Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). This condition may eventually lead to inflammation (esophagitis), metaplasia (Barrett’s esophagus), and progression to esophageal cancer. Uncomplicated GERD can be managed with lifestyle changes and over-the-counter medications. Sometimes, however, stronger medications or surgery may be required to ease symptoms and prevent complications.

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Epidemiology and Etiology

Definition

Gastroesophageal reflux disease (GERD) is a digestive disorder caused by the reflux of stomach contents into the esophagus.

Epidemiology

  • Prevalence 19%–28% in North America
  • Risk factors:
    • Obesity
    • Smoking
    • Caffeine
    • Alcohol
    • Lack of physical activity
    • Anxiety/depression
    • Stress
    • Eating habits (large meals, eating before bed)
    • Pregnancy
    • Medications (nitrates, calcium channel blockers)
    • Scleroderma
    • Zollinger-Ellison syndrome causing increased acid secretion

Etiology

  • Increased transient lower esophageal sphincter relaxations (TLESRs)
  • Decreased lower esophageal sphincter (LES) pressure
  • Impaired esophageal motility
  • Delayed gastric emptying
  • Hiatal hernia

Pathophysiology and Clinical Presentation

Physiology

  • LES:
    • A 3–4 cm smooth muscle structure at the gastroesophageal junction
    • Maintains a high-pressure zone between the esophagus and the stomach
    • Relaxes transiently in response to meals
  • Some reflux of stomach contents is normal, but cleared by esophageal contractions.

Pathophysiology

Factors leading to increased exposure of esophageal mucosa to gastric acid/contents:

  • Increased frequency and duration of reflux episodes
    • Incompetent LES (lower baseline pressure)
    • Increased frequency of TLESRs
    • Hiatal hernia (shorter and weaker LES)
    • Increased intragastric pressure (delayed gastric emptying)
  • Decreased clearance of refluxed material: esophageal motility disorders
Esophageal reflux

Pathophysiology of gastroesophageal reflux (GERD):
Left image (normal): The LES, a structure at the gastroesophageal junction, maintains a high-pressure zone between the esophagus and the stomach. This prevents the reflux of gastric contents. The LES relaxes transiently in response to meals.
Right image (GERD): An incompetent LES (lower baseline pressure) and increased frequency of TLESRs are among the factors causing GERD.

Image by Lecturio.

Clinical presentation

  • Esophageal symptoms
    • Typical:
      • Heartburn (most common)
      • Regurgitation (migration of gastric contents up to the hypopharynx/mouth)
    • Atypical (prompting further investigation):
      • Dysphagia/odynophagia (secondary to mucosal irritation/damage)
      • Belching, nausea
      • Chest pain
      • Globus sensation (“lump in the throat”)
  • Extraesophageal symptoms (reflux into the larynx, mouth, and respiratory tract)
    • Laryngitis
    • Cough
    • Hoarseness/dysphonia
    • Sore throat
    • Dental erosions
    • Water brash (hypersalivation)

Diagnosis

Clinical diagnosis

  • Empiric (no further workup needed)
  • Classic symptoms: heartburn +/- regurgitation
  • Symptoms resolve with medications.
  • No alarming features or extraesophageal symptoms

Ambulatory pH monitoring

  • Gold standard
  • Used to confirm the diagnosis and check the adequacy of treatment
  • Performed for 24 or 48 hours
  • Measures the amount of time the pH is < 4.0 (tends to produce symptoms)
  • Reliably detects:
    • Pathologic acid exposure
    • Frequency of reflux episodes 
    • Correlation of symptoms with reflux episodes
  • For patients with extraesophageal symptoms
  • For GERD refractory to medications
  • For patients with no endoscopic findings
Esophagus ph monitoring

Ambulatory esophageal pH monitoring: This test aids in the diagnosis of GERD and evaluates the adequacy of treatment in those with persistent symptoms. In this image, the device with a pH sensor is placed transnasally, and is attached to a portable data recorder.

Image by Lecturio.

Esophagogastroduodenoscopy (EGD)

  • Not necessary for a typical GERD presentation
  • For alarming features (if complications of GERD/malignancies suspected):
    • Dysphagia/odynophagia
    • Chest pain
    • Long-standing symptoms (> 5 years)
    • Age > 50
    • Anemia/melena/hematemesis
    • Weight loss
    • Persistent vomiting
    • Gastrointestinal cancer in 1st-degree relative
Barretts esophagus

Esophagogastroduodenoscopy of a patient with persistent GERD: The image shows replacement of the squamous epithelium with columnar epithelium (Barrett’s esophagus).

Image: “Barretts esophagus” by US National Library of Medicine. License: CC BY 2.0

Upper gastrointestinal (GI) series (barium swallow)

  • Limited use in diagnosing GERD itself
  • May show strictures, tumors, hiatal hernias, and severe esophagitis

Esophageal manometry

  • To rule out esophageal motility disorders
  • Usually done prior to anti-reflux surgery if this surgery is considered

Management

Noninvasive management

  • Lifestyle modifications
    • Avoid eating < 3 hours before bedtime.
    • Weight loss (if obese)
    • Elevate the head of the bed (if with nocturnal symptoms).
    • Avoid triggers (e.g., alcohol, coffee, spices).
    • Smoking cessation
  • Medical therapy
    • Proton pump inhibitors (PPIs):
      • Most effective therapy 
      • Most common maintenance therapy
      • Accomplish healing of esophagitis, if present
      • Examples: omeprazole, pantoprazole
    • Histamine receptor (H2) antagonists:
      • Not as effective as PPIs
      • Can be added at bedtime for patients on PPIs with nocturnal symptoms
      • Examples: famotidine, cimetidine

Surgical management

  • Indications:
    • Presence of hiatal hernia along with the symptoms of GERD
    • Refractory symptoms after giving maximal medical therapy
    • Side effects of medications
    • Desire to discontinue medications
  • Endoscopic therapy:
    • Transoral incisionless fundoplication
    • Stretta procedure (radiofrequency application to LES)
  • Surgery:
    • Fundoplication:
      • Gastric fundus is wrapped around the lower esophagus
      • Complete (Nissen, 360º)
      • Partial (Toupet, 270º; Dor, 180º)
      • Concomitant repair of hiatal hernia, if present
    • Gastric bypass if obesity is present (BMI > 35)

Complications

Erosive esophagitis

  • 30% of patients with untreated GERD
  • Irregular or linear multiple ulcerations in the distal esophagus
  • Graded based on severity (Los Angeles Classification of Gastroesophageal Reflux Disease):
    • Grade A: mucosal breaks < 5 mm in length
    • Grade B: at least 1 mucosal break > 5 mm (not continuous between adjacent mucosal folds)
    • Grade C: at least 1 mucosal break (continuous between mucosal folds, but not circumferential)
    • Grade D: Mucosal break involves at least ¾ of luminal circumference.

Esophageal stricture

  • Results from healing of erosive esophagitis
  • Collagen deposition and contraction lead to luminal narrowing.
  • Causes dysphagia to solids/food impaction
  • Treated with endoscopic dilation and PPIs to prevent recurrence
Upper gastrointestinal series Stricture

Upper gastrointestinal series: A severe stricture measuring 85 mm along the longitudinal axis was observed extending from the middle to lower thoracic esophagus caused by reflux esophagitis

Image: “Upper gastrointestinal series” by Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. License: CC BY 4.0

Barrett’s esophagus

  • Columnar intestinal metaplasia of the squamous mucosa of distal esophagus
  • Precursor to esophageal adenocarcinoma
  • Diagnosed by endoscopy with biopsy
  • Salmon-colored mucosa on white-light endoscopy
Long segment Barrett’s esophagus

Long segment of Barrett’s esophagus

Image: “Long segment Barrett’s esophagus” by Japan Esophageal Society. License: CC BY 4.0

Esophageal adenocarcinoma

  • GERD and/or Barrett’s esophagus are well-established risk factors.
  • Affects the distal 3rd of the esophagus
  • Appears as mass, stricture, or large ulcer on endoscopy
  • Patients present with dysphagia, weight loss, and anemia.

Differential Diagnosis

The following conditions are differential diagnoses of GERD/reflux esophagitis:

  • Pill-induced esophagitis: also presents with retrosternal pain and dysphagia; however, a history of taking triggering medication and the presence of odynophagia since the early stages of the disease help differentiate pill-induced esophagitis from reflux esophagitis. Frequently, symptoms resolve on discontinuation of offending medication.
  • Infectious esophagitis: typically presents with retrosternal pain in immunocompromised patients. Decreased immunity and odynophagia early in the disease help differentiate infectious esophagitis from reflux esophagitis. Diagnosis is confirmed by biopsy.
  • Eosinophilic esophagitis: also presents with retrosternal pain and dysphagia; however, the presence of concurrent atopy or asthma helps differentiate eosinophilic esophagitis from reflux esophagitis. For confirmation, EGD with biopsy is required.
  • Corrosive esophagitis: also presents with retrosternal pain and dysphagia. The disease can present with injuries to adjacent structures such as mediastinitis. The history of ingesting a corrosive and the presence of odynophagia differentiate corrosive esophagitis from reflux esophagitis.
  • Esophageal motility disorders: frequently present with dysphagia and chest pain. These disorders are disruptions of normal esophageal peristalsis. Esophageal motility disorders are diagnosed with esophageal manometry. The disorders may be present on their own or co-exist with reflux.

References

  1. Clarrette D.M. (2018). Gastroesophageal Reflux Disease (GERD). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140167/
  2. Kahrilas P.J. Clinical manifestations and diagnosis of gastroesophageal reflux in adults. Retrieved 22 November 2020, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-gastroesophageal-reflux-in-adults?search=GERD&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3
  3. Kahrilas P.J. Medical management of gastroesophageal reflux disease in adults. Retrieved 22 November 2020, from https://www.uptodate.com/contents/medical-management-of-gastroesophageal-reflux-disease-in-adults?search=GERD&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

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