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Gastroesophageal Reflux Disease

Shani Woolard and Jennifer Christie

Clinical Vignette

A 50-year-old man with a history of hypertension and hyperlipidemia presents with a 4-month history of chest discomfort. He describes the discomfort as a burning and occasionally a pressure sensation in the mid-sternal area. The discomfort often occurs 45 minutes after eating a meal and lasts for about 3 hours, gradually improving thereafter. He occasionally awakens in the morning with a sore throat, cough, and bitter taste in his mouth. He has tried over-the-counter ranitidine, with only minimal relief. He was recently seen in the emergency department for an episode of severe chest pain. A cardiac work-up, including an electrocardiogram, cardiac enzymes, and a stress echocardiogram, was negative. Physical examination reveals a well-built, well-nourished man in no apparent distress. The blood pressure is 137/84?mmHg, pulse rate 72 per minute, respiratory rate 14 per minute, and body mass index 30. The physical examination is otherwise unremarkable.

General

• Gastroesophageal reflux disease (GERD) is defined as symptoms or tissue damage caused by the reflux of gastric contents into the esophagus.
• GERD is a common disorder, affecting almost half of the US population, with varying severity. Some 40% of the US population experiences reflux symptoms about once per month, 20% complain of symptoms once per week, and 7-10% report daily symptoms.
• GERD affects 10-20% of western populations. It is less common in Asian and African countries.
• It is estimated that GERD costs the US nearly $2 billion each week in lost productivity.

The most common symptoms of GERD are heartburn and regurgitation. GERD is the most common cause of noncardiac chest pain.

Risk Factors

• Advancing age (>65?years)
• Obesity
• Genetic factors
• Alcohol use
• Pregnancy
• Smoking

Spectrum of GERD

• The clinical spectrum of GERD ranges from nonerosive reflux disease (NERD) to erosive esophagitis (Figure 1.1). NERD is defined as symptoms of acid reflux without evidence of esophageal damage, such as mucosal erosions or breaks on esophagogastroduodenoscopy (EGD) in patients who are not on acid-suppressive therapy.
• A small proportion of patients will develop metaplasia of the squamous esophageal epithelium to columnar epithelium (Barrett's esophagus). Barrett's esophagus is a risk factor for adenocarcinoma.
• Some patients who present with heartburn have 'functional' heartburn. This is defined as a burning retrosternal discomfort in the absence of gastroesophageal reflux or an esophageal motor disorder. Ambulatory pH testing may be useful to differentiate NERD from functional heartburn.

Figure 1.1 Clinical spectrum of GERD. (*May be associated with erosive esophagitis; NERD, nonerosive esophageal reflux disease.)

Pathophysiology

• Transient lower esophageal sphincter relaxations (TLESRs):
  • The etiology of GERD is multifactorial; however, 'aberrant' TLESRs are the major pathophysiologic factors in many patients with GERD.
  • A TLESR is defined as relaxation of the lower esophageal sphincter in response to gastric distension. In healthy persons, TLESRs occur in the absence of a swallow, last 10-30 seconds, and result in physiologic gastroesophageal reflux.
  • TLESRs are regulated by the neurotransmitter ?-aminobutyric acid (GABA) acting on GABA type B receptors located in the peripheral nervous system, as well as in the brainstem.
  • In many cases, GERD is thought to be caused by an increased number or a prolonged duration of TLESRs.
• Gastric factors:
  • Increased gastric acid production as well as delayed gastric emptying with distention may trigger TLESRs.
• Diminished esophageal clearance:
  • Poor esophageal clearance due to defects in primary or secondary esophageal peristalsis allows prolonged exposure of the esophageal mucosa to acid.
• Diet and medications:
  • Dietary factors such as acidic foods, caffeine, alcohol, peppermint, and chocolate may reduce lower esophageal sphincter (LES) tone or increase gastric acid production.
  • Medications such as calcium channel blockers, hormones (e.g., progesterone, cholecystokinins, secretin), beta-adrenergic agonists (albuterol), nitrates, and barbiturates can decrease LES tone, thereby predisposing to gastroesophageal reflux.
  • Smoking has also been associated with a predisposition to gastroesophageal reflux.
• Hiatal hernia:
  • A hiatal hernia usually occurs when there is a defect in the diaphragmatic hiatus that allows the proximal stomach to herniate above the diaphragm and into the thorax. It is unclear how this predisposes to gastroesophageal reflux. The barrier function of the LES to prevent the reflux of gastric contents into the esophagus is thought to be disrupted. Large hiatal hernias also lead to increased acid dwell times in the distal esophagus.

Clinical Features

• Thorough history-taking detailing the onset and duration of symptoms and the association of symptoms with meals and diet should be conducted. 'Alarm symptoms' such as vomiting, gastrointestinal bleeding, weight loss, dysphagia, early satiety, and symptoms of cardiac disease should be elicited.
• Patients may present with typical (classic) or atypical symptoms.
• Typical symptoms:
  • Heartburn is described as a burning sensation in the substernal area that may radiate to the neck and/or back.
  • Regurgitation is the feeling of stomach contents traveling retrograde from the stomach up to the chest and often into the mouth.
  • Dysphagia (difficulty swallowing) is reported in about 30% of patients with GERD, even in the absence of esophageal inflammation or a stricture.
  • Less common symptoms associated with GERD include water brash, burping, hiccups, nausea, and vomiting. Water brash is the sudden appearance of a sour or salty fluid in the mouth, and represents secretions from the salivary glands in response to acid reflux. Odynophagia (painful swallowing) occurs when there is severe esophagitis.
  • The sensitivity of typical symptoms for detecting GERD is poor.
• Atypical symptoms:
  • Patients may present with chest pain, chronic cough, difficult-to-treat asthma, and laryngeal symptoms such as hoarseness, throat clearing, or throat pain.
  • Patients with atypical symptoms are less likely than patients with typical symptoms to have endoscopic evidence of esophagitis or Barrett's esophagus. They also have a less predictable response to therapy. Ambulatory esophageal pH testing (see later) is not as sensitive for diagnosing GERD in patients with atypical symptoms as it is in patients with typical symptoms.
• In uncomplicated GERD, physical findings are minimal or absent.

GERD as the etiology of chest pain should be pursued only after potentially life-threatening cardiac etiologies have been excluded.

Diagnosis

Trial of Proton Pump Inhibitor (PPI) Therapy

• A PPI trial is the simplest approach for diagnosing GERD and evaluating symptom response to treatment.
• A 30-day trial of a PPI (omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole, dexlansoprazole) once daily (taken 1 hour before breakfast) is recommended. If the patient has GERD, symptoms will usually improve within 1-2 weeks.
• The pooled sensitivity of a PPI trial for diagnosing GERD is 78% with a specificity of 54% when compared with 24-hour pH testing.

A PPI trial is recommended as the initial diagnostic and therapeutic intervention in patients with uncomplicated GERD. In patients who fail a PPI trial, additional testing is recommended.

Barium Swallow

• This is a radiographic test that can detect reflux of barium contrast into the esophagus after the patient drinks the contrast solution (see Chapter 27).
• A barium swallow can evaluate other potential mechanical causes for the symptoms (e.g., stricture, neoplasm); however, the test lacks sensitivity (20-30%) to assess mucosal damage. Therefore, barium swallow studies should not be used to diagnose GERD.

Upper Endoscopy

• Upper endoscopy (esophagogastroduodenoscopy, EGD) allows direct visualization of the esophageal mucosa.
• The test has a high sensitivity (90-95%) for diagnosing GERD, but the specificity is only 50%.
• The spectrum of findings on upper endoscopy in persons with GERD includes normal mucosa and esophageal inflammation characterized by erythema, erosions, mucosal breaks, bleeding, and ulceration of the esophageal mucosa.
• Upper endoscopy is recommended for all patients with alarm symptoms such as weight loss, dysphagia, hematemesis, and bleeding.
• Upper endoscopy is used to detect complications of GERD such as stricture or Barrett's esophagus and other...