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Gastroesophageal reflux disease (GERD)
GERD: Any symptomatic condition or histopathologic alteration resulting from episodes of gastroesophageal reflux.
Reflux esophagitis: endoscopy
GERD Symptoms in the absence of
esophagitis-> 24-hour esophageal pH monitor
Acid sensitive esophagus No gold standard for the recognition or
exclusion of GERD. Heartburn is an indicator of GERD.
GERD in the 1970s found that 7% of individuals
experienced heartburn daily, 14% weekly, and 15% monthly.
55% to 81% no esophagitis. an autopsy study: < 1/6 patients with
Barrett's metaplasia was recognized clinically prior to death.
Risk factors of GERD
Male preponderance of esophagitis (2 :1 to 3 :1) and of Barrett's metaplasia (10 :1).
Pregnancy: 48~79% heartburn. Whites Geographic variation: very low rates in Africa
and Asia and high rates in North America and Europe.
Agents decrease LES pressure NSAIDs: peptic strictures
Erosive esophagitis
Complications: peptic stricture, pseudodiverticula, Barrett's metaplasia, inflammatory polyps, and reactive changes that can mimic dysplasia.
Perforation and fistulization: rare.
Pathogenesis Exposure of gastric secretions Functional integrity of the esophagogastric
junction: intrinsic LES pressure, extrinsic compression of the LES by the crural diaphragm, the intra-abdominal location of the LES, integrity of the phrenoesophageal ligament, and maintenance of the acute angle of His between the distal esophagus and proximal stomach with its flap valve function
Mechanisms of Reflux
1. Transient LES relaxation: mild
2. Hypotensive LES
3. Diaphragmatic sphincter, hiatal hernia, and other anatomic variables
Delayed Gastric Emptying
May exacerbate GERD
A potential cofactor exacerbating GERD rather than a cause of GERD.
Esophageal Acid Clearance
Titration by swallowed saliva. Increase salivation: oral lozenges,
chewing gum, or bethanechol chloride. Salivation ceases during sleep
Esophageal Acid Clearance
Hiatal hernia: the most prolonged supine acid clearance
Correlates with both the severity of esophagitis and the presence of Barrett's metaplasia
Impairments of Esophageal Emptying
Ineffective esophageal motility: ≥ 30% hypotensive (<30 mm Hg) or failed contractions
Reflux of fluid from the hernia sac during swallowing: complete emptying with only 1/3 of test swallows
Tissue Injury
Hydrogen ion gastroesophageal refluxate is a
heterogeneous mixture: pepsin, bile acids, trypsin,lysolecithin & food hyperosmolarity
Clinical Presentation & Natural History – Typical Symptoms
The most common symptoms: heartburn, acid regurgitation, and dysphagia
Heartburn (pyrosis): Some patients with severe esophagitis or Barrett's metaplasia do not report having any heartburn.
Typical Symptoms
Regurgitation Dysphagia: > 30%; caused by peptic
stricture, a Schatzki ring (B ring), peristaltic dysfunction, or simple mucosal inflammation. Abnormal sensitivity to bolus movement during peristalsis.
Typical Symptoms -- Less common
Water brash: excessive salivation resulting from a vagal reflex triggered by esophageal acidification.
Globus sensation: perception of a lump or fullness in the throat that is felt irrespective of swallowing.
Odynophagia: likely related to an esophageal ulcer or deep erosion
Atypical Symptoms
Posterior Laryngitis: 4% to 10% evaluated by otolaryngologists; chronic hoarseness, posterior laryngeal erythema and edema, contact ulceration of the vocal folds, and vocal fold granulomata.
Asthma: effect of esophageal acid perfusion on pulmonary function is minimal on researches, but clinical data suggest that treatment of GERD in asthma patients usually improves respiratory symptoms.
Atypical Symptoms
Cough: postnasal drip, asthma, and GERD (10% to 40%) constitute an estimated 80% to 90% of cases in chronic cough. acid stimulation of nerve endings in the esophagus-> activate the cough center; besides, actived vagally mediated esophagotracheobronchial reflex
Noncardiac Chest Pain About 30% of patients have normal CAG. Once cardiac ischemia is ruled out,
esophagus is often implicated. Episodes of chest pain were often
associated with reflux The mechanism is unclear: maybe
esophageal afferent nerves discriminate poorly.
Natural History
1 to 3 years prior to seeking medical attention Esophagitis: recurrence in approximately 80%,
most within 3 months of discontinuation of therapy
Mortality (other than adenocarcinoma) is minimal: 0.1 per 100,000.
Peptic stricture: 8% to 20% Ulceration: 5%-> decreasing due to PPI. Bleeding <2%
Differential Diagnosis
Infectious esophagitis, pill esophagitis, peptic ulcer disease, dyspepsia, biliary colic, CAD, and esophageal motor disorders.
CAD must be given early consideration because of its potentially lethal implications
Associated condition Pregnancy: 50% to 80% Scleroderma: 90% with esophageal
function impairment (diminished peristaltic amplitude in the smooth muscle segment of the esophagus and diminished or absent LES pressure). MCTD can occur also.
Associated condition
Sjögren's syndrome: disrupts normal salivary secretion and interferes with esophageal acid clearance
Diabetic gastroparesis, intestinal pseudo-obstruction, and collagen vascular disorders: Changes in gastric emptying
Zollinger-Ellison syndrome
Management The primary goal: symptom relief. Diagnostic evaluation: in selected GERD
patients to confirm the diagnosis, direct therapy, or identify complications.
Severe or atypical symptoms: intensive medical therapy is appropriate as the initial treatment plan and may in fact help establish the diagnosis of GERD.
Diagnostic Evaluation Indication: extremely chronic heartburn
(possibility of Barrett's metaplasia?), refractory to treatment, or warning signs of dysphagia, odynophagia, gastrointestinal bleeding, or weight loss.
Endoscopy: the first diagnostic test; specificity of 90% to 95% in erosive esophagitis, but sensitivity is poor (only 30~40% of patients with GERD have esophagitis indicated by endoscopy). Grading: the Los Angeles system A-D.
Further tests
(1) Atypical symptoms (2) identifying why GERD therapy has failed.
Bernstein test: reproduce symptoms by perfusing the esophagus with 0.1 N HCl. Typical symptoms: sensitivity 42%~100%, and specificity 50%~100%. Atypical symptoms: sensitivity 7%~27%; high specificity is maintained.
Further test -- Ambulatory 24-hour pH monitor
The most widely used test probe 5 cm above LES Abnormal: time of pH <4; value >3.5%. Lack of high sensitivity (25~30%) The principal indication: patients without
endoscopic esophagitis or evaluating the efficacy of medical or surgical treatment
Further test Empirical trial of potent antisecretory
therapy: PPI for 1- to 2-week; including no reflux in 24 hr pH monitor
False-positive : peptic ulcer disease or malignancy ?
Esophageal manometry: minimal use except detecting major motor disorders or evaluating peristaltic function prior to antireflux surgery.
Nonprescription Therapy
>36% of the U.S. population suffers from heartburn at least once a month (Am J Dig Dis
21:953, 1976), but few seek medical care. 27% of adult Americans take antacids more than twice a month.
life-style modifications over-the-counter histamine-2 (H2)
receptor antagonists
Life-style modifications Head of the bed elevation, avoidance of
tight fitting garments, weight loss, dietary modification, restriction of alcohol use and elimination of smoking.
Avoid a supine position after meals and should not eat within 3 hours of bedtime
Chewing gum for mild GERD.
Acid Suppressive Medications The most common and effective
treatment H2RA: Tachyphylaxis & inability to
suppress meal related acid secretion effectively. (therapeutic gain 10~24%)
PPI: only act on membrane bound activated H+, K+-ATPase-> 30 minutes before meals.
Prokinetic Drugs Metoclopramide: antidopaminergic agent, also
acts as a 5-HT3 antagonist, a 5-HT4 agonist, and a cholinomimetic. Minimal effect but 25% P’ts have CNS side effects.
Cisapride: 5-HT3 antagonist and 5-HT4 agonist activity, release of acetylcholine from postganglionic nerve endings of the myenteric plexus. As efficacious as standard H2RA therapy in controlling symptoms and healing grade 1 to 2 esophagitis. Cardiotoxic effects especially in combination with agents that are metabolized by the cytochrome P-450 system.
Maintenance Therapy A study: Omeprazole significantly more
effective than either ranitidine or cisapride alone, and the combination of omeprazole and cisapride was the most effective.
The median dose to maintain remission: at or near the dose required for healing esophagitis.
Nonerosive GERD
Elimination of heartburn: a more difficult therapeutic end point than esophagitis healing
Data do not support “ nonerosive GERD is more responsive to therapy than erosive esophagitis, and easily treated with less potent antisecretory therapy”.
Intermittent or on-demand therapy may be adequate for symptom control in endoscopy-negative GERD.
Antireflux Surgery
Laparoscopic Nissen (360°) fundoplication and the Toupet (270°) fundoplication
Repair hiatal hernia and increase resting LES pressure; decrease frequency and/or effectiveness of tLESR.
Mortality rate of 0.2% Dysphagia, gas bloating, and flatulence: some
(4/57 in a study) need reoperation.
Antireflux Surgery Indication: (1) failed medical therapy (2)
medical success in a young healthy patient unwilling to take or intolerant of long-term PPI therapy (3) persistent symptoms due to regurgitation (laryngitis, asthma, bronchiectasis).