Gastroesophageal reflux disease, commonly referred to as GERD or acid reflux, is a condition in which the liquid content of the stomach regurgitates (backs up or refluxes) into the esophagus. The liquid can inflame and damage the lining (cause esophagitis) of the esophagus although visible signs of inflammation occur in a minority of patients. The regurgitated liquid usually contains acid and pepsin that are produced by the stomach. (Pepsin is an enzyme that begins the digestion of proteins in the stomach.)
The refluxed liquid also may contain bile that has backed-up into the stomach from the duodenum. (The duodenum is the first part of the small intestine that attaches to the stomach.) Acid is believed to be the most injurious component of the refluxed liquid. Pepsin and bile also may injure the esophagus, but their role in the production of esophageal inflammation and damage is not as clear as the role of acid.
GERD is a chronic condition. Once it begins, it usually is life-long. If there is injury to the lining of the esophagus (esophagitis), this also is a chronic condition. Moreover, after the esophagus has healed with treatment and treatment is stopped, the injury will return in most patients within a few months. Once treatment for GERD is begun, therefore, it usually will need to be continued indefinitely although it is argued that in some patients with intermittent symptoms and no esophagitis, treatment can be intermittent and done only during symptomatic periods.
In fact, the reflux of the stomach's liquid contents into the esophagus occurs in most normal individuals. One study found that reflux occurs as frequently in normal individuals as in patients with GERD. In patients with GERD, however, the refluxed liquid contains acid more often, and the acid remains in the esophagus longer. It has also been found that liquid refluxes to a higher level in the esophagus in patients with GERD than normal individuals.
As is often the case, the body has ways (mechanisms) to protect itself from the harmful effects of reflux and acid. For example, most reflux occurs during the day when individuals are upright. In the upright position, the refluxed liquid is more likely to flow back down into the stomach due to the effect of gravity. In addition, while individuals are awake, they repeatedly swallow, whether or not there is reflux.
Each swallow carries any refluxed liquid back into the stomach. Finally, the salivary glands in the mouth produce saliva, which contains bicarbonate. With each swallow, bicarbonate-containing saliva travels down the esophagus. The bicarbonate neutralizes the small amount of acid that remains in the esophagus after gravity and swallowing have removed most of the liquid.
Gravity, swallowing, and saliva are important protective mechanisms for the esophagus, but they are effective only when individuals are in the upright position. At night during sleep, gravity is not in effect, swallowing stops, and the secretion of saliva is reduced. Therefore, reflux that occurs at night is more likely to result in acid remaining in the esophagus longer and causing greater damage to the esophagus.
Certain conditions make a person susceptible to GERD. For example, GERD can be a serious problem during pregnancy. The elevated hormone levels of pregnancy probably cause reflux by lowering the pressure in the lower esophageal sphincter (see below). At the same time, the growing fetus increases the pressure in the abdomen. Both of these effects would be expected to increase reflux. Also, patients with diseases that weaken the esophageal muscles (see below), such as scleroderma or mixed connective tissue diseases, are more prone to develop GERD.
The symptoms of uncomplicated GERD are primarily heartburn (sometimes interpreted as chest pain), regurgitation, and nausea. Other symptoms occur when there are complications of GERD and will be discussed with the complications.
When acid refluxes back into the esophagus in patients with GERD, nerve fibers in the esophagus are stimulated. This nerve stimulation results most commonly in heartburn, the pain that is characteristic of GERD. Heartburn usually is described as a burning pain in the middle of the chest. It may start high in the abdomen or may extend up into the neck. In some patients, however, the pain may be sharp or pressure-like, rather than burning. Such pain can mimic heart pain (angina). In other patients, the pain may extend to the back.
Since acid reflux is more common after meals, heartburn is more common after meals. Heartburn is also more common when individuals lie down because without the effects of gravity, reflux occurs more easily, and acid is returned to the stomach more slowly. Many patients with GERD are awakened from sleep by heartburn.
Episodes of heartburn may occur infrequently or frequently, but episodes tend to happen periodically. This means that the episodes are more frequent or severe for a period of several weeks or months, and then they become less frequent or severe or even absent for several weeks or months. This periodicity of symptoms provides the rationale for intermittent treatment in patients with GERD who do not have esophagitis.
Nevertheless, heartburn is a life-long problem, and it almost always returns.
Regurgitation is the appearance of refluxed liquid in the mouth. In most patients with GERD, usually only small quantities of liquid reach the esophagus, and the liquid remains in the lower esophagus. Occasionally in some patients with GERD, larger quantities of liquid, sometimes containing food, are refluxed and reach the upper esophagus.
At the upper end of the esophagus is the upper esophageal sphincter (UES). The UES is a circular ring of muscle that is very similar in its actions to the LES. That is, the UES prevents esophageal contents from backing up into the throat. When small amounts of refluxed liquid and/or foods breach (get through) the UES and enter the throat, there may be an acid taste in the mouth. If larger quantities breach the UES, patients may suddenly find their mouths filled with the liquid or food. What's more, frequent or prolonged regurgitation can lead to acid-induced erosions of the teeth.
Nausea is uncommon in GERD. In some patients, however, it may be frequent or severe and may result in vomiting. In fact, in patients with unexplained nausea and/or vomiting, GERD is one of the first conditions to be considered. It is not clear why some patients with GERD develop mainly heartburn and others develop mainly nausea.
One of the simplest treatments for GERD is referred to as life-style changes, a combination of several changes in habit, particularly related to eating.
As discussed above, reflux of acid is more injurious at night than during the day. At night, when individuals are lying down, it is easier for reflux to occur. The reason that it is easier is because gravity is not opposing the reflux, as it does in the upright position during the day. In addition, the lack of an effect of gravity allows the refluxed liquid to travel further up the esophagus and remain in the esophagus longer.
These problems can be overcome partially by elevating the upper body in bed. The elevation is accomplished either by putting blocks under the bed's feet at the head of the bed or, more conveniently, by sleeping with the upper body on a foam rubber wedge. These maneuvers raise the esophagus above the stomach and partially restore the effects of gravity. It is important that the upper body and not just the head be elevated. Elevating only the head does not raise the esophagus and fails to restore the effects of gravity.
Elevation of the upper body at night generally is recommended for all patients with GERD. Nevertheless, most patients with GERD have reflux only during the day and elevation at night is of little benefit for them. It is not possible to know for certain which patients will benefit from elevation at night unless acid testing clearly demonstrates night reflux.
However, patients who have heartburn, regurgitation, or other symptoms of GERD at night are probably experiencing reflux at night and definitely should elevate their upper body when sleeping. Reflux also occurs less frequently when patients lie on their left rather than their right sides.
Several changes in eating habits can be beneficial in treating GERD. Reflux is worse following meals. This probably is so because the stomach is distended with food at that time and transient relaxations of the lower esophageal sphincter are more frequent. Therefore, smaller and earlier evening meals may reduce the amount of reflux for two reasons.
First, the smaller meal results in lesser distention of the stomach. Second, by bedtime, a smaller and earlier meal is more likely to have emptied from the stomach than is a larger one. As a result, reflux is less likely to occur when patients with GERD lie down to sleep.
Certain foods are known to reduce the pressure in the lower esophageal sphincter and thereby promote reflux.
These foods should be avoided and include:
- caffeinated drinks.
Fatty foods (which should be decreased) and smoking (which should be stopped) also reduce the pressure in the sphincter and promote reflux.
In addition, patients with GERD may find that other foods aggravate their symptoms. Examples are spicy or acid-containing foods, like citrus juices, carbonated beverages, and tomato juice. These foods should also be avoided.
One novel approach to the treatment of GERD is chewing gum. Chewing gum stimulates the production of more bicarbonate-containing saliva and increases the rate of swallowing. After the saliva is swallowed, it neutralizes acid in the esophagus. In effect, chewing gum exaggerates one of the normal processes that neutralize acid in the esophagus. It is not clear, however, how effective chewing gum actually is in treating heartburn. Nevertheless, chewing gum after meals is certainly worth a try.
Despite the development of potent medications for the treatment of GERD, antacids remain a mainstay of treatment. Antacids neutralize the acid in the stomach so that there is no acid to reflux. The problem with antacids is that their action is brief. They are emptied from the empty stomach quickly, in less than an hour, and the acid then re-accumulates.
The best way to take antacids, therefore, is approximately one hour after meals, which is just before the symptoms of reflux begin after a meal. Since the food from meals slows the emptying from the stomach, an antacid taken after a meal stays in the stomach longer and is effective longer. For the same reason, a second dose of antacids approximately two hours after a meal takes advantage of the continuing post-meal slower emptying of the stomach and replenishes the acid-neutralizing capacity within the stomach.
Antacids may be aluminum, magnesium, or calcium based. Calcium-based antacids (usually calcium carbonate), unlike other antacids, stimulate the release of gastrin from the stomach and duodenum. Gastrin is the hormone that is primarily responsible for the stimulation of acid secretion by the stomach.
Therefore, the secretion of acid rebounds after the direct acid-neutralizing effect of the calcium carbonate is exhausted. The rebound is due to the release of gastrin, which results in an overproduction of acid. Theoretically at least, this increased acid is not good for GERD.
Acid rebound, however, has not been shown to be clinically important. That is, treatment with calcium carbonate has not been shown to be less effective or safe than treatment with antacids not containing calcium carbonate. Nevertheless, the phenomenon of acid rebound is theoretically harmful. In practice, therefore, calcium-containing antacids such as Tums and Rolaids are not recommended. The occasional use of these calcium carbonate-containing antacids, however, is not believed to be harmful. The advantages of calcium carbonate-containing antacids are their low cost , the calcium they add to the diet, and their convenience as compared to liquids.
Aluminum-containing antacids have a tendency to cause constipation, while magnesium-containing antacids tend to cause diarrhea. If diarrhea or constipation becomes a problem, it may be necessary to switch antacids or alternately use antacids containing aluminum and magnesium.
Although antacids can neutralize acid, they do so for only a short period of time. For substantial neutralization of acid throughout the day, antacids would need to be given frequently, at least every hour.
The first medication developed for more effective and convenient treatment of acid-related diseases, including GERD, was a histamine antagonist, specifically cimetidine (Tagamet). Histamine is an important chemical because it stimulates acid production by the stomach. Released within the wall of the stomach, histamine attaches to receptors (binders) on the stomach's acid-producing cells and stimulates the cells to produce acid. Histamine antagonists work by blocking the receptor for histamine and thereby preventing histamine from stimulating the acid-producing cells. (Histamine antagonists are referred to as H2 antagonists because the specific receptor they block is the histamine type 2 receptor.)
Because histamine is particularly important for the stimulation of acid after meals, H2 antagonists are best taken 30 minutes before meals. The reason for this timing is so that the H2 antagonists will be at peak levels in the body after the meal when the stomach is actively producing acid. H2 antagonists also can be taken at bedtime to suppress nighttime production of acid.
H2 antagonists are very good for relieving the symptoms of GERD, particularly heartburn. However, they are not very good for healing the inflammation (esophagitis) that may accompany GERD. In fact, they are used primarily for the treatment of heartburn in GERD that is not associated with inflammation or complications, such as erosions or ulcers, strictures, or Barrett's esophagus.
Four different H2 antagonists are available by prescription, including cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid). All four are also available over-the-counter (OTC), without the need for a prescription. However, the OTC dosages are lower than those available by prescription.
Proton pump inhibitors
The second type of drug developed specifically for acid-related diseases, such as GERD, was a proton pump inhibitor (PPI), specifically, omeprazole (Prilosec). A PPI blocks the secretion of acid into the stomach by the acid-secreting cells. The advantage of a PPI over an H2 antagonist is that the PPI shuts off acid production more completely and for a longer period of time. Not only is the PPI good for treating the symptom of heartburn, but it also is good for protecting the esophagus from acid so that esophageal inflammation can heal.
PPIs are used when H2 antagonists do not relieve symptoms adequately or when complications of GERD such as erosions or ulcers, strictures, or Barrett's esophagus exist. Five different PPIs are approved for the treatment of GERD, including omeprazole (Prilosec, Dexilant), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium).
A sixth PPI product consists of a combination of omeprazole and sodium bicarbonate (Zegerid). PPIs (except for Zegarid) are best taken an hour before meals. The reason for this timing is that the PPIs work best when the stomach is most actively producing acid, which occurs after meals. If the PPI is taken before the meal, it is at peak levels in the body after the meal when the acid is being made.
Pro-motility drugs work by stimulating the muscles of the gastrointestinal tract, including the esophagus, stomach, small intestine, and/or colon. One pro-motility drug, metoclopramide (Reglan), is approved for GERD. Pro-motility drugs increase the pressure in the lower esophageal sphincter and strengthen the contractions (peristalsis) of the esophagus. Both effects would be expected to reduce reflux of acid. However, these effects on the sphincter and esophagus are small. Therefore, it is believed that the primary effect of metoclopramide may be to speed up emptying of the stomach, which also would be expected to reduce reflux.
Pro-motility drugs are most effective when taken 30 minutes before meals and again at bedtime. They are not very effective for treating either the symptoms or complications of GERD. Therefore, the pro-motility agents are reserved either for patients who do not respond to other treatments or are added to enhance other treatments for GERD.
Foam barriers provide a unique form of treatment for GERD. Foam barriers are tablets that are composed of an antacid and a foaming agent. As the tablet disintegrates and reaches the stomach, it turns into foam that floats on the top of the liquid contents of the stomach. The foam forms a physical barrier to the reflux of liquid. At the same time, the antacid bound to the foam neutralizes acid that comes in contact with the foam.
The tablets are best taken after meals (when the stomach is distended) and when lying down, both times when reflux is more likely to occur. Foam barriers are not often used as the first or only treatment for GERD. Rather, they are added to other drugs for GERD when the other drugs are not adequately effective in relieving symptoms. There is only one foam barrier, which is a combination of aluminum hydroxide gel, magnesium trisilicate, and alginate (Gaviscon).
The drugs described above usually are effective in treating the symptoms and complications of GERD. Nevertheless, sometimes they are not. For example, despite adequate suppression of acid and relief from heartburn, regurgitation, with its potential for complications in the lungs, may still occur. Moreover, the amounts and/or numbers of drugs that are required for satisfactory treatment are sometimes so great that drug treatment is unreasonable. In such situations, surgery can effectively stop reflux.
The surgical procedure that is done to prevent reflux is technically known as fundoplication and is called reflux surgery or anti-reflux surgery. During fundoplication, any hiatal hernial sac is pulled below the diaphragm and stitched there. In addition, the opening in the diaphragm through which the esophagus passes is tightened around the esophagus. Finally, the upper part of the stomach next to the opening of the esophagus into the stomach is wrapped around the lower esophagus to make an artificial lower esophageal sphincter.
All of this surgery can be done through an incision in the abdomen (laparotomy) or using a technique called laparoscopy. During laparoscopy, a small viewing device and surgical instruments are passed through several small puncture sites in the abdomen. This procedure avoids the need for a major abdominal incision.
Surgery is very effective at relieving symptoms and treating the complications of GERD. Approximately 80% of patients will have good or excellent relief of their symptoms for at least 5 to 10 years.
Nevertheless, many patients who have had surgery — perhaps as many as half — will continue to take drugs for reflux. It is not clear whether they take the drugs because they continue to have reflux and symptoms of reflux or if they take them for symptoms that are being caused by problems other than GERD. The most common complication of fundoplication is swallowed food that sticks at the artificial sphincter. Fortunately, the sticking usually is temporary. If it is not transient, endoscopic treatment to stretch (dilate) the artificial sphincter usually will relieve the problem. Only occasionally is it necessary to re-operate to revise the prior surgery.
Very recently, endoscopic techniques for the treatment of GERD have been developed and tested. One type of endoscopic treatment involves suturing (stitching) the area of the lower esophageal sphincter, which essentially tightens the sphincter.
A second type involves the application of radio-frequency waves to the lower part of the esophagus just above the sphincter. The waves cause damage to the tissue beneath the esophageal lining and a scar (fibrosis) forms. The scar shrinks and pulls on the surrounding tissue, thereby tightening the sphincter and the area above it.
A third type of endoscopic treatment involves the injection of materials into the esophageal wall in the area of the LES. The injected material is intended to increase pressure in the LES and thereby prevent reflux. In one treatment the injected material was a polymer.
Unfortunately, the injection of polymer led to serious complications, and the material for injection is no longer available. Another treatment involving injection of expandable pellets also was discontinued. Limited information is available about a third type of injection which uses gelatinous polymethylmethacrylate microspheres.
Endoscopic treatment has the advantage of not requiring surgery. It can be performed without hospitalization. Experience with endoscopic techniques is limited. It is not clear how effective they are, especially long-term. Because the effectiveness and the full extent of potential complications of endoscopic techniques are not clear, it is felt generally that endoscopic treatment should only be done as part of experimental trials.
Prevention of transient LES relaxation
Transient LES relaxations appear to be the most common way in which acid reflux occurs. Although there are available drugs that prevent relaxations, they have too many side effects to be generally useful. Much attention is being directed at the development of drugs that prevent these relaxations without accompanying side effects.