, causality unproven
• Dementia: Conflicting data, recent large studies show no association
• Gastric cancer: Possible increased risk in H. pylori-infected patients (eradicate H. pylori before long-term PPI)
• Small intestinal bacterial overgrowth (SIBO): Theoretical, limited evidence

Clinical Approach:

• PPIs are safe for long-term use when indicated (severe GORD, Barrett's, refractory symptoms)
• Use lowest effective dose
• Periodically reassess need (attempt step-down)
• Monitor magnesium in high-risk patients (diuretics, elderly)
• Benefits outweigh risks in moderate-severe GORD

Rebound Acid Hypersecretion:

• Occurs in ~40-60% on PPI withdrawal (especially high-dose, long-duration)
• Mechanism: Hypergastrinaemia during PPI therapy → parietal cell hyperplasia → increased acid secretion on stopping
• Lasts 2-8 weeks
• Managed by: Gradual tapering, temporary H2RA use

H2 Receptor Antagonists (H2RAs)

Mechanism: Competitive inhibition of histamine H₂ receptors on parietal cells → reduced acid secretion

Available Agents:

Efficacy:

• Inferior to PPIs for GORD symptom control and healing
• Tachyphylaxis: Tolerance develops within 2 weeks of continuous use (limits utility)
• Role in GORD:
  • "Nocturnal acid breakthrough on PPI: Add bedtime H2RA (famotidine 20-40mg)"
  • Step-down from PPI
  • Mild, intermittent symptoms

Nocturnal Acid Breakthrough:

• Defined as intragastric pH \u003c4 for \u003e1 hour during night despite twice-daily PPI
• Occurs in ~70% of patients on PPI
• Add bedtime H2RA (e.g., famotidine 20mg at night) → improved nocturnal pH control

Alginates (Gaviscon)

Mechanism:

• Form a viscous foam "raft" that floats on top of gastric contents
• Physically displaces the "acid pocket" away from gastro-oesophageal junction
• Provides physical barrier to reflux
• Contains antacids (calcium carbonate, sodium bicarbonate) for immediate symptom relief

Efficacy:

• Effective for postprandial symptoms and mild reflux
• Duration of action: ~3-4 hours
• Combination with PPI: Synergistic for refractory symptoms

Indications:

• Pregnancy (safe, first-line)
• Mild, intermittent symptoms
• Postprandial symptoms
• Adjunct to PPI therapy

Prokinetics

Aim to improve oesophageal clearance and gastric emptying; limited evidence in GORD, not routinely recommended. [26]

Not recommended routinely; reserve for proven gastroparesis component.

Antacids

• Immediate symptom relief (neutralize existing acid)
• No role in healing or long-term management
• Useful for breakthrough symptoms on PPI
• Examples: Calcium carbonate, magnesium hydroxide, aluminum hydroxide

3. Surgical Management

Indications for Anti-Reflux Surgery

1. High-volume regurgitation despite PPI (PPIs reduce acid but not volume)
2. Proven GORD (pH/impedance documented) with PPI intolerance/side effects
3. Patient preference: Young patients desiring to avoid lifelong medication
4. Large hiatus hernia with mechanical symptoms (dysphagia, volvulus)
5. Refractory symptoms despite maximal medical therapy (with objective reflux confirmation)

NOT indicated for:

• Extraoesophageal symptoms without proven reflux
• Functional heartburn (no objective reflux on testing)
• Poor surgical candidates

Pre-Operative Assessment (MANDATORY)

1. Upper GI Endoscopy: Document anatomy, rule out malignancy
2. High-Resolution Manometry: ESSENTIAL
   • Rule out achalasia (contraindication - fundoplication worsens achalasia)
   • Rule out severe dysmotility (aperistalsis, scleroderma-like) - relative contraindication
   • Assess peristaltic reserve
3. pH/Impedance Monitoring: Confirm pathological reflux (objective evidence mandatory before surgery)
4. Barium swallow: Assess anatomy (hiatus hernia size, oesophageal length)

Surgical Techniques

Laparoscopic Nissen Fundoplication - Most common procedure

Technique:

• 360° wrap of gastric fundus around lower oesophagus
• Reduces hiatus hernia
• Crural repair (tightens hiatus)
• Recreates intra-abdominal oesophageal segment
• Restores acute angle of His

Outcomes: [27]

• Symptom control: 85-90% at 5 years
• Heartburn resolution: ~90%
• PPI cessation: ~85%
• Long-term efficacy: Declines over 10-20 years (~50% back on PPIs at 10 years)

Complications:

Laparoscopic Partial Fundoplication - Alternative to Nissen

Toupet (270° posterior wrap) or Dor (180-200° anterior wrap)

• Less dysphagia and gas-bloat than Nissen
• Slightly higher reflux recurrence than Nissen
• Preferred in patients with weak peristalsis (manometry: failed peristalsis)

LINX Device - Magnetic sphincter augmentation

Technique:

• Ring of magnetic beads placed around gastro-oesophageal junction
• Augments LOS pressure
• Opens with swallowing (magnetic attraction overcome by bolus)
• Closes between swallows

Outcomes:

• Effective reflux control in ~70-80%
• Less dysphagia than fundoplication
• Concerns: Dysphagia (10-20%), device erosion (rare), MRI compatibility (conditional)

Contraindications:

• Need for future MRI (relative - MRI-conditional devices available)
• Suspected oesophageal dysmotility

LOTUS Trial (Landmark Evidence) [27]

Trial: Esomeprazole vs. Laparoscopic Antireflux Surgery for chronic GORD (5-year follow-up)

Results:

• Remission rates similar (medical 92% vs. surgical 85%)
• Surgery: Higher early adverse events, more dysphagia
• Medical: 15% required dose escalation
• Conclusion: Both treatments effective; surgery not superior to optimized medical therapy for symptom control alone

Interpretation: Surgery is a valid option for selected patients (especially young, high-volume regurgitation, proven reflux) but not superior to PPI therapy for typical reflux symptoms.

4. Endoscopic Therapies

Multiple endoscopic procedures developed to avoid surgery; limited long-term efficacy, not widely adopted:

• Stretta radiofrequency ablation: Radiofrequency to LOS → reduced compliance
• EndoCinch: Endoscopic suturing to create plication
• Transoral incisionless fundoplication (TIF): Endoscopic fundoplication

Evidence: Short-term improvement, but high recurrence rates; not recommended in guidelines.

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8. Complications

Oesophageal Complications

1. Erosive Oesophagitis

• Mucosal breaks, erosions, ulceration (Los Angeles Grade A-D)
• Symptoms: Odynophagia, dysphagia, bleeding (occult or overt)
• Complications: Stricture, bleeding, perforation (rare)
• Management: High-dose PPI, heal over 8-12 weeks

2. Peptic Stricture

• Chronic inflammation → fibrosis → luminal narrowing
• Prevalence: 10-15% of chronic GORD (reduced with PPI era)
• Symptoms: Progressive dysphagia (solids initially)
• Diagnosis: OGD (exclude malignant stricture - biopsies mandatory)
• Management:
  • "Endoscopic dilation: Balloon or bougie dilation (may require multiple sessions)"
  • "High-dose PPI: Prevent re-stenosis"
  • "Intralesional steroid injection: For refractory strictures"
  • "Surgery: Refractory cases (dilation + fundoplication)"

3. Barrett's Oesophagus - Pre-malignant condition [28]

Definition: Replacement of normal stratified squamous epithelium with columnar epithelium containing intestinal metaplasia (goblet cells) in the distal oesophagus.

Epidemiology:

• Prevalence: ~1-2% general population, ~10-15% of GORD patients undergoing OGD
• Male predominance: 3:1
• Caucasian predominance
• Risk factors: Chronic GORD (\u003e5 years), male, age \u003e50, obesity, smoking, family history

Diagnosis:

• Endoscopy: Salmon-pink columnar mucosa extending ≥1cm proximal to gastro-oesophageal junction
• Prague C\u0026M Classification: e.g., C2M4 = 2cm circumferential, 4cm maximal extent
• Histology: Intestinal metaplasia with goblet cells (Alcian blue staining)

Progression Risk:

• No dysplasia: ~0.3-0.5% per year progress to adenocarcinoma [28]
• Low-grade dysplasia (LGD): ~0.5-1% per year
• High-grade dysplasia (HGD): ~6-8% per year

Surveillance: BSG Guidelines (2023):

Management:

• No dysplasia: PPI therapy (reduce acid exposure), lifestyle modification, surveillance
• Low-grade dysplasia: Confirmed by 2 pathologists → Endoscopic ablation (radiofrequency ablation - RFA) vs. surveillance
• High-grade dysplasia or intramucosal carcinoma: Endoscopic therapy:
  • "Endoscopic mucosal resection (EMR): Visible lesions"
  • "Radiofrequency ablation (RFA): Flat dysplastic mucosa"
  • "Goal: Complete eradication of intestinal metaplasia"

4. Oesophageal Adenocarcinoma

• Arises from Barrett's metaplasia → dysplasia → adenocarcinoma sequence
• Increasing incidence in Western countries (6-fold increase since 1970s) [29]
• Poor prognosis (5-year survival ~15-20% overall; ~50% if early stage)
• Risk factors: Barrett's (especially long-segment), male, smoking, obesity
• Symptoms: Dysphagia, weight loss, odynophagia (ALARM symptoms)
• Management: Multidisciplinary (endoscopic resection for early disease, oesophagectomy, chemoradiotherapy)

Extraoesophageal Complications

1. Chronic Respiratory Disease

Asthma:

• Exacerbation of pre-existing asthma (especially nocturnal symptoms)
• Mechanisms: Microaspiration, vagal reflex bronchoconstriction
• However: PPI therapy does not improve asthma control in most RCTs (suggests association rather than causation)

Chronic Cough:

• Persistent, non-productive cough
• May be only symptom (no heartburn) in up to 75%
• Response to PPI variable and slow (may take 2-3 months)

Recurrent Pneumonia:

• Aspiration of refluxed gastric contents (particularly nocturnal)
• Recurrent right lower lobe infiltrates
• Elderly, supine reflux, neurological impairment

Idiopathic Pulmonary Fibrosis (IPF):

• High prevalence of GORD in IPF (\u003e70%)
• Unclear if GORD contributes to IPF pathogenesis or is consequence of respiratory mechanics
• Some evidence that anti-reflux therapy (medical or surgical) may slow IPF progression

2. ENT Complications (Laryngopharyngeal Reflux)

• Posterior laryngitis: Erythema, oedema of posterior larynx/arytenoids
• Vocal cord granulomas/polyps
• Contact ulcers: Posterior larynx
• Subglottic stenosis: Rare, severe
• Laryngeal carcinoma: Possible association (controversial)

3. Dental Erosion

• Erosion of palatal surfaces of teeth (vs. labial surfaces with dietary acids)
• Enamel demineralization
• Occurs with chronic regurgitation
• Preventive: Dental hygiene, fluoride, avoid brushing immediately after reflux

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9. Prognosis and Outcomes

Natural History

• Chronic, relapsing condition: 80-90% relapse within 6-12 months of stopping PPI therapy
• Quality of Life Impact: Significant impairment comparable to chronic diseases (hypertension, heart failure) [30]
• Complications: Develop in minority (~10-15% develop stricture, Barrett's, or severe erosive disease)

Factors Predicting Poor Outcome

• Large hiatus hernia
• Severe erosive oesophagitis (LA Grade C/D)
• Nocturnal reflux
• Obesity (BMI \u003e30)
• Delayed gastric emptying
• Hypotensive LOS

Quality-Adjusted Life Years (QALY) Data

Medical Therapy:

• PPI therapy: Highly cost-effective (QALY gained at low cost) [31]
• Improved quality of life comparable to surgical intervention at 5 years

Surgical Therapy:

• Initial high cost, but cost-effective over 10+ years (avoiding lifelong medication) in young patients [31]
• QALY gains similar to medical therapy at 5 years (LOTUS trial)

Barrett's Progression

• Progression to cancer: Overall ~0.3-0.5% per year (low absolute risk) [28]
• Long-segment Barrett's (\u003e3cm): Higher risk than short-segment
• Dysplasia: Major risk factor (HGD: 6-8% annual risk)
• Protective factors: PPI therapy may reduce progression risk (conflicting data), surveillance enables early detection

Mortality

• GORD itself is NOT life-threatening in the vast majority
• Mortality primarily from:
  • Oesophageal adenocarcinoma (in Barrett's progressors)
  • Aspiration pneumonia (elderly, neurologically impaired)
  • "Surgical complications (rare: \u003c0.5% perioperative mortality)"

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10. Evidence and Guidelines

Key Guidelines

Landmark Evidence

1. LOTUS Trial (2011) - Medical vs. Surgical Therapy [27]

• Trial: Esomeprazole 20-40mg vs. Laparoscopic Antireflux Surgery (Nissen fundoplication)
• N = 554 patients with chronic GORD
• Follow-up: 5 years
• Primary outcome: Time to treatment failure
• Results:
  • "Remission rates: Medical 92% vs. Surgical 85% (non-inferior)"
  • "Adverse events: Higher in surgical group (dysphagia, gas-bloat)"
  • "PPI use: 15% of medical group required dose escalation"
• Conclusion: Both treatments effective; surgery NOT superior to optimized PPI therapy for symptom control

2. Jacobson et al. (2018) - Weight Loss and GORD [14]

• Meta-analysis: Weight loss interventions and GORD symptoms
• Results: Significant dose-response relationship between weight loss and symptom improvement
• Conclusion: Weight loss should be first-line recommendation for overweight/obese GORD patients

3. Richter et al. (2001) - PPI for Asthma in GORD

• Trial: High-dose PPI vs. placebo in asthmatic patients with GORD
• Result: No improvement in asthma outcomes despite improved reflux control
• Conclusion: GORD treatment does NOT improve asthma (despite epidemiological association)

4. Spechler et al. (2001) - NERD Pathophysiology

• Demonstrated that NERD patients have genuine acid reflux (pH monitoring) despite normal endoscopy
• Identified dilated intercellular spaces as histological hallmark
• Established NERD as distinct entity requiring objective testing

5. Sharma et al. (2016) - Barrett's Progression Rates [28]

• Meta-analysis: Progression from non-dysplastic Barrett's to adenocarcinoma
• Result: 0.33% per year (lower than previous estimates)
• Conclusion: Justifies less intensive surveillance strategies

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11. Special Populations

Pregnancy

• Prevalence: 40-85% of pregnant women experience reflux
• Mechanisms:
  • Progesterone-mediated LOS relaxation
  • Mechanical compression from gravid uterus
  • Delayed gastric emptying
• Management:
  • "First-line: Lifestyle modification, alginates (safe)"
  • "Second-line: PPIs (omeprazole, lansoprazole generally safe - Category B/C)"
  • "Avoid: H2RAs less well-studied"
• Prognosis: Typically resolves postpartum

Elderly

• Increased prevalence (age-related LOS dysfunction)
• Higher complication risk (stricture, Barrett's, cancer)
• Drug interactions: Careful with PPI interactions (clopidogrel, warfarin)
• Fracture risk: Ensure adequate calcium/vitamin D
• Aspiration risk: Higher (impaired swallowing, recumbent position)

Scleroderma/Connective Tissue Disease

• Severe oesophageal dysmotility (smooth muscle atrophy, fibrosis)
• Aperistalsis: Ineffective oesophageal clearance
• Severe reflux: Hypotensive LOS + impaired clearance
• Management: High-dose PPI (often require BD dosing), prokinetics (limited benefit), NOT surgical candidates (fundoplication worsens dysphagia)

Non-Erosive Reflux Disease (NERD)

• 60-70% of GORD patients
• Normal endoscopy despite genuine reflux
• Diagnosis: Requires pH/impedance monitoring (demonstrate acid exposure)
• Pathophysiology: Oesophageal hypersensitivity, dilated intercellular spaces
• Management: Often PPI-resistant (30-40% non-responders); consider neuromodulators (TCA, SSRI)

Functional Heartburn

• Heartburn symptoms WITHOUT objective reflux on pH monitoring
• Part of functional oesophageal disorder spectrum
• Diagnosis of exclusion: Normal OGD, normal pH/impedance
• Management:
  • Reassurance
  • "Neuromodulators: Low-dose tricyclic antidepressants (amitriptyline 10-25mg), SSRI"
  • Psychological therapies (CBT, hypnotherapy)
  • NOT surgery (will not benefit)

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12. Patient and Layperson Explanation

What is GORD?

GORD (Gastro-Oesophageal Reflux Disease) - also called "acid reflux" or "heartburn"

• occurs when the muscular valve at the top of your stomach (the lower oesophageal sphincter) becomes weak or leaky. This allows harsh stomach acid to splash back up into your food pipe (oesophagus), causing a burning pain in your chest.

Think of the valve like a one-way door that should only open when you swallow food. In GORD, this door doesn't close properly, so acid "refluxes" (flows backward) into the wrong place.

What causes it?

Several factors can weaken the valve or increase reflux:

• Being overweight: Extra weight around your tummy pushes on your stomach, forcing acid upward
• Certain foods: Fatty meals, chocolate, coffee, alcohol, and spicy foods can relax the valve
• Smoking: Weakens the valve and increases acid production
• Hiatus hernia: Part of your stomach pushes up through your diaphragm (the breathing muscle), disrupting the valve
• Pregnancy: Hormones relax the valve, and the baby pushes on your stomach
• Some medications: Including certain blood pressure tablets, painkillers, and treatments for angina

What are the symptoms?

The classic symptoms are:

• Heartburn: A burning sensation in your chest, especially after eating or when lying down
• Acid regurgitation: Sour or bitter-tasting fluid coming up into your throat or mouth
• Difficulty swallowing (this needs urgent investigation)
• Chest pain (always get chest pain checked to rule out heart problems first!)

Some people have "silent reflux" with:

• Chronic cough
• Hoarse voice
• Feeling of a lump in the throat

Is it dangerous?

For most people, GORD is painful but not dangerous. However, if acid keeps burning your food pipe for many years, it can cause:

• Scarring (stricture): Makes swallowing difficult
• Barrett's oesophagus: Cells in your food pipe change (a small risk of developing cancer, so requires monitoring)
• Oesophageal cancer: Rare, but the most serious complication

See your doctor urgently if you have:

• Difficulty swallowing
• Unexplained weight loss
• Vomiting blood
• Black, tarry stools

How is it treated?

1. Lifestyle Changes (often the most effective!):

• Lose weight if overweight (the single best thing you can do)
• Avoid trigger foods: Coffee, alcohol, chocolate, fatty/spicy foods
• Don't eat late: No food within 3 hours of bedtime
• Raise the head of your bed: Use blocks under the bed legs (not just extra pillows)
• Stop smoking
• Eat smaller meals

2. Medications:

• Antacids (Gaviscon, Rennie): Quick relief for mild symptoms
• Proton Pump Inhibitors (PPIs): Tablets like omeprazole or lansoprazole that "turn off" acid production
  • Take 30-60 minutes before breakfast (not at bedtime!) for best effect
  • Very effective for most people
  • Safe for long-term use when needed

3. Surgery (for severe cases):

• An operation (usually keyhole surgery) to tighten the valve
• Called "fundoplication"
• wraps part of your stomach around your food pipe
• Effective, but has side effects (difficulty burping, bloating)

Are PPIs safe long-term?

Yes, for most people. PPIs are very safe when used appropriately. There are some small risks with long-term use:

• Slightly increased risk of gut infections
• Possible reduced absorption of magnesium, calcium, and vitamin B12
• Your doctor will monitor you if you need long-term treatment

The benefits far outweigh the risks if you have troublesome reflux.

When will I get better?

• Mild GORD: Often improves with lifestyle changes alone
• Moderate GORD: Usually well-controlled with PPIs; you may need to take them long-term
• GORD is chronic: Symptoms often come back if you stop treatment, but this is manageable

What should I do now?

1. Try lifestyle changes (especially weight loss if overweight)
2. See your GP if symptoms persist - they can prescribe PPIs
3. Seek urgent help if you have difficulty swallowing, weight loss, or vomiting blood

Most people with GORD can be effectively managed and live normal, comfortable lives with the right treatment.

---

13. Examination Focus

Common Viva Questions and Model Answers

Q1: "A 45-year-old man presents with heartburn. When would you refer for endoscopy?"

Model Answer: "I would refer for urgent OGD (2-week-wait) if he has any red flag symptoms:

• Dysphagia
• Unexplained weight loss
• Persistent vomiting
• Evidence of GI bleeding (haematemesis, melaena)
• Epigastric mass
• Iron deficiency anaemia

Additionally, NICE guidelines recommend urgent OGD for patients over 55 years presenting with new-onset dyspepsia, as this carries increased risk of gastric malignancy.

For routine OGD, I would refer if:

• Symptoms are refractory to PPI therapy
• He requires long-term, high-dose PPI and has risk factors for Barrett's (male, \u003e50, chronic symptoms \u003e5 years)
• For Barrett's surveillance (if previously diagnosed)

If he is under 55 with typical symptoms and no red flags, I would manage empirically with lifestyle modification and a trial of PPI without endoscopy."

---

Q2: "What is the mechanism of action of PPIs, and why is timing of administration important?"

Model Answer: "PPIs are irreversible inhibitors of the H⁺/K⁺ ATPase proton pump on gastric parietal cells. They are prodrugs that require acid activation in the parietal cell secretory canaliculus, where they are converted to the active sulphenamide form. This active form then forms a covalent disulfide bond with the proton pump, permanently inactivating it. Recovery of acid secretion requires synthesis of new pumps, taking 24-48 hours.

Timing is critical because PPIs only bind to actively secreting pumps. Food stimulates gastric acid secretion and activates the proton pumps. Therefore, PPIs should be taken 30-60 minutes before meals (typically before breakfast), allowing the drug to be absorbed and present in parietal cells when pumps are activated by food. Taking PPIs at bedtime or on an empty stomach significantly reduces efficacy because fewer pumps are active.

For twice-daily dosing (in refractory GORD), the second dose should be taken before the evening meal, not at bedtime."

---

Q3: "Describe the pathophysiology of hiatus hernia and its role in GORD."

Model Answer: "A Type I (sliding) hiatus hernia occurs when the gastro-oesophageal junction and proximal stomach herniate superiorly through the oesophageal hiatus into the posterior mediastinum. This is present in 50-94% of GORD patients.

The hernia contributes to GORD through multiple mechanisms:

1. Loss of crural diaphragm compression: The LOS moves from the positive-pressure abdominal cavity into the negative-pressure thorax, losing the extrinsic 'pinchcock' effect of the right crus of the diaphragm.

2. Shortened intra-abdominal LOS: Reduces the pressure gradient across the sphincter.

3. Acid pocket formation: A layer of unbuffered gastric acid collects above the hernia sac at the gastro-oesophageal junction, representing the 'first in line' to reflux.

4. Impaired oesophageal clearance: The hernia disrupts normal oesophageal shortening and peristaltic efficiency.

5. Increased TLOSRs: Distension of the hernia sac triggers vagal reflexes promoting transient LOS relaxations.

6. Reduced basal LOS pressure: Mechanical stretching of the sphincter.

Large hiatus hernias may cause mechanical symptoms (dysphagia, volvulus) independent of reflux and may be an indication for surgical repair."

---

Q4: "A patient with GORD fails to respond to standard-dose PPI. What is your approach?"

Model Answer: "I would approach this systematically:

Step 1: Confirm Adherence and Optimize Dosing

• Check the patient is taking PPI 30-60 minutes before breakfast (most common cause of 'failure')
• Ensure adequate duration (minimum 4-8 weeks)
• Increase to twice-daily dosing (before breakfast and evening meal)
• Consider switching to a different PPI (variable metabolism)

Step 2: Review Lifestyle and Exacerbating Factors

• Weight loss if BMI \u003e25
• Review medications (NSAIDs, calcium channel blockers, nitrates, bisphosphonates)
• Reinforce dietary triggers, smoking cessation, head-of-bed elevation

Step 3: Investigate

• Upper GI endoscopy: Rule out alternative diagnoses (eosinophilic oesophagitis, stricture, malignancy), complications, or severe erosive disease
• If OGD normal and symptoms persist: pH-impedance monitoring (on PPI):
  • "Persistent acid reflux: Inadequate acid suppression → increase PPI dose, check compliance"
  • "Non-acid reflux: Volume/bile/weakly acidic reflux → consider surgery, alginates"
  • "No reflux: Functional heartburn → consider neuromodulators (TCA/SSRI)"

Step 4: Additional Medical Therapy

• Add bedtime H2RA (famotidine 20-40mg) for nocturnal acid breakthrough
• Alginates (Gaviscon) for postprandial symptoms

Step 5: Surgical Referral

• If proven refractory reflux (on pH testing) despite maximal medical therapy
• High-volume regurgitation
• Patient preference
• Pre-operative: Manometry (rule out achalasia/severe dysmotility) + pH monitoring (confirm pathological reflux)"

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Q5: "What is Barrett's oesophagus and how do you manage it?"

Model Answer: "Barrett's oesophagus is replacement of the normal stratified squamous epithelium of the distal oesophagus with columnar epithelium containing intestinal metaplasia (goblet cells). It is a pre-malignant condition representing the principal risk factor for oesophageal adenocarcinoma.

Epidemiology:

• Prevalence ~10-15% of GORD patients undergoing OGD
• 3:1 male predominance
• Risk factors: Chronic GORD \u003e5 years, male, age \u003e50, Caucasian, obesity, smoking, family history

Diagnosis:

• Endoscopy: Salmon-pink columnar mucosa extending ≥1cm above the gastro-oesophageal junction (Prague C\u0026M classification)
• Histology: Intestinal metaplasia with goblet cells (mandatory for diagnosis)

Progression Risk:

• No dysplasia: ~0.3-0.5% per year progression to adenocarcinoma
• Low-grade dysplasia: ~0.5-1% per year
• High-grade dysplasia: ~6-8% per year

Management:

Non-Dysplastic Barrett's:

• PPI therapy (standard or high-dose)
• Lifestyle modification (weight loss, smoking cessation)
• Surveillance endoscopy with systematic biopsies (Seattle protocol):
  • "Short-segment (\u003c3cm): Every 3-5 years"
  • "Long-segment (≥3cm): Every 2-3 years"

Low-Grade Dysplasia (LGD):

• Confirm with second expert pathologist
• Options:
  • "Endoscopic ablation (radiofrequency ablation - RFA): Increasingly preferred"
  • "Intensive surveillance: Every 6 months"

High-Grade Dysplasia or Intramucosal Carcinoma:

• Endoscopic therapy (NOT surveillance):
  • "Endoscopic mucosal resection (EMR): Visible lesions"
  • "Radiofrequency ablation (RFA): Flat dysplastic mucosa"
  • "Goal: Complete eradication of intestinal metaplasia"
• PPI therapy during and after ablation

Invasive Adenocarcinoma:

• Multidisciplinary team (MDT) discussion
• Staging (CT, PET, EUS)
• Treatment: Oesophagectomy ± neoadjuvant chemotherapy/chemoradiotherapy"

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Q6: "What are the indications and contraindications for anti-reflux surgery?"

Model Answer: "Indications:

1. High-volume regurgitation refractory to PPI (PPIs reduce acid but not volume)
2. Proven GORD with PPI intolerance or side effects
3. Patient preference: Young patients wishing to avoid lifelong medication
4. Large hiatus hernia with mechanical symptoms (volvulus, dysphagia)
5. Refractory symptoms despite maximal medical therapy with objective confirmation of reflux on pH/impedance monitoring

Contraindications:

Absolute:

• Achalasia (fundoplication worsens achalasia - manometry mandatory pre-op)
• Inability to tolerate general anaesthesia
• Functional heartburn (no objective reflux on pH testing - surgery will not help)

Relative:

• Severe oesophageal dysmotility (aperistalsis, scleroderma-like) - high risk of post-operative dysphagia
• Short life expectancy
• Morbid obesity (consider weight loss first)
• Previous extensive upper abdominal surgery (technically challenging)

Pre-Operative Assessment (MANDATORY):

1. Upper GI endoscopy: Assess anatomy, rule out malignancy
2. High-resolution manometry: ESSENTIAL - rule out achalasia and assess peristaltic function
3. pH/impedance monitoring: Confirm pathological reflux (objective evidence required)
4. Barium swallow: Assess hiatus hernia size, oesophageal length

The most common operation is laparoscopic Nissen fundoplication (360° wrap). Outcomes show 85-90% symptom control at 5 years, but efficacy declines over time with ~50% back on PPIs at 10 years. Complications include dysphagia (10-20%), gas-bloat syndrome (10-40%), and wrap disruption (5-15%)."

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Q7: "Explain the 'H. pylori paradox' in GORD."

Model Answer: "The H. pylori paradox refers to the observation that Helicobacter pylori infection, which is the principal cause of peptic ulcer disease and gastric cancer, paradoxically protects against GORD.

Mechanism:

• H. pylori colonization, particularly when involving the gastric corpus, causes chronic atrophic gastritis
• Atrophy of acid-secreting parietal cells → reduced gastric acid output
• Lower acid production → less acidic refluxate → reduced oesophageal injury

Clinical Implications:

1. Inverse relationship: Populations with high H. pylori prevalence have lower GORD rates
2. Post-eradication reflux: Eradicating H. pylori can unmask or worsen pre-existing GORD in susceptible individuals by restoring normal (higher) acid secretion
3. Therapeutic dilemma:
   • Eradicate H. pylori: Cure peptic ulcer disease, reduce gastric cancer risk
   • Consequence: May worsen reflux symptoms

Evidence:

• Meta-analyses show small but significant increase in GORD symptoms post-H. pylori eradication
• Effect most pronounced in patients with pre-existing reflux tendency

Clinical Practice:

• Still eradicate H. pylori when indicated (peptic ulcer disease, dyspepsia, gastric cancer prevention)
• Warn patients of potential reflux symptoms
• Prescribe PPI if reflux symptoms emerge post-eradication
• Benefits of eradication (ulcer healing, cancer prevention) outweigh reflux risk"

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High-Yield Examination Facts

Definitions:

• GORD: Troublesome symptoms and/or complications resulting from reflux of gastric contents
• NERD: Non-Erosive Reflux Disease - typical reflux symptoms with normal endoscopy (60-70% of GORD)
• Barrett's Oesophagus: Intestinal metaplasia of distal oesophageal epithelium (pre-malignant)

Pathophysiology:

• TLOSRs (Transient LOS Relaxations): Account for \u003e70% of reflux episodes
• Hypotensive LOS: \u003c10 mmHg pressure
• Acid pocket: Unbuffered acid layer at GOJ - first to reflux

Red Flags 🚩: Dysphagia, Weight loss, Haematemesis, Age \u003e55 + new dyspepsia

Los Angeles Classification: Grade A-D (based on mucosal break size and extent)

Lyon Consensus: AET \u003e6% = proven GORD; AET 4-6% = borderline; AET \u003c4% = normal

PPI Mechanism: Irreversible H⁺/K⁺ ATPase inhibition; take 30-60 min before food

Barrett's Progression: 0.3-0.5% per year (no dysplasia) → adenocarcinoma

Surgery: Nissen fundoplication - 360° wrap; Pre-op manometry mandatory (rule out achalasia)

Complications: Gas-bloat (10-40%), dysphagia (10-20%), wrap disruption (5-15%)

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14. References

Primary Sources

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31. Arguedas MR, Heudebert GR, Klapow JC, et al. Re-examination of the cost-effectiveness of surgical versus medical therapy in patients with gastroesophageal reflux disease: the value of long-term data collection. Am J Gastroenterol. 2004;99(6):1023-1028. [PMID: 15180720]

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference only. All clinical decisions should be individualized to patient circumstances and made in consultation with appropriate specialists. Always refer to the most current clinical guidelines and seek senior advice for complex cases.

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Document Metadata:

• Content Type: Topic Summary (Condition)
• Target Examination: MRCP, FRACP, Postgraduate Gastroenterology
• Difficulty Level: Moderate-High
• Last Updated: 2026-01-06
• Author: MedVellum Evidence-Based Content Team
• Evidence Base: 18 PubMed-indexed citations
• Word Count: ~11,500 words
• Line Count: 1,067 lines