Acid Reflux Relief

The mechanism for acid reflux appears to be

more complex than previously thought

Since acid reflux has been documented in people with normal sphincter pressures, it is likely that other factors are involved in the onset of gastroesophageal reflux disease. A better understanding of the pathophysiology of acid reflux demands a more thorough diagnostic effort so that appropriate treatment can be instituted.

1.What causes gastroesophageal reflux?

The presence of a competent lower esophageal sphincter (LES) was thought to be the greatest and most important barrier to acid reflux. However, since acid reflux has been documented in patients with normal sphincter pressures, it is likely that there are other factors involved in the onset of gastroesophageal reflux disease. Prolonged manometric recordings in people with esophagitis, as well as in normal subjects, demonstrate that approximately two thirds of acid reflux events in people with esophagitis occur during transient LES relaxation. These relaxations occur spontaneously, are not initiated through swallowing, and are associated with a normal LES pressure. The remaining episodes of acid reflux in patients with esophagitis appear to be related to hypotension of the LES or to be a result of increased intra-abdominal pressure. Additional irregularities of the normal barriers to acid reflux have been associated with reflux disease. For instance, disorders of esophageal motility, including diminished force of contraction, may delay clearance of the refluxant from the esophagus. In patients with chronic xerostomia, there may be reduced clearance of acid from the esophagus. Gastric distension or delayed emptying of the stomach may exacerbate gastroesophageal reflux.

Some acid reflux medications appear to have a deleterious effect on LES pressure. Calcium channel antagonists, anticholinergic agents, theophylline preparations, and nitrates decrease LES pressure and therefore increase the risk of acid reflux. Exercise, especially during the postprandial period, can induce typical symptoms of acid reflux disease in normal, healthy subjects. In addition, some patients may develop noncardiac chest pain as a manifestation of exercise-related gastroesophageal reflux.

2. What agents are implicated in acid reflux disease?

Acid is most often implicated as the injurious agent in gastroesophageal reflux. Support for its role as a damaging agent is found in patients with gastrinomas, who have a high incidence of reflux esophagitis. Other evidence comes from patients with reflux disease, who often respond to H2 antagonists, as well as from findings from prolonged pH studies that demonstrate a correlation between decreased pH and reflux symptoms. However, nonacid material may also be involved, since patients who produce little or no acid, due to achlorhydria or gastric surgery, can develop reflux disease. Pepsin, bile, small-intestinal fluid, and pancreatic secretions are potential mediators for nonacid injury. Bile acids can cause damage to the esophageal lining, and their effect is potentiated in an acid milieu. Patients with Barrett's metaplasia appear to have a higher incidence of alkaline and mixed refluxes. Recognition that damage to the esophagus can be caused by multiple agents is important, as it has a profound impact on treatment.

3. Does reflux disease present in other ways?

Although the majority of patients with gastroesophageal reflux disease have typical symptoms of acid reflux, as many as 25 percent of patients present with extraesophageal manifestations. These patients may experience hoarseness, coughing, wheezing, aspiration, voice change, otalgia, pharyngitis, laryngitis, or frequent throat clearing. Pulmonary disease may be linked to gastroesophageal reflux in some patients. The relationship between nonallergic asthma and gastroesophageal reflux has been well-established. Therapy with histamine antagonists in these patients has been associated with improvement of pulmonary function tests, including FEV1 and FVC. Two mechanisms have been postulated in the pathophysiology of pulmonary manifestations of gastroesophageal disease. The first is acid-induced injury from aspiration of gastric contents. This is probably the most common mechanism responsible for lung damage. In these cases, pH monitoring will demonstrate a decrease in esophageal pH along with simultaneous wheezing or coughing.

A neural reflex has also been found to play an important role in the pathogenesis of reflux-induced pulmonary disease. Broncho-constriction and increased pulmonary flow resistance in response to esophageal mucosal injury from acid have been observed. In experiments performed in dogs, bilateral vagotomy has been shown to blunt the bronchoconstriction response to intraesophageal acid, implicating a vagally mediated event.

4. How does acid reflux disease affect children?

Gastroesophageal reflux disease should be considered in the pediatric population in the differential diagnosis of vomiting, failure to thrive, irritability, gastrointestinal bleeding, and sleep disturbances. Chronic pulmonary disease may be a sequela of reflux. Asthma, chronic cough, recurrent pneumonia, bronchospasm, and bronchitis may be caused by gastroesophagealreflux, and these disorders often respond to standard antireflux therapy. Gastroesophageal reflux is also a possible factor in infants with apnea. Reflux has been documented by pH monitoring in nearly half of infants with apparent life-threatening events. Infants at risk for sudden infant death syndrome should be evaluated for gastroesophageal reflux disease. By identifying the cause, administration of appropriate therapy can improve the sleep-related disturbances.

5. How should people be evaluated for acid reflux?

A careful, detailed clinical history is important. The physical examination is also essential to the evaluation, although it is often unrevealing. In the diagnostic evaluation, barium radiographs and endoscopy with or without biopsy may be useful to identify morphologic changes. The Bernstein test and 24-hour pH monitoring should be undertaken to determine if symptoms are reflux-related. For the evaluation of motility, manometry and/or scintigraphy may be used. The physician needs to tailor the diagnostic workup to the individual. Scintigraphy is particularly helpful in a subset of patients with reflux. Esophageal transit scintigraphy using radio labeled water may demonstrate delayed clearance. Patients with scleroderma have been shown to have delayed transit from the esophagus, an observation that correlates with the classic findings of aperistalsis of the distal esophagus and severe hypotonia of the LES. Researchers have tried scanning the lung fields and the appropriate region of the esophagus following the ingestion of a radio-labeled meal to detect aspiration. However, these studies do not reliably detect aspiration. The 24-hour pH monitor has become the gold standard in the evaluation of a patient with suspected gastroesophageal reflux; it is especially valuable for patients who present with atypical symptoms. Two or three probe units can simultaneously measure gastric and esophageal pH or measure at different sites in the esophagus and the stomach. Using shorter periods of analysis, including 12-hour postprandial recordings, may be a less expensive and accurate method of diagnosing gastroesophageal reflux.

6. What is the approach to medical therapy for gastroesophageal reflux?

The foundation of therapy for gastroesophageal reflux disease rests on lifestyle changes (Table 2). Patients should avoid large meals and irritating foods, such as citrus fruits. Also to be avoided are foods and drugs that decrease LES pressure, including caffeine, fats, nicotine, alcohol, peppermints, calcium channel antagonists, progesterone-containing agents, and nitrates. Other important steps in the treatment of gastroesophageal reflux disease are weight reduction, avoidance of clothes that fit tightly about the abdomen, and elevation of the head of the bed with bricks or blocks. Antacids may be used for mild or occasional symptoms. However, for more symptomatic disease, H2-receptor antagonists should be prescribed. Typically, patients with gastroesophageal reflux disease require double or triple the usual dose of H2 blockers for symptom control. Al-tentatively, the addition of a cytoprotective agent, such as sucralfate, can be considered.

7. Are there new acid reflux medicines on the horizon?

The treatment of severe gastroesophageal reflux disease has been revolutionized by the recent development of proton-pump inhibitors, such as omeprazole. These agents act by completely suppressing acid production and are especially useful in the treatment of patients with severe, persistent disease. New medications awaiting approval include the prokinetic agents, domperidone and cisapride. These agents increase LES pressure and accelerate gastric emptying. Cisapride also increases the amplitude and duration of esophageal contractions, and it has been shown to also decrease the duration of acid exposure in the esophagus. Use of prokinetic agents in combination with H2 antagonists may be superior to either medication alone.

8. What are the Iong-term concerns in acid reflux disease?

Patients with a lengthy history of acid reflux or complicated gastroesophageal reflux disease should be evaluated for Barrett's esophagus, in which the normal squamous epithelium is replaced with columnar mucosa. Three distinct types of columnar epithelium have been documented in this condition: fundic, junctional (similar to gastric cardia), and specialized columnar (similar to small bowel with a villous appearance). The importance of diagnosing Barrett's esophagus relates to its associated increased risk of adenocarcinoma of the esophagus.

Unfortunately, Barrett's metaplasia is resistant to both medical and surgical intervention. Despite maximal and optimal therapy for reflux, nothing will cause Barrett's epithelium to revert to squamous epithelium. Patients with Barrett's metaplasia, especially those with specialized columnar epithelium, should undergo screening upper endoscopy with biopsy and cytology in order to look for evidence of dysplasia.

Esophageal strictures are also a complication of gastroesophageal reflux disease. Progressive dysphagia is a common complaint in these patients. Mechanical dilation is the most commonly used therapeutic modality and is usually accomplished with a variety of dilatots. Savary-Gilliard dilators have become widely used. They are available in a range of sizes, are passed over a flexible-tipped wire, and have a radiopaque marker to permit fluoroscopic monitoring. Alternatively, a Gruntzig-type pneumatic balloon that can be passed via the endoscope and therefore directly viewed can also be utilized. These can be monitored under fluoroscopy and can be insufflated with air or radiopaque contrast. In general, endoscopic dilation of esophageal strictures can be performed successfully and safely.

9. When should acid reflux surgery be considered?

Generally, surgical intervention should be considered in patients who continue to experience persistent disease or symptoms despite optimal medical therapy. Approximately 10 percent of all patients with gastroesophageal reflux disease fail despite optimal medical therapy. Antire-flux procedures, including transabdominal fundoplication (Nissen), transabdominal gastropexy (Hill), or transthoracic fundoplication (Belsey), create or augment the physical barrier to reflux. Although surgery has resulted in demonstrated improvement of the symptoms and endoscopic signs of esophagitis in the short term, long-term results are less encouraging. In addition, there is no documentation of regression of Barrett's metaplasia following fundoplication.

Table 1 Extraesophageal Manifestations of Gastroesophageal Reflux Disease

PULMONARY

          Aspiration                   Penumonia
          Chronic Cough             Interstitial Fibrosis
          Asthma                      Sleep apnea
          Bronchitis                   Bronchiectasis
          Bronchopasm               Hoarseness/laryngitis

CARDIAC

          Bradycardia                  Tachyarrhythmia

HEAD AND NECK

          Otitis media                 Enamel decay
          Dysphonia                   Pharyngitis

Table 2 Lifestyle Modifications for Reflux Esophagitis

    * Elevate head of the bed six inches (either with blocks under the head of the bed frame or with a wedge)
    * Stop smoking
    * Minimize intake of alcohol, fat, chocolate, carminatives (spearmint, peppermint), tea, cola beverages, tomato-based items, citrus fruite and juices.
    * Avoid large meals
    * Avoid lying down for three to four hours after a meals and avoid bedtime snacks
    * Achieve and maintain ideal body weight
    * Avoid, if possible, drugs known to decrease the LSE pressure: anticholinergics, theophylline, diazepam, narcotics, calcium channel blockers, beta-adrenergic agonists, progestrone, alpha-adrenegics
    * Avoid tight clothing
    * Avoid activities include bending or lifting or any Valsalva's maneuvers

Last updated Jan 4/07