Gastroesophageal Reflux Disease


·                      3. WHEN DOES GERD OCCUR?
·                      4. ACID AND NONACID REFLUX
·                      5. CLINICAL RISK FACTORS FOR GERD
·                      6. DAMAGE CAUSED BY REFLUX
·                      7. SYMPTOMS OF GERD
·                      8. DIAGNOSIS OF GERD
·                      9. TREATMENT OPTIONS FOR GERD
·                      10. APPROACH TO MANAGEMENT OF GERD

 Gastroesophageal Reflux Disease (GERD)

Mechanism of disease, Risk factors, Clinical spectrum, Diagnosis and Treatment

Raj K Goyal, MD



Gastroesophageal Reflux Disease (GERD) includes a spectrum of diseases caused by reflux or backflow of stomach contents into the esophagus and then into the throat and the mouth. Reflux of acid causes inflammation in the esophagus, throat and the lungs.

Consequences of esophageal inflammation include peptic esophagitis, ulcer, scarring or stricture, and columnar cell metaplasia (Barrett’s esophagus). Invasion of refluxed material above the esophagus causes pharyngitis, laryngitis, pulmonary aspiration and oral manifestations.


GERD is a very common malady.  Heartburn is a symptom of esophagitis that is only one manifestation of GERD; and  a Gallop poll survey revealed that 7% of the population experiencedheartburn symptoms daily, 14% weekly, and 44% monthly. Clearly, GERD is one of the very common clinical disorders.



Occasional GER is normal and occurs in all of us because normal stomach and esophageal pressure gradients favor esophageal reflux. The normal gastric pressure is higher than esophageal pressure. Moreover, swallowed food is normally carried rapidly through the esophagus but is stored in the stomach for acid digestion for several hours. Thus the stomach provides a large reservoir of acid and food that can reflux into the esophagus.


Excessive GER is prevented normally by elaborate antireflux mechanisms that provide barriers to reflux. These barriers keep reflux episodes to a minimum and prevent development of GERD. The antireflux mechanisms include: 1) anatomic configuration of the gastroesophageal junction; 2) esophageal sphincters; and 3) diaphragmatic sling in the esophageal hiatus.  

The esophagus is a narrow muscular pipe, about 20 cm long in adults that is located in the posterior part of the chest.  It is a continuation of the throat (pharynx) that passes through the chest and enters the abdomen through an opening in the diaphragm to open into the stomach. The anatomy of the gastroesophageal junction is specialized to provide an antireflux barrier (see Figure 1). First of all, the lowermost part of the esophagus is located below the diaphragm, in the abdominal cavity. The abdominal segment is kept closed by higher abdominal pressure thus preventing GER. The esophagus enters the stomach at an angle (called angle of His) and into the stomach at a point below the dome (fundus) of the stomach. This configuration helps avoid GER.  Moreover, there is a flap of mucosa that arises from the region of the angle of His and covers the esophageal opening like a valve. The gastric sling fibers contribute to the angle if His and are present at the base of the valve. Contraction of the gastric sling fibers accentuate the angle and enforce action of the mucosal valve to close the esophageal opening and avoid reflux.

Gastroesophageal Reflux Disease

At either end of the wall of the esophagus is specialized to form sphincters or valve like barriers to flow. The upper esophageal sphincter (UES or pharyngoesophageal sphincter) is located at junction the esophagus with the pharynx.  The lower esophageal sphincter (LES or gastroesophageal sphincter) is present at the junction of esophagus with the stomach. The upper and the lower esophageal sphincters normally keep closed to prevent reflux. The esophageal sphincters normally open only transiently to permit passage of the swallowed food bolus into the stomach.

The diaphragmatic opening of the esophagus is formed by special muscles that form sling around the esophagus. The diaphragmatic crural muscle constitute external sphincter around the distal esophagus.


Normally, damage caused by refluxed acid is avoided by a variety of defense mechanisms that include prompt clearing of the refluxed acid, neutralization of the acid by salivary and esophageal bicarbonate secretion and an inherent property of the esophageal lining to defend against acid, called mucosal defense mechanism



GERD occurs when there is excessive GER due to major breakdown of antireflux barriers. The failure of antireflux barriers occurs due to development of hiatal hernia, incompetence of the esophageal sphincters and gastric stasis.  Hiatal hernia disrupts the normal anatomy of the gastroesophageal junction. Hiatal hernia leads to thoracic placement of the abdominal esophagus, obliteration of the angle of His and the mucosal flap. Moreover, hiatal hernia is associated with widening of the esophageal hiatus and weakening of the diaphragmatic external lower esophageal sphincter mechanism. The incidence of sliding hiatal hernia increases with age.

The failure of LES barrier function occurs when it is rendered permanently hypotensive or when a normotensive LES relaxes inappropriately thereby promoting reflux. Permanently hypotensive LES occurs due to primary or secondary muscle disease of the lower esophageal sphincter. Inappropriate LES relaxation is transient reflex relaxation of the LES, mediated by neural reflex. This reflex is similar to belch reflex and has been called transient LES relaxation (TLESR), in order to distinguish it from sustained LES hypotension. Elevation in stomach pressure and stasis of food also predispose to esophago-gastric reflux.

The upper esophageal sphincter guards against invasion of reflux above the esophagus, into the throat, voice box, lungs and mouth. Breakdown of the barrier function of the upper esophageal sphincter leads to Supraesophageal complications of GERD.


If excessive reflux occurs, its damaging effect of acid and pepsin are countered by esophageal mucosal defenses. The exact nature of the defense mechanisms is not well understood. However, breakdown of defenses against the invading acid leads to severe mucosal damage. 


Acid and the enzyme, pepsin, secreted by the stomach are important components of gastric contents that reflux into the esophagus. Pepsin can only digest esophageal lining when acid is present. Therefore, acid is the most important damaging agent. However, intestinal enzymes and bile can backup into the stomach and then reflux into the esophagus and cause reflux damage. Nonacid reflux causes nonacid GERD that present special problems in diagnosis and treatment as these cases do not respond to acid suppression therapy. With the current availability of powerful acid suppressants, nonacid GERD is emerging as important clinical condition.



GERD is a particularly frequent problem in infants and children and the elderly. Infants and children can not express heartburn and may present with regurgitation, vomiting and failure to thrive.


There are many life style factors that increase the risk of GERD. These include age, weight gain, increased intragastric pressure, certain diets and smoking. Infants have a high incidence of gastroesophageal reflux. The incidence of GERD also increases with advancing age. Recent weight gain is an important precipitating factor in heartburn. Weight gain, bending and abdominal exercises including jogging, thigh belts and girdles increase pressure in the stomach and promote reflux. A large meal, particularly one with a chemical composition that delays gastric emptying or causes relaxation of the LES also predisposes to reflux. For example, a large fatty meal may delay gastric emptying and relax LES. Beverages such as colas, coffee and tea containing high levels of caffeine also relax LES. Smoking is a potent inhibitor of LES pressure and therefore a very important risk factor for GER.


Pregnancy is often associated with GERD. In the first trimester, hormonal changes that are responsible for morning sickness can lead to reflux. In the third trimester, increasing intra-abdominal pressure is responsible for reflux.


Certain systemic diseases also predispose to GERD. Coronary artery disease shares many risk factors such as age, obesity and smoking with GERD. Moreover, many treatments such as coronary vasodilators reduce LES tone and lead to reflux. Chronic bronchitis and chronic obstructive lung disease share with GERD smoking as a common risk factor and reduced oxygen concentration in the blood impairs the normal tone of the LES. Scleroderma and other connective tissue disorders may involve smooth muscle of the esophagus and the lower sphincter and predispose to GERD. Moreover, scleroderma involves the entire esophageal smooth muscle leading to weak and ineffective esophageal peristaltic contractions that fail to clear the esophagus of the refluxed acid; therefore, acid stays in the esophagus for longer periods, thus worsening the esophageal damage. Delayed emptying of stomach due to obstruction to stomach outlet or poor stomach motility is also an important risk factor for GERD. 


Certain surgical procedures require destruction of the lower sphincter for treatment of the underlying disease or are associated with gastric stasis and may therefore predispose to reflux. For example, cutting of non-opening lower esophageal for treatment of dysphagia in patients with achalasia may be complicated by GERD. Abnormal gastric stasis of food acid either as a complication of gastric surgery or due to other causes may lead to GERD. Abnormal accumulation of fluid in the abdomen (ascites) or an abdominal mass may increase intragastric pressure and predispose to reflux.


A large variety of commonly used drugs are also risk factors for GERD. Common among them are drugs that relax smooth muscles. These include coronary artery dilators that are used for treatment of coronary artery disease, bronchodilators that are used for treatment of chronic bronchitis, asthma and chronic obstructive lung disease, and penile vasodilators that are used for erectile dysfunction. All these smooth muscle relaxants also relax the lower esophageal sphincter and make it incompetent to prevent reflux.


Reflux of gastric contents can produce extensive damage to the esophagus, throat, lungs, ear, nose and mouth depending upon the extent of the reflux.


The esophageal mucosal lining is very different from the lining of the stomach. Whereas the lining of the stomach can withstand acid damage, the esophageal lining is very sensitive to acid damage. Moreover, the ability of the esophageal mucosa to defend against the acid damage may vary in different individuals and in the same individual under different circumstances. This property of the esophageal mucosa to defend against the acid injury is called mucosal defense.

The biology of esophageal mucosal defense mechanisms is under investigation. Briefly, it includes changes in penetration of acid into the depths of the mucosa and changes in the ability of the cells lining the esophagus to protect them from acid. Certain medications may worsen esophageal mucosal damage. These medications include ulcerogenic drugs such as acetylsalicylic acid and non-steroidal anti-inflammatory agents.

Acid damage to the esophageal mucosa is repaired in different ways depending upon the circumstances. Often the damaged mucosa is well repaired so that no grossly visible sign of the damage is apparent. These cases are called non-erosive esophagitis (NERD). These cases show no signs of damage visible to the naked eye on endoscopy.  However, the mucosal biopsies may show microscopic changes suggestive of enhanced reparative processes, such as an increase in the number of basal cells. Dilation of the intercellular spaces, indicating passages for the invasion by acid has been proposed as the earliest changes of mucosal damage. Such cases may have symptoms of reflux and heartburn with normal endoscopy and are given a diagnosis of non-erosive esophagitis (NERD).

Classical cases reflux damage show mucosal erosions or superficial ulcers. These erosions can vary in size and depth and may expose and include mucosal blood vessels in the erosions leading to bleeding. These cases are classified as having erosive esophagitis.

Sometimes ulceration and inflammation extend deeper in the esophageal wall resulting in deep peptic ulcer of the esophagus. Healing of the deep inflammation and ulcer leads to scarring and fibrosis that may occlude the esophageal lumen.  This condition is called peptic stricture.

Repair of the damaged esophageal mucosa may also occur by a more acid resistant type of columnar epithelium – a condition called metaplasia. Metaplasia is defined as replacement of one type of mucosa with another kind. The replacement of damaged esophageal squamous epithelium by the metaplastic columnar epithelium has been called Barrett’s esophagus. The metaplastic epithelium is a mosaic of different types of columnar cells including the so called specialized intestinal metaplastic epithelium. It has been called specialized because it is different from any normal epithelium present anywhere in the gut including stomach and intestines. The development of Barrett’s esophagus occurs painlessly without the patient being aware that it is happening. Barrett’s esophagus is of special clinical importance because it may progress to esophageal cancer (see knol on Barrett’s Esophagus). Deep peptic ulcer of the esophagus and esophageal stricture are often associated with Barrett’s esophagus.   

Acid penetration in the inflamed esophageal mucosa stimulates mucosal nerves that conduct sensation of pain and heat thus producing heartburn. The severity of heartburn does not correlate with the severity of mucosal damage. Severe esophageal damage may exist in the absence of significant heartburn. In fact the heartburn often abates when Barrett’s esophagus develops.


If acid reflux extends beyond the esophagus, it produces supra esophageal manifestations.

This occurs when the reflux material is copious and when the upper esophageal sphincter mechanism is compromised. Supraesophageal manifestations may include Pharyngitis, laryngitis, sinusitis, asthma, chronic bronchitis, aspiration pneumonia, pulmonary fibrosis, sinusitis, otitis and dental erosions.



GERD produces a very wide spectrum of clinical manifestations depending upon the extent and severity of the damage. Regurgitation is experience of backflow of stomach contents into the esophagus and the throat. Acid tasting fluid may be experienced in the mouth and the throat. Sometimes the patient may experience warm fluid climbing up the throat.

Distal esophagus is most often affected by reflux and in severe cases more proximal parts of the esophagus are also involved.  Esophageal symptoms include: regurgitation, heartburn, dysphagia, bleeding and chest pain.

Heartburn is pain of burning quality that is experienced in the region of the heart, namely the retrosternal area or behind the chest in the midline. Heartburn associated with regurgitation is characteristic of reflux esophagitis.  However, heartburn may be experienced in some esophageal motility disorders, including achalasia.  Sometimes, pain in coronary artery disease may be interpreted as heartburn.

Bleeding may be overt in the form of vomiting of blood or occult internal bleeding presenting as anemia. Bleeding occurs from mucosal erosions or esophageal ulcer.

Dysphagia may occur due to peptic stricture or from esophageal adenocarcinoma from Barrett’s esophagus.

Chest pain of associated with GERD may  be confused with angina-like pain or atypical chest pain that neither resembles typical heartburn nor is exertion related. GERD is the commonest cause of noncardiac chest pain (see knol on noncardiac chest pain).

When reflux extends above the esophagus to damage pharynx, voice box, lungs and mouth, symptoms such as hoarseness, throat irritation, globus sensation, chronic cough, sinus pain, ear ache, dental erosion and halitosis may be experienced.

It is important to point out that extent and the severity of reflux damage may not correlate.  For example, reflux damage extending above the esophagus may occur in the absence of severe lower esophageal damage.


Diagnosis of GERD can be suspected by its symptoms.  The most characteristic symptoms of GERD are regurgitation and heartburn.  Heartburn is most frequently described as a sub-sternal (under the middle of the chest) burning that occurs after meals and often worsens when lying down. Patients usually self diagnose the condition. Physicians can more precisely perform symptom analysis to diagnose GERD.

A. Therapeutic Trial

The diagnosis of GERD can be substantiated by the so called therapeutic trial that involves treating patients with medications to suppress the production of acid by the stomach. If the heartburn then is diminished to a large extent, the diagnosis of GERD is substantiated. It is important to keep in mind that 20% of patients may respond to a placebo (inactive) pill or, indeed, to any treatment. These patients may be suffering from diseases other than GERD. Therefore, history and response to therapy can only provide a presumptive diagnosis of GERD related esophagitis. For a definitive diagnosis, further diagnostic test are needed. In clinical practice, further investigations are performed if the symptoms persist, there is a long history of heartburn or warning symptoms such as bleeding, dysphagia and weight loss are present.

B. Endoscopy 
Esophagoscopy involves visualization of the esophageal mucosa through a flexible tube that is swallowed by the patient and a video of the esophageal mucosal appearance is made with an optical laser. Esophagoscopy is always combined with examination of the pharynx, and further extension of the imaging device into the stomach (gastroscopy) and upper small intestine (duodenoscopy) and therefore the procedure is called esophago-gastro-duodenoscopy or EGD.

The esophagus of up to 70% of the patients with symptoms of reflux may appear normal on endoscopy. These patients may have endoscopically negative esophagitis or nonerosive reflux disease (NERD). However, endoscopy readily recognizes inflamed esophagus (esophagitis) with erosions (superficial breaks in the esophageal lining) and is called erosive reflux disease (ERD). Esophagitis with deep peptic ulcers (deep craters) and peptic strictures may be seen.  Most importantly, endoscopy may reveal that abnormal columnar mucosa has replaced the normal esophageal mucosa, a condition called Barrett’s esophagus. The diagnosis of Barrett’s esophagus is confirmed by biopsy. Barrett’s esophagus may be associated with erosive esophagitis, deep peptic ulcer, peptic stricture or adenocarcinoma. Finally, endoscopy may recognize other problems that may be causing GERD-like symptoms. For example, infectious causes of esophagitis, eosinophilic esophagitis resemble reflux esophagitis. Gastritis, duodenitis and gastric and duodenal ulcers may cause lower midline chest pai

C. Biopsies 
Biopsies of the esophageal mucosa can be obtained by a biopsy forceps carried on a flexible wire that can be inserted through an opening channel in the endoscope. Cutting a small piece of mucosa with biopsy forceps is not painful. Biopsy tissue can be subjected to microscopic examination. Biopsies may help establish causes of esophageal inflammation including acid reflux and other than acid reflux, particularly infections. Moreover, biopsies are the only means of diagnosing the cellular changes of Barrett's esophagus and carcinoma.

D. Barium X-rays 
X-ray of the esophagus (esophagogram) is performed by swallowing radio-opaque barium (called barium swallow). It is usually combined with x-rays of the whole upper gastrointestinal tract including the stomach and upper small intestines (called upper gastrointestinal (UGI) series). X-rays can not identify esophageal mucosal inflammation unless severe damage is present such as ulcers and strictures. X-rays often identify hiatal hernias, stomach ulcers or gastric stasis. Unless it is very severe, finding of gastroesophageal reflux on x-rays does not distinguish normal GER from GERD.

E. Ear, Nose, Throat and Pulmonary Examination 
When GERD affects the throat or larynx and causes symptoms of cough, hoarseness, or sore throat, patients often first visit an ear, nose, and throat (ENT) specialist. The ENT specialist frequently finds signs of inflammation of the throat or larynx... however, distinguishing inflammation due to other causes including smoking, is often difficult to distinguish from reflux induced damage. Often acid-suppression is used as a therapeutic trial.

F. Special test for diagnosis of GERD

Special tests for diagnosing GERD are needed in difficult to diagnose cases

a. Esophageal acid reflux testing 
Whether reflux of acid is present and how bad it is when it does occur can be definitively determined by 24 hour esophageal pH recording. Esophageal pH monitoring can be performed using a nasally introduced catheter or a pH capsule (Bravo*) anchored in the lower esophagus.  A pH sensor for nasal placement consists of a thin flexible wire, carrying a pH sensor at its tip that is passed through the nose and positioned in the esophagus.  Changes in esophageal pH are registered onto a portable recorder. Episodes of esophageal reflux are recorded as periods of esophageal pH less than 4 and analyzed.

In order to avoid prolonged nasal intubation, a small pH sensitive wireless capsule can be implanted in the distal esophagus. The capsule implantation requires endoscopy and intubation which are removed after implantation of the capsule. The capsule can transmit information on esophageal pH to an external receiver for up to 48 hours. Despite obvious advantages, use of the capsule has some limitations such as cost, technical problems with capsule attachment and chest pain.

Esophageal pH testing is used only in difficult to diagnose cases of GERD. For example, it may be used in cases that fail to respond to acid suppression treatment.  Almost 10 to 20 percent of patients may not improve with treatment for GERD. This lack of response to treatment could be caused by suboptimal treatment or persistent symptoms that are not related to acid reflux such as changes in esophageal sensitivity, nonacid reflux or wrong diagnosis of GERD. Finding of abnormal acid reflux, while the patient is on continued medication, suggests suboptimal treatment and calls for better compliance, and changes in treatment strategy. Finding of no abnormal reflux despite continued symptoms, suggest either increased sensitivity or wrong diagnosis. These latter findings require further tests to distinguish between the two.

Esophageal pH testing is also often used to evaluate patients prior to endoscopic or surgical treatment for GERD. These interventional therapies are effective only in the well documented cases of acid reflux. Therefore, proper patient selection is necessary to avoid treatment failures. Only patients with symptoms and well documented acid reflux should be subjected to interventional therapies. Recent studies suggest that nonacid reflux may also cause esophageal symptoms. Nonacid reflux may be tested by impedance studies.

b. Esophageal nonacid reflux testing

Esophageal pH recording does not identify reflux of nonacid gastroesophageal contents. Nonacid gastroesophageal reflux can be measured by esophageal impedance recording.

Esophageal pH and impedance studies can be performed simultaneously using instrumentation that can monitor both these parameters.

c. Esophageal motility testing 
Esophageal motility testing requires placement of an assembly of multiple sensors that sense pressures from different regions of the esophagus. The number of sensors used varies in different manometry laboratories. A large number of sensors may be used to simultaneously record pressure at every centimeter or three sensors can be used to record pressures 5 cm apart.  Similarly, the pressure sensors may consist of open tip perfused catheters or solid state pressure sensors. The catheter assembly is passed through a nostril, down the back of the throat, and into the esophagus. Pressures in the esophagus and esophageal sphincters between and during swallows of sips of water are recorded.

Esophageal motility study is not directly useful in the diagnosis of GERD. However, it may be useful in differential diagnosis of GERD from esophageal motility disorders such as diffuse esophageal spasm and achalasia. Esophageal manometry is also useful prior to surgical or endoscopic treatment for GERD. This may help document the severity of LES or UES hypotension and efficiency of esophageal peristalsis that may influence the type of antireflux surgery. Esophageal manometry is also helpful in excluding misdiagnosis of GERD instead of a motility disorder and association of a motility disorder with GERD that may compromise the results of antireflux intervention.

d. Esophageal Acid perfusion test 
in reflux acid esophagitis, heartburn is thought to be due to the exposure of esophageal nerve endings in the damaged mucosa to refluxing acid. Healthy esophageal mucosa does not cause heartburn when exposed to acid. Therefore, the acid perfusion test (also called Bernstein test) is used to determine if heartburn is caused by acid reflux. A thin tube is passed through one nostril, down the back of the throat, and into the middle of the esophagus. A dilute, hydrochloric acid solution (0.1 normal HCl) or physiologic salt solution is alternately perfused through the catheter and into the esophagus. The patient does not know which solution is being perfused. If acid but not salt solution produces pain, the diagnosis of acid reflux esophagitis is suggested.

e.Esophageal distension test

Esophageal over-distension causes activation of esophageal nociceptors that elicit chest pain.  In the presence of increased sensitivity of the esophageal nerves, even a small degree of distension may elicit chest pain. In this test, patient’s experience of pain in response to balloon distension is recorded. Esophageal distension studies are useful in establishing increased esophageal sensitivity in patients with non-erosive esophagitis.

f. Gastric emptying studies 
Gastric stasis predisposes to GER. Therefore, assessment of gastric emptying may provide important information in the pathogenesis and management of a subset of cases of GER. For gastric emptying studies, the patient eats a meal labeled with a radioactive substance. A radioactive sensor is placed over the stomach and the rate of gastric emptying is measured.

When severe delayed gastric emptying is associated with GERD, a mechanical cause of gastric stasis should be investigated and treated. Milder cases associated with motility disorders should be treated with dietary modifications and prokinetic agents. Gastric emptying studies should be performed prior to surgical antireflux intervention. This is helpful in assessing postoperative results and to incorporate surgical techniques to improve gastric emptying.

Some patients with GERD have symptoms of nausea and vomiting. An evaluation of gastric emptying may be useful in identifying patients whose symptoms are due to gastric stasis rather than to GERD.



Life-style changes could have a very strong effect on GER. Life style changes include a combination of several changes in habit, particularly related to eating.

Normal upright posture helps prevent backflow of stomach acid into the esophagus and gravity also helps return of any refluxed material back into the stomach. Lying down, as during sleep, eliminates the beneficial effect of gravity on reflux and the gastric acid may reflux more frequently, reach higher levels of the esophagus and stay in the esophagus longer. Prevention of this cycle of events can be accomplished by elevating the head-end of the bed with blocks (about 4”) placed under the head of the bed or by placing a wedge in the upper half of the bed. Elevating only the head does restore the effect of gravity on the esophagus. Elevation of the upper body at night may be helpful in all patients with GERD, but is essential for patients who have heartburn, regurgitation, aspiration or other symptoms of GERD.  Lying on the left side also reduces the amount and frequency of reflux compared with lying on the right side.

Changes in the volume, timing and type of food intake may be useful in prevention of reflux. Over-distension of the stomach predisposes to reflux and also promotes reflux by relaxation of the lower sphincter. Reflux is common after a large meal. A smaller size of meal and avoiding intake of large quantities of water or fluids with meals may help avoid reflux. Since a large meal may be particularly harmful before retiring to bed, a smaller and earlier evening meal may reduce the amount of reflux. Smaller evening meals may also lower the volume of acid secretion resulting in overall lower residual gastric volume.

The nature of food may have an effect on esophageal mucosa, lower esophageal sphincter and gastric motility and thereby affect symptoms and the occurrence of GERD. Acidic content, osmolality and irritants in the food may increase the experience of heartburn. Certain acidic juices, such as citrus juice, tomato juice, carbonated beverages, wines, and highly osmolar spicy food cause heartburn in some patients with GERD. Peppers may produce bad heartburn in subjects who are not used to it; however, in chronic users, peppers may not cause heartburn due to desensitization.

Some foods decrease LES pressure and others delay gastric emptying and thus promote reflux. These food constituents and additives include: chocolate, peppermint, alcohol, and caffeinated drinks. Fatty foods also delay gastric emptying

Smoking has a powerful inhibitory effect on the pressure in the sphincter and, therefore, promotes reflux. In addition, patients with GERD may find that other foods aggravate their symptoms. Such foods should be avoided.


a. Antacids 
Over-the-counter antacids remain a mainstay of self treatment of heartburn. Antacids neutralize refluxed esophageal and secreted gastric acid so that there is no acid to reflux. The action of acid is prompt. The problem with antacids is that they are quickly emptied from the empty stomach and do not produce sustained acid neutralization. Therefore, antacids donor provide efficient neutralization night.

Common antacids are aluminum, magnesium, or calcium salts. Aluminum-containing antacids can cause constipation and magnesium-containing antacids cause diarrhea. Certain antacid preparation use a mixture of aluminum and magnesium based compounds to avoid these side effects.  Calcium-based antacids such as calcium carbonate (Tums, Rolaids) can elevate serum calcium levels and stimulate the hormone gastrin. Release of gastrin may lead to rebound overproduction of gastric acid. Gastric rebound may predispose to GER after initial gastric neutralization by calcium containing antacids. Calcium containing antacids may provide a source of calcium for patients who require calcium supplementation.

Because of the prompt acid neutralization, antacids provide immediate relief of heartburn.  For long-term gastric acid neutralization, antacids may be taken approximately one hour after meals and a second dose of antacid is administered two hours after a meal. Even so, antacids do not provide sustained neutralization of gastric acid unless they are administered on an hourly basis or as continuous gastric infusion. Administration of very large quantities of antacids increase gastric volume and may lead to nonacid reflux.

Antacids may be combined with a foam barrier. For example, Gaviscon* is a combination of aluminum hydroxide gel, magnesium trisilicate and alginate. Alginate tablet disintegrates as it reaches the stomach and turns into foam that floats on the top of the stomach contents. The foam is thought to form a physical barrier to the reflux of acid. Moreover, the antacid bound to the foam neutralizes acid that comes in contact with the foam. The tablets are taken after meals and on lying down.

b. Histamine-2 (H2) receptor antagonists 
Stomach acid is produced by special acid producing cells called parietal cells that are located in the stomach wall. Histamine is produced in the enterochromoffin cells and is released in response to feeding.  Histamine binds with H2receptors on the parietal cells to stimulate acid secretion.  Histamine 2 receptor antagonists bind to the Hreceptors and block the action of histamine, thereby inhibiting gastric acid secretion.

Unlike antacids, H2 receptor antagonists act by suppressing secretion of stomach acid. Therefore, Hblockers are effective in relieving heartburn symptoms. However, H2 blockers only partially suppress gastric acid. Because of their weak effect on suppressing acid secretion, they are not very good for healing erosive esophagitis associated with GERD. Therefore, H2 receptor blockers are used for treatment of heartburn in non-erosive esophagitis in GERD, but not in GERD associated with erosive esophagitis, ulcers and strictures.

Four different Hantagonists have been approved by the FDA for treatment of GERD, including cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid). Tagamet-HB (100 mg), Zantac-75 (5mg),   Axid-AR (75mg) and PepsidAC (combination of famotidine 10 mg or 20 mg, and calcium carbonate) are also available over-the-counter (OTC), without the need for a prescription. Tagamet is available in generic form as cimetidine. The OTC dosages are lower than those available by prescription. H2 antagonists are best taken 30 minutes before meals so that its level will peak at meal time when stomach acid secretion will be at its maximum. H2 antagonists are also administered at bedtime to suppress nighttime production of acid. These agents may relieve heartburn but do not heal erosive esophagitis.

c. Proton pump inhibitors 
Proton pump inhibitors (PPI) act directly on the parietal cells to block the proton pump that is responsible for acid secretion. The PPI shut off acid production more completely and for a longer period of time than Hreceptor blockers. Because of their very effective acid suppression, PPIs are used as first line treatment or when Hantagonists do not relieve symptoms adequately or when complications of GERD such as erosions, ulcers, or strictures are present.

Five different PPIs are FDA approved for the treatment of GERD, including omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix). Omeprazole OTC (20 mg) is approved for over the counter use and is less expensive than its physician prescribed version.

Timing of PPI administration is very important for its optimal acid suppressive action. PPIs work best when the stomach is most actively producing acid, which occurs after meals. Moreover, PPIs are pro-drugs that require conversion to active agent by acid secretion. is, Administration of a PPI 30 minute before a meal yields peak levels of PPI that coincide with active acid secretion. For the same reason, a PPI should not be combined with H2 receptor blocker.

d. Pro-kinetic drugs 
Prokinetic drugs are those that enhance gastrointestinal transit. Currently, only one prokinetic drug, metoclopramide (Reglan), is approved for GERD. It increases lower esophageal sphincter pressure and strengthens esophageal peristaltic contractions. It is thought that the main beneficial effect of metoclopramide may by enhancing gastric emptying. These drugs are not effective for treating symptoms of heartburn but may be added to other treatments in case of suboptimal response. Metoclopramide is not available over the counter. These drugs are recommended to be taken 30 minutes before meals and again at bedtime.


A variety of endoscopic techniques have been developed for GERD endotherapy. These devices are designed to change the anatomic configuration of the gastroesophageal junction and improve function of the LES. They include devices such as: Entreyx, Gatekeeper, His-Wiz, SelfStitch, Esophyx, EndoCinch and NDOPlicator. Many of these devices have been withdrawn from the market because of undesired complications and side effects. EndoCinch involves mucosal suturing and NDO Plicator produces full thickness placation.  They are still undergoing clinical trials for their efficacy and safety. So far clinical studies of their usefulness have focused on uncomplicated and mild cases of GERD.


Over the years, a variety of operations have been developed to correct impaired antireflux barriers. These have included reduction of hiatal hernia (Allison’s repair), Belsey repair and Nissen fundoplication. Nissen fundoplication has been shown to be effective in prevention of reflux. Post-operative complications include recurrence of hiatal hernia and gastroesophageal reflux (20% to 40%). Major complications such as esophageal obstruction and leak may occur in less than 5% and operative mortality is around 1%.



Most sufferers of simple short duration heartburn or reflux self treat with life style changes and over-the-counter medications Life style changes as described above.  Over the counter medications include antacids, H2 receptor blockers and PPI. H2 receptor blockers and PPI are available over the counter in doses that are smaller than available for medical prescription.


The most important reason for treating GERD is to relieve symptoms of heartburn. While non-erosive esophagitis (NERD) may be source of severe heartburn or chest pain, it may not progress to erosive esophagitis and associated complications even if untreated or partially treated. Therefore whatever treatment that relieves symptoms is acceptable. However, erosive esophagitis may lead to complications and should be aggressively treated to healing and kept healed with effective acid suppressive therapy.  Serious complications of esophageal peptic ulcer are prevented if the ulcer is kept healed by proper acid suppression. Similarly, peptic strictures respond to endoscopic esophageal dilation only when effective acid suppression is provided. Erosive esophagitis associated with Barrett esophagus also require effective suppression of stomach acid; however, acid suppression may not prevent either extension of the Barrett’s mucosa or its progression to cancer (see knol on Barrett’s Esophagus).


Medical help should be sought when there are alarm symptoms such as dysphagia, overt bleeding, anemia, weight loss or loss of appetite. Medical help should also be sought if there is a long history of reflux and heartburn.  With a history of longstanding heartburn, it is prudent to seek medical advice even if the symptoms have improved. This is because development of Barrett’s metaplasia may be associated with a decrease in symptoms of heartburn. These situations usually call for endoscopic evaluation of the esophagus. Medical help should also be sought if chest pain is atypical, exert ional or associated with squeezing in the chest, particularly if there is history or risk factors for coronary artery disease. In general, if the symptoms persist despite simple self treatment, medical evaluation should be done.


The physician will obtain a careful history and perform a physical examination. Coronary artery disease and other causes of chest pain are excluded. The presence of alarm symptoms such as bleeding, anemia and dysphagia, weight loss or certain atypical symptoms often lead to a decision to perform an EGD.

Diagnosis of deep peptic ulcer requires aggressive PPI therapy; peptic stricture requires treatment with dilation and aggressive PPI. Esophagitis associated with Barrett’s esophagus is treated like erosive esophagitis and a surveillance plan to detect early adenocarcinoma is put in place.

Uncomplicated cases of GERD are separated from erosive esophagitis. These cases require aggressive PPI therapy to heal esophagitis that takes 8 to 12 weeks. A repeat EGD to document healing is usually not necessary.  Non-erosive esophagitis and healed erosive esophagitis cases require long-term acid suppression for symptom control. Most patients require life long PPI therapy. Patients with NERD could be treated with H2 receptor blockers if they can produce symptomatic relief. It is important to ensure that PPI is taken 30-40 min before breakfast, in order to have optimal acid suppression.

Almost 30% to 40% of these cases may not improve on PPI. Often these are cases have either normal or minimally abnormal EGD. The usual causes of poor response are poor compliance, persistence of nonacid reflux, and non-reflux associated chest pain.

It is this subset of patients in whom 24 hour pH recording, pH plus impedance recording or esophageal motility studies may be useful. If elevated esophageal acid reflux parameters are present while on therapy, changes in life style measure, proper administration of PPI or increase in PPI dose is recommended.

If no acid reflux is identified, symptoms may be due to nonacid reflux or non-reflux related chest pain. Nonacid reflux can be diagnosed by impedance studies. Nonacid reflux requires treatment with endoscopic or laparoscopic fundoplication. If no acid or nonacid reflux is found, symptoms may be due to esophageal hypersensitivity and may be associated with anxiety state, panic attacks or depression. This diagnosis calls for special treatment. 

Further Reading 


  1. Diamant, NE. Pathophysiology of gastroesophageal reflux disease. GI Motility online (2006) doi:10.1038/gimo21
  2. Fass, R. M.D. and Dickman, R. Nonerosive reflux disease. GI Motility online (2006) doi:10.1038/gimo42
  3. Harding, SM. Gastroesophageal reflux and chronic cough. GI Motility online (2006) doi:10.1038/gimo77
  4. Hogan, WJ. Endoscopic therapy for gastroesophageal reflux disease. GI Motility online (2006) doi:10.1038/gimo55
  5. Holloway, RH. Esophageal manometry. GI Motility online (2006) doi:10.1038/gimo30
  6. Kahrilas, PJ, and Pandolfino, JE. Hiatus hernia. GI Motility online (2006) doi:10.1038/gimo48
  7. Lee, R, and Mittal, R. Heartburn and esophageal pain. GI Motility online (2006) doi:10.1038/gimo75
  8. Lowe, RC. Medical management of gastroesophageal reflux disease. GI Motility online (2006) doi:10.1038/gimo54
  9. Lundell, L. Reflux esophagitis and peptic strictures. GI Motility online (2006) doi:10.1038/gimo43
  10. McCormick, SE, and Kozarek RA. Endoscopic evaluation of esophageal motility disorders. GI Motility online (2006) doi:10.1038/gimo29
  11. Minjarez, RC and Jobe, BA. Surgical therapy for gastroesophageal reflux disease. GI Motility online (2006) doi:10.1038/gimo56
  12. Mittal RK, Goyal RK. Sphincter mechanisms at the lower end of the esophagus. GI Motility online (2006) doi: 10, 1038/gimo 14
  13. Nurko, SM. and Furuta,GT. Eosinophilic esophagitis. GI Motility online (2006) doi:10.1038/gimo49
  14. Orenstein, SR. Oral, pharyngeal, and esophageal motor disorders in infants and children. GI Motility online (2006) doi:10.1038/gimo38
  15. Orlando, RC. Esophageal mucosal defense mechanisms. GI Motility online (2006) doi:10.1038/gimo15
  16. Postma, GN, and Halum, SL. Laryngeal and pharyngeal complications of gastroesophageal reflux disease. GI Motility online (2006) doi:10.1038/gimo46
  17. Robbins J, Bridges, AD, and aylor. A. Oral, pharyngeal and esophageal motor function in aging. GI Motility online (2006) doi:10.1038/gimo39
  18. Sachin Wani, M.D. and Prateek Sharma. Barrett's adenocarcinoma. GI Motility online (2006) doi:10.1038/gimo45
  19. Sengupta, JN. Esophageal sensory physiology. GI Motility online (2006) doi:10.1038/gimo16
  20. Shaker R. Reflex interaction of pharynx, esophagus, and airways. GI Motility online (2006) doi:10.1038/gimo11
  21. Sontag, SJ. and Harding, SM. Gastroesophageal reflux and asthma. GI Motility online (2006) doi:10.1038/gimo47
  22. Spechler, SJ. Barrett's esophagus. GI Motility online (2006) doi:10.1038/gimo44
  23. Tutuian, R, and Castell, DO. Gastroesophageal reflux monitoring: pH and impedance. GI Motility online (2006) doi:10.1038/gimo31
Wise JL and Murray, JA. Oral, pharyngeal and esophageal motility disorders in systemic diseases. GI Motility online (2006) doi:10.1038/gimo40.