Introduction
Background
Excessive retrograde movement of acid-containing gastric secretions or bile and acid-containing secretions from the duodenum and stomach into the esophagus is the etiologic effector of gastroesophageal reflux disease (GERD). Reflux of these secretions to some degree into the esophagus is prevalent in the United States. A study by Richter and a Gallup Organization National Survey estimated that 25-40% of healthy adult Americans experience symptomatic GERD, most commonly manifested clinically by pyrosis (heartburn), at least once a month (Richter, 1992; Gallup, 1988). Furthermore, approximately 7-10% of the adult population in the United States experiences such symptoms on a daily basis.
In most of these people, endogenous defense mechanisms either limit the amount of noxious material that is introduced into the esophagus or rapidly clear the material from the esophagus so that symptoms and esophageal mucosal irritation are minimized. Examples of the defense mechanisms include actions of the lower esophageal sphincter (LES) and normal esophageal motility.
When the defense mechanisms are defective or become overwhelmed so that the esophagus is bathed in acid or bile and acid-containing fluid for prolonged periods, GERD can be said to exist. Patients typically have numerous daily episodes of symptomatic reflux, including pyrosis, water brash or sour taste in the mouth, nighttime coughing or aspiration, pneumonia or pneumonitis, bronchospasm, and laryngitis and voice changes including hoarseness. In addition, objective evidence of esophageal damage can be seen on esophagogastroduodenoscopy as manifested by the incremental grades of esophagitis discussed below.
For excellent patient education resources, visit eMedicine's Heartburn/GERD/Reflux Center. Also, see eMedicine's patient education articles Reflux Disease (GERD), Gastroesophageal Reflux Disease (GERD) FAQs, and Understanding Heartburn/GERD Medications.
Related Medscape topics:
Resource Center GERD
Resource Center Pneumonia
CME Optimizing Clinical Outcomes and Patient Compliance in the Management of GERD
CME Role of Reflux Monitoring in the Evaluation of Patients With Suspected GERD
CME/CE Moderate Weight Gain in Women Linked to GERD
CME Applications of Acid-Suppression Therapy in GERD/Acid-Related Disorders
Pathophysiology
Schematically, the esophagus, LES, and stomach can be envisioned as a simple plumbing circuit as described by Stein and coworkers (Stein, 1992). The esophagus functions as an antegrade pump, the LES as a valve, and the stomach as a reservoir. The abnormalities that contribute to GERD can stem from any component of the system. Poor esophageal motility decreases clearance of acidic material. A dysfunctional LES allows reflux of large amounts of gastric juice, and delayed gastric emptying can increase volume and pressure in the reservoir until the valve mechanism is defeated, leading to GERD. From a medical or surgical standpoint, it is extremely important to identify which of these components is defective so that effective therapy can be applied.
Esophageal defense mechanisms can be broken down into 2 categories, ie, esophageal clearance and mucosal resistance. Proper esophageal clearance is an extremely important factor in preventing mucosal injury. Normal clearance limits the amount of time the esophagus is exposed to refluxed acid or bile and gastric acid mixtures. Abnormal peristalsis can cause inefficient and delayed acid clearance. Whether peristaltic dysfunction is secondary to esophageal exposure to acids or a primary defect is not understood clearly. In a review by Kahrilas et al, peristaltic dysfunction was progressively more common in patients with greater degrees of esophagitis (Kahrilas, 1986). Abnormal peristalsis was identified in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis.
Buttar and associates described the importance of esophageal mucosal resistance as a protective mechanism (Buttar, 2001). They classified the factors into pre-epithelial, epithelial, and postepithelial defenses. When the defenses fail, esophagitis and other complications of reflux disease arise.
Proper LES function is the most important factor in preventing or limiting GERD. The LES is defined by manometry as a zone of elevated intraluminal pressure at the esophagogastric junction. LES dysfunction is the most common etiology of GERD. Dysfunction of the LES occurs via one of several mechanisms. There can be transient relaxation of the LES (most common mechanism), permanent LES relaxation, and transient increase of intra-abdominal pressure that overcomes the LES pressure. Transient relaxation of the LES can be caused by foods (coffee, alcohol, chocolate, fatty meals), medications (beta-blockers, nitrates, calcium channel blockers, anticholinergics), and nicotine.
Delayed gastric emptying may cause GERD. The postulated mechanism is an increase in gastric contents resulting in increased intragastric pressure and, ultimately, increased pressure against the LES. This pressure eventually defeats the LES and leads to reflux. However, objective studies have produced conflicting data regarding the role of delayed gastric emptying in the pathogenesis of GERD.
When discussing mechanisms for GERD, the issue of hiatal hernia must be addressed. It has been well proven that not all patients with hiatal hernias have symptomatic reflux. Buttar and coworkers state that a hiatal hernia may contribute to reflux via a variety of mechanisms. The LES may migrate proximally into the chest and lose its abdominal HPZ, or the length of the HPZ may decrease. The diaphragmatic hiatus may be widened by a large hernia, which impairs the ability of the crura to function as an external sphincter. Finally, gastric contents may be trapped in the hernial sac and reflux proximally into the esophagus during relaxation of the LES.
To summarize, GERD can be caused by malfunction of 1 or more defense mechanisms involving the esophagus (pump), the LES (valve), and the stomach (reservoir).
Frequency
United States
Western dietary habits have made GERD a common disease. Richter and associates reported that 25-40% of Americans experience symptomatic GERD at some point. Approximately 7-10% of Americans experience symptoms of GERD on a daily basis. The actual number of individuals with GERD is probably higher, since most people control the symptoms with over-the-counter medications.
International
The prevalence of GERD internationally appears to be less than in Western society. This appears to be related to the high fat diet typically consumed by Westerners.
Mortality/Morbidity
Complications of GERD include the development of esophagitis, strictures, and Barrett esophagus. Most of the mortality associated with this disease is not due to reflux but to the sequelae of these complications.
- Esophagitis is the most common complication of GERD (see Image 4). Esophagitis may be diagnosed using endoscopy, although it cannot always be appreciated on endoscopy. As many as 50% of symptomatic patients with GERD demonstrate no evidence of esophagitis on endoscopy. Still, documentation of this complication is important in diagnosing GERD. Degrees of esophagitis are described by the Savary-Miller classification as follows.
- Grade I: Single or multiple erosions are found on a single fold; erosions may be erythematous or exudative.
- Grade II: Multiple erosions affect multiple folds.
- Grade III: Multiple circumferential erosions are noted.
- Grade IV: Ulcer, stricture, and esophageal shortening are noted.
- Grade V: Barrett epithelium is noted.
- Strictures are advanced forms of esophagitis and are caused by circumferential fibrosis due to chronic deep injury. Strictures can result in dysphagia and a short esophagus. They can be visualized on upper gastrointestinal (GI) tract studies and endoscopy. Presence of a stricture with a history of reflux also can help diagnose GERD.
- The most serious complication of long-standing or severe GERD is the development of Barrett esophagus. This is defined by metaplastic conversion of the normal distal squamous esophageal epithelium to columnar epithelium. Histologic examination of esophageal biopsy specimens is required to make the diagnosis. Varying degrees of dysplasia may be found on histologic examination. Barrett esophagus with intestinal type metaplasia has malignant potential and is a risk factor for the development of esophageal adenocarcinoma. The incidence of adenocarcinoma of the esophagus is increasing steadily in Western society. Currently, adenocarcinoma accounts for more than 50% of esophageal cancers in Western industrialized nations.
Race
Compared with other groups, white men are at higher risk for the development of Barrett esophagus and esophageal adenocarcinoma. Otherwise, no race is more predisposed than another to developing GERD.
Sex
No sex predilection appears to exist for the development of symptomatic GERD.
Age
GERD is present in all age groups; typically, prevalence increases in individuals older than 40 years.
Anatomy
A thorough discussion of the anatomy of the esophagus and stomach is beyond the scope of this article. This discussion focuses on the pertinent anatomy involved in GERD.
The distal thoracic esophagus is located to the left side of midline. The abdominal esophagus begins as the esophagus enters the abdomen through the esophageal hiatus in the diaphragm. At this point, the esophagus is surrounded by fibroelastic tissue termed the phrenoesophageal membrane or ligament. This membrane arises from the subdiaphragmatic fascia. A prominent fat pad located on the anterior surface of the esophagus marks the lower limit of the phrenoesophageal membrane. This lower limit corresponds to the gastroesophageal junction.
The LES, or more accurately, the distal esophageal high-pressure zone (HPZ) is located in the distal intra-abdominal esophagus. In adults, this HPZ can be anywhere from 2-5 cm in length. Maintenance of an adequate intra-abdominal HPZ is crucial in preventing GERD. This HPZ does not correspond to any visible anatomic structure. It is a zone created by a complex architecture of smooth muscle fibers, and it typically is identified during manometry.
In addition to the esophagus and stomach, an understanding of the esophageal hiatus is mandatory. The hiatus is formed by the right and left diaphragmatic crura. These crura form a sling around the distal esophagus. Both crura originate from the right crus of the diaphragm. The actual contribution the crura provide in maintaining an adequate length of intra-abdominal esophagus is not understood clearly; however, careful identification and closure of the crura during surgical treatment is crucial for preventing reflux disease. Hiatal hernias can be encountered frequently in patients with reflux disease. Reduction of the hernias and crural closure is key to restoring an adequate intra-abdominal length of esophagus and recreating the HPZ.
Usually, GERD is caused by a malfunction of one or more of these anatomic features. Proper surgical treatment requires complete preoperative and intraoperative evaluation and correction of all defective features.
Presentation
Patients with GERD can exhibit a variety of symptoms, both typical and atypical. Typical symptoms include heartburn, regurgitation, and dysphagia. Atypical symptoms include noncardiac chest pain, asthma, pneumonia, hoarseness, and aspiration.
Heartburn is the most common symptom. A clear positional relationship can be demonstrated with exacerbations while the patient is lying supine or bending over. History of nausea, vomiting, or regurgitation should alert the physician to evaluate for delayed gastric emptying. Dysphagia can be an advanced symptom and can be due to a primary underlying esophageal motility disorder, a motility disorder secondary to esophagitis, or stricture formation.
The diagnosis of GERD in patients with atypical symptoms can be difficult. When patients present with atypical complaints, the diagnosis of GERD must be kept in mind. Patients with recurrent aspiration can have asthma, history of pneumonias, and progressive pulmonary fibrosis. Additionally, hoarseness can be present due to chronic laryngeal irritation. Chest pain is another presenting symptom that can be difficult to evaluate. In these patients, excluding cardiac etiology is important prior to labeling the pain as noncardiac chest pain secondary to GERD.
Preferred Examination
The assessment of patients who present with complaints consistent with GERD begins with a thorough history and physical examination. In obtaining a history, the physician must concentrate on the clinical details mentioned above. A thorough history helps the clinician make or highly suspect the diagnosis prior to performance of any tests. If a patient presents with a classic history for reflux disease, medical treatment may be initiated without further testing. If the patient has persistent symptoms despite medical treatment or is considering surgical intervention, further testing is indicated.
Several tests can be obtained to confirm the diagnosis and ascertain the etiology of GERD, including the following:
- Barium swallow/upper GI series: Barium esophagogram findings can demonstrate anatomy and possible complications of reflux disease (strictures). Reflux and inadequate gastric emptying may also be demonstrated.
- Upper GI endoscopy: Endoscopic findings demonstrate anatomy and possible complications of reflux disease (esophagitis, Barrett esophagitis, strictures). Using the patient's history and pathologic analysis of biopsy specimens obtained during endoscopy, the diagnosis of GERD can be made.
- Manometry: Manometry can help evaluate LES pressure and esophageal amplitudes and may demonstrate esophageal motility disorders.
- Twenty-four–hour pH testing: This test can help make the diagnosis of reflux disease by calculation of the Johnson-DeMeester score and correlation of the patient's symptoms with reflux episodes. Sensitivity and specificity of this test for GERD are 96% and 95%, respectively.
- Nuclear medicine gastric emptying studies are sensitive in evaluating for incomplete gastric emptying.
Not all of these tests are ordered during the workup in a patient with GERD. Mandatory studies include upper GI endoscopy and manometry. Endoscopy can help confirm the diagnosis of reflux by demonstrating complications of reflux (esophagitis, strictures, Barrett esophagus) and can help in evaluating the anatomy (eg, hiatal hernia, masses, strictures). Manometry helps surgical planning by determining the LES pressure and identifying any esophageal motility disorders. Esophageal amplitudes and propagation of esophageal swallows also are evaluated.
Optional studies include 24-hour pH probe test and upper GI series. Use of 24-hour pH testing helps confirm the diagnosis in patients in whom the history is not clear, atypical symptoms dominate the clinical picture, or endoscopy shows no complications of reflux disease. Upper GI series can be ordered to further delineate the anatomy. Hiatal hernias can be evaluated (size) and reflux can be demonstrated. In addition, gastric emptying can be evaluated to a limited. If a question exists regarding inadequate gastric emptying or if the patient has a history of nausea and vomiting, a nuclear medicine gastric emptying study can be obtained.
At the authors' institution, endoscopy, manometry, and 24-hour pH studies are obtained routinely. Upper GI series and nuclear medicine gastric emptying studies are ordered only if clinically indicated.
Presently, no role exists for CT, MRI, or ultrasonography in the routine evaluation of patients with reflux disease.
Limitations of Techniques
A conclusive diagnosis of reflux disease cannot be made by using barium esophagography. This technique is not sensitive for detection of motility disorders.
Endoscopy cannot help make a diagnosis of motility disorders.
The 24-hour pH probe test does not help evaluate either anatomy or motility abnormalities.
Manometry does not help evaluate anatomy.
Nuclear medicine gastric-emptying study does not help in assessing the anatomy and cannot help in the diagnosing reflux disease.
Each type of study has attendant strengths and weaknesses. The studies must be viewed as complementary. In combination, their use increases sensitivities and limits weaknesses.
Differential Diagnoses
Barrett Esophagus
Brain, Colloid Cyst
Esophagus, Carcinoma
Gastric Ulcer
Hiatal Hernia
Other Problems to Be Considered
Gastroparesis
Delayed gastric emptying
Alkaline reflux
More on Gastroesophageal Reflux |
 Overview: Gastroesophageal Reflux |
| Imaging: Gastroesophageal Reflux |
| Follow-up: Gastroesophageal Reflux |
| Multimedia: Gastroesophageal Reflux |
| References |
| Next Page » |
References
Aksglaede K, Funch-Jensen P, Thommesen P. Radiological demonstration of gastroesophageal reflux. Diagnostic value of barium and bread studies compared with 24-hour pH monitoring. Acta Radiol. Nov 1999;40(6):652-5. [Medline].
Baker ME, Rice TW. Radiologic evaluation of the esophagus: methods and value in motility disorders and GERD. Semin Thorac Cardiovasc Surg. Jul 2001;13(3):201-25. [Medline].
Buttar NS, Falk GW. Pathogenesis of gastroesophageal reflux and Barrett esophagus. Mayo Clin Proc. Feb 2001;76(2):226-34. [Medline].
Chen MY, Ott DJ, Sinclair JW, et al. Gastroesophageal reflux disease: correlation of esophageal pH testing and radiographic findings. Radiology. Nov 1992;185(2):483-6. [Medline].
Chen YM, Ott DJ, Gelfand DW, Munitz HA. Multiphasic examination of the esophagogastric region for strictures, rings, and hiatal hernia: evaluation of the individual techniques. Gastrointest Radiol. 1985;10(4):311-6. [Medline].
Creteur V, Thoeni RF, Federle MP, et al. The role of single and double-contrast radiography in the diagnosis of reflux esophagitis. Radiology. Apr 1983;147(1):71-5. [Medline].
Delattre JF, Avisse C, Marcus C, Flament JB. Functional anatomy of the gastroesophageal junction. Surg Clin North Am. Feb 2000;80(1):241-60. [Medline].
Gallup Organization. Heartburn Across America: A Gallup Organization National Survey. Princeton, NJ: Gallup Org;1988.
Johnston BT, Troshinsky MB, Castell JA, Castell DO. Comparison of barium radiology with esophageal pH monitoring in the diagnosis of gastroesophageal reflux disease. Am J Gastroenterol. Jun 1996;91(6):1181-5. [Medline].
Kahrilas PJ, Dodds WJ, Hogan WJ, et al. Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology. Oct 1986;91(4):897-904. [Medline].
Katzka DA, Rustgi AK. Gastroesophageal reflux disease and Barrett''s esophagus. Med Clin North Am. Sep 2000;84(5):1137-61. [Medline].
Levine MS, Rubesin SE. Diseases of the esophagus: diagnosis with esophagography. Radiology. Nov 2005;237(2):414-27. [Medline].
Locke GR 3rd, Talley NJ, Fett SL, et al. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. May 1997;112(5):1448-56. [Medline].
Madsen E, Aksglaede K, Jacobsen NO, et al. Gastro-oesophageal reflux demonstrated by radiography. A supplement to 24-h pH monitoring. Acta Radiol. Sep 2001;42(5):521-5. [Medline].
Mattioli S, Lugaresi ML, Di Simone MP, et al. The surgical treatment of the intrathoracic migration of the gastro-oesophageal junction and of short oesophagus in gastro-oesophageal reflux disease. Eur J Cardiothorac Surg. Jun 2004;25(6):1079-88. [Medline].
Richter JE. Surgery for reflux disease: reflections of a gastroenterologist. N Engl J Med. Mar 19 1992;326(12):825-7. [Medline].
Richter JE. Diagnostic tests for gastroesophageal reflux disease. Am J Med Sci. Nov 2003;326(5):300-8. [Medline].
Scheffer RC, Samsom M, Haverkamp A, et al. Impaired bolus transit across the esophagogastric junction in postfundoplication dysphagia. Am J Gastroenterol. Aug 2005;100(8):1677-84. [Medline].
Stein HJ, DeMeester TR. Outpatient physiologic testing and surgical management of foregut motility disorders. Curr Probl Surg. Jul 1992;29(7):413-555. [Medline].
Yamamoto AJ, Levine MS, Katzka DA, et al. Short-segment Barrett''s esophagus: findings on double-contrast esophagography in 20 patients. AJR Am J Roentgenol. May 2001;176(5):1173-8. [Medline].
Younes Z, Johnson DA. Diagnostic evaluation in gastroesophageal reflux disease. Gastroenterol Clin North Am. Dec 1999;28(4):809-30, v. [Medline].
Giannini EG, Zentilin P, Dulbecco P, Vigneri S, Scarlata P, Savarino V. Management strategy for patients with gastroesophageal reflux disease: a comparison between empirical treatment with esomeprazole and endoscopy-oriented treatment. Am J Gastroenterol. Feb 2008;103(2):267-75. [Medline].
Katz PO. Medical therapy for gastroesophageal reflux disease in 2007. Rev Gastroenterol Disord. 2007;7(4):193-203. [Medline].
Chen CL, Robert JJ, Orr WC. Sleep symptoms and gastroesophageal reflux. J Clin Gastroenterol. Jan 2008;42(1):13-7. [Medline].
Further Reading
Keywords
hiatal hernia, heartburn, reflux regurgitation, GERD, gastric reflux, gastroesophageal reflux disease, acid reflux, bile reflux, esophageal clearance, pyrosis, esophagitis, esophageal strictures, Barrett esophagus, dysphagia
