dyspepsia (indigestion)

What is dyspepsia (indigestion)?

Dyspepsia is one of the most common ailments of the bowel (intestines), affecting an estimated 20% of persons in the United States. Perhaps only 10% of those affected actually seek medical attention for their dyspepsia. Dyspepsia is not a particularly good term for the ailment since it implies that there is "dyspepsia" or abnormal digestion of food, and this most probably is not the case. In fact, another common name for dyspepsia is indigestion, which, for the same reason, is no better than the term dyspepsia! Doctors frequently refer to the condition as non-ulcer dyspepsia.
Dyspepsia (indigestion) is best described as a functional disease. (Sometimes, it is called functional dyspepsia.) The concept of functional disease is particularly useful when discussing diseases of the gastrointestinal tract. The concept applies to the muscular organs of the gastrointestinal tract-esophagus, stomach, small intestine, gallbladder, and colon. What is meant by the term, functional, is that either the muscles of the organs or the nerves that control the organs are not working normally, and, as a result, the organs do not function normally, and the dysfunction causes the symptoms. The nerves that control the organs include not only the nerves that lie within the muscles of the organs but also the nerves of the spinal cord and brain.
Some gastrointestinal diseases can be seen and diagnosed with the naked eye, such as ulcers of the stomach. Thus, ulcers can be seen at surgery, on X-rays, and by endoscopy. Other diseases cannot be seen with the naked eye but can be seen and diagnosed under the microscope. For example, gastritis (inflammation of the stomach) can be diagnosed by microscopic examination of biopsies of the stomach. In contrast, gastrointestinal functional diseases cannot be seen with the naked eye or with the microscope. In some instances, the abnormal function can be demonstrated by tests (for example, gastric emptying studies or antro-duodenal motility studies). However, the tests often are complex, are not widely available, and do not reliably detect the functional abnormalities. Accordingly, and by default, functional gastrointestinal diseases are those that involve abnormal function of gastrointestinal organs in which the abnormalities cannot be seen in the organs with either the naked eye or the microscope.
Occasionally, diseases that are thought to be functional are ultimately found to be associated with abnormalities that can be seen. Then, the disease moves out of the functional category. An example of this would be Helicobacter pylori (H. pylori) infection of the stomach. Some patients with mild upper gastrointestinal symptoms who were thought to have abnormal function of the stomach or intestines have been found to have stomachs infected with H. pylori. This infection can be diagnosed under the microscope by identifying the bacterium. When patients are treated with antibiotics, the H. pylori and symptoms disappear. Thus, recognition of infections with Helicobacter pylori has removed some patients' systems from the functional disease category.
The distinction between functional disease and non-functional disease may, in fact, be blurry. Thus, even functional diseases probably have associated biochemical or molecular abnormalities that ultimately will be able to be measured. For example, functional diseases of the stomach and intestines may be shown ultimately to be associated with reduced or increased levels of normal chemicals within the gastrointestinal organs, the spinal cord, or the brain. Should a disease that is demonstrated to be due to a reduced or increased chemical still be considered a functional disease? In this theoretical situation, we can't see the abnormality with the naked eye or the microscope, but we can measure it. If we can measure an associated or causative abnormality, should the disease no longer be considered functional, even though the disease (symptoms) are being caused by abnormal function? The answer is unclear.
Despite the shortcomings of the term, functional, the concept of a functional abnormality is useful for approaching many of the symptoms originating from the muscular organs of the gastrointestinal tract. To repeat, this concept applies to those symptoms for which there are no associated abnormalities that can be seen with the naked eye or the microscope.
While dyspepsia is a major functional disease(s), it is important to mention several other functional diseases. A second major functional disease is the irritable bowel syndrome, or IBS. The symptoms of IBS are thought to originate primarily from the small intestine and/or colon. The symptoms of IBS include abdominal pain that is accompanied by alterations in bowel movements (defecation), primarily constipation or diarrhea. In fact, dyspepsia and IBS may be overlapping diseases since up to half of patients with IBS also have symptoms of dyspepsia. A third distinct functional disorder is non-cardiac chest pain. This pain may mimic heart pain (angina), but it is unassociated with heart disease. In fact, non-cardiac chest pain is thought to result from a functional abnormality of the esophagus.
Functional disorders of the gastrointestinal tract often are categorized by the organ of involvement. Thus, there are functional disorders of the esophagus, stomach, small intestine, colon, and gallbladder. The amount of research that has been done with functional disorders is greatest in the esophagus and stomach (for example, non-cardiac chest pain, dyspepsia), perhaps because these organs are easiest to reach and study. Research into functional disorders affecting the small intestine and colon (IBS) is more difficult to conduct and there is less agreement among the research studies. This probably is a reflection of the complexity of the activities of the small intestine and colon and the difficulty in studying these activities. Functional diseases of the gallbladder (referred to as biliary dyskinesia), like those of the small intestine and colon, also are more difficult to study, and at present they are less well-defined. Each of the functional diseases is associated with its own set of characteristic symptoms.

 

 

What are the symptoms of dyspepsia (indigestion)?

We usually think of symptoms of dyspepsia as originating from the upper gastrointestinal tract, primarily the stomach and first part of the small intestine. These symptoms include:

• upper abdominal pain (above the navel),
• belching,
• nausea (with or without vomiting),
• abdominal bloating (the sensation of abdominal fullness without objective distention),
• early satiety (the sensation of fullness after a very small amount of food), and,
•  abdominal distention (swelling as opposed to bloating).

The symptoms most often are provoked by eating, which is a time when many different gastrointestinal functions are called upon to work in concert. This tendency to occur after meals is what gave rise to the notion that dyspepsia might be caused by an abnormality in the digestion of food.
It is appropriate to discuss belching in detail since it is a commonly misunderstood symptom associated with dyspepsia. The ability to belch is almost universal. Belching, also known as burping or eructating, is the act of expelling gas from the stomach out through the mouth. The usual cause of belching is a distended (inflated) stomach that is caused by swallowed air or gas. The distention of the stomach causes abdominal discomfort, and the belching expels the air and relieves the discomfort. The common reasons for swallowing large amounts of air (aerophagia) or gas are gulping food or drink too rapidly, anxiety, and carbonated beverages. People often are unaware that they are swallowing air. Moreover, if there is not excess air in the stomach, the act of belching actually may cause more air to be swallowed. "Burping" infants during bottle or breastfeeding is important in order to expel air in the stomach that has been swallowed with the formula or milk.
Excessive air in the stomach is not the only cause of belching. For some people, belching becomes a habit and does not reflect the amount of air in their stomachs. For others, belching is a response to any type of abdominal discomfort and not just to discomfort due to increased gas. Everyone knows that when they have mild abdominal discomfort, belching often relieves the problem. This is because excessive air in the stomach often is the cause of mild abdominal discomfort; as a result, people belch whenever mild abdominal discomfort is felt-whatever the cause.
If the problem causing the discomfort is not excessive air in the stomach, then belching does not provide relief. As mentioned previously, it even may make the situation worse by increasing air in the stomach. When belching does not ease the discomfort, the belching should be taken as a sign that something may be wrong within the abdomen and that the cause of the discomfort should be sought. Belching by itself, however, does not help the physician determine what may be wrong because belching can occur in virtually any abdominal disease or condition that causes discomfort.

What causes dyspepsia (indigestion)?

It's not surprising that many gastrointestinal diseases have been associated with dyspepsia. However, many non-gastrointestinal diseases also have been associated with dyspepsia. Examples of the latter include diabetes, thyroid disease, hyperparathyroidism (overactive parathyroid glands), and severe kidney disease. It is not clear, however, how these non-gastrointestinal diseases might cause dyspepsia. A second important cause of dyspepsia is drugs. It turns out that many drugs are frequently associated with dyspepsia, for example, nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), antibiotics, and estrogens). In fact, most drugs are reported to cause dyspepsia in at least some patients.

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As discussed previously, most dyspepsia (not due to non-gastrointestinal diseases or drugs) is believed to be due to abnormal function of the muscles of the organs of the gastrointestinal tract or the nerves controlling the organs. The nervous control of the gastrointestinal tract, however, is complex. A system of nerves runs the entire length of the gastrointestinal tract from the esophagus to the anus in the muscular walls of the organs. These nerves communicate with other nerves that travel to and from the spinal cord. Nerves within the spinal cord, in turn, travel to and from the brain. (The gastrointestinal tract is exceeded in the numbers of nerves it contains only by the spinal cord and brain.) Thus, abnormal function of the nervous system in dyspepsia might occur in a gastrointestinal muscular organ, the spinal cord, or the brain.
The nervous system controlling the gastrointestinal organs, as with most other organs, contains both sensory and motor nerves. The sensory nerves continuously sense what is happening (activity) within the organ and relay this information to nerves in the organ's wall. From there, information can be relayed to the spinal cord and brain. The information is received and processed in the organ's wall, the spinal cord, or the brain. Then, based on this sensory input and the way the input is processed, commands (responses) are sent to the organ over the motor nerves. Two of the most common motor responses in the intestine are contraction or relaxation of the muscle of the organ and secretion of fluid and/or mucus into the organ.
As already mentioned, abnormal function of the nerves of the gastrointestinal organs, at least theoretically, might occur in the organ, spinal cord, or brain. Moreover, the abnormalities might occur in the sensory nerves, the motor nerves, or at processing centers in the intestine, spinal cord, or brain.
Some researchers argue that the cause of functional diseases is abnormalities in the function of sensory nerves. For example, normal activities, such as stretching of the small intestine by food, may give rise to sensory signals that are sent to the spinal cord and brain, where they are perceived as painful. Other researchers argue that the cause of functional diseases is abnormalities in the function of motor nerves. For example, abnormal commands through the motor nerves might produce painful spasm (contraction) of the muscles. Still others argue that abnormally functioning processing centers are responsible for functional diseases because they misinterpret normal sensations or send abnormal commands to the organ. In fact, some functional diseases may be due to sensory dysfunction, motor dysfunction, or both sensory and motor dysfunction. Others may be due to abnormalities within the processing centers.
An important concept that is relevant to these several potential mechanisms (causes) of functional diseases is the concept of "visceral hypersensitivity". This concept states that diseases affecting the gastrointestinal organs (viscera) "sensitize" (alter the responsiveness of) the sensory nerves or the processing centers to sensations coming from the organ. According to this theory, a disease such as colitis (inflammation of the colon) can cause permanent changes in the sensitivity of the nerves or processing centers of the colon. As a result of this prior inflammation, normal stimuli are perceived (felt) as abnormal (for example, as being painful). Thus, a normal colonic contraction may be painful. It is not clear what prior diseases might lead to hypersensitivity in people, although infectious diseases (bacterial or viral) of the gastrointestinal tract are mentioned most often. Visceral hypersensitivity has been demonstrated clearly in animals and people. Its role in the common functional diseases, however, is unclear.
Another potential cause of dyspepsia is bacterial overgrowth of the small intestine (small intestinal bacterial overgrowth or SIBO), although the frequency with which this condition causes dyspepsia has not been determined, and there is little research in the area. The relationship between overgrowth and dyspepsia needs to be pursued, however, since many of the symptoms of dyspepsia are also symptoms of bacterial overgrowth. Overgrowth can be diagnosed by hydrogen breath testing and is treated primarily with antibiotics.
Other diseases and conditions can aggravate functional diseases, including dyspepsia. Anxiety and/or depression are probably the most commonly-recognized exacerbating factors for patients with functional diseases. Another aggravating factor is the menstrual cycle. During their periods, women often note that their functional symptoms are worse. This corresponds to the time during which the female hormones, estrogen and progesterone, are at their highest levels. Furthermore, it has been observed that treating women who have dyspepsia with leuprolide (Lupron), an injectable drug that shuts off the body's production of estrogen and progesterone, is effective at reducing symptoms of dyspepsia in premenopausal women. These observations support a role for hormones in the intensification of functional symptoms.

What is the course of dyspepsia (indigestion)?

Dyspepsia is a chronic disease that usually lasts years, if not a lifetime. It does, however, display periodicity, which means that the symptoms may be more frequent or severe for days, weeks, or months and then less frequent or severe for days, weeks, or months. The reasons for these fluctuations are unknown. Because of the fluctuations, it is important to judge the effects of treatment over many weeks or months to be certain that any improvement is due to treatment and not simply to a natural fluctuation in the frequency or severity of the disease.

What are the complications of dyspepsia (indigestion)?

The complications of functional diseases of the gastrointestinal tract are relatively limited. Since symptoms are most often provoked by eating, patients who alter their diets and reduce their intake of calories may lose weight. However, loss of weight is unusual in functional diseases. In fact, loss of weight should suggest the presence of non-functional diseases. Symptoms that awaken patients from sleep also are more likely to be due to non-functional than functional disease.

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Most commonly, functional diseases interfere with patients' comfort and daily activities. Individuals who develop nausea or pain after eating may skip breakfast or lunch because of the symptoms they experienc. Patients also commonly associate symptoms with specific foods (for example, milk, fat, vegetables). Whether or not the associations are real, these patients will restrict their diets accordingly. Milk is the most common food that is eliminated, often unnecessarily, and this can lead to inadequate intake of calcium and osteoporosis. The interference with daily activities also can lead to problems with interpersonal relationships, especially with spouses. Most patients with functional disease live with their symptoms and infrequently visit physicians for diagnosis and treatment.

How is dyspepsia diagnosed (indigestion)?

Dyspepsia is diagnosed primarily on the basis of typical symptoms and the exclusion of non-functional gastrointestinal diseases (including acid-related diseases), non-gastrointestinal diseases, and psychiatric illness. There are tests for identifying abnormal gastrointestinal function directly, but they are limited in their ability to do so.

Exclusion of other diseases

Exclusion of non-functional gastrointestinal disease
As always, a detailed history from the patient and a physical examination frequently will suggest the cause of dyspepsia. Routine screening blood tests often are performed looking for clues to unsuspected diseases. Examinations of stool also are a part of the evaluation since they may reveal infection, signs of inflammation, or blood and direct further diagnostic testing. Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic. Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear. (Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease.) If bacterial overgrowth of the small intestine is being considered, breath hydrogen testing can be considered.
There are many tests to exclude non-functional gastrointestinal diseases. The primary issue, however, is to decide which tests are reasonable to perform. Since each case is individual, different tests may be reasonable for different patients. Nevertheless, certain basic tests are often performed to exclude non-functional gastrointestinal disease. These tests identify anatomic (structural) and histological (microscopic) diseases of the esophagus, stomach, and intestines.
Both X-rays and endoscopies can identify anatomic diseases. Only endoscopies, however, can diagnose histological diseases because biopsies (samples of tissue) can be taken during the procedure. The X-ray tests include:

• The esophagram and video-fluoroscopic swallowing study for examining the esophagus
• The upper gastrointestinal series for examining the stomach and duodenum
• The small bowel series for examining the small intestine
• The barium enema for examining the colon and terminal ileum.
• The computerized tomography (CT) scan for examining the small intestine

The endoscopic tests include:

• Upper gastrointestinal endoscopy (esophago-gastro-duodenoscopy or EGD) to examine the esophagus, stomach and duodenum
• Colonoscopy to examine the colon and terminal ileum
• Endoscopy also is available to examine the small intestine, but this type of endoscopy is complex, not widely available, and of unproven value in dyspepsia.

For examination of the small intestine, there is also a capsule containing a tiny camera and transmitter that can be swallowed (capsule endoscopy). As the capsule travels through the intestines, it transmits pictures of the inside of the intestines to an external recorder for later review. The capsule is not widely available and its value, particularly in dyspepsia, has not yet been proven.
Newer endoscopes, similar to those used for EGD and colonoscopy are available that allow the entire small intestine to be examined. Unlike the capsule, however, the endoscope has channels in it that allow instruments to be passed into the intestine to collect samples of tissue (biopsies) and to treat abnormal findings such as polyps.
X-rays are easier to perform and less costly than endoscopies. The skills necessary to perform gastrointestinal X-rays, however, are becoming rare among radiologists because they are doing them less often. Therefore, the quality of the X-rays often is not as high as it used to be, and, as a result, CT scans of the small intestine are replacing small intestinal X-rays. As noted previously, endoscopies have an advantage over X-rays since at the time of endoscopies, biopsies can be taken to diagnose or exclude histological diseases, something that X-rays cannot do.

Exclusion of acid-related gastrointestinal diseases
Because they are so common, the most important non-functional gastrointestinal diseases to exclude are acid-related diseases that cause inflammation and ulceration of the esophagus, stomach, and duodenum. Infection of the stomach with Helicobacter pylori, an infection that is closely associated with some acid-related diseases, is included in this group. It is not clear, however, how often Helicobacter pylori causes dyspepsia. Moreover, the only way of excluding this bacterium as a cause of dyspepsia in a particular patient is by eliminating the infection (if it is present) with appropriate antibiotics. If dyspepsia is substantially improved by eradication, it is likely that the bacterium was responsible. Helicobacter pylori infection also can be diagnosed (or excluded) by blood tests, biopsy of the stomach, urea breath test, or a stool test.
Endoscopy is a good way of diagnosing or excluding acid-related inflammation. If no signs of inflammation are present, acid-related diseases are unlikely. Nevertheless, some patients without signs of inflammation respond to potent and prolonged suppression of acid, suggesting that acid is causing their dyspepsia. Therefore, many physicians will use potent suppression of acid in dyspepsia as a means to both treat and diagnose. Thus, if dyspepsia improves substantially (more than 50% to 75%) with suppression of acid, they consider it likely that acid is responsible for the dyspepsia. For this purpose, it is important to use potent acid suppression with proton pump inhibitors (PPIs), such as:

• omeprazole (Prilosec, Zegerid),
• lansoprazole (Prevacid),
• rabeprazole (Aciphex),
• pantoprazole (Protonix) or
• esomeprazole (Nexium).

Treatment often is given at higher than recommended doses for 12 weeks or more before a decision is made about the effect of treatment on the symptoms. (A short course for just a few days or weeks is not enough.) If the symptoms of dyspepsia do not improve, it even may be reasonable to check the amount of acid produced by the stomach (and also the reflux of acid into the esophagus) by 24 hour ph monitoring to be certain that the acid-suppressing drugs are effectively suppressing acid. (Up to 10% of patients are resistant to the effects of even the PPIs.)

Exclusion of non-gastrointestinal disease
Patients with dyspepsia often undergo abdominal ultrasonography (US), computerized tomography (CT or CAT scans), or magnetic resonance imaging (MRI). These tests are used primarily to diagnose non-intestinal diseases. (Although the tests also are capable of diagnosing intestinal diseases, their value for this purpose is limited. X-ray and endoscopy are better.) It is important to realize that US, CT, and MRI are powerful tests and may uncover abnormalities that are unrelated to dyspepsia. The most common example of this is the finding of gallstones that, in fact, are causing no symptoms. (Up to 50% of gallstones cause no symptoms.) This can cause a problem if the gallstones are assumed to be causing the dyspepsia. Surgical removal of the gallbladder with its gallstones (cholecystectomy) is unlikely to relieve the dyspepsia. (Cholecystectomy would be expected to relieve only the characteristic symptoms that gallstones can cause.) Additional tests to exclude non-gastrointestinal diseases may be appropriate in certain specific situations, although certainly not in most patients.

Exclusion of psychiatric disease
The possibility of psychiatric (psychological or psychosomatic) illness often arises in patients with dyspepsia because the symptoms are subjective and no objective abnormalities can be identified. Psychiatric illness may complicate dyspepsia, but it is unclear if psychiatric illness causes dyspepsia. If there is a possibility of psychiatric illness, a psychiatric evaluation is appropriate.

Specific tests of gastrointestinal function

Esophageal motility study

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Functional disorders of the esophagus can be identified with esophageal motility studies (manometry). For these studies, a pressure-sensing tube is swallowed and positioned within the esophagus. Contractions of the esophageal muscle normally cause increases in pressure within the esophagus that can be monitored by the catheter during and between swallows of water. Among the abnormalities that can be seen are abnormally high or abnormally low pressures during swallow-associated contractions and/or during spontaneous contractions unassociated with swallows.

Gastric emptying study and electrogastrogram
Slow emptying of the stomach is a common functional abnormality that can lead to bloating, nausea, and vomiting. Rapid emptying of the stomach is relatively uncommon and can lead to abdominal pain and diarrhea. Both of these abnormalities--slow and rapid emptying--can be identified by a gastric emptying study.
The most common type of emptying study is a nuclear medicine study. In this test, patients drink or eat food labeled with radioactive material. A Geiger counter-like device then is placed over the abdomen and the speed with which the radioactive drink or food empties from the stomach is monitored.
The electrogastrogram (EGG) is like the electrocardiogram (ECG) for the heart. Electrodes that are taped to the upper abdomen monitor the electrical activity generated by the muscle of the stomach. Abnormalities of the electrical rhythm of the stomach frequently are associated with dyspeptic symptoms, particularly nausea and vomiting. EGGs are not commonly available and are considered a research tool.

Barostatic study
A barostat is an instrument that is used to measure pressure and determine the compliance (flexibility) of a gastrointestinal organ. Compliance is a term that describes the effect that internal stretching has on the organ. The greater the compliance of an organ, the less there is tension (pressure) generated when the organ is stretched from within.
Compliance is important to the normal function of gastrointestinal organs. For example, as food fills the stomach during a meal, the muscles of the stomach must relax (comply) to accommodate the increasing volume of food. If the stomach does not relax properly, the pressure in the stomach increases abnormally. It is believed that abnormally high pressures within the stomach (due to reduced compliance) can lead to symptoms such as early satiety (the feeling of abdominal fullness or pain after only a small amount of food has been ingested).
The barostat includes a balloon that is placed within a gastrointestinal organ through the mouth or anus. As the balloon is progressively blown up and stretches the organ, the pressure within the organ is measured by the barostat. In this way, abnormal compliance can be identified. Barostats can be placed in the esophagus, stomach, small intestine or colon. Barostatic studies, however, probably should be considered experimental. In fact, barostats and expertise in their use are available in only a limited number of centers.

Small intestinal transit study
Small intestinal transit studies measure the speed with which food travels through the small intestine. In the most common type of transit study, a test meal that has been labeled with a radioactive material is ingested. A Geiger-counter-like device is placed over the abdomen and is used to follow the radioactive material through the small intestine and into the colon. Rapid transit is associated with abdominal pain and diarrhea. Slow transit also may be associated with abdominal pain. Although transit studies are not difficult to conduct, they are not frequently used because experience with their use is not wide-spread. They probably should be considered experimental.

Antro-duodenal motility study
Antro-duodenal motility studies measure the pressures that are generated by the contractions of the muscles of the antrum (outlet) of the stomach and the duodenum. For these studies, a pressure-sensing tube is swallowed or passed through the nose and positioned in the distal (outlet) part of the stomach (the antrum) and the first part of the small intestine (the duodenum). Pressures are measured with the stomach empty and after a test meal. Abnormally high or low pressures as well as uncoordinated contractions can be identified. These abnormalities are believed to be associated with symptoms of dyspepsia. Antro-duodenal motility studies and expertise in their use are not widely available.

Gallbladder emptying studies
Gallbladder emptying studies determine how well the gallbladder empties. Between meals, the gallbladder stores bile that is produced by the liver. After meals, the muscles of the gallbladder contract and squeeze out (empty) most of the bile into the intestine. In the intestine, the bile assists with the digestion of food.
For a gallbladder emptying study, a radioactive material is injected intravenously. The radioactive material is removed from the blood by the liver and accumulates with the bile in the gallbladder. The gallbladder then is stimulated to contract with either a meal or an intravenous injection of a hormone, called cholecystokinin. A Geiger-counter-like device is placed over the abdomen and the speed with which the radioactivity leaves the gallbladder and enters the intestine is monitored. Emptying studies of the gallbladder are widely available since this technology is used for several purposes other than measurement of gallbladder emptying.
It has been suggested that abnormally slow emptying of the gallbladder may be associated with abdominal pain. Unfortunately, however, the studies that support the association between slow gallbladder emptying and symptoms are weak. Moreover, many people have abnormally slow emptying of the gallbladder but no symptoms. For these reasons, abnormal emptying studies of the gallbladder have not been widely accepted for diagnosing functional disorders of the gallbladder. The lack of a clear association between dyspepsia and abnormalities of gallbladder emptying is important since it means that patients with abnormal emptying may not be improved by removal of their gallbladders.

How is dyspepsia (indigestion) treated?

The treatment of dyspepsia is a difficult and unsatisfying topic because so few drugs have been studied and have shown to be effective. Moreover, the drugs that have been shown to be useful have not been substantially effective. This difficult situation exists for many reasons, as follows:

• Life-threatening illnesses (for example, cancer, heart disease, and high blood pressure) are the illnesses that capture the public's interest and, more importantly, research funding. Dyspepsia is not a life-threatening illness and has received little research funding. Because of the lack of research, an understanding of the physiologic processes (mechanisms) that are responsible for dyspepsia has been slow to develop. Effective drugs cannot be developed until there is an understanding of these mechanisms.
•  
• Research in dyspepsia is difficult. Dyspepsia is defined by subjective symptoms (such as pain) rather than objective signs (for example, the presence of an ulcer). Subjective symptoms are more unreliable than objective signs in identifying homogenous groups of patients. As a result, groups of patients with dyspepsia who are undergoing treatment are likely to contain some patients who do not have dyspepsia, which may dilute (negatively affect) the results of the treatment. Moreover, the results of treatment must be evaluated on the basis of subjective responses (such as improvement of pain). In addition to being more unreliable, subjective responses are more difficult to measure than objective responses (for example, healing of an ulcer).
•  
• Different subtypes of dyspepsia (for example, abdominal pain and abdominal bloating) are likely to be caused by different physiologic processes (mechanisms). It also is possible, however, that the same subtype of dyspepsia may be caused by different mechanisms in different people. What's more, any drug is likely to affect only one mechanism. Therefore, it is unlikely that any one medication can be effective in all-even most-patients with dyspepsia, even patients with similar symptoms. This inconsistent effectiveness makes the testing of drugs particularly difficult. Indeed, it can easily result in drug trials that demonstrate no efficacy (usefulness) when, in fact, the drug is helping a subgroup of patients.
•  
• Subjective symptoms are particularly prone to responding to placebos (inactive drugs). In fact, in most studies, 20% to 40% of patients with dyspepsia will improve if they receive inactive drugs. Now, all clinical trials of drugs for dyspepsia require a placebo-treated group for comparison with the drug-treated group. The large placebo response means that these clinical trials must utilize large numbers of patients to detect meaningful (significant) differences in improvement between the placebo and drug groups. Therefore, these trials are expensive to conduct.

The lack of understanding of the physiologic processes (mechanisms) that cause dyspepsia has meant that treatment usually cannot be directed at the mechanisms. Instead, treatment usually is directed at the symptoms. For example, nausea is treated with medications that suppress nausea but do not affect the cause of the nausea. On the other hand, the psychotropic drugs (antidepressants) and psychological treatments (such as cognitive behavioral therapy) treat hypothetical causes of dyspepsia (for example, abnormal function of sensory nerves and the psyche) rather than the symptoms. Treatment for dyspepsia often is similar to that for irritable bowel syndrome (IBS) even though the causes of IBS and dyspepsia are likely to be different.

Education
It is important to educate patients with dyspepsia about their illness, particularly by reassuring them that the illness is not a serious threat to their physical health (though it may be to their emotional health). Patients need to understand the mechanisms (causes) for the symptoms. Most importantly, they need to understand the medical approach to the problem and the reasons for each test or treatment. Education prepares patients for a potentially prolonged course of diagnosis and trials of treatment. Education also may prevent patients from falling prey to the charlatans who offer unproven and possibly dangerous treatments for dyspepsia. Many symptoms are tolerable if patients' anxieties about the seriousness of their symptoms can be relieved. It also helps patients deal with symptoms when they feel that everything that should be done to diagnose and treat, in fact, is being done. The truth is that psychologically healthy people can tolerate a good deal of discomfort and continue to lead happy and productive lives.

Diet
Dietary factors have not been well-studied in the treatment of dyspepsia. Nevertheless, patients often associate their symptoms with specific foods (such as salads and fats). Although specific foods might worsen the symptoms of dyspepsia, they are not the cause of dyspepsia. (Intolerance to specific foods, for example, lactose intolerance (milk) and allergies to wheat, eggs, soy, and milk protein are not considered functional diseases. The common placebo response in functional disorders such as dyspepsia also may explain the improvement of symptoms in some people with the elimination of specific foods.
Dietary fiber often is recommended for patients with IBS, but fiber has not been studied in the treatment of dyspepsia. Nevertheless, it probably is reasonable to treat patients with dyspepsia with fiber if they also have constipation.
Intolerance to lactose (the sugar in milk) often is blamed for dyspepsia. Since dyspepsia and lactose intolerance both are common, the two conditions may coexist. In this situation, restricting lactose will improve the symptoms of lactose intolerance, but will not affect the symptoms of dyspepsia. Lactose intolerance is easily determined by testing the effects of lactose (hydrogen breath testing) or trying a strict lactose elimination diet. If lactose is determined to be responsible for some or all of the symptoms, elimination of lactose-containing foods is appropriate. Unfortunately, many patients stop drinking milk or eating milk-containing foods without good evidence that it improves their symptoms. This often is detrimental to their intake of calcium which may contribute to osteoporosis.
One of the food substances most commonly associated with the symptoms of dyspepsia is fat. The scientific evidence that fat causes dyspepsia is weak. Most of the support is anecdotal (not based on carefully done, scientific studies). Nevertheless, fat is one of the most potent influences on gastrointestinal function. (It tends to slow down the gastrointestinal muscles while it causes the muscles of the gallbladder to contract.) Therefore, it is possible that fat may worsen dyspepsia even though it doesn't cause it. Moreover, reducing the ingestion of fat might relieve symptoms. A strict low fat diet can be accomplished fairly easily and is worth trying. Additionally, there are other health-related reasons for reducing dietary fat.
Another dietary factor, fructose and fructose-related sugars, has been suggested as a cause of dyspepsia since many people do not fully digest and absorb them before they reach the distal intestine. It is diagnosed with a hydrogen breath test using fructose and treated with elimination of fructose-containing foods from the diet. Unfortunately, fructose and its related sugars are widespread among fruits and vegetables and are found in high concentrations in many food products sweetened with corn syrup. Thus, an elimination diet is more difficult to maintain.

Psychotropic drugs
Patients with functional disorders, including dyspepsia, are frequently found to be suffering from depression and/or anxiety. It is unclear, however, if the depression and anxiety are the cause or result of the functional disorders or are unrelated to these disorders. (Depression and anxiety are common and, therefore, their occurrence together with functional disorders may be coincidental.) Several clinical trials have shown that antidepressants are effective in IBS in relieving abdominal pain. Antidepressants also have been shown to be effective in unexplained (non-cardiac) chest pain, a condition thought to represent a dysfunction of the esophagus. Antidepressants have not been studied adequately in other types of functional disorders, including dyspepsia. It probably is reasonable to treat patients with dyspepsia with psychotropic drugs if they have moderate or severe depression or anxiety.
The antidepressants work in dyspepsia and in functional esophageal pain at relatively low doses that have little or no effect on depression. It is believed, therefore, that these drugs work not by combating depression, but in different ways (through different mechanisms). For example, these drugs have been shown to adjust (modulate) the activity of the nerves and to have analgesic (pain-relieving) effects as well.
Commonly used psychotropic drugs include the tricyclic antidepressants, desipramine (Norpramine) and trimipramine (Surmontil). Although studies are encouraging, it is not yet clear whether the newer class of antidepressants, the serotonin-reuptake inhibitors such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), are effective in functional disorders, including dyspepsia.

Psychological treatments
Psychological treatments include cognitive-behavioral therapy, hypnosis, psychodynamic or interpersonal psychotherapy, and relaxation/stress management. Few studies of psychological treatments have been conducted in dyspepsia, although more studies have been done in IBS. Thus, there is little scientific evidence that they are effective in dyspepsia, although there is some evidence that they are effective in IBS.
Hypnosis has been proposed as an effective treatment for IBS. It is unclear exactly how effective hypnosis is, or how it works.

Promotility drugs
One of the leading theories for the cause of dyspepsia is abnormalities in the way gastrointestinal muscles function. The function of muscles may be abnormally increased, abnormally decreased, or it may by uncoordinated. There are medications, called smooth muscle relaxants, that can reduce the activity of the muscles and other drugs that can increase the activity of the muscles, called the promotility drugs.
Many of the symptoms of dyspepsia can be explained on the basis of reduced activity of the gastrointestinal muscles that results in slowed transport (transit) of food through the stomach and intestine. (It is clear, as discussed previously, that there are other causes of these symptoms in addition to slowed transit.) Such symptoms include nausea, vomiting, and abdominal bloating. When transit is severely affected, abdominal distention (swelling) also may occur and can result in abdominal pain. (Early satiety is unlikely to be a function of slowed transit because it occurs too early for slowed transit to have consequences.) Theoretically, drugs that speed up the transit of food should, in at least some patients, relieve symptoms of dyspepsia that are due to slow transit.
The number of promotility drugs that are available for use clinically is limited. Studies of their effectiveness in dyspepsia are even more limited. The most studied drug is cisapride (Propulsid), a promotility drug that was withdrawn from the market because of serious cardiac side effects. (Newer drugs that have similar effects but lack the toxicity are being developed.) The few studies with cisapride for dyspepsia were inconsistent in their results. Some studies demonstrated benefits whereas others showed no benefit. Cisapride was effective in patients with severe emptying problems of the stomach (gastroparesis) or severely slowed transit of food through the small intestine (chronic intestinal pseudo-obstruction). These two diseases may or may not be related to dyspepsia.
Another promotility drug that is available is erythromycin, an antibiotic that stimulates gastrointestinal smooth muscle as one of its side effects. Erythromycin is used to stimulate smooth muscles of the gastrointestinal tract at doses that are lower than those used for treating infections. There are no studies of erythromycin in dyspepsia, but erythromycin is effective in gastroparesis and probably also in chronic intestinal pseudo-obstruction.
Metoclopramide (Reglan) is another promotility drug that is available. It has not been studied, however, in dyspepsia. Moreover, it is associated with some troubling side effects. Therefore, it may not be a good drug to undergo further testing in dyspepsia.
Domperidone (Motilium) is a promotility drug that is available in the U.S., but requires a special permit from the US Food and Drug administration. As a result, it is not very commonly prescribed. It is an effective drug with minimal side effects.

Smooth muscle relaxants
The most widely studied drugs for the treatment of abdominal pain in functional disorders are a group of drugs called smooth-muscle relaxants.
The gastrointestinal tract is primarily composed of a type of muscle called smooth muscle. (By contrast, skeletal muscles such as the biceps are composed of a type of muscle called striated muscle.) Smooth muscle relaxant drugs reduce the strength of contraction of the smooth muscles but do not affect the contraction of other types of muscles. They are used in functional disorders, particularly IBS, with the assumption (not proven) that strong or prolonged contractions of smooth muscles in the intestine-spasms-are the cause of the pain in functional disorders. There are even smooth muscle relaxants that are placed under the tongue, as is nitroglycerin for angina, so that they may be absorbed rapidly.
There are not enough studies of smooth muscle relaxants in dyspepsia to conclude that they are effective at reducing pain. Since their side effects are few, these drugs probably are worth trying. As with all drugs that are given to control symptoms, patients should carefully evaluate whether or not the smooth muscle relaxant they are using is effective at controlling the symptoms. If it is not clearly effective, the option of discontinuing the relaxant should be discussed with a physician.
Commonly used smooth muscle relaxants are hyoscyamine (Levsin, Anaspaz, Cystospaz, Donnamar) and methscopolamine (Pamine, Pamine Forte). Other drugs combine smooth muscle relaxants with a sedative chlordiazepoxide hydrochloride and clidinium bromide (Donnatal, Librax), but there is no evidence that the addition of sedatives adds to the effectiveness of the treatment.

What is a reasonable approach to the diagnosis and treatment of dyspepsia (indigestion)?

The initial approach to dyspepsia, whether it be treatment or testing, depends on the patient's age, symptoms and the duration of the symptoms. If the patient is younger than 50 years of age and serious disease, particularly cancer, is not likely, testing is less important. If the symptoms are typical for dyspepsia and have been present for many years without change, then there is less need for testing, or at least extensive testing, to exclude other gastrointestinal and non-gastrointestinal diseases.
On the other hand, if the symptoms are of recent onset (weeks or months), progressively worsening, severe, or associated with "warning" signs, then early, more extensive testing is appropriate. Warning signs include loss of weight, nighttime awakening, blood in the stool or the material that is vomited (vomitus), and signs of inflammation, such as fever or abdominal tenderness. Testing also is appropriate if, in addition to symptoms of dyspepsia, there are other prominent symptoms that are not commonly associated with dyspepsia.
If there are symptoms that suggest conditions other than dyspepsia, tests that are specific for these diseases should be done first. The reason is that if these other tests disclose other diseases, it may not be necessary to do additional testing. Examples of such symptoms and possible testing include:

• Vomiting: upper gastrointestinal endoscopy to diagnose inflammatory or obstructing diseases; gastric emptying studies and/or electrogastrography to diagnose impaired emptying of the stomach.

• Abdominal distention with or without increased flatulence: upper gastrointestinal and small intestinal x-rays to diagnose obstructing diseases; hydrogen breath testing to diagnose bacterial overgrowth of the small intestine.

For a patient with typical symptoms of dyspepsia who requires testing to exclude other diseases, a standard screening panel of blood tests would reasonably be included. These tests might reveal clues to non-gastrointestinal diseases. Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic. Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear. Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease. A plain x-ray of the abdomen might be done during an episode of abdominal pain (to look for intestinal blockage or obstruction). Testing for lactose intolerance or a trial of a strict lactose-free diet should be considered. The physician's clinical judgment should determine the extent to which initial testing is appropriate.
Once testing has been done to an extent that is appropriate for the clinical situation, it is reasonable to first try a therapeutic trial of stomach acid suppression to see if symptoms improve. Such a trial probably should involve a PPI (proton pump inhibitor) for 8 to 12 weeks. If there is no clear response of symptoms, the options then are to discontinue the PPI or confirm its effectiveness in suppressing acid with 24 hour acid testing. If there is a clear and substantial decrease in symptoms with the PPI, then decisions need to be made about continuing acid suppression and which drugs to use.
Another therapeutic approach is to test for Helicobacter pylori infection of the stomach (with blood, breath or stool tests) and to treat patients with infection to eradicate the infection. It may be necessary to retest patients after treatment to prove that treatment has effectively eradicated the infection, particularly if dyspeptic symptoms persist after treatment.
If treatment with a PPI has satisfactorily suppressed acid according to acid testing (or acid suppression has not been measured) and yet the symptoms have not improved, it is reasonable to conduct further testing as described above. Esophago-gastro-duodenoscopy, or EGD, (and, possibly, colonoscopy) would be the next consideration, probably with multiple biopsies of the stomach and duodenum (and colon if colonoscopy is done). Finally, small intestinal x-rays and an ultrasound examination of the gallbladder might be done. An abdominal ultrasound examination, CT scan, or MRI scan can exclude non-gastrointestinal diseases. Once appropriate testing has been completed, empiric trials of other drugs (for example, smooth muscle relaxants, psychotropic drugs, and promotility drugs) can be done. (An empiric trial of a drug is a trial that is not based on an understanding of the exact cause of the symptoms)
If all of the appropriate testing reveals no disease that could be causing the symptoms and the dyspeptic symptoms have not responded to empiric treatments, other, more specialized tests should be considered. These tests include hydrogen breath testing to diagnose bacterial overgrowth of the small intestine, gastric emptying studies, EGG, small intestinal transit studies, and antro-duodenal motility and barostatic studies. These specialized studies probably should be done at centers that have experience and expertise in diagnosing and treating functional diseases.

What is in the future for dyspepsia (indigestion)?

The future of dyspepsia will depend on our increasing knowledge of the processes (mechanisms) that cause dyspepsia. Acquiring this knowledge, in turn, depends on research funding. Because of the difficulties in conducting research in dyspepsia, this knowledge will not come quickly. Until we have an understanding of the mechanisms of dyspepsia, newer treatments will be based on our developing a better understanding of the normal control of gastrointestinal function, which is proceeding more rapidly. Specifically, there is intense interest in intestinal neurotransmitters, which are chemicals that the nerves of the intestine use to communicate with each other. The interactions of these neurotransmitters are responsible for adjusting (modulating) the functions of the intestines, such as contraction of muscles and secretion of fluid and mucus.
5-hydroxytriptamine (5-HT or serotonin) is a neurotransmitter that stimulates several different receptors on nerves in the intestine. Examples of experimental drugs for intestinal neurotransmission are sumatriptan (Imitrex) and buspirone (Buspar). These drugs are believed to reduce the responsiveness (sensitivity) of the sensory nerves to what's happening in the intestine by attaching to a particular 5-HT receptor, the 5-HT1 receptor. The 5-HT1 receptor drugs, however, have received only minimal study so far and their role in the treatment of dyspepsia, if any, is unknown.
Promotility drugs similar to cisapride, as previously discussed, are being pursued actively.

Dyspepsia (Indigestion) At A Glance

• Dyspepsia is a functional disease in which the gastrointestinal organs, primarily the stomach and first part of the small intestine, function abnormally. It is a chronic disease in which the symptoms fluctuate in frequency and intensity.
• Theories of the cause of dyspepsia include abnormal input from intestinal sensory nerves, abnormal processing of input from the sensory nerves, and abnormal stimulation of the intestines by motor nerves.
• The primary symptoms of dyspepsia are upper abdominal pain, belching, nausea, vomiting, abdominal bloating, early satiety, and abdominal distention (swelling). The symptoms most often are provoked by eating.
• Dyspepsia is diagnosed on the basis of typical symptoms and the absence of other gastrointestinal diseases, particularly acid-related diseases and non-gastrointestinal diseases that might give rise to the symptoms.
• Testing in dyspepsia is directed primarily at excluding the presence of other gastrointestinal diseases and non-gastrointestinal diseases. Some patients may require specific testing of certain gastrointestinal functions.
• Treatment in dyspepsia is primarily with education as well as smooth muscle relaxant and promotility drugs. There also may be a role for anti-depressant drugs and dietary changes.
• Future advances in the treatment of dyspepsia depend on a clearer understanding of its cause(s).

Heartburn Pictures .., Foods to Eat, Foods to Avoid

Will Eating This Give Me Heartburn?

Good question -- and the answer might not be what you expect. First, here are a few basic facts about heartburn, which has nothing to do with the heart. Heartburn is a burning discomfort from the chest area up to the throat. It can happen when stomach acid refluxes, or flows up, through a valve called the lower esophageal sphincter and irritates the esophagus. Certain foods can trigger heartburn, but you may have a little more food freedom than you think

Heartburn Trigger: Too Much Food

The first thing to think about, in terms of curbing heartburn, isn't this or that specific food. It's the amount of food you eat at a time. When it comes to heartburn risk, the sheer volume of what you eat matters. And this is one case where bigger isn't better. No matter what the food is, how good it looks, or how much you like it, eating too much food at once makes heartburn more likely. Tip: Try using smaller plates to trim your portions.

Heartburn Trigger: Eating on the Go

Always eating in a hurry? Shoveling food down is also a no-no, if you want to tame heartburn. Leslie Bonci, MPH, RD, CSSD, director of sports nutrition at the University of Pittsburgh Medical Center, says the three G's -- grab, gulp, and go -- don't make for good digestion and can make GERD (gastroesophageal reflux disease) symptoms more likely. Heartburn is a GERD symptom. So slow down when you eat if you're concerned about heartburn symptoms.