Gastro-Oesophageal Reflux Disease

1. Clinical Overview

Summary

Gastro-oesophageal reflux disease (GORD) is defined as a condition that develops when reflux of gastric contents causes troublesome symptoms and/or complications. [1] It represents one of the most common gastrointestinal disorders encountered in both primary and secondary care settings, with a significant impact on quality of life and healthcare costs. The hallmark symptoms are heartburn (pyrosis) and acid regurgitation, though a substantial minority present with atypical or extra-oesophageal manifestations. [2]

The pathophysiology centres on dysfunction of the anti-reflux barrier, predominantly through transient lower oesophageal sphincter relaxations (TLOSRs), allowing retrograde flow of gastric acid, pepsin, and bile into the oesophagus. [3] While the oesophageal mucosa has protective mechanisms, prolonged or repeated acid exposure leads to epithelial damage, inflammation, and in some cases, metaplastic change.

Diagnosis in uncomplicated cases is primarily clinical, with empirical proton pump inhibitor (PPI) therapy serving both diagnostic and therapeutic purposes. The presence of alarm features—particularly dysphagia, weight loss, or gastrointestinal bleeding—mandates urgent upper gastrointestinal endoscopy to exclude malignancy. [4] Management follows a stepwise approach incorporating lifestyle modifications, acid suppression therapy, and in selected cases, surgical intervention.

Complications include erosive oesophagitis, peptic stricture, Barrett's oesophagus (intestinal metaplasia), and oesophageal adenocarcinoma. The advent of effective acid suppression with PPIs has dramatically reduced the incidence of severe complications, though long-term medication use raises questions about safety that require balanced clinical judgment. [5]

Key Facts

• Definition: Reflux of gastric contents causing troublesome symptoms (affecting quality of life) and/or complications (oesophagitis, stricture, Barrett's, adenocarcinoma) [1]
• Global Prevalence: 13% (range 2.5-51% depending on region and diagnostic criteria); highest in Western countries, lowest in Asia [6]
• Weekly Symptoms: Approximately 20% of adults in Western populations [6]
• Demographics: Increases with age; male predominance for complications (Barrett's, adenocarcinoma); obesity is strongest modifiable risk factor [7]
• Pathognomonic Features: Typical GORD defined as heartburn and/or regurgitation; positive response to PPI supports diagnosis [8]
• Gold Standard Investigation: Clinical diagnosis for typical symptoms; upper GI endoscopy (OGD) if alarm features or diagnostic uncertainty [4]
• First-line Treatment: Lifestyle modification plus standard-dose PPI for 4-8 weeks [1,4]
• Prognosis: Chronic relapsing condition; 70-80% relapse within 6-12 months of stopping PPI; excellent symptom control with maintenance therapy; cancer risk low except in Barrett's oesophagus [9]

Clinical Pearls

PPI Pharmacology Pearl: PPIs require acid activation and work on actively secreting proton pumps. Maximal efficacy achieved when taken 30-60 minutes BEFORE meals (particularly breakfast), NOT after. This timing allows drug absorption and concentration at parietal cells when acid secretion is stimulated by food. [10]

Barrett's Screening Pearl: Consider screening endoscopy in patients with multiple risk factors: male sex, age greater than 50, white ethnicity, chronic GORD symptoms greater than 5 years, hiatus hernia, obesity (BMI greater than 30), family history of Barrett's or oesophageal adenocarcinoma. [11] Annual cancer risk in non-dysplastic Barrett's is 0.2-0.5%. [12]

Extra-Oesophageal Pearl: Atypical presentations include chronic cough (most common), laryngitis, asthma exacerbations, and dental erosions. These require higher level of diagnostic certainty (often pH-impedance monitoring) as PPI response is less predictable than in typical GORD. [13]

Refractory GORD Pearl: True PPI-refractory GORD is uncommon (less than 10%). Before escalating therapy, verify: (1) compliance, (2) correct timing (before meals), (3) adequate dose (standard once daily), (4) adequate duration (4-8 weeks). Then consider functional heartburn, eosinophilic oesophagitis, or non-acid reflux. [14]

De-escalation Pearl: After initial 4-8 week course achieving symptom control, attempt step-down to lowest effective dose or on-demand therapy. Approximately 30% can stop PPI; 70% require maintenance. [15] This reduces unnecessary long-term exposure and cost.

Surgical Candidate Pearl: Fundoplication is most successful in young patients (less than 50 years) with objective evidence of reflux (abnormal pH study), good symptom response to PPI, normal oesophageal motility on manometry, and desire to discontinue medication. [16]

Why This Matters Clinically

GORD is the most common upper gastrointestinal diagnosis in the Western world, accounting for 4-5 million GP consultations annually in the UK alone. While the majority of cases are benign and highly responsive to acid suppression, the condition carries significant implications:

Quality of Life Impact: Untreated GORD substantially impairs quality of life scores comparable to chronic conditions such as diabetes or heart failure. [17] The recurrent nature of symptoms affects sleep, work productivity, and dietary enjoyment.

Cancer Risk Stratification: GORD is the strongest risk factor for oesophageal adenocarcinoma, one of the fastest-rising malignancies in Western populations. [18] Identifying patients at higher risk (those with Barrett's oesophagus) allows surveillance and early intervention. The incidence of oesophageal adenocarcinoma has increased 6-fold over the past 30 years.

Healthcare Economics: PPIs are among the most widely prescribed medications globally. In 2020, over 15 million PPI prescriptions were issued in England. [19] Rational prescribing—using PPIs when indicated, at the lowest effective dose, with periodic review—is essential for cost-effective care.

Alarm Symptom Recognition: Distinguishing uncomplicated GORD from upper GI malignancy is a critical clinical skill. Dysphagia, weight loss, and anaemia mandate urgent investigation; delayed diagnosis of oesophageal or gastric cancer significantly worsens prognosis.

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2. Epidemiology

Global Prevalence and Distribution

GORD exhibits marked geographical variation, reflecting differences in genetics, diet, lifestyle, and diagnostic criteria. [6]

Temporal Trends:

• GORD prevalence has increased 2-3 fold over the past 30 years in Western countries [7]
• Parallels rise in obesity and metabolic syndrome
• Oesophageal adenocarcinoma incidence (GORD complication) increased 6-fold since 1970s [18]

Symptom Frequency

Demographics

Age:

• Prevalence increases steadily with age [7]
• Peak incidence in 60-70 year age group
• Complications (Barrett's, adenocarcinoma) predominantly affect older adults (greater than 50 years)

Sex:

• Symptoms: Similar prevalence in men and women [7]
• Erosive oesophagitis: Male predominance (2:1) [7]
• Barrett's oesophagus: Male predominance (3:1) [11]
• Oesophageal adenocarcinoma: Male predominance (7:1) [18]

Ethnicity:

• White populations have higher rates than Asian populations [6]
• Barrett's oesophagus and adenocarcinoma disproportionately affect white individuals [11,18]

Risk Factors

Modifiable Risk Factors

Most Important Modifiable Factor: Weight loss in obese patients reduces GORD symptoms by 40-50% and is the strongest evidence-based lifestyle intervention. [25]

Non-Modifiable Risk Factors

Medical Conditions Associated with GORD

Medications Associated with GORD

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3. Pathophysiology

Normal Anti-Reflux Barrier

The anti-reflux barrier is a multi-component system preventing retrograde flow of gastric contents:

1. Lower Oesophageal Sphincter (LOS)

• Anatomical: 3-4 cm high-pressure zone at gastro-oesophageal junction [3]
• Physiological: Tonic contraction maintained by intrinsic smooth muscle tone
• Normal resting pressure: 10-30 mmHg [3]
• Reinforced by vagal excitatory input and hormones (gastrin increases; cholecystokinin, secretin, glucagon decrease)

2. Crural Diaphragm

• Right diaphragmatic crus forms a sling around oesophageal hiatus [26]
• Extrinsic compression during inspiration and increased intra-abdominal pressure
• Hiatus hernia disrupts this mechanism

3. Angle of His

• Acute angle (less than 90°) of gastro-oesophageal junction entry creates a flap-valve effect [3]
• Lost when hiatus hernia develops (obtuse angle)

4. Oesophageal Clearance Mechanisms

• Primary peristalsis: Clears refluxate in 6-8 seconds [3]
• Secondary peristalsis: Triggered by oesophageal distension
• Saliva: 1-1.5 litres daily; bicarbonate buffering (neutralises acid) [3]

5. Oesophageal Mucosal Resistance

• Pre-epithelial: Mucus and bicarbonate layer
• Epithelial: Tight junctions between squamous cells; rapid cell turnover
• Post-epithelial: Submucosal blood flow removes hydrogen ions

Pathophysiological Mechanisms in GORD

Primary Mechanism: Transient LOS Relaxations (TLOSRs)

TLOSRs account for 70-80% of reflux episodes in GORD patients. [3]

Characteristics:

• Spontaneous LOS relaxation (pressure less than 2 mmHg) lasting 10-60 seconds [3]
• NOT triggered by swallowing (unlike normal LOS relaxation with deglutition)
• Mediated by vagal pathway involving mechanoreceptors in gastric fundus
• Triggered by gastric distension, high-fat meals, chocolate, peppermint [3]
• More frequent in GORD patients; occur both post-prandially and during sleep

Neuromuscular Mechanism:

• Afferent: Gastric distension → vagal mechanoreceptors
• Central: Brainstem nucleus tractus solitarius
• Efferent: Vagal efferents → enteric nervous system → nitric oxide (NO) and vasoactive intestinal peptide (VIP) release [3]
• Result: LOS smooth muscle relaxation

Secondary Mechanisms

1. Reduced Basal LOS Pressure

• 20-40% of GORD patients have hypotensive LOS (less than 10 mmHg) [3]
• Associated with severe GORD and hiatus hernia
• Multifactorial: Structural LOS abnormalities, chronic inflammation, medications

2. Hiatus Hernia [26]

• Type I (Sliding): Gastro-oesophageal junction migrates above diaphragm (95% of hernias)
  • Disrupts diaphragmatic sphincter
  • Loses angle of His
  • Acid pooling in hernial sac
  • Present in 90% of erosive oesophagitis cases [26]
• Type II-IV (Paraesophageal): Less common; mechanical complications rather than GORD

3. Impaired Oesophageal Clearance

• Reduced saliva production (xerostomia, Sjögren's syndrome) [3]
• Impaired peristalsis (scleroderma, achalasia) [29]
• Supine position (gravity effect lost; nocturnal reflux particularly damaging) [21]

4. Delayed Gastric Emptying

• Gastroparesis (diabetes, post-surgical) [30]
• Gastric outlet obstruction
• Increases gastric distension and TLOSR frequency

5. Increased Intra-Abdominal Pressure

• Obesity (strongest association) [22]
• Pregnancy [28]
• Ascites
• Chronic cough (creates vicious cycle)

Refluxate Composition and Mucosal Injury

Refluxate Components:

• Hydrochloric acid (pH 1-2): Primary damaging agent
• Pepsin: Proteolytic enzyme; active at pH less than 4; damages epithelium [33]
• Bile acids: Reflux from duodenum; particularly damaging at pH 4-7 (non-acid reflux) [33]
• Pancreatic enzymes (trypsin): Contribute to mucosal injury in alkaline reflux

Mechanisms of Mucosal Damage:

Step 1: Epithelial Barrier Disruption

• Hydrogen ion penetration through intercellular spaces (dilated by acid) [33]
• Damage to tight junctions between squamous epithelial cells
• pH in epithelium drops; cellular acidification

Step 2: Cellular Injury

• Mitochondrial dysfunction; ATP depletion [33]
• Reactive oxygen species (ROS) generation
• Necrosis and apoptosis of epithelial cells

Step 3: Inflammation

• Eosinophil, neutrophil, and T-lymphocyte infiltration [33]
• Inflammatory cytokine release (IL-1β, IL-6, IL-8, TNF-α)
• Histological oesophagitis

Step 4: Basal Cell Hyperplasia and Papillary Elongation

• Compensatory proliferation attempting repair [33]
• Histological features diagnostic of reflux oesophagitis

Step 5 (Chronic): Complications

• Ulceration (erosive oesophagitis)
• Fibrosis and stricture formation
• Barrett's metaplasia (columnar epithelium replaces squamous)
• Dysplasia and adenocarcinoma (in Barrett's)

Molecular Pathophysiology of Barrett's Oesophagus

Barrett's oesophagus represents a metaplastic adaptation to chronic acid and bile exposure. [11]

Metaplastic Sequence:

1. Chronic inflammation and epithelial injury
2. Squamous epithelial cell death
3. Activation of stem/progenitor cells (possibly from oesophageal submucosal glands or gastric cardia)
4. Columnar metaplasia with intestinal phenotype (goblet cells)
5. Molecular alterations: CDX2 expression (intestinal transcription factor), loss of p16 tumour suppressor [11]

Progression to Adenocarcinoma:

• Metaplasia → Low-grade dysplasia → High-grade dysplasia → Adenocarcinoma [11,12]
• Molecular pathway involves: p53 mutation, p16 loss, chromosomal instability, ERBB2 amplification
• Annual risk: Non-dysplastic Barrett's 0.2-0.5%; Low-grade dysplasia 0.7%; High-grade dysplasia 7% [12]

Non-Erosive Reflux Disease (NERD)

60-70% of GORD patients have no endoscopic oesophagitis. [34]

Mechanisms in NERD:

• Microscopic inflammation (not visible endoscopically) [34]
• Oesophageal hypersensitivity: Upregulation of TRPV1 receptors (capsaicin receptor) on sensory nerves [34]
• Central sensitisation: Altered pain processing
• Lower acid burden than erosive disease, yet similar symptoms due to heightened sensitivity

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4. Clinical Presentation

Typical Symptoms

The Montreal Definition classifies GORD symptoms as "oesophageal syndromes" (typical) and "extra-oesophageal syndromes" (atypical). [1]

Heartburn (Pyrosis)

Definition: Burning retrosternal discomfort rising from the epigastrium towards the neck [1]

Characteristics:

• Most common GORD symptom (75-90% of patients) [2]
• Postprandial timing (especially after large, fatty, or late meals) [24]
• Worse on lying flat or bending over (loss of gravity) [21]
• Relieved by standing upright or antacids
• May radiate to throat, jaw, or between shoulder blades

Differential Diagnosis of Heartburn:

• Cardiac: Angina, myocardial infarction (CRITICAL to exclude in high-risk patients)
• Oesophageal: Oesophageal spasm, achalasia, eosinophilic oesophagitis
• Gastric/duodenal: Peptic ulcer disease, gastritis
• Functional: Functional heartburn (normal endoscopy and pH study)

Key Distinguishing Features:

• GORD heartburn: Postprandial, worse lying down, relief with antacids, no radiation to arms
• Cardiac pain: Exertional, crushing, radiation to left arm/jaw, diaphoresis, dyspnoea (though overlap exists)

Regurgitation

Definition: Effortless return of gastric contents to the pharynx or mouth [1]

Characteristics:

• Second most common GORD symptom (60% of patients) [2]
• Bitter or sour taste ("acid brash")
• Occurs particularly when bending, lifting, or lying down
• NO nausea or retching (differentiates from vomiting)
• May be associated with "water brash" (sudden salivation as protective response)

Clinical Significance:

• Strong predictor of GORD (specificity 95%) [2]
• Aspiration risk: Nocturnal regurgitation can cause cough, choking, laryngospasm
• Poor quality of life impact (embarrassment, dietary restriction)

Dyspepsia

Definition: Epigastric pain, fullness, early satiety, bloating [1]

In GORD:

• Overlaps significantly (30-40% of GORD patients have dyspepsia) [35]
• May reflect gastric or duodenal pathology (peptic ulcer, H. pylori gastritis)
• Functional dyspepsia and GORD are frequently comorbid

Atypical / Extra-Oesophageal Symptoms

Up to 30% of GORD patients present primarily with atypical symptoms. [13] These manifestations are less specific, making diagnosis challenging.

Important Caveats on Atypical GORD:

1. Lower PPI response rate (50-60%) compared to typical GORD (80-90%) [13]
2. Higher diagnostic threshold required: pH-impedance monitoring often needed for confirmation
3. Exclude other causes first: ENT pathology, pulmonary disease, cardiac disease
4. Longer PPI trial duration: 8-12 weeks (vs 4-8 weeks for typical symptoms) [13]

Nocturnal GORD

25% of GORD patients experience predominantly nocturnal symptoms. [21]

Characteristics:

• Awakening with heartburn, regurgitation, cough, choking
• Aspiration risk (recurrent pneumonia, chronic bronchitis)
• Worse supine position (gravity effect lost; saliva production ceases during sleep)
• Sleep disturbance (poor quality of life; daytime fatigue)

Clinical Significance:

• Longer oesophageal acid contact time during sleep (impaired clearance) [21]
• Higher risk of erosive oesophagitis and Barrett's [21]
• Management: Elevate head of bed; avoid late meals; consider twice-daily PPI

Alarm Features (Red Flags)

[!CAUTION] ALARM SYMPTOMS REQUIRING URGENT INVESTIGATION (2-WEEK WAIT OGD)

• Dysphagia (progressive difficulty swallowing solids then liquids) — suggests stricture or malignancy [4]
• Odynophagia (painful swallowing) — suggests severe oesophagitis, infection, or malignancy [4]
• Unintentional weight loss (greater than 5% body weight) — raises concern for malignancy [4]
• Gastrointestinal bleeding (haematemesis, melaena, or occult bleeding) — suggests ulceration, erosive disease, or malignancy [4]
• Persistent vomiting — risk of dehydration, malnutrition; may indicate obstruction [4]
• Iron deficiency anaemia (unexplained) — suggests chronic blood loss; exclude upper and lower GI malignancy [4]
• Age greater than 55 years with NEW-onset dyspepsia — increased malignancy risk in this age group [4]
• Epigastric mass — suggests advanced gastric cancer [4]
• Previous gastric surgery or family history of upper GI cancer — increased cancer risk [4]

Clinical Action:

• Urgent OGD referral (2-week wait pathway in UK) [4]
• Do NOT trial PPI empirically when alarm features present (may mask malignancy temporarily)
• Investigate promptly to avoid delayed cancer diagnosis

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5. Clinical Examination

General Inspection

Usually Normal: The majority of uncomplicated GORD patients have entirely normal physical examination.

Assess for:

• General health and nutritional status (cachexia suggests malignancy or severe disease)
• Body habitus: BMI (obesity is strongest modifiable risk factor) [22]
• Dental examination: Erosions of posterior molars (chronic acid exposure) [36]
• Anaemia: Conjunctival pallor (suggests chronic blood loss)

Abdominal Examination

Usual Findings:

• Soft, non-tender abdomen
• No organomegaly or masses

May Find:

• Epigastric tenderness (non-specific; common in dyspepsia)
• Epigastric mass (alarm feature; suggests gastric malignancy) [4]
• Obesity (waist circumference greater than 102 cm male, 88 cm female) [22]

Systemic Examination

Look For Associated Conditions:

Red Flag Physical Signs

• Cachexia/weight loss (malignancy)
• Palpable epigastric mass (gastric cancer)
• Virchow's node (left supraclavicular lymphadenopathy — gastric cancer metastasis)
• Hepatomegaly (liver metastases)
• Ascites (advanced malignancy)

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6. Investigations

Diagnostic Strategy

The investigation pathway is determined by symptom pattern, alarm features, and age. [4]

┌─────────────────────────────────────────────────────────────────┐
│                  PATIENT WITH REFLUX SYMPTOMS                   │
└─────────────────────────────────────────────────────────────────┘
                              ↓
┌─────────────────────────────────────────────────────────────────┐
│            ASSESS FOR ALARM FEATURES AND AGE                    │
│  • Dysphagia, weight loss, GI bleeding, anaemia                 │
│  • Age > 55 with new-onset dyspepsia                             │
└─────────────────────────────────────────────────────────────────┘
                              ↓
                   ┌──────────┴──────────┐
                   │                     │
         Alarm Features           No Alarm Features
         OR Age > 55               AND Age less than 55
                   │                     │
                   ↓                     ↓
      ┌────────────────────────┐  ┌────────────────────────────┐
      │   URGENT OGD           │  │  CLINICAL DIAGNOSIS        │
      │   (2-week wait)        │  │  Empirical PPI 4-8 weeks   │
      │   DO NOT delay with    │  │  Lifestyle modification    │
      │   PPI trial            │  │                            │
      └────────────────────────┘  └────────────────────────────┘
                                              ↓
                                  ┌───────────┴──────────┐
                                  │                      │
                         Symptoms Resolve      Symptoms Persist
                                  │                      │
                                  ↓                      ↓
                    ┌──────────────────────┐  ┌──────────────────────┐
                    │ Step-down PPI to     │  │ Check compliance &   │
                    │ lowest effective     │  │ timing of PPI        │
                    │ dose or on-demand    │  │ Double-dose PPI BD   │
                    │                      │  │ for 4 weeks          │
                    └──────────────────────┘  └──────────────────────┘
                                                          ↓
                                                          │
                                                Still Refractory
                                                          ↓
                                              ┌──────────────────────┐
                                              │ OGD                  │
                                              │ pH-impedance         │
                                              │ Manometry            │
                                              │ Consider:            │
                                              │ - Functional         │
                                              │ - Eosinophilic oeso. │
                                              │ - Non-acid reflux    │
                                              │ - Surgery if proven  │
                                              └──────────────────────┘

Upper Gastrointestinal Endoscopy (OGD)

Indications: [4]

1. Alarm features (dysphagia, weight loss, bleeding, anaemia)
2. Age greater than 55 with new-onset dyspepsia
3. Persistent symptoms despite 4-8 weeks PPI therapy
4. Barrett's surveillance
5. Pre-operative assessment before fundoplication
6. Diagnostic uncertainty

Endoscopic Findings:

Los Angeles Classification of Oesophagitis [38]

Other Endoscopic Findings:

• Barrett's Oesophagus: Salmon-pink columnar mucosa extending proximal to gastro-oesophageal junction [11]
  • Prague C and M criteria (Circumferential and Maximal extent)
  • Requires biopsy confirmation of intestinal metaplasia (goblet cells)
  • Surveillance protocol depends on length and dysplasia
• Hiatus Hernia: Gastro-oesophageal junction greater than 2 cm above diaphragmatic hiatus [26]
  • Common (present in 90% of severe oesophagitis) [26]
  • Size correlates with severity
• Peptic Stricture: Circumferential narrowing (typically smooth, symmetrical) [39]
  • Complication of chronic oesophagitis
  • Requires dilation plus high-dose PPI
• Eosinophilic Oesophagitis: Linear furrows, concentric rings, white exudates, stricture [40]
  • Important differential diagnosis in PPI-refractory dysphagia
  • Requires high eosinophil count on biopsy (≥15 per high-power field)

Normal Endoscopy (60-70% of GORD patients): [34]

• Does NOT exclude GORD (Non-Erosive Reflux Disease — NERD)
• Consider pH-impedance monitoring if diagnosis uncertain or symptoms refractory

Ambulatory pH and Impedance Monitoring

24-Hour Ambulatory pH Monitoring:

Method:

• Transnasal catheter with pH sensor positioned 5 cm above LOS (manometry-guided) [8]
• Record pH for 24 hours OFF PPI (typically stopped 7 days prior) [8]
• Patient logs symptoms (heartburn, regurgitation)

Parameters:

• Acid Exposure Time (AET): Percentage of time pH less than 4 [8]
  • "Normal: less than 4% of total time; less than 6% upright; less than 1.5% supine [8]"
  • "Pathological: > 6% total time (Lyon Consensus) [8]"
  • "Borderline: 4-6% (requires additional evidence for diagnosis) [8]"
• Symptom Association Probability (SAP): Statistical correlation between symptoms and acid events [8]
  • Positive if > 95% (symptoms related to acid)

Indications:

• Refractory symptoms despite PPI (to confirm true acid reflux vs functional) [14]
• Pre-operative assessment (objective evidence required before fundoplication) [16]
• NERD with normal endoscopy (diagnostic confirmation) [34]
• Atypical symptoms with uncertain GORD diagnosis [13]

24-Hour Impedance-pH Monitoring:

Advantage Over pH Alone: Detects both acid AND non-acid reflux [41]

• Impedance measures changes in electrical resistance as refluxate passes (regardless of pH)
• Useful when pH monitoring negative but symptoms suggest reflux (non-acid/weakly acidic reflux) [41]
• Identifies reflux type: Liquid, gas, mixed

Indications:

• PPI-refractory symptoms (to detect non-acid reflux, which pH monitoring misses) [14,41]
• Post-fundoplication symptoms (to assess adequacy of surgery) [16]

Oesophageal Manometry

Method:

• High-resolution manometry with 36-channel catheter [42]
• Measures LOS pressure, peristaltic function, and oesophageal body contractility

Indications: [42]

• Pre-operative assessment (MANDATORY before fundoplication): Excludes achalasia and severe motility disorders (contraindications to fundoplication) [16]
• Atypical chest pain (to detect oesophageal spasm)
• Dysphagia with normal endoscopy (to detect motility disorders)

NOT a primary diagnostic test for GORD (TLOSRs cannot be reliably measured during short study) [42]

Findings in GORD:

• Often normal
• May show ineffective oesophageal motility (failed peristalsis; weak contractions) [42]
• Hypotensive LOS (basal pressure less than 10 mmHg) [3]

Barium Swallow

Largely Superseded by Endoscopy

Remaining Indications:

• Anatomical assessment of large hiatus hernia [26]
• Pre-operative planning for complex hernias
• Dysphagia with failed endoscopy (oropharyngeal dysfunction; Zenker's diverticulum)

Findings:

• Hiatus hernia (type and size)
• Stricture (smooth vs irregular — irregular suggests malignancy)
• Spontaneous reflux (low sensitivity/specificity for GORD diagnosis) [26]

Helicobacter pylori Testing

Controversial in GORD [43]

Rationale:

• H. pylori causes gastritis (may present with dyspepsia similar to GORD) [43]
• Test-and-treat recommended for dyspepsia in high-prevalence areas [43]
• Eradication does NOT worsen GORD (previous concern now refuted) [43]

Testing Methods:

• Non-invasive: Urea breath test (gold standard) or stool antigen
• Invasive: Endoscopic biopsy (if OGD performed anyway)

Recommendation: Consider in dyspeptic GORD patients, particularly if NOT already on PPI (which reduces test sensitivity). [4,43]

Laboratory Tests

Not Routinely Required for GORD Diagnosis

Consider:

• Full blood count: If anaemia suspected (iron deficiency suggests chronic blood loss) [4]
• Iron studies: If microcytic anaemia (to confirm iron deficiency)
• Serum gastrin: If refractory to PPI or multiple ulcers (to exclude Zollinger-Ellison syndrome) [31]

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7. Management

Treatment Principles

1. Lifestyle modification (all patients) [1,4]
2. Pharmacotherapy (stepwise acid suppression) [1,4]
3. Surgical intervention (selected patients) [16]
4. Surveillance (Barrett's oesophagus) [11]
5. De-escalation (minimize long-term PPI use) [15]

Lifestyle Modifications

Evidence quality varies; strongest evidence for weight loss. [25]

Most Important Message: Weight loss in overweight/obese patients is the ONLY lifestyle intervention with robust evidence. [25]

Pharmacotherapy

Antacids and Alginates

Mechanism:

• Antacids (calcium carbonate, magnesium hydroxide): Neutralize acid; rapid but short-lasting relief [44]
• Alginates (sodium alginate — Gaviscon): Form a foam raft floating on gastric contents; physical barrier [44]

Role:

• Mild/intermittent symptoms
• On-demand use
• Adjunct to PPI (for breakthrough symptoms)
• Pregnancy (safe) [28]

Examples:

• Gaviscon (alginate)
• Rennie (calcium carbonate)
• Maalox (aluminium/magnesium hydroxide)

Efficacy: Symptom relief only; do NOT heal oesophagitis [44]

H2 Receptor Antagonists (H2RAs)

Mechanism: Competitive inhibition of histamine at parietal cell H2 receptors; reduce acid secretion by 60-70% [45]

Examples:

• Famotidine 20-40 mg BD (ranitidine withdrawn in many countries due to NDMA contamination)
• Cimetidine 400 mg BD (less commonly used; drug interactions via CYP450 inhibition)

Efficacy:

• Inferior to PPIs for symptom control and healing [45]
• Healing rate: 50-60% at 12 weeks (vs 80-90% for PPI) [45]

Role:

• Second-line (if PPI intolerant or contraindicated — rare)
• Nocturnal acid breakthrough (addition of bedtime H2RA to PPI) — evidence limited [45]
• Tachyphylaxis develops within 2 weeks of continuous use [45]

Proton Pump Inhibitors (PPIs) — First-Line Therapy

Mechanism: [10]

• Irreversible inhibition of H+/K+-ATPase (proton pump) on parietal cell apical membrane
• Requires acid activation (prodrug converted to active sulphenamide in acidic parietal cell canaliculus)
• Binds covalently to cysteine residues on proton pump
• Profound acid suppression: 90-95% reduction in acid secretion [10]
• Duration: 24-48 hours (until new proton pumps synthesized)

Available PPIs:

Dosing Principles:

• Timing: 30-60 minutes BEFORE meals (typically breakfast) [10]
  • "Rationale: PPI requires actively secreting proton pumps for maximal binding; food stimulates acid secretion"
  • "Common error: Taking AFTER meals (significantly reduces efficacy)"
• Duration: 4-8 weeks for initial symptom control and healing [1,4]
• Step-down: After achieving control, reduce to lowest effective dose or on-demand [15]
• Double-dose: 30% of patients require twice-daily dosing (before breakfast and dinner) [1]

Efficacy: [46]

• Symptom relief: 80-90% of GORD patients [46]
• Oesophagitis healing: 80-90% at 8 weeks (dose- and grade-dependent) [38,46]
• Superior to H2RAs in all outcomes [45,46]

PPI Non-Response (10-20%): [14]

• First: Verify compliance and timing (most common cause)
• Second: Increase to double-dose (before breakfast and dinner) [14]
• Third: Switch PPI (10-15% respond to different PPI due to CYP2C19 polymorphism) [14]
• Fourth: Investigate (OGD, pH-impedance) to confirm diagnosis and exclude other pathology [14]

CYP2C19 Polymorphism: [10]

• PPIs (especially omeprazole) metabolized by CYP2C19
• Extensive metabolizers (70% Caucasian): Standard metabolism; standard dose adequate
• Poor metabolizers (20% Asian, 3% Caucasian): Slow metabolism; higher drug levels; better response
• Rapid metabolizers (30% population): Fast metabolism; lower drug levels; may need higher dose [10]
• Genetic testing NOT routinely performed; clinical trial of alternative PPI if poor response

Long-Term PPI Use: Benefits vs Risks [5,47]

Benefits:

• Symptom control in 70-80% requiring maintenance [15]
• Prevention of complications (stricture, bleeding, Barrett's progression)
• Excellent safety profile in most patients

Potential Risks (Associations, NOT Proven Causation): [5,47]

Critical Appraisal:

• Most "risks" are from observational studies (confounding, bias)
• Absolute risk increases are SMALL even where associations exist
• For patients with proven GORD and symptomatic benefit, benefits OUTWEIGH risks [5,47]
• Appropriate prescribing: Use PPI when indicated; use lowest effective dose; periodic review; attempt de-escalation

PPI De-Escalation and On-Demand Therapy [15]

Rationale:

• Minimize unnecessary long-term use
• Reduce cost
• Mitigate potential (small) long-term risks

Step-Down Strategy: [15]

1. After 4-8 weeks of standard-dose PPI achieving symptom control
2. Attempt reduction to:
   • Lower dose once daily (e.g., omeprazole 10 mg OD), OR
   • On-demand therapy (PPI taken when symptoms occur)
3. Review at 4 weeks

Success Rates: [15]

• 30% can discontinue PPI entirely (symptoms do not recur)
• 40% can reduce to on-demand therapy
• 30% require maintenance standard-dose PPI (severe GORD, erosive oesophagitis, Barrett's)

On-Demand Therapy: [15]

• Suitable for mild-moderate GORD
• Patient takes PPI when symptoms occur; stops when controlled
• Reduces PPI consumption by 50% vs continuous
• Effective in 70-80% of mild-moderate GORD [15]

Maintenance Therapy Indications: [1,15]

• Severe erosive oesophagitis (LA Grade C/D)
• Barrett's oesophagus
• Complications (stricture, bleeding)
• Rapid symptom relapse on discontinuation (quality of life justification)

Surgical Management

Laparoscopic Fundoplication

Indications: [16]

• Young patient (typically less than 50 years) wishing to avoid lifelong medication
• Objective evidence of reflux (abnormal pH study)
• Good symptomatic response to PPI (predicts good surgical outcome)
• Large hiatus hernia (≥3 cm) with symptoms
• Refractory GORD despite maximal medical therapy (after excluding non-compliance and alternative diagnoses)

Contraindications: [16]

• Absent or poor PPI response (predicts poor surgical outcome)
• Severe oesophageal dysmotility (achalasia, scleroderma) — manometry MANDATORY pre-op
• High anaesthetic risk
• Uncertain diagnosis (pH study not confirming reflux)

Nissen (Complete) Fundoplication: [16]

• 360° gastric fundus wrap around distal oesophagus
• Creates high-pressure zone
• Efficacy: 85-90% symptom control at 10 years [16]
• Complications:
  • Dysphagia (10-20%; usually transient; 3-5% persistent) [16]
  • Gas-bloat syndrome (inability to belch/vomit; abdominal bloating) — 10-15% [16]
  • Diarrhoea (5-10%; vagal nerve injury) [16]
  • Wrap herniation/slippage (3-5%) [16]

Partial Fundoplication (Toupet — 270°): [16]

• Alternative to Nissen
• Lower dysphagia rate (5-10%)
• Slightly lower anti-reflux efficacy vs Nissen [16]

Pre-Operative Workup: [16]

1. OGD (document anatomy, exclude malignancy)
2. pH-impedance study (confirm abnormal reflux OFF PPI)
3. Manometry (MANDATORY — exclude achalasia, severe dysmotility)
4. Barium swallow (if large hiatus hernia — anatomical planning)

Post-Operative Outcomes: [16]

• Excellent/good result: 70-85% at 5-10 years
• PPI discontinuation: 60-70%
• Redo surgery rate: 5-10% (wrap failure)
• Long-term patient satisfaction: 80-90%

LINX Device (Magnetic Sphincter Augmentation)

Mechanism: [48]

• Ring of magnetic beads placed around LOS
• Augments LOS pressure
• Opens with swallowing (oesophageal distension)
• Closes after swallow (magnetic attraction)

Advantages vs Fundoplication: [48]

• Less invasive
• Preserves belching/vomiting
• Lower dysphagia rate (5-10%)

Disadvantages: [48]

• MRI contraindication (relative — newer devices MRI-conditional)
• Less long-term data than fundoplication
• Device erosion/migration (rare — less than 1%)

Efficacy: [48]

• 80-85% symptom control at 5 years
• PPI discontinuation: 70-75%

Indications: [48]

• Similar to fundoplication
• Preference for less anatomically disruptive procedure

Transoral Incisionless Fundoplication (TIF)

Endoscopic alternative — early data; less durable than laparoscopic fundoplication. [49]

Management of Complications

Peptic Stricture

Definition: Narrowing of oesophageal lumen due to fibrosis from chronic inflammation [39]

Presentation: Progressive dysphagia (solids → liquids) [39]

Management: [39]

1. Endoscopic dilation: Bougienage or balloon dilation; repeat as needed
2. High-dose PPI: Omeprazole 40 mg BD (reduces recurrence)
3. Surgery: If recurrent stricture despite maximal medical/endoscopic therapy

Outcomes: 70-80% respond to dilation plus PPI; 20-30% require repeat dilations [39]

Barrett's Oesophagus

Definition: Replacement of normal squamous epithelium by columnar epithelium with intestinal metaplasia (goblet cells) [11]

Diagnosis: [11]

• Endoscopic appearance: Salmon-pink mucosa extending proximal to gastro-oesophageal junction
• Prague C&M classification (Circumferential and Maximal extent in cm)
• Histological confirmation: Intestinal metaplasia on biopsy

Cancer Risk: [12]

• Non-dysplastic Barrett's: 0.2-0.5% per year progression to adenocarcinoma [12]
• Low-grade dysplasia: 0.7% per year [12]
• High-grade dysplasia: 7% per year [12]

Surveillance Protocol (BSG 2014): [11]

Endoscopic Therapy for Dysplasia: [11]

• Radiofrequency ablation (RFA): Thermal destruction of Barrett's mucosa; 80-90% complete eradication [11]
• Endoscopic mucosal resection (EMR): Removal of visible lesions
• Cryotherapy: Alternative ablation method
• Combination: EMR for visible lesions + RFA for remaining Barrett's

Medical Therapy:

• PPI: Continue indefinitely (may reduce progression risk; symptom control) [11]
• Aspirin: Observational data suggest reduced cancer risk; not yet standard recommendation [50]

Oesophageal Adenocarcinoma

Epidemiology: [18]

• Incidence increased 6-fold since 1970s in Western countries
• Male predominance (7:1)
• 90% arise in Barrett's oesophagus [18]

Risk Factors: [18]

• Barrett's oesophagus (strongest risk factor)
• GORD (long-standing, severe)
• Obesity
• Male sex, white ethnicity
• Smoking, alcohol

Presentation:

• Progressive dysphagia
• Weight loss
• Anaemia

Management: Surgical resection (oesophagectomy) ± neoadjuvant chemotherapy/radiotherapy (beyond scope of GORD topic)

Prognosis: 5-year survival 15-20% (often diagnosed late) [18]

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8. Prognosis and Outcomes

Natural History

Chronic Relapsing Condition: [9]

• 70-80% relapse within 6-12 months of stopping PPI [9]
• Severity fluctuates over time
• Progression to complications (stricture, Barrett's) is uncommon with modern PPI therapy (less than 5%) [9]

Symptom Patterns:

• 30% have intermittent symptoms (on-demand therapy suitable)
• 40% have chronic mild-moderate symptoms (maintenance low-dose PPI)
• 30% have chronic severe symptoms (maintenance standard-dose PPI or surgery)

Quality of Life Impact

Untreated GORD: [17]

• Quality of life scores comparable to chronic heart failure, diabetes, angina [17]
• Impairment domains: Sleep, diet, work productivity, social function

PPI-Treated GORD: [17]

• Significant improvement in quality of life (approaching normal population)
• Residual symptoms in 20-30% despite PPI

Nocturnal GORD: [21]

• Particularly severe quality of life impact (sleep disturbance, daytime fatigue)
• Higher erosive oesophagitis rates

Cancer Risk

Overall Population with GORD:

• Very low risk of oesophageal adenocarcinoma (less than 0.1% per year) [18]

Barrett's Oesophagus:

• Non-dysplastic: 0.2-0.5% per year [12]
• Low-grade dysplasia: 0.7% per year [12]
• High-grade dysplasia: 7% per year [12]

Risk Mitigation:

• PPI therapy may reduce progression risk (observational data) [11]
• Surveillance endoscopy allows early detection
• Endoscopic therapy for dysplasia prevents invasive cancer [11]

Mortality

GORD Itself:

• NOT associated with increased mortality (benign condition)

Complications:

• Oesophageal adenocarcinoma: Poor prognosis (5-year survival 15-20%) [18]
• Aspiration pneumonia: Rare; can occur with severe nocturnal regurgitation

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9. Special Populations

Pregnancy

Prevalence: 40-85% of pregnant women experience heartburn [28]

Pathophysiology:

• Hormonal: Progesterone reduces LOS tone [28]
• Mechanical: Gravid uterus increases intra-abdominal pressure

Management: [28]

1. Lifestyle: Small frequent meals, avoid late meals, elevate head of bed
2. Antacids/alginates: SAFE (first-line) — Gaviscon
3. H2RAs: SAFE (ranitidine previously used; now famotidine)
4. PPIs: SAFE (omeprazole, lansoprazole) — use if antacids/H2RAs insufficient [28]

Safety Data:

• Large cohort studies show NO increased teratogenicity with PPIs [28]
• Benefits typically outweigh theoretical risks

Resolution: Symptoms usually resolve postpartum

Elderly

Considerations:

• Higher prevalence of GORD
• Higher risk of complications (erosive oesophagitis, Barrett's, stricture)
• Lower alarm symptom threshold (age > 55 is alarm feature itself) [4]
• Polypharmacy: Many medications worsen GORD (CCBs, anticholinergics)
• PPI risks (fracture, C. diff) slightly higher but still small absolute risk [47]

Management:

• Lower threshold for OGD (to exclude malignancy)
• PPI effective and generally safe; use lowest effective dose
• Fracture risk: Ensure calcium/vitamin D adequacy; falls assessment

Scleroderma (Systemic Sclerosis)

Prevalence: 50-90% have severe GORD [29]

Pathophysiology:

• Smooth muscle atrophy in distal oesophagus → aperistalsis [29]
• Severe LOS hypotension
• Impaired oesophageal clearance

Management: [29]

• High-dose PPI (often double-dose)
• Prokinetic agents (metoclopramide, erythromycin) — limited efficacy
• Endoscopic dilation for stricture (common complication)
• Fundoplication contraindicated (poor motility)

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10. Evidence and Guidelines

Key Clinical Guidelines

NICE CG184: Gastro-oesophageal reflux disease and dyspepsia in adults (2014, updated 2019) [4]

Key Recommendations:

• Empirical PPI for typical GORD (no alarm features, age less than 55)
• Urgent OGD for alarm features or age > 55 with new dyspepsia
• Step-down PPI after initial treatment
• Review long-term PPI annually

ACG Clinical Guideline: Diagnosis and Management of GORD (2022) [1]

Key Recommendations:

• Lyon Consensus criteria for pH monitoring (acid exposure time > 6% pathological) [8]
• PPI timing: 30-60 minutes before meals
• Wireless pH monitoring preferred (better tolerance)
• Weight loss strongest lifestyle intervention

BSG Guidelines on Barrett's Oesophagus (2014) [11]

Key Recommendations:

• Endoscopic surveillance intervals based on length and dysplasia
• Endoscopic therapy (RFA) for dysplasia
• Consider screening in high-risk patients (> 50 years, male, chronic GORD > 5 years, family history)

Lyon Consensus (2018) [8]

Defines GORD Using Objective Metrics:

• Proven GORD: Acid exposure time > 6% OR severe oesophagitis (LA C/D) OR long Barrett's (> 3 cm)
• Borderline: Acid exposure time 4-6% OR mild oesophagitis (LA A/B) OR short Barrett's (less than 3 cm)
• Excluded: Acid exposure time less than 4% AND normal endoscopy AND negative impedance

Key Evidence

PPI Efficacy

Meta-Analysis (Khan 2002): [46]

• 33 RCTs; 10,000+ patients
• PPI healing rate: 84% at 8 weeks
• H2RA healing rate: 52% at 12 weeks
• Number needed to treat (NNT): 3 for PPI vs placebo

PPI Safety

Freedberg 2017 Systematic Review: [47]

• Observational studies show associations with fracture, C. diff, pneumonia, CKD
• Absolute risk increases SMALL
• Causation NOT proven for most associations
• Benefits outweigh risks for indicated use

Lifestyle Modifications

Singh 2022 Systematic Review: [25]

• Weight loss: Moderate-quality evidence; symptom improvement
• Head-of-bed elevation: Low-quality evidence; nocturnal symptoms
• Dietary modifications: Very low-quality evidence; individual variation

Fundoplication Efficacy

Galmiche 2011 RCT (LOTUS Trial): [16]

• 288 patients randomized to PPI vs fundoplication
• 5-year outcomes: Similar symptom control
• Fundoplication: More dysphagia, bloating; fewer reflux symptoms
• PPI: 15% crossed over to surgery; Surgery: 12% resumed PPI

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11. Patient Explanation

What is GORD?

GORD stands for gastro-oesophageal reflux disease. It occurs when stomach acid flows back up into your food pipe (oesophagus), causing symptoms like heartburn—a burning sensation in your chest—and an acid taste in your mouth.

What causes it?

There's a muscular valve at the bottom of your food pipe that normally keeps stomach acid where it belongs. In GORD, this valve relaxes when it shouldn't, or doesn't close properly, allowing acid to escape upwards. Being overweight, eating large meals, lying down after eating, and certain foods can make this worse.

How common is it?

Very common—about 1 in 5 adults in the UK experience regular heartburn. Most people have mild symptoms that are easily controlled with lifestyle changes and medication.

What are the symptoms?

• Heartburn: Burning feeling in your chest, especially after meals or when lying down
• Acid regurgitation: Bitter or sour taste in your mouth
• Difficulty swallowing (this needs urgent medical attention)
• Cough or hoarse voice (less common)

When should I see a doctor urgently?

Seek immediate medical advice if you have:

• Difficulty swallowing (food getting stuck)
• Unintentional weight loss
• Vomiting blood or passing black, tarry stools
• Severe, persistent chest pain (especially if you're unsure whether it's heartburn or a heart problem)

If you're over 55 and have new symptoms of heartburn or indigestion, see your GP promptly.

What tests might I need?

Most people with typical heartburn don't need tests—your doctor can diagnose GORD from your symptoms and see if medication helps.

You'll need a camera test (endoscopy) if you have any worrying symptoms (see above), if you're over 55 with new symptoms, or if medication doesn't help.

How is GORD treated?

Lifestyle Changes:

• Lose weight if you're overweight (this is the most effective change you can make)
• Avoid eating large meals late at night (finish eating 3 hours before bed)
• Raise the head of your bed by 15-20 cm (use blocks under bed legs, not just pillows)
• Reduce trigger foods if you notice they make symptoms worse (common triggers: fatty foods, chocolate, caffeine, alcohol, spicy foods)
• Stop smoking

Medication:

• Antacids (like Gaviscon, Rennie): Quick relief for mild symptoms
• Proton pump inhibitors (PPIs) (like omeprazole, lansoprazole): Most effective treatment; reduces stomach acid production
  • Take 30-60 minutes BEFORE breakfast (not after meals)
  • Usually prescribed for 4-8 weeks initially
  • Many people can reduce the dose or take them only when needed after initial treatment
• H2 receptor antagonists (like famotidine): Less effective than PPIs; alternative if PPIs don't suit you

Surgery:

• Rarely needed
• An option for younger people who don't want lifelong medication or have severe symptoms despite medication
• Involves wrapping part of the stomach around the lower food pipe to strengthen the valve

Is GORD dangerous?

For most people, GORD is not dangerous—it's uncomfortable but not harmful. However, long-term, severe GORD can occasionally lead to complications:

• Oesophagitis: Inflammation of the food pipe (heals with medication)
• Stricture: Narrowing of the food pipe (rare with modern treatment)
• Barrett's oesophagus: Changes to the lining of the food pipe; increases cancer risk slightly (requires monitoring)

Cancer of the oesophagus is rare (less than 1 in 1,000 people with GORD), but the risk is higher if you have Barrett's oesophagus—that's why doctors monitor this carefully.

Are PPIs safe for long-term use?

PPIs are very safe for most people, even when taken long-term. You may have read about risks like bone fractures, infections, or kidney problems—these risks are very small and much smaller than the benefits of treating GORD.

Your doctor will review your medication regularly and use the lowest dose that keeps your symptoms under control.

What can I expect?

GORD is usually a long-term condition. Many people need ongoing medication, but symptoms are well-controlled. About 1 in 3 people can stop medication after initial treatment; others may need long-term, lower-dose treatment or tablets only when symptoms occur.

Your symptoms may fluctuate over time, but with the right treatment, you should be able to eat, sleep, and go about your daily activities without significant discomfort.

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12. Examination Focus

Viva Points

Opening Statement:

"GORD is a chronic condition where reflux of gastric contents causes troublesome symptoms—primarily heartburn and regurgitation—or complications such as oesophagitis, stricture, Barrett's oesophagus, or adenocarcinoma. Diagnosis is clinical in typical cases without alarm features. The mainstay of treatment is lifestyle modification plus proton pump inhibitors, taken before meals for maximal efficacy. Alarm features—dysphagia, weight loss, bleeding, or age over 55 with new symptoms—require urgent endoscopy to exclude malignancy. Barrett's oesophagus is a premalignant complication requiring surveillance. Fundoplication is effective in selected patients desiring medication-free symptom control."

Key Examination Points:

1. Definition: Reflux causing troublesome symptoms/complications [1]
2. Epidemiology: 10-20% Western adults; increasing with obesity [6,7]
3. Pathophysiology: Transient LOS relaxations (70-80% of reflux events); hiatus hernia disrupts barrier [3,26]
4. Clinical Features: Heartburn (retrosternal burning, postprandial, worse lying down); regurgitation (acid/bitter taste) [2]
5. Alarm Features: Dysphagia, weight loss, GI bleeding, anaemia, age > 55 [4]
6. Investigations: Clinical diagnosis; OGD if alarms or refractory; pH monitoring for diagnostic uncertainty [4,8]
7. Management: Lifestyle (weight loss most effective) + PPI (30-60 min before meals; 4-8 weeks; step-down thereafter) [1,4,25]
8. Complications: Erosive oesophagitis (80-90% heal with PPI); stricture (endoscopic dilation + PPI); Barrett's (surveillance; RFA for dysplasia); adenocarcinoma (0.2-0.5%/year in Barrett's) [11,12,38]
9. Surgery: Fundoplication in young patients with proven reflux, good PPI response, desire to stop medication; requires pre-op manometry [16]
10. Prognosis: Chronic relapsing; 70-80% relapse off PPI; excellent symptom control with treatment [9]

Common Exam Questions and Model Answers

Q: What is the most common mechanism of reflux in GORD? A: Transient lower oesophageal sphincter relaxations (TLOSRs), accounting for 70-80% of reflux episodes. These are inappropriate LOS relaxations not associated with swallowing, triggered by gastric distension and mediated via a vagal reflex involving nitric oxide and VIP release. [3]

Q: Why are PPIs taken before meals rather than after? A: PPIs are prodrugs requiring acid activation. They irreversibly bind to actively secreting proton pumps. Taking PPIs 30-60 minutes before meals allows drug absorption and concentration at parietal cells when acid secretion is maximally stimulated by food, resulting in maximal efficacy. [10]

Q: What is the Lyon Consensus? A: An international consensus (2018) defining GORD using objective metrics from pH monitoring and endoscopy. Proven GORD: acid exposure time > 6%, OR severe oesophagitis (LA C/D), OR Barrett's > 3 cm. Borderline: AET 4-6%, OR mild oesophagitis (LA A/B). Normal: AET less than 4% with normal endoscopy. [8]

Q: What is the cancer risk in Barrett's oesophagus? A: Non-dysplastic Barrett's: 0.2-0.5% annual risk of progression to adenocarcinoma. Low-grade dysplasia: 0.7% per year. High-grade dysplasia: 7% per year. Surveillance intervals are determined by dysplasia status and Barrett's length. [11,12]

Q: What investigations are mandatory before fundoplication? A: (1) OGD to document anatomy and exclude malignancy; (2) pH-impedance monitoring to objectively confirm pathological reflux off PPI; (3) Manometry to exclude achalasia and severe oesophageal dysmotility (both contraindications to fundoplication). [16]

Q: How do you manage PPI-refractory GORD? A: Step 1: Verify compliance and timing (before meals). Step 2: Increase to double-dose PPI (BD). Step 3: Switch to alternative PPI (CYP2C19 polymorphism). Step 4: Investigate with OGD (exclude eosinophilic oesophagitis, stricture, malignancy) and pH-impedance monitoring (confirm ongoing reflux vs functional heartburn vs non-acid reflux). [14]

Q: What is the strongest evidence-based lifestyle modification for GORD? A: Weight loss in overweight or obese patients. A 10% reduction in body weight reduces GORD symptoms by 40-50%. This is the ONLY lifestyle modification with high-quality evidence. Other recommendations (dietary triggers, head elevation) have weaker or anecdotal evidence. [25]

Q: What are the long-term risks of PPI therapy? A: Observational studies suggest small associations with hip fracture (RR 1.25), C. difficile infection (OR 1.7), hypomagnesaemia (rare), and possibly CKD. However, absolute risk increases are SMALL, causation is not proven for most associations, and benefits of PPI therapy for indicated use outweigh risks. Use lowest effective dose and review regularly. [5,47]

Clinical Case Scenarios

Scenario 1: Typical GORD

• 45-year-old obese male, 3-month history heartburn and regurgitation, worse after meals and lying down, no alarm features
• Management: Lifestyle advice (weight loss, avoid late meals, head elevation) + omeprazole 20 mg OD before breakfast for 4-8 weeks; review and step-down if controlled; no OGD required

Scenario 2: Alarm Features

• 60-year-old male, 2-month history progressive dysphagia to solids, 7 kg weight loss, new-onset heartburn
• Management: Urgent OGD (2-week wait); do NOT trial PPI empirically; exclude oesophageal/gastric malignancy; consider stricture, achalasia

Scenario 3: PPI-Refractory

• 50-year-old female, persistent heartburn despite omeprazole 20 mg OD for 8 weeks, no alarm features
• Management: Check compliance and timing (before meals?); increase to omeprazole 20 mg BD for 4 weeks; if still refractory, perform OGD and pH-impedance monitoring; consider alternative diagnoses (eosinophilic oesophagitis, functional heartburn, non-acid reflux)

Scenario 4: Barrett's Oesophagus

• 55-year-old male, OGD for chronic GORD shows 4 cm Barrett's oesophagus with intestinal metaplasia, no dysplasia
• Management: Continue PPI indefinitely; surveillance OGD every 2-3 years (Barrett's ≥3 cm); repeat biopsy; counsel on cancer risk (0.2-0.5%/year); lifestyle modification (weight loss, smoking cessation)

Scenario 5: Surgical Candidate

• 35-year-old male, excellent symptom response to lansoprazole 30 mg OD, wishes to discontinue lifelong medication, no alarm features
• Management: Pre-op workup (OGD, pH-impedance OFF PPI to confirm pathological reflux, manometry to exclude motility disorder); if suitable, offer laparoscopic Nissen fundoplication; counsel on dysphagia risk, gas-bloat, 10-15% may resume PPI

Common Mistakes in Examinations

• ❌ Not asking about alarm features (dysphagia, weight loss, bleeding, age > 55)
• ❌ Performing OGD in all GORD patients (unnecessary in typical presentation, age less than 55, no alarms)
• ❌ PPI timing error (taking after meals instead of 30-60 min before)
• ❌ Not attempting PPI step-down after initial treatment (leaving patients on long-term standard-dose unnecessarily)
• ❌ Missing Barrett's surveillance (not knowing surveillance intervals or endoscopic therapy indications)
• ❌ Attributing all chest pain to GORD without excluding cardiac cause (especially in high-risk patients)
• ❌ Offering fundoplication without pre-op pH study and manometry (inadequate workup)
• ❌ Overstating PPI risks (unnecessarily withholding effective therapy due to media scare stories)
• ❌ Not recognizing NERD (60-70% have normal endoscopy; diagnosis still GORD if typical symptoms and PPI response)
• ❌ Forgetting the strongest lifestyle modification (weight loss) and over-emphasizing weaker evidence (dietary triggers)

SBA Question Example

A 52-year-old woman with a 10-year history of GORD undergoes routine surveillance endoscopy. A 5 cm segment of Barrett's oesophagus is identified. Biopsies show intestinal metaplasia without dysplasia. She is asymptomatic on lansoprazole 30 mg once daily. What is the most appropriate next step in her management?

A. Discharge with lifestyle advice only B. Surveillance endoscopy in 5 years C. Surveillance endoscopy in 2-3 years D. Endoscopic radiofrequency ablation E. Oesophagectomy

Answer: C Explanation: Barrett's oesophagus ≥3 cm without dysplasia requires surveillance endoscopy every 2-3 years according to BSG guidelines. [11] Barrett's less than 3 cm would be every 3-5 years (B incorrect). Endoscopic ablation (D) is indicated for dysplasia, not non-dysplastic Barrett's. Surgery (E) is for high-grade dysplasia or cancer. Discharge (A) is inappropriate given malignant potential (0.2-0.5%/year).

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13. Related Topics

Related Conditions (Differential Diagnoses)

• Peptic Ulcer Disease: Epigastric pain; H. pylori; OGD diagnostic
• Functional Dyspepsia: Normal OGD; Rome IV criteria; overlap with GORD
• Eosinophilic Oesophagitis: Dysphagia; food impaction; esophageal rings; high eosinophils on biopsy [40]
• Achalasia: Progressive dysphagia (solids AND liquids); regurgitation; barium bird's beak; manometry diagnostic [42]
• Oesophageal Spasm: Non-cardiac chest pain; corkscrew oesophagus on barium; manometry diagnostic [42]
• Oesophageal Cancer: Alarm features; progressive dysphagia; weight loss; OGD diagnostic
• Gastric Cancer: Alarm features; epigastric mass; weight loss; OGD diagnostic
• Coronary Artery Disease: CRITICAL differential for chest pain; ECG, troponin, stress test [37]

Related Gastroenterology Topics

• Barrett's Oesophagus (covered in Complications section)
• Oesophageal Adenocarcinoma
• Hiatus Hernia
• H. pylori Gastritis
• Functional Heartburn (normal endoscopy and pH study; overlap with GORD)

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Last Reviewed: 2026-01-09 | MedVellum Editorial Team