Gastroesophageal reflux disease (GERD) is the most common and costly digestive disease. It accounts for over 8 million outpatient visits in the United States each year, and annual prescriptions for proton pump inhibitors (PPIs) to diagnose and manage GERD are estimated to exceed 8.2 billion, totalling over 10 billion in cost. GERD is a chronic disorder resulting from the retrograde flow of gastroduodenal contents into the esophagus or adjacent organs, and producing a variable spectrum of symptoms, with or without tissue damage. Transient inappropriate relaxation of the lower esophageal sphincter (LES) is the predominant pathophysiologic mechanism in the majority of GERD patients. Hiatal hernia, reduced LES pressure, or delayed gastric emptying may also play a role in patients with moderate to severe disease.

A. Epidemiology

The prevalence of GERD in the United States appears to be increasing. In Western populations, 25% of people report having heartburn at least once a month, 12% at least once per week, and 5% describe having symptoms on a daily basis. There appears to be no gender predominance of heartburn symptoms; men and women are affected equally. The relationship of age and reflux is unclear. One study has suggested an association between advancing age and fewer reflux symptoms but the presence of more severe esophagitis. There is an unequivocal positive association between body mass index and reflux symptoms, and the increasing rate of obesity has been proposed as a cause of growth in GERD incidence. Inappropriate relaxation of the LES can be exacerbated by obesity. Even moderate weight gain among persons of normal weight is thought to cause or exacerbate reflux symptoms. These epidemiologic characteristics should be considered when evaluating a patient with typical and atypical GERD.

B. Pathogenesis

Pathologic reflux of gastric contents occurs when the refluxate overcomes the antireflux barriers of the gastroesophageal junction, typically in a postprandial state. The antireflux barrier of the gastroesophageal junction is anatomically and physiologically complex and vulnerable to a number of potential mechanisms of reflux. The primary antireflux mechanism is the LES, a segment of smooth muscle in the lower esophagus that is chronically contracted to maintain a pressure that is approximately 15 mm Hg above intragastric pressure. The crural diaphragm, composed of striated muscles and forming the esophageal hiatus, also contributes to the antireflux barrier at the gastroesophageal junction. The two main patterns of LES dysfunction associated with GERD are (1) a hypotensive LES and (2) pathologic transient LES relaxations. Anatomic disruption of the gastroesophageal junction, commonly associated with a hiatal hernia and proximal migration of the LES, contributes to the pathogenesis of reflux disease by impairing LES function. Transient LES relaxations account for the majority of reflux events in individuals with normal LES pressure and clinically mild reflux disease. Chronically low LES pressure is the predominant GERD mechanism in patients with severe reflux disease, such as in patients with scleroderma.

Gastric factors can play a significant role in producing GERD. Gastric factors that promote GERD include increased gastric volume after meals, increased gastric pressure due to obesity, recumbency after meals, and delayed gastric emptying or gastroparesis, which can be idiopathic or drug induced. Increased gastric distention can cause an increase in transient LES relaxations and the volume of refluxate, particularly in GERD patients with large hiatal hernias. Delayed gastric emptying, or gastroparesis, may be present in approximately 15% of patients with GERD and is frequently underdiagnosed.

Other factors that decrease LES pressure and contribute to GERD are medications, lifestyle behaviors, and the ingestion of certain foods. Certain medicines can exacerbate GERD by lowering LES pressure; others can cause esophagitis by direct mucosal injury (Table 11–1). Certain foods, beverages, and behaviors will cause heartburn by reducing LES pressure (Table 11–2). Fatty foods, peppermint, chocolate, caffeinated beverages, alcohol, and smoking can all decrease LES pressure.

A. Symptoms and Signs

GERD is defined in a guideline by the American College of Gastroenterology as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. The typical manifestations of GERD are heartburn, regurgitation, and dysphagia. Other symptoms associated with GERD include water brash, a globus (lump in the throat) sensation, odynophagia, and nausea. Heartburn (pyrosis) is defined as a retrosternal burning discomfort located in the epigastric area that may radiate up toward the neck and typically occurs in the postprandial period, especially after a high-fat or a large-volume meal. Postural changes such as bending over often exacerbate patients’ symptoms. Symptoms can also be aggravated by ingestion of certain foods or beverages, such as tomato sauce, peppermint, chocolate, coffee, tea, and alcohol. When assessing a patient with heartburn symptoms, the duration and severity of symptoms should be investigated. Patients who present with typical symptoms with a minimum frequency of twice a week for 4–8 weeks or more should be considered as having GERD. At initial presentation, it is important to consider a patient’s age and the presence of “alarm signs” (Table 11–3). New-onset symptoms over age 50 or the presence of any alarm signs necessitates the evaluation of GERD symptoms with an upper endoscopy or imaging modality to rule out any signs of underlying malignancy.

Atypical manifestations of GERD refer to symptoms that are extraesophageal, including pulmonary, ear, nose, and throat manifestations, as well as noncardiac chest pain (Table 11–4). According to published studies in the literature, pathologic GERD can be found in 30–80% of adult patients with asthma, although their causal relationship is not completely clear. GERD may serve as a trigger for asthma via microaspiration of gastric acid with subsequent airway irritation or vagally mediated effects of acid on the upper airway. However, changes in the thoracoabdominal pressure gradient from asthma-induced pulmonary hyperinflation may disrupt the antireflux barrier and the use of bronchodilators may also lower the LES tone, thus promoting reflux. While GERD should be considered as a possible etiology in adults with new-onset asthma, prior studies did not show significant benefits in routine use of acid-suppressing agents for management of all asthma patients. Expert opinion guidelines suggest empiric acid-suppression therapy for asthma patients with typical esophageal symptoms of GERD. In the absence of concomitant esophageal symptoms, the empiric use of acid-suppressing agents among asthmatics remains controversial. An increasing incidence of GERD has also been associated with other pulmonary disorders such as idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease. Similarly, the causal relationship and the role of reflux therapy in the management of these pulmonary disorders, especially in the absence of esophageal symptoms, need further investigation. In laryngopharyngeal reflux, the regurgitated gastric contents reach the upper aerodigestive tract, leading to ear, nose, and throat symptoms such as chronic cough, hoarseness, sore throat, globus sensation, and otitis media.

Patients with gastroparesis and GERD may present with concomitant nausea, vomiting, or early satiety. These patients may not respond to antisecretory agents alone, as the refluxate contains bile and digestive enzymes in addition to gastric acid. Gastroparesis should be suspected in patients with an acute or subacute onset of GERD, particularly after an episode of viral upper respiratory infection or gastroenteritis. The natural history of GERD with acute gastroparesis is that the majority of patients will achieve symptomatic resolution, although some will need treatment with prokinetic agents. Antisecretory agents may offer some symptomatic relief and reduce gastric volume. Dietary changes such as low-fat, frequent, small meals may also be helpful in controlling symptoms.

B. Laboratory, Imaging, and Endoscopic Studies

Classic GERD can be diagnosed by taking a thorough symptom history and confirmed by a complete response to medical therapy (a “PPI test”). In general, diagnostic testing is reserved for patients who fail to respond to a trial of adequate medical therapy or for patients who have alarm symptoms with GERD (Figure 11–1). Available tests include upper GI series, upper endoscopy, 24-hour esophageal pH monitoring with or without impedance, and wireless capsule pH study.