creation date: 2025-07-13 16:25
tags: Pathologies

Gastroesophageal Reflux Disease

Background

Definitions

Gastroesophageal reflex disease (GERD) encompasses a spectrum of severity involving reflux of gastric content into the esophagus.

Physiologic gastroesophageal reflux: short-lived, asymptomatic, postprandial episode that is normal
Reflux hypersensitivity or functional heartburn: symptom of reflex with normal upper endoscopy and normal esophageal acid exposure
True nonerosive reflux disease: quantifiable esophageal acid exposure in absence of esophagitis
Reflux/erosive esophagitis: subset of GERD with endoscopic evidence of esophageal erosions around area of gastroesophageal junction
Extraesophageal GERD: involvement of upper respiratory tract and other structures outside of the esophagus

Etiology & Pathophysiology

GERD exists as a spectrum as defined above. The severity of GERD is thought to be dependent on the level of dysfunction of the antireflux barrier.

The antireflux barrier is complex and functionally serves to prevent reflux of gastric fluid during recumbence, increased intra-abdominal pressure, or during swallow-induced lower esophageal sphincter relaxation. It also allows for venting of gas or vomiting. This barrier consist of an interplay of:

Intrinsic lower esophageal sphincter (LES)
Gastroesophageal flap valve formed by oblique angle of LES entering the stomach (angle of His)
Crural diaphragm (acting as extrinsic sphincter) - particularly effective for pinching during abdominal strain and shallow inspiration to pulse bolus into stomach to prevent swallow-induced reflux

Dysfunction of the antireflux barrier may take the form of:

Anatomic distortion of native esophagogastric junction
Weakning or loss of LES

The extent of gastric fluid impact depends on the intragastric pH and the time the refluxate spends in contact with the esophageal mucosa. The effect of the refluxate is worsened by:

Ineffective esophageal motility
Re-reflux (retrograde bolus flow due to hiatal hernias)
Diminished salivary function (cannot neutralize acid)

The symptom experience is also mediated by the sensitivity of the esophagus. This explains the poor correlation between subjective symptom severity and the objective severity of mucosal damage.

Risk factors

Factors that may contribute to the development of pathologic reflux include:

Obesity
Pregnancy and exogenous estrogen (may reduce LES tone)
Diet (fat, chocolate, peppermint, caffeine, alcohol, smoking)
Medications
- Decrease LES function: anticholinergics, nitrates, calcium channel blockers, erectile dysfunction medicines, TCAs, opioids, theophylline, benzodiazepines, barbiturates
- Delayed gastric emptying: GLP-1 agonists
Psychosocial factors (period of stress or sleep deprivation may exacerbate symptoms)
Helicobacter pylori (may be etiologic or protective)

Clinical Presentation

Signs & Symptoms

The classic symptoms of GERD are:

Heartburn / pyrosis (burning sensation in the retrosternal area, usually postprandial)
Regurgitation (perception of flow of refluxed content into the mouth or hypopharynx)

Other symptoms include:

Dysphagia (may suggest reflux esophagitis)
Odynophagia (rare; may suggest esophageal ulcer)
Chest pain (may mimic angina pectoris)
Water brash or hypersalivation
Globus sensation (constant perception of lump in throat)
Nausea

History & Physical Exam

History should include:

Alarm features as described below
Severity of symptoms and effect on QoL
Previous treatment/alleviating factors

Diagnosis

Criteria

Diagnosis is typically made clinically if symptoms as classical. However, in cases without classic symptoms, further workup is required (eg. undifferentiated chest pain).

Upper endoscopy may diagnose erosive esophagitis. This is done using the Los Angeles classification system:

LA grade A: erosions limited to mucosal fold(s) and ≤5 mm
LA grade B: erosions limited to mucosal fold(s) and >5 mm
LA grade C: erosions over mucosal folds but over < 3/4 of circumference
LA grade D: confluent erosions extending over for > 3/4 of circumference

Work-up

Upper gastrointestinal endoscopy
For patients with alarm features or risk factors for Barrett’s esophagus, an upper endoscopy is performed (if not already performed within last 3 months).

Upper endoscopy is not required to diagnose GERD but can rule out concerning conditions.

Esophageal manometry
Esophageal manometry is used to rule out an esophageal motility disorder. It does not aid diagnosis of GERD but can allow for correct placement of pH probes.

Ambulatory esophageal pH monitoring
In patients with persistent symptoms, a diagnosis of GERD can be confirmed and treatment adequacy assessed with pH monitoring. There are three approaches:

Transnasal (24h monitoring, electrode placed 5 cm above manometrically defined upper limit of LES)
Wireless monitoring (2-4 days of monitoring, capsule-shaped device placed into the distal esophageal mucosa)
Esophageal monitoring with impedance

Differential

Other diagnoses include:

Infectious esophagitis
Pill esophagitis
Eosinophilic esophagitis

Specific symptom differentials are discussed separately.

Red Flags / Complications

Red flags / alarm features
Further evaluation should be prompted if:

New onset of dyspepsia in patient ≥ 60 years
Evidence of gastrointestinal bleeding (hematemesis, melena, hematochezia, occult blood in stool)
Iron deficiency anemia
Anorexia
Unexplained weight loss
Dysphagia
Odynophagia
Persistent vomiting
Gastrointestinal cancer in a first-degree relative

Esophageal complications
Barrett’s Esophagus

Change in lining of the lower esophagus to those of stomach
Risk of malignant transformation
Risk factors include:
- Duration of GERD of at least 5 to 10 years
- Age 50 years or older
- Male sex
- White individuals
- Hiatal hernia
- Obesity
- Nocturnal reflux
- Tobacco use (past or current)
- First-degree relative with Barrett’s esophagus and/or adenocarcinoma

Others

Esophageal stricture
Esophageal adenocarcinoma

Extraesophageal

Chronic laryngitis
Exacerbation of asthma

Management

Initial Management

Upper endoscopy may produce recommendations for treatment. If no endoscopy is done, the initial treatment is determined by symptom severity, frequency, and timing.

Education and Lifestyle

Lifestyle modifications include:

Limitation of dietary triggers
Weight loss for overweight or obese patients
Smoking cessation

Additionally changes can be made for nocturnal symptoms:

Avoiding late meals (<3 hours before lying down)
Sleeping in the left lateral decubitus position (moves gastric content away from GE junction)
Elevation of head of bed

Pharmacotherapy

Empiric therapy without endoscopic findings
In patients with mild, intermittent symptoms, a step-up approach is used. Each step should last 2-8 weeks. Note, prior effective/ineffective treatments.

Antacids, alginates, or H2 antihistamine prn
H2 antihistamine BID
Proton pump inhibitor once daily

For severe or frequent symptoms, options include:

PPI once daily x 8 weeks
Potassium-competitive acid blocker (vonoprazan)

Esophagitis
For patients with erosive esophagitis LA grade B and above, initial therapy options are:

Vonoprazan 20 mg daily x 8 weeks (preferred, superior for healing erosions)
PPI once daily (cheaper alternative)

Barrett’s esophagus
In addition to indefinite PPI therapy, patients with Barrett’s requires regular surveillance for malignancy.

Considerations for Pregnancy or Breastfeeding

Therapy is the same except for a few considerations.

Avoid sodium bicarbonate containing antacids (risk of metabolic alkalosis and fluid overload)
For PPIs, omeprazole, lansoprazole, and pantoprazole are most studied in pregnancy

Refractory GERD

For patients with incomplete response to therapy, refer to gastroenterology for further evaluation.

MD Notes

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