What is acid reflux?

Recurrent heartburn, when properly defined, is the hallmark of Acid Reflux Disease and enables the diagnosis to be made by the history alone. The heartburn associated with Acid Reflux Disease typically occurs once or twice per day and lasts from a few minutes to an hour or more if untreated. This pattern recurs, but with considerable variation in frequency and severity. However, neither the frequency, severity, nor duration of heartburn predicts disease severity on endoscopy. Acid Reflux Disease can also be associated with dysphagia, an alarm symptom because it raises concern for the presence of a peptic stricture or adenocarcinoma arising in Barrett's esophagus. For this reason, dysphagia is an indication for early endoscopy.

The damage in Acid Reflux Disease is best assessed by upper endoscopy and esophageal biopsy. Endoscopy may reveal friability, erosions, ulcers, strictures, or Barrett's esophagus in a third of subjects. In the other two thirds, endoscopic findings are normal but esophageal biopsy may show basal cell hyperplasia, elongation of the rete pegs, inflammatory cell infiltrates, cell edema, dilated intercellular spaces in squamous epithelium, or any combination of these findings. “Dilated intercellular spaces” is the earliest detectable lesion in NERD and correlates with heartburn because it reflects “leakiness” of the paracellular pathway to refluxed gastric acid. A barium swallow or upper gastrointestinal series may also detect ulcers, strictures, and hiatal hernias, but it does not reliably detect inflammation, erosions, or Barrett's esophagus.

Although Acid Reflux Disease is often used synonymously with reflux damage to the esophagus, Acid Reflux Disease includes reflux damage to the oropharynx, larynx, and respiratory tract. Consequently, symptoms and signs of Acid Reflux Disease can include sore throat/pharyngitis, earache/otitis, eroded tooth enamel, hoarseness/laryngitis, bronchitis/chronic cough, asthma/wheezing, and aspiration pneumonia. With the exception of pneumonia, which occurs as a result of gross regurgitation and aspiration of mixed gastric content, damage to the oropharynx, larynx, and airways is mediated by refluxed gastric acid. Asthma (wheezing) and bronchitis (chronic cough) can be triggered either directly by contact of acid with airway epithelium (microaspiration) or indirectly through an esophagopulmonary vagal reflex initiated by contact of acid with esophageal epithelium. The frequency with which Acid Reflux Disease causes, as opposed to being caused by, wheezing/asthma, chronic cough/bronchitis, and hoarseness/laryngitis is unknown.

Associated Conditions
Acid Reflux Disease can develop as a consequence of other conditions, such as Zollinger-Ellison syndrome, scleroderma, diabetes mellitus, nasogastric intubation, and pregnancy.

Antegrade esophageal flow is achieved by the act of swallowing with the initiation of primary peristalsis. Gastroesophageal reflux is prevented by the physiologic lower esophageal sphincter (LES).
When the LES fails to function as an effective barrier to reflux, gastroesophageal reflux develops, with the associated complications of mucosal inflammation (reflux esophagitis).
Gastroesophageal reflux disease (GERD) refers to the varied clinical manifestations of reflux of stomach and duodenal contents into the esophagus and is preferable to the term "reflux esophagitis." Although GERD may be associated with a sliding hiatal hernia, the term "symptomatic hiatal hernia" tends to emphasize an anatomic entity and not the underlying pathophysiology. GERD can be characterized by any combination of symptoms and radiologic, endoscopic, or pathologic changes. In its milder manifestations, it is a common disease; its most florid state is uncommon but may be life-threatening.
HEARTBURN
Heartburn is the most common manifestation of esophageal disease and may occur in up to 20% of the population. The term "burning" rather than "pain" is usually used, although heartburn can increase in intensity until it is perceived as chest pain. Patients often illustrate heartburn with a movement of the open hand up and down the sternum, as compared with the stationary, tightly clenched fist of angina pectoris. Heartburn is usually relieved, even if only temporarily, by taking antacids. A constant burning unrelieved by antacids may well be of esophageal origin, but it does not represent heartburn. Heartburn is often worse after recumbency or lifting and may follow overeating or alcoholic indiscretion.
REGURGITATION
Regurgitation of fluid contents into the mouth often accompanies heartburn. Sometimes regurgitation is associated with eructation; often it accompanies bending over, lifting, or lying down at night. The bitter regurgitated fluid is often described as yellow-brown or green. Regurgitation at night may lead to stridor or to wheezing, a hoarse voice, and other respiratory symptoms from unrecognized reflux.
SPONTANEOUS ESOPHAGEAL CHEST PAIN
In addition to the discomfort from severe reflux, which can advance from heartburn into pain, abnormal contractile activity of the esophageal muscle can cause severe chest pain that is clinically indistinguishable from angina pectoris in terms of intensity, radiation, relationship to exercise, and even response to nitroglycerin. pain of esophageal origin can radiate directly through to the back and is often found in patients who also have dysphagia. Esophageal chest pain can last from several seconds to many hours.

Extraesophageal Manifestations
It has been suggested that GER may be the cause of a wide spectrum of conditions including noncardiac chest pain, asthma, posterior laryngitis, chronic cough, recurrent pneumonitis, and even dental erosion. Some of these patients have classical reflux symptoms, but many are “silent refluxers,” contributing to problems in making the diagnosis. Furthermore, it may be difficult to establish a causal relationship even if GER can be documented by testing (e.g., pH studies), because patients may simply have two common diseases without a cause-and-effect relationship.

Chest Pain

GER-related chest pain may mimic angina pectoris. The chest pain is usually described as squeezing or burning, substernal in location, and radiating to the back, neck, jaw, or arm. It often is worse after meals, awakens the patient from sleep, and may worsen during periods of emotional stress. Heavy exercise, even treadmill testing, may provoke GER. Reflux-related chest pain may last minutes to hours, often resolves spontaneously, and may be eased with antacids. Most patients with GERD-induced chest pain have heartburn symptoms. Early studies suggested that spastic motility disorders were the most common esophageal cause of chest pain. However, more recent studies using ambulatory esophageal pH and pressure monitoring suggest that about 25% to 50% of patients with noncardiac chest pain have GERD. Overall, these series of reports found that 41% of patients had abnormal 24-hour pH test results, whereas 32% had chest pain that was clearly associated with acid reflux. Patients with coronary artery disease commonly have coexisting esophageal diseases, but the evidence that GER causes ischemic pain is controversial. The mechanism for GERD-related chest pain is not clearly understood and probably is multifactorial, related to H + ion concentration, volume and duration of acid reflux, and secondary esophageal spasm.

Asthma and Other Pulmonary Diseases

The association of GERD and pulmonary diseases was recognized by Sir William Osler, who recommended that asthmatic patients should “learn to take their large daily meal at noon to avoid nighttime asthma which occurred if they ate a full supper.” More recent studies suggest the coexistence of the two diseases in up to 80% of asthmatic patients, irrespective of the use of bronchodilators. GERD should be considered in asthmatic patients who present in adulthood, those without an intrinsic component, and those not responding to bronchodilators or steroids. Up to 30% of patients with GERD-related asthma have no other esophageal complaints. Other pulmonary diseases associated with GERD include aspiration pneumonia, interstitial pulmonary fibrosis, chronic bronchitis, bronchiectasis, and possibly cystic fibrosis, neonatal bronchopulmonary dysplasia, and sudden infant death syndrome. Proposed mechanisms of reflux-induced asthma are either aspiration of gastric contents into the lungs with secondary bronchospasm or activation of a vagal reflex from the esophagus to the lungs causing bronchoconstriction. Animal and human studies report bronchoconstriction after esophageal acidification, but the response tends to be mild and unpredictable. In contrast, intratracheal infusion of even small amounts of acid induces profound and reproducible bronchospasm in cats. The reflux of acid into the trachea as compared with the esophagus alone predictably caused marked changes in peak expiratory flow rates in asthmatic patients. Although either mechanism may be responsible for reflux-induced asthma, most patients probably suffer from intermittent microaspiration.

Ear, Nose, and Throat Diseases

GERD may be associated with a variety of laryngeal conditions and symptoms, of which reflux laryngitis is perhaps the most common. These patients present with hoarseness, globus sensation, frequent throat clearing, recurrent sore throat, and prolonged voice warmup. Ear, nose, and throat signs attributed to GERD include posterior laryngitis with edema and redness, vocal cord ulcers and granulomas, leukoplakia, and even carcinoma. These changes usually are limited to the posterior third of the vocal cords and interarytenoid areas, both in close proximity to the upper esophageal sphincter. GERD is the third leading cause of chronic cough (after sinus problems and asthma), accounting for 20% of cases. Dental erosion, defined as the loss of tooth structure by chemical processes not involving bacteria, can be caused by GER in healthy persons and in patients with bulimia. Despite the association between ear, nose, and throat diseases and GERD, overt esophagitis usually is absent, and most patients have only mild reflux symptoms, if any. Microaspiration of gastric contents is the most likely cause of these complaints. Animal studies find that the combination of acid and pepsin is very injurious to the larynx. Human studies report that proximal esophageal acid exposure, especially at night while sleeping, is significantly increased in patients with laryngeal symptoms and signs.

Classical Reflux Symptoms
Heartburn is the classical symptom of GERD, with patients generally reporting a burning feeling, rising from the stomach or lower chest and radiating toward the neck, throat, and occasionally the back. Usually, it occurs postprandially, particularly after large meals or the consumption of spicy foods, citrus products, fats, chocolates, and alcohol. Recumbency and bending over may exacerbate heartburn. When heartburn dominates the patients’ complaints, it has very high specificity (89%), but low sensitivity (38%) for GERD as diagnosed by abnormal 24-hour esophageal pH testing. The diagnosis of GERD usually is based on the occurrence of heartburn on 2 or more days a week, although less frequent symptoms do not preclude the disease. Although this symptom is an aid to diagnosis, the frequency and severity of heartburn do not predict the degree of esophageal damage. Heartburn is caused by acid stimulation of sensory nerve endings in the deeper layers of the esophageal epithelium. These nerve endings are normally protected by a relatively impermeable epithelium, but with epithelial changes caused by reflux, they may be stimulated by H + or spicy foods.

Other common symptoms of GERD are acid regurgitation and dysphagia. The effortless regurgitation of acidic fluid, especially after meals and exacerbated by stooping or recumbency, is highly suggestive of GERD. Among patients with daily regurgitation, the LES pressure usually is low, many have associated gastroparesis, and esophagitis is common. For these reasons, acid regurgitation may be more difficult to control medically then classical heartburn complaints. Dysphagia is reported by more than 30% of patients with GERD. It usually occurs in the setting of long-standing heartburn, with slowly progressive dysphagia primarily for solids. Weight loss is uncommon because patients have good appetites. The most common causes are a peptic stricture or Schatzki ring, but other causes include severe esophageal inflammation alone, peristaltic dysfunction, and esophageal cancer arising from Barrett esophagus.

Less common reflux-associated symptoms include water brash, odynophagia, burping, hiccups, nausea, and vomiting. Water brash is the sudden appearance in the mouth of a slightly sour or salty fluid. It is not regurgitated fluid, but rather secretions from the salivary glands in response to acid reflux. Odynophagia, pain on swallowing, can occasionally be seen with severe ulcerative esophagitis. However, its presence should raise the suspicion of an alternative cause of esophagitis, especially infections (candidiasis, herpes) or pills (tetracycline, potassium chloride, quinine, vitamin C, alendronate).

In contrast to the previously described symptomatic presentations, some patients with GERD are asymptomatic. This is particularly true in elderly patients because of decreased acidity of the reflux material or decreased pain perception. Many elderly patients present first with complications of GERD because of long-standing disease with minimal symptoms. For example, up to one third of patients with Barrett esophagus are insensitive to acid at the time of presentation.