Approach to the Patient with Heartburn and Reflux (Gastroesophageal Reflux Disease)

Francis X. Campion

James M. Richter

Heartburn is a nearly universal experience. In the United States, an estimated 6% of people experience frequent heartburn. In Asian nations, approximately 5% of persons report gastroesophageal reflux disease (GERD), but the incidence appears to be growing. In 2008, the “Montreal definition” of GERD was created by an expert panel of clinicians. They defined GERD as “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.” “Troublesome” simply means that the symptoms are adversely affecting a person’s well-being. Further categorization is based upon presence of esophageal injury. Additionally, there are a group of conditions associated with the extraesophageal effects of acid reflux. GERD symptoms are characteristically exacerbated by large meals, supine posture, or bending over and temporarily alleviated by food or antacids. Heartburn ranges in severity from an occasional episode of postprandial discomfort without sequelae to a syndrome of severe esophageal inflammation that can lead to bleeding, stricture, and malignant transformation. Key tasks include deciding who requires endoscopic assessment and selecting the most cost-effective approach to controlling symptoms and preventing serious sequelae.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15)

Normal Esophageal Physiology

The physiologic action of the lower esophageal sphincter (LES) is critical to maintaining a pressure barrier between the stomach and the esophagus. The LES is a complicated region of smooth muscle modulated by the interaction of hormonal, neural, and dietary factors. The hormone gastrin increases its resting tone, whereas estrogens, progesterone, glucagon, secretin, and cholecystokinin all decrease sphincter pressure. Vagus nerve input helps maintain resting tone, as does α-adrenergic stimulation. Pharmacologic agents that increase sphincter tone include bethanechol, metoclopramide, pentobarbital, histamine, edrophonium, and antacids. Anticholinergics, theophylline, meperidine, and the calcium channel blockers all decrease the resting tone. Saliva may add an important protective mechanism, inducing peristalsis in addition to aiding in washout, dilution, and neutralization of acid refluxed into the esophagus.

Mechanisms of Reflux

GERD is a multifactorial problem, involving reduction in resting LES tone, transient episodes of inappropriate relaxation of the LES, irritant action of gastric acid and digestive enzymes, decreased secondary peristalsis, and defective mucosal resistance to caustic liquids. Also implicated are impaired esophageal clearance of acid from the esophagus and delayed gastric emptying.

LES pressures vary and overlap enormously between those with and without symptomatic reflux. Normal pressure ranges from 12 to 30 mm Hg. LES pressures below 6 mm Hg are apt to allow reflux, and those above 20 mm Hg usually prevent it. Pressures between 6 and 20 mm Hg are found in both patients and controls. In many patients, reflux occurs as a result of transient episodes of inappropriate sphincter relaxation rather than low basal tone.

Anatomic factors, such as the presence of a hiatus hernia, are not as important as they once were believed to be, but patients with hiatus hernia may be modestly predisposed to reflux disease. A portion of the esophagus must be situated intraabdominally for optimal esophageal function and sphincter competence; moreover, peristaltic clearing of acid is impaired in patients with a hiatus hernia. Obesity increases the risk of symptomatic GERD, particularly in premenopausal women and those taking estrogen, suggesting a contributing role for estrogen.

Contributing factors include tobacco, ethanol, chocolate, and foods with high concentrations of fat or carbohydrate, all of which decrease LES pressure and increase heartburn. Citrus fruits and fruit juices may exacerbate symptoms; the mechanism by which they cause heartburn is not clear. Although pregnancy may cause reflux because of increased intraabdominal pressure, the primary reason for heartburn in pregnancy is reduced sphincter pressure as a consequence of increased circulating levels of progesterone and estrogen. Reflux can be precipitated in normal persons by exercise, with jogging after meals the most common cause. There is no clear etiologic link between Helicobacter pylori infection and GERD; in fact, the frequency of H. pylori in GERD populations appears to be lower than in those without GERD.

Clinical Features

Heartburn

Heartburn often accompanies gastroesophageal reflux. The patient characteristically complains of retrosternal ache or burning within 30 to 60 minutes of eating, especially after large meals. Symptoms are made worse by lying down or bending over; many patients learn to avoid lying down after meals. Reflux may trigger chest pain that can mimic cardiac angina, with some patients describing chest heaviness or pressure that, like angina, may radiate to the neck, jaw, or shoulders (see Chapters 20 and 60).

Regurgitation

Regurgitation of fluid or food particles may occur, particularly at night. The patient may describe soiling of the pillow with gastric contents or may awake because of coughing or a strangling sensation. Nocturnal aspiration is occasionally associated with gastroesophageal reflux and can cause recurrent pneumonias, bronchospasm, and chronic cough. Patients with reflux sometimes describe a reflex salivary hypersecretion or “water brash.” Water brash is especially common in children, but direct questioning is often required to determine its occurrence. Hoarseness, sore throat, and the feeling of a lump in the throat are other common otolaryngologic manifestations of reflux.

Painful or Difficult Swallowing (Odynophagia, Dysphagia)

Painful or difficult swallowing usually suggests long-standing reflux disease with active inflammation, stricture, or both. Solid food may stick in the distal esophagus (with or without stricture formation), although food usually passes into the stomach after repeated swallowing or drinking liquids unless a fairly tight obstruction is present (see Chapter 60). Odynophagia is seen in cases complicated by severe erosion and may be a symptom of malignancy or infection.

Barrett Esophagus and Adenocarcinoma

A severity-related risk for adenocarcinoma of the esophagus is conferred by symptomatic reflux. In a substantial number of patients with long-standing severe reflux, a premalignant change develops that is referred to as Barrett esophagus, which denotes metaplastic columnar epithelialization of the distal esophagus. Barrett esophagus is believed to represent a reparative response to tissue injury from chronic exposure to gastric acid, pepsin, and bile. Histologically, the normal stratified squamous epithelium of the mucosa is replaced by columnar epithelium. Dysplastic transformation may ensue and eventually lead to adenocarcinoma.

The link between Barrett and adenocarcinoma was identified in the 1970s, and the initial concern was quite high. However, subsequent large population studies have lowered the risk estimates, with current estimates 0.12% (1 case per 860 patient-years) for the development of esophageal cancer in patients with Barrett. Evidence shows that patients with Barrett esophagus have the life expectancy similar to the general population and esophageal cancer is actually an uncommon cause of death in persons with Barrett regardless of the cancer screening strategy. However, the survival of patients with esophageal adenocarcinoma is poor and remains the driving force in screening programs.

Esophageal Ulcers, Strictures, and Hemorrhage

Esophageal ulcers, strictures, and hemorrhage may also develop as a consequence of chronic severe esophagitis. Bleeding may be slow and chronic, resulting in iron deficiency anemia, or brisk, resulting in hematemesis.

Dental Erosions

Dental erosions occur in a substantial proportion of patients with marked reflux as a consequence of the effects of acid and bile on tooth enamel. Patients with teeth erosions of unknown etiology are often found to have reflux on evaluation.

Reflux-Induced Asthma and Laryngitis

Reflux-induced asthma and laryngitis are among the airway consequences of chronic GERD. Unexplained wheezing, voice change, chronic cough, and lump in the throat are among the symptoms reported; reflux must be considered when such complaints develop in the absence of a known cause.

DIFFERENTIAL DIAGNOSIS (5,13,16, 17, 18 and 19)

The diagnosis of GERD is secure when the patient describes heartburn and experiences regurgitation of stomach contents. However, many patients report only a dull substernal discomfort or ache, and in such circumstances, the physician must consider myocardial ischemia, esophageal spasm or high-amplitude esophageal peristalsis, eosinophilic esophagitis, cholelithiasis, and mediastinal inflammation. Gastroesophageal reflux may accompany peptic ulcer disease (particularly in gastric hypersecretory conditions) and cancer of the gastroesophageal junction. Esophageal infections with opportunistic organisms such as cytomegalovirus, herpesvirus, and Candida albicans can cause heartburn in the immunocompromised host. Reflux esophagitis may also accompany intestinal dysmotility syndromes, including intestinal pseudoobstruction and scleroderma. Diabetic gastroparesis may predispose a patient to reflux and heartburn because of retarded emptying of gastric contents.

WORKUP (5,6,13,16, 17, 18, 19, 20, 21, 22 and 23)

History

The characteristic history of a retrosternal burning sensation radiating upward, associated with large meals and supine posture, is virtually diagnostic of reflux disease. An attempt should
be made to identify any aggravating factors, such as intake of fatty foods, concentrated sweets, chocolate, alcohol, peppermint, coffee, tea, anticholinergics, calcium channel blockers, and theophylline compounds. The use of drugs capable of causing esophageal injury (nonsteroidal anti-inflammatory drugs, quinidine, wax-matrix potassium chloride tablets, tetracycline, and bisphosphonates) should also be elicited. Inquiry should be made regarding response to food or antacids. Surgery near the gastroesophageal junction (e.g., antireflux surgery or vagotomy) may predispose the patient to reflux disease. A history of Raynaud phenomenon raises the possibility of scleroderma. Consideration of achalasia, malignancy, esophagitis, and stricture is indicated if dysphagia is part of the clinical presentation (see Chapter 60).

Diagnostic Studies and Empiric Trials

Since GERD is a clinical diagnosis, no single test is accepted as the standard for the diagnosis of reflux disease. A careful history is sufficient to establish the diagnosis in the majority of patients, and laboratory tests are needed only in atypical or severe cases. When a classic reflux story is elicited, initial therapy can be instituted on the basis of history alone for simple heartburn in a young patient. A brief trial of high-dose proton pump inhibitor therapy is a reasonably sensitive (75%) and cost-effective confirmatory test in patients with classic GERD symptoms.

Upper Endoscopy and Biopsy

Upper endoscopy should be considered for patients with any of the “alarm features” such as dysphagia, weight loss, anemia, or positive fecal occult blood test. Biopsy is done during endoscopy to target any areas of suspected metaplasia or dysplasia. If the mucosa shows no visual abnormalities, it is still appropriate to biopsy to evaluate for eosinophilic esophagitis. A detailed evaluation is especially important in older patients, in whom the risk for malignancy is increased (see Table 61-1).

Esophageal pH Monitoring and Physiologic Testing

Esophageal pH monitoring for 24 hours is the most sensitive and specific test for reflux, but usually unnecessary for common cases of GERD. However, it does allow correlation of distal esophageal pH with symptoms and can be of help in confusing situations, such as atypical chest pain, ENT, and pulmonary symptoms (see Chapter 60). Two-channel pH monitoring includes a second probe near the proximal esophagus and may identify acid reflux causing airway irritation. Two other tests, esophageal manometry and esophageal impedance studies can be even more sensitive than the pH probe by giving some inference of the volume of refluxant.

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