LUGANSK STATE MEDICAL UNIVERSITY DEPARTMENT OF INTERNAL MEDICINE No.3
Lecture:
Gastroesophageal Reflux Disease Lecturer: Assistant professor: Shuper V.A.
Course: 4th Time: 90 minute.
Lugansk, 2008.
Gastroesophageal Reflux Disease S1 GERD is one of the most prevalent gastrointestinal disorders. Population-based studies show that up to 15% of individuals have heartburn and/or regurgitation at least once a week and 7% have symptoms daily Background Gastroesophageal reflux is a normal physiological phenomenon experienced intermittently by most people, particularly after a meal. Gastroesophageal reflux disease (GERD) occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit, causing symptoms with or without associated esophageal mucosal injury (ie, esophagitis). The cumulative effects of GER depend on the amount of refluxed material per episode, the frequency of reflux episodes, the rate of clearance of the esophagus by gravity and peristaltic contraction, and the rate of neutralization of gastric acid by salivary secretion. Pathophysiology The physiological and anatomical factors that prevent the reflux of gastric juice from the stomach into the esophagus include the following: •The lower esophageal sphincter (LES) must have a normal length and pressure and a normal number of episodes of transient relaxation (relaxation in the absence of swallowing). •The gastroesophageal junction must be located in the abdomen so that the diaphragmatic crura can assist the action of the LES, thus functioning as an extrinsic sphincter. The presence of a hiatal hernia disrupts this synergistic action and can promote reflux. •Esophageal clearance must be able to neutralize the acid refluxed through the LES. (Mechanical clearance is achieved with esophageal peristalsis. Chemical clearance is achieved with saliva.) •The stomach must empty properly. Abnormal gastroesophageal reflux is caused by the abnormalities of one or more of the following protective mechanisms: • A functional (frequent transient LES relaxation) or mechanical (hypotensive LES) problem of the LES is the most common cause of GERD (surgical damage to the LES, and esophagitis, scleroderma-like diseases, myopathy associated with chronic intestinal pseudo-obstruction, incompetence of the diaphragmatic crural muscle). • Certain foods (eg, coffee, alcohol), medications (eg, calcium channel blockers, nitrates, beta-blockers, sildenafil), or hormones (eg, progesterone) can decrease the pressure of the LES. • Obesity is a contributing factor in GERD, probably because of the increased intra-abdominal pressure. Some studies have shown that GERD is highly prevalent in patients who are morbidly obese and that a high body mass index (BMI) is a risk factor for the development of GERD. The
mechanism by which a high BMI increases esophageal acid exposure is not completely understood. Increased intragastric pressure and gastroesophageal pressure gradient, incompetence of the LES, and increased frequency of transient LES relaxations may all play a role in the pathophysiology of the disease in patients who are morbidly obese. Race • White males are at a greater risk for Barrett esophagus and adenocarcinoma than other populations. Sex No sexual predilection exists. GERD is as common in men as in women. • The male-to-female ratio for esophagitis is 2:1-3:1. The male-to-female ratio for Barrett esophagus is 10:1. •
Age GERD occurs in all age groups. • The prevalence of GERD increases in people older than 40 years. •
S2 CLINICAL PICTURE History GERD can cause typical (esophageal) symptoms or atypical (extraesophageal) symptoms. However, a diagnosis of GERD based on the presence of typical symptoms is correct in only 70% of patients. Typical (esophageal) symptoms include the following: o Heartburn is the most common typical symptom of GERD. Heartburn is felt as a retrosternal sensation of burning or discomfort that usually occurs after eating or when lying down or bending over. o Regurgitation is an effortless return of gastric and/or esophageal contents into the pharynx. Regurgitation can induce respiratory complications if gastric contents spill into the tracheobronchial tree. o Dysphagia occurs in approximately one third of patients because of a mechanical stricture or a functional problem (eg, nonobstructive dysphagia secondary to abnormal esophageal peristalsis). Patients with dysphagia experience a sensation that food is stuck, particularly in the retrosternal area. Persistent dysphagia suggests development of a peptic stricture. Most patients with peptic stricture have a history of several years of heartburn preceding dysphagia. However, in one-third of patients, dysphagia is the presenting symptom. Rapidly progressive dysphagia and weight loss may indicate the development of adenocarcinoma in Barrett's esophagus. o Bleeding occurs due to mucosal erosions or Barrett's ulcer. o Many patients with GERD remain asymptomatic or self-treated and do not seek attention until severe complications occur.
S3. Atypical (extraesophageal) symptoms include the following: o
Coughing and/or wheezing are respiratory symptoms (chronic cough, bronchoconstriction, pharyngitis, laryngitis, bronchitis, or pneumonia,
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pulmonary fibrosis, chronic asthma) resulting from the aspiration of gastric contents into the tracheobronchial tree or from the vagal reflex arc producing bronchoconstriction. Approximately 50% of patients who have GERD-induced asthma do not experience heartburn. Hoarseness results from irritation of the vocal cords by gastric refluxate. Hoarseness is often experienced by patients in the morning. Reflux is the most common cause of noncardiac chest pain, accounting for approximately 50% of cases. Patients can present to the emergency department with pain resembling a myocardial infarction.
S2. Complications Approximately 50% of patients with gastric reflux develop esophagitis. Esophagitis is classified into the following 4 grades based on its severity: o Grade I - Erythema o Grade II - Linear nonconfluent erosions o Grade III - Circular confluent erosions o Grade IV - Stricture or Barrett esophagus (Barrett esophagus is thought to be caused by the chronic reflux of gastric juice into the esophagus. Barrett esophagus occurs when the squamous epithelium of the esophagus is replaced by the intestinal columnar epithelium. Barrett esophagus is present in 8-15% of patients with GERD and may progress to adenocarcinoma. Physical Noncontributory, absence of special objective data. DIFFERENTIAL DIAGNOSIS 1. Achalasia. Achalasia is a primary esophageal motility disorder characterized by failure of a hypertensive LES to relax and the absence of esophageal peristalsis. These abnormalities cause a functional obstruction at the gastroesophageal junction. 2. Cholelithiasis. Because they are common, gallstones often coexist with other gastrointestinal conditions. Little evidence suggests that gallstones cause chronic abdominal pain, heartburn, postprandial distress, bloating, flatulence, constipation, or diarrhea. 3. Coronary Artery Atherosclerosis. Reflux is the most common cause of noncardiac chest pain, accounting for approximately 50% of cases. Patients can present to the emergency department with pain resembling a myocardial infarction. Reflux should be ruled out (using esophageal manometry and 24h pH testing if necessary) once a cardiac cause for the chest pain has been excluded. Alternatively, a therapeutic trial of a high-dose proton pump inhibitor (PPI) can be tried. 4. Esophageal Cancer. GERD is the most common predisposing factor for adenocarcinoma of the esophagus. 10-15% of patients who undergo endoscopy for evaluation of GERD symptoms are found to have Barrett
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epithelium. Adenocarcinoma may develop in these patients, representing the last event of a sequence that starts with the development of GERD and progresses to (Barrett) metaplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. The risk of adenocarcinoma among patients with Barrett metaplasia has been estimated to be 30-60 times that of the general population. • Dysphagia is the most common presenting symptom. Dysphagia is initially experienced for solids, but eventually it progresses to include liquids. • Weight loss is the second most common symptom and occurs in more than 50% of people with esophageal carcinoma. • Pain can be felt in the epigastric or retrosternal area. It can also be felt over bony structures, representing a sign of metastatic disease. • Hoarseness caused by invasion of the recurrent laryngeal nerve is a sign of unresectability. • Respiratory symptoms can be caused by aspiration of undigested food or by direct invasion of the tracheobronchial tree by the tumor. Esophageal Spasm. Etiology of esophageal spasm is unknown. Theories include gastric reflux or a primary nerve or motor disorder. Because of the similarity of symptoms of reflux disease and esophageal spasm, many patients may be misdiagnosed with reflux. Furthermore, reflux and spasm can occur concomitantly. Chronic Gastritis Irritable Bowel Syndrome. Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology. Peptic Ulcer Disease
ADDITIONAL INVESTIGATIONS I. Lab Studies • Laboratory tests are seldom useful in establishing a diagnosis of GERD. II. Imaging Studies 1. Barium esophagogram o Barium esophagogram is particularly important for patients who experience dysphagia. o Barium esophagogram can show the presence and location of a stricture and the presence and shape of a hiatal hernia. 2.
Esophagogastroduodenoscopy (Upper endoscopy) o Esophagogastroduodenoscopy (EGD) identifies the presence and severity of esophagitis and the possible presence of Barrett esophagus. o EGD also excludes the presence of other diseases (eg, peptic ulcer) that can present similarly to GERD.
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Although EGD is frequently performed to help diagnose GERD, it is not the most cost-effective diagnostic study because esophagitis is present in only 50% of patients with GERD.
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S4. Savary-Miller classification
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Los Angeles classification
III. Other tests 1. Esophageal manometry o Esophageal manometry defines the function of the LES and the esophageal body (peristalsis). o Esophageal manometry is essential for correctly positioning the probe for the 24-hour pH monitoring. Ambulatory 24-hour pH monitoring Ambulatory 24-hour pH monitoring is the criterion standard in establishing a diagnosis of GERD with a sensitivity of 96% and a specificity of 95%. Ambulatory 24-hour pH monitoring quantifies the gastroesophageal reflux and allows a correlation between the symptoms of reflux and the episodes of reflux. Patients with endoscopically confirmed esophagitis do not need pH monitoring to establish a diagnosis of GERD. 2.
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Indications for esophageal manometry and prolonged pH monitoring 1. Persistence of symptoms while taking adequate antisecretory therapy, such as PPI therapy. 2. Recurrence of symptoms after discontinuation of acid-reducing medications. 3. Investigation of atypical symptoms, such as chest pain or asthma, in patients without esophagitis. 4. Confirmation of the diagnosis in preparation for antireflux surgery.
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3. Radionuclide measurement of gastric emptying Although delayed gastric emptying is present in as many as 60% of patients with GERD, this emptying is usually a minor factor in the pathogenesis of the disease in most patients (except in patients with advanced diabetes mellitus or connective tissue disorders). Patients with delayed gastric emptying typically experience postprandial bloating and fullness in addition to other symptoms.
TREATMENT Medical Care
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Treatment is a stepwise approach. The goals are to control symptoms, to heal esophagitis, and to prevent recurrent esophagitis or other complications. The treatment is based on lifestyle modification and control of gastric acid secretion. I. Lifestyle modifications include the following: • Losing weight (if overweight) • Avoiding alcohol, chocolate, citrus juice, and tomato-based products • Avoiding large meals • Waiting 3 hours after a meal before lying down • Elevating the head of the bed 20 cm II.
Pharmacologic therapy
S6. Antacids were the standard treatment in the 1970s and are still effective in controlling mild symptoms of GERD. Antacids should be taken after each meal and at bedtime. ο Histamine H2 receptor antagonists are the first line agents for patients with mild-to-moderate symptoms and grades I-II esophagitis. Histamine H2 receptor antagonists are effective for healing only mild esophagitis in 7080% of patients with GERD and for providing maintenance therapy to prevent relapse. (cimetidine, 300 mg; ranitidine, 150 mg bid; famotidine, 20 mg bid; nizatidine, 150 mg bid) ο Additional H2 blocker therapy has been reported to be useful in patients with severe disease (particularly those with Barrett esophagus) who have nocturnal acid production. ο PPIs are the most powerful medications available. They should be used only when GERD has been objectively documented. PPIs work by blocking the final step in the H+ ion secretion by the parietal cell. Omeprazole (20 mg/d), lansoprazole (30 mg/d), pantoprazole (40 mg/d), esomeprazole (40 mg/d), or rabeprazole (20 mg/d) for 8 weeks can heal erosive esophagitis in up to 90% of patients. The drug is taken 15 to 30 min before breakfast and can be maintained indefinitely. Refractory patients can double the dose and administer it twice a day before meals. They have few adverse effects and are well tolerated for long-term use. However, recent data have shown that PPIs can interfere with calcium homeostasis and aggravate cardiac conduction defects. They have also been responsible for hip fracture in postmenopausal women. ο Prokinetic agents improve the motility of the esophagus and stomach. The prokinetic drugs include bethanechol, metoclopramide, and cisapride. Bethanechol is a cholinergic antagonist that causes increased LES pressure, peristalsis, and salivary flow. However, this agent is contraindicated in patients with asthma. Metoclopramide is a dopamine antagonist that may improve gastric emptying but is associated with extrapyramidal side effects. Cisapride has been taken off the market because of significant drug-drug interactions leading to dysrhythmias. ο
These agents are somewhat effective but only in patients with mild symptoms; other patients usually require additional acid-suppressing medications, such as PPIs. Long-term use of prokinetic agents may have serious, even potentially fatal, complications and should be discouraged.
III. Surgical Care Approximately 80% of patients have a recurrent but nonprogressive form of GERD that is controlled with medications. Other 20% of patients have a progressive form of the disease and may develop severe complications. For patients who develop complications, surgical treatment should be considered at an earlier stage to avoid the serious consequences. Indications for fundoplication include the following: • Patients with symptoms that are not completely controlled by PPI therapy can be considered for surgery. • Surgery can also be considered in patients with well-controlled disease who desire definitive, one-time treatment. • The presence of Barrett esophagus is an indication for surgery. • The presence of extraesophageal manifestations of GERD: respiratory manifestations; ear, nose, and throat manifestations; dental manifestations. • Young patients. • Poor patient compliance to medications • Postmenopausal women with osteoporosis • Patients with cardiac conduction defects • Cost of medical therapy The main surgical method is Laparoscopic fundoplication . Laparoscopic fundoplication is performed under general endotracheal anesthesia. The fundus of the stomach is wrapped around the esophagus to create a new valve at the level of the gastroesophageal junction. Laparoscopic fundoplication lasts 2-2.5 hours. The hospital stay is approximately 2 days. Patients resume regular activities within 2-3 weeks. Approximately 92% of patients obtain resolution of symptoms after undergoing laparoscopic fundoplication.