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Gastroesophageal Reflux Disease. Pathogenesis. Symptoms

Gastroesophageal Reflux Disease. Pathogenesis. SymptomsGastroesophageal reflux disease (GERD) is one of the most common chronic disorders of the upper gastrointestinal tract presenting to primary care physicians and gastroenterologists. Epidemiological studies suggest that between 21% and 44% of the adult population report symptoms of heartburn on a monthly basis and 18% of these individuals use nonprescription medications for this problem. In addition, GERD is reported by 45%–85% of women during pregnancy.

While the associated mortality is low, there is significant morbidity and the patient’s quality of life can be greatly affected. Variable in severity and prognosis, it is a disorder that leads to irritation and eventual injury to the esophageal mucosa. Of patients with symptomatic GERD, 40% will develop a major complication including erosive reflux esophagitis, which potentially can lead to stricture formation, esophageal ulceration and hemorrhage.

Although symptoms of the disease can improve and even disappear, long-term studies suggest that these patients will have significant morbidity after their diagnosis. Therefore, patients with gastroesophageal reflux disease may require lifelong therapy, which will require pharmacists to play an interactive role in managing this disease.

Pathogenesis

Normally, a muscular valve at the lower end of the esophagus called the lower esophageal sphincter (LES) keeps gastric contents within the stomach and out of the esophagus. This band of smooth muscle maintains a resting pressure that is more than 12 mmHg higher than the intragastric pressure, thus providing a barrier against gastric reflux. When an individual swallows, a gastroesophageal peristaltic wave causes the LES to relax, and gastric contents can reflux. Healthy individuals may experience some degree of gastroesophageal reflux after a meal. However, GERD patients experience a more frequent retrograde flow of gastric contents through an incompetent gastroesophageal junction. The development and severity of gastroesophageal reflux disease is contingent on the duration, frequency and injurious effects of the gastric contents on the esophageal mucosa (especially when pH is less than 4.0). Factors that contribute to the pathogenesis of GERD include inappropriate relaxation of the lower esophageal sphincter, delayed gastric emptying, acid hypersecretion, failed esophageal peristalsis, impaired mucosal defenses and hiatal hernia. Of these contributory factors, a compromised LES (i.e., transient LES relaxation, low LES resting pressure) is thought to be the more important pathogenesis of gastroesophageal reflux disease.

Symptoms

The disease encompasses a broad spectrum of symptoms and clinical disorders, from heartburn without esophagitis to severe complications (Table 1).

Table 1. Symptoms of GERD
CommonHeartburn, early satiety, brackish taste

Acid regurgitation

Epigastric pain

Dysphagia

Major Atypical

Respiratory complaints: asthma, chronic sinusitis

Noncardiac chest pain

Nausea

Hoarseness, cough

The most frequent symptoms include heartburn and acid regurgitation, but combinations of symptoms are common. Many patients have heartburn along with epigastric pain. Up to 50% of patients with evidence of esophagitis at endoscopy present with atypical symptoms, such as noncardiac chest pain, hoarseness, nausea, and respiratory problems. The symptoms and severity of disease are not predictive with the degree of esophageal damage as evidenced at endoscopy.

Heartburn symptoms may actually decrease as the esophageal opening narrows due to esophageal stricture, because the stricture prevents acid reflux. All patients with alarm symptoms such as dysphagia, weight loss, bleeding or anemia (Table 2) should be evaluated by a physician before therapy is initiated.

Table 2. Alarm Symptoms
Serious damage may have already occurred if the patient experiences these symptoms:Dysphagia: difficulty swallowing or a feeling that food is trapped behind the breast bone

Bleeding: vomiting blood or having tarry, black bowel movements

Choking: sensation of acid refluxed into the windpipe causing shortness of breath, coughing, or hoarseness of voice

Weight loss, anemia

The natural course of the disease may vary, in which patients have intermittent attacks with prolonged periods of remission. However, a number of complications can develop related to the disease.

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