Health Questions and Answers

Gastroesophageal Reflux Disease

What is gastroesophageal reflux disease (GERD)? How common is it?
GERD is a pathologic condition of symptoms and injury to the esophagus caused by percolation of gastric or gastroduodenal contents into the esophagus. GERD is extremely common. One survey of hospital employees showed that 7% experienced heartburn daily, 14% experienced symptoms weekly, and 15% monthly. Other studies have suggested a 3-4% prevalence of GERD among the general population, with a prevalence increase to approximately 5% in people older than age 55. Pregnant women have the highest incidence of daily heartburn at 48-79%. The distribution of GERD between the sexes is equal, but men are more likely to suffer complications of GERD esophagitis (2-3:1) and Barrett’s esophagus (10:1).

What are the typical symptoms of GERD?
Heartburn is usually characterized as a midline retrosternal burning sensation that radiates to the throat and, occasionally, to the intrascapular region. Patients often place the open hand over the sternal area and flip the wrist in an up-and-down motion to simulate the nature and location of the heartburn symptoms. Mild symptoms of heartburn are often relieved within 3-5 minutes of ingesting milk or antacids. Other symptoms of GERD include the following:

  1. Regurgitation consists of eructation of gastric juice or stomach contents into the pharynx and is often accompanied by a noxious bitter taste. Regurgitation is most common after a large meal and occurs usually with stooping or assuming a recumbent posture.
  2. Dysphagia (difficulty in swallowing) is usually caused by a benign stricture of the esophagus in patients with long-standing GERD. Solid foods, such as meat and bread, are often precipitants of dysphagia. Dysphagia implies significant narrowing of the esophageal lumen, to usually a luminal diameter <13 mm. Prolonged dysphagia, associated with inability to swallow saliva, requires prompt evaluation and often endoscopic removal.
  3. Waterbrash is an uncommon symptom but highly suggestive of GERD. Patients literally foam at the mouth because the salivary glands produce up to 10 mL/min of saliva as an esophagosalivary reflex response to acid reflux.

Is gastrointestinal (GI) hemorrhage a common symptom of GERD?
No. Endoscopic evaluation of patients with upper GI hemorrhage has identified erosive GERD as the cause in only 2-6% of cases.

What is odynophagia? Is it a common symptom of GERD?
Odynophagia is a painful substernal sensation associated with swallowing that should not be confused with dysphagia. Odynophagia rarely results from GERD. Instead, odynophagia is caused by infections (monilia, herpes simplex virus, and cytomegalovirus), ingestion of corrosive agents or pills (tetracycline, vitamin C, iron, quinidine, estrogen, aspirin, alendronate [Fosamax], or nonsteroidal anti-inflammatory drugs), or cancer.

What clues about GERD can be gleaned from the physical exam?

  1. Severe kyphosis is often associated with hiatal hernia and GERD, especially when a body brace is necessary.
  2. Tight-fitting corsets or clothing (in men or women) can increase intra-abdominal pressure and may cause stress reflux.
  3. Abnormal phonation may suggest high GERD and vocal cord injury. When hoarseness is due to high GERD, the voice is often coarse or gravelly and may be worse in the morning, whereas in other causes of hoarseness, excessive voice use or abuse leads to worsening later in the day.
  4. Wheezing or asthma and pulmonary fibrosis have been associated with GERD. Patients often give a history of postprandial or nocturnal regurgitation with episodes of coughing or choking caused by near or partial aspiration.
  5. Loss of enamel on the lingual surface of the teeth may be seen in severe GERD, although it is more common in patients with rumination syndrome or bulimia.
  6. Esophageal dysfunction may be the predominant component of scleroderma or mixed connective tissue disease. Inquiry about symptoms of Raynaud’s syndrome and examination for sclerodactyly, taut skin, and calcinosis are important.
  7. Cerebral palsy, Down syndrome, and mental retardation are commonly associated with GERD.
  8. Children with peculiar head movements during swallowing may have Sandifer’s syndrome.
  9. Some patients unknowingly swallow air (aerophagia) that triggers a burp, belch, and heartburn cycle.

The observant clinician may detect this behavior during the interview and physical exam.

Do healthy persons have GERD?
Yes. Healthy persons may regurgitate acid or food contents into the esophagus, especially after a large meal late at night. In normal persons, the natural defense mechanisms of the lower esophageal sphincter barrier and esophageal clearance are not overwhelmed, hence symptoms and injury do not occur. Ambulatory esophageal pH studies have shown that healthy persons have acid reflux into the esophagus <2% of the daytime (upright position) and <0.3% of the nighttime (supine position).

How can swallowing and salivary production be associated with GERD?
Reflux of gastric contents into the esophagus often stimulates salivary production and increased swallowing. Saliva has a neutral pH, which helps to neutralize the gastric refluxate. Furthermore, the swallowed saliva initiates a peristaltic wave that strips the esophagus of refluxed material (clearance). During the awake upright period, persons swallow 70 times/h; this rate increases to 200 times/h during meals. Swallowing is least common during sleep (<10 times/h), and arousal from sleep to swallow during GERD may be reduced by sedatives or alcohol ingestion. Patients with Sjögren’s syndrome and smokers have reduced salivary production and prolonged esophageal acid clearance times.
What clearance defects are associated with GERD?

  1. Esophageal. Normally, reflux of gastric contents into the esophagus stimulates a secondary peristaltic or clearance wave to remove the injurious refluxate from the esophagus. The worst case of ineffective esophageal clearance is seen in patients with scleroderma. The lower esophageal sphincter barrier is nonexistent, and there is no primary or secondary peristalsis of the esophagus (hence, no clearance).
  2. Gastric. Gastroparesis may lead to excessive quantities of retained gastroduodenal and food contents. Larger volumes of stagnant gastric contents predispose to esophageal reflux.

How may the gastroesophageal (GE) barrier be compromised?
The normal lower esophageal sphincter (LES) is 3-4 cm long and maintains a resting tone of 10-30 mmHg pressure. The LES acts as a barrier against GERD. When the LES pressure is <6 mmHg, GERD is common; however, the presence of “normal” LES pressure does not predict absence of GERD. In fact, LES pressure <10 mmHg is found in a minority of people with GERD. Recent studies have shown that transient LES relaxations (tLESRs) are important in the pathogenesis of GERD. During tLESR, the sphincter inappropriately relaxes and free gastric reflux occurs.

What other medical conditions may mimic symptoms of GERD?

The differential diagnosis of GERD includes coronary artery disease, gastritis, gastroparesis, infectious and pill-induced esophagitis, peptic ulcer disease, biliary tract disease, and esophageal motor diseases.

How can GERD be distinguished from coronary artery disease?

In the evaluation of patients with retrosternal chest pain, the clinician must always be mindful that patients with GERD do not die, but patients with new-onset angina or an acute myocardial infarction with symptoms mimicking GERD can. Clues that a patient’s chest pain is cardiac in origin include radiation of the pain to the neck, jaw, or left shoulder/upper extremity; associated shortness of breath and/or diaphoresis; precipitation of pain by exertion; and relief of pain with sublingual nitroglycerin. Physical findings of new murmurs or gallops or abnormal rhythms are also suggestive of a cardiac origin. Although positive findings on an electrocardiogram (ECG) are helpful in the evaluation of patients with chest pain, the absence of ischemic ECG changes should not discourage the clinician from excluding a cardiac etiology for the patient’s symptoms.

How should patients with symptoms of GERD be evaluated?
Evaluation of patients with GERD may be guided by the severity of symptoms. Patients without symptoms of high GERD (aspiration or hoarseness) or dysphagia may be given careful instruction about lifestyle modification and a diagnostic trial of H2-blocker therapy and followed clinically. Diagnostic evaluation is warranted when symptoms of GERD are chronic or incompletely responsive to medical therapy. Esophagogastroduodenoscopy (EGD) is the single best test for evaluation of GERD. Up to 50% of patients with GERD do not have macroscopic evidence of esophagitis at the time of endoscopy. In this group, more sensitive GER testing may be necessary or alternative diagnoses considered.

What are the more sophisticated esophageal function tests? How can they be used appropriately in the evaluation of patients with GERD?
Clinical tests of GERD may be divided into three categories:

  • Acid sensitivity
    Acid perfusion (Bernstein) test
    24- to 48-hour ambulatory esophageal pH monitoring
  • Esophageal barrier and motility
    Esophageal manometry
    Gastroesophageal scintiscanning
    Standard acid reflux (modified Tuttle) test
    24- to 48-hour ambulatory esophageal pH monitoring
  • Esophageal acid clearance time
    Standard acid reflux clearance test (SART)
    24- to 48-hour ambulatory esophageal pH monitoring

Do all patients with GERD need esophageal function testing?
No. Testing should be reserved for patients who fail medical therapy or in whom the correlation of reflux symptoms is in doubt.

When is ambulatory esophageal pH monitoring helpful?
Ambulatory esophageal pH monitoring is helpful in evaluating patients refractory to standard medical therapy. Acid hypersecretion is often seen in patients with GERD, and esophageal pH monitoring may be helpful in titrating the dose of H2-blocker or proton pump inhibitor (PPI). Persistence of acid reflux on “adequate” doses of a PPI should raise the possibility of patient noncompliance or Zollinger-Ellison syndrome.
The Bravo capsule (Medtronix, Inc., Minneapolis, MN) is a new wireless technology that permits more physiologic intraesophageal monitoring for acid reflux. The Bravo capsule is the size of a gel cap and placed with or without endoscopic assistance 6 cm above the squamocolumnar junction. The capsule is “stapled” to the esophageal mucosal permitting more physiologic and prolonged intra-esophageal monitoring. Some investigators have begun to “staple” the capsule in the proximal esophagus to evaluate patients with atypical reflux symptoms, such as hoarseness, throat tightness, asthma, and interstitial lung disease.

When are esophageal manometry and scintiscanning helpful?
Esophageal manometry is helpful in evaluating the competency of the LES barrier and the body of the esophagus for motor dysfunction. Severe esophagitis may be the sole manifestation of early scleroderma. When ambulatory pH testing is not available, scintiscanning has been shown to be helpful.

What are some of the new endoscopic treatments for GERD?

  1. Endoluminal gastroplication (ELGP): Endocinch by CR Bard, Inc., or Endoscopic Suturing Device by Wilson Cook, Inc.
  2. Single full-thickness plication: NDO Endoplication System by NDO Surgical, Inc. (not FDA approved)
  3. Coagulation injury: Stretta by Curon Medical, Inc.
  4. Polymer injection: Enteryx by Boston Scientific Corp.

What is Barrett’s esophagus? How is it managed?
Barrett’s esophagus is a metaplastic degeneration of the normal esophageal lining, which is replaced with a premalignant, specialized columnar epithelium. It is seen in roughly 5-7% of patients with uncomplicated reflux but in up to 30-40% of patients with scleroderma or dysphagia.
Currently, there is no proven method to eliminate Barrett’s esophagus. Preliminary studies of laser or bicap ablation of the metaplastic segment followed by alkalization of the gastroesophageal refluxate are encouraging. The need for cancer surveillance is discussed elsewhere in this book.

Is there an association between obstructive sleep apnea (OSA) and GERD?
Yes. Nocturnal acid reflux is seen in 54-72% of persons with OSA. Administration of nighttime continuous positive airway pressure (CPAP) and/or proton pump inhibitor therapy have been shown to decrease apnea and acid reflux events.

Does the presence of heartburn symptoms predict a GERD-related cough etiology?
No. There is poor correlation between symptoms of heartburn and cough. Between 43% and 75% of patients with GERD-related cough do not have heartburn symptoms. Both medical treatment with PPIs and surgical antireflux procedures have been reported to be effective for GERD-related cough. Caveats include:

  • 35% response rate to omeprazole 40 mg two times/day after 2 weeks
  • Results of surgical antireflux procedures are best when preoperative esophageal manometry is normal and response to PPI is positive.

What is the best method to evaluate for possible GERD-related cough?
The first step is to exclude non-GERD-related etiologies: angiotensin-converting inhibitors, environmental irritants, smoking, parenchymal lung disease, allergic rhinitis and pneumonitis, and asthma and sinusitis, which are often “silent.” Symptom relief after a 2-week trial of Prilosec (or equivalent), 40 mg two times/day, is a cost-effective approach. Patients who do not respond should be considered for further evaluation, including esophageal manometry/pH testing and/or EGD.

What is the most efficient, cost-effective method to evaluate hoarse patients for EPR?
The first step in the evaluation of hoarseness should be exclusion of structural ear, nose, and throat (ENT) disorders, including neoplasm. The next step is an empiric trial of double-dose PPI for 2-3 months. Most EPR-related hoarseness improves with acid suppression (60-96%). Patients responding to PPIs may stop the medication and be monitored for recurrence of symptoms. Hoarse patients with a negative ENT evaluation, who fail PPI therapy, should undergo formal esophageal pH analysis.

Can gastroesophageal reflux worsen asthma?
Yes. Numerous studies have shown that reflux symptoms are common among asthmatics (65-72%) and that medical and surgical antireflux treatment may improve pulmonary function.

How does gastroesophageal reflux worsen asthma?
Several mechanisms are theorized to explain GERD-induced bronchospasm:

  • Asthmatics with GERD have been shown to have autonomic dysregulation with heightened vagal response, which is presumed to be responsible for the decrease in LES pressure and more frequent transient relaxations of the LES, which promote reflux.
  • Esophageal reflux may incite a vagal-mediated esophagobronchial reflex of airway hyperreactivity.
  • Microaspiration of gastric juice has been shown to activate a local axonal reflex involving release of substance P, which leads to airway edema. The finding of lipid-laden alveolar macrophages among asthmatics demonstrates aspiration of gastric material into the pulmonary tree.

Which patients with GERD should be considered for a surgical antireflux procedure?
Any young, healthy patient with chronic GERD requiring lifelong PPI medical therapy may be considered for an antireflux procedure. Other indications include failed medical therapy, complicated GERD (e.g., bleeding, recurrent strictures), medical success at excessive cost in young, otherwise healthy patients, and problematic symptoms due to regurgitation (asthma, hoarseness, cough).

What is the best endoscopic or surgical antireflux procedure?
Rapid advances in endoscopic and laparoscopic surgery make this question unanswerable. Novel endoscopic suturing, burning, and injection techniques are exciting, but results are only preliminary. A comparative trial of endoscopic and surgical antireflux techniques is necessary.

What cytochrome p-450 (CYP-450) systems are involved in the metabolism of PPIs?
All of the PPIs undergo some hepatic metabolism through the CYP-450 system. The CYP-2C19 and CYP-3A4 microsomal enzymes are responsible for the majority of PPI hepatic metabolism. Genetic polymorphism with CYP-2C19 is common; about 5% of Americans and 20% of Asians are deficient in this enzyme. Omeprazole decreases the metabolism of phenytoin and warfarin R-isomer (CYP-2C9), diazepam (CYP-2C19), and cyclosporine (CYP-3A4).

How do esomeprazole (Nexium) and omeprazole (Prilosec) differ?
Omeprazole is a racemic mixture of both the S- and R-isomers, whereas esomeprazole is a “pure” form of the S-isomer. Less esomeprazole (S-isomer) is metabolized by the CYP-2C19 pathway, leading to greater area under the curve and better intragastric acid suppression for 24 hours. Esomeprazole is the only PPI shown to be statistically superior to omeprazole in healing erosive esophagitis at 8 weeks (90-94% efficacy rate).

Date Last Modified: March 21, 2010



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