Esophageal mucosal defense mechanisms

The esophageal defensive system includes several basic mechanisms. The anti-reflux barrier (LES and the crural diaphragm) and the clearance mechanism that limit the frequency and volume of the refluxate as well as the duration 36 . The third defense mechanism is the esophageal mucosal resistance, which prevents injury by acid, pepsin and other components of the refluxate. Tissue resistance is constituted of structures grouped in three areas pre-epithelial, epithelial and post-epithelial 36 ....

Extraesophageal

Apnea is a frequently cited extraesophageal manifestation of reflux in infants, but the causal relationship is controversial, despite being examined by multiple investigators. Most episodes of apnea of prematurity occur in the post-prandial period, and likely follow bouts of regurgitation, and yet studies using impedance and monitoring cardiorespiratory events have been contradictory 52 , 53 . In 21 infants with a history of intermittent reflux and apnea, 81 of apneic events did not follow...

Complicated GERD

The important esophageal complications of chronic reflux are strictures, Barrett's esophagus, and adenocarcinoma. Aggressive medical management, preferably with proton pump inhibitors, and close follow-up, using tests to assess symptoms and severity of reflux, are warranted in complicated GERD. Surgical management is contemplated in patients who remain unresponsive to medical therapy. Exposure of the esophagus to acid and perhaps to pepsin is crucial to the pathogenesis of reflux strictures...

Lower esophageal sphincter intrinsic sphincter hypotension

Gastroesophageal reflux disease can occur in the context of diminished LES pressure either by strain-induced or free reflux. Strain-induced reflux occurs when a hypotensive LES is overcome and blown open in association with an abrupt increase of intraabdominal pressure 34 . Manometric data suggest that this rarely occurs when the LES pressure is greater than 10 mmHg 34 , 35 . It is also a rare occurrence in patients without hiatus hernia 33 . Free reflux is characterized by a fall in...

Antireflux barrier

Failure of the anti-reflux barrier is considered the most important factor in the pathogenesis of GERD. It is presently accepted that the two major elements that compose the anti-reflux barrier are the lower esophageal sphincter (LES) and the crural diaphragm. The LES is a thickened ring of tonically contracted circular smooth muscle that generates a 2-4 cm high pressure zone at the gastroesophageal junction and serves as a mechanical barrier between the stomach and the esophagus. The right...

Mechanisms of EGJ dysfunction in GERD

Reflux occurs with either intermittent or constant compromise of the EGJ high-pressure zone. An added element to EGJ competence is EGJ opening and the degree to which the EGJ opens during periods in which the high-pressure zone is compromised. Just as with the upper esophageal sphincter, it has become apparent that sphincter opening is not synonymous with sphincter relaxation. During swallowing, despite being neurally inhibited, the EGJ must open to facilitate the esophago-gastric flow of a...

Proton pump inhibitors

Proton Pump Inhibitors (PPI's) offer the optimal defense strategy against GERD in the elderly 35 . The proton pump is the final common pathway for acid secretion in the stomach, and it is located on the luminal surface of gastric parietal cells. The modification of this pump by the drug causes a more consistent and profound inhibition than can be obtained by modifying the basal receptors (Histamine and Acetylcholine) 76 . Proton pump inhibitors produce more frequent and rapid symptom relief and...

References

1 Storr M, Meining A, Allescher HD (2000) Pathophysiology and pharmacological treatment of gastroesophageal reflux disease. Dig Dis 18 93-102 2 Kahrilas PJ (1998) Gastroesophageal reflux disease and its complications. In Sleisenger and Fordtran's gastrointestinal and liver disease. Pathophysiology diagnosis management (Feldman M, Scharschmidt BF, Sleisenger MH, eds), 6th ed. Philadelphia, PA W. B. Saunders, p 498-516 3 Kahrilas PJ, Dodds WJ, Hogan WJ, Kern M, Arndorfer RC, Reece A (1986)...

Erosive esophagitis

Multiple studies have shown that only 30-40 of patients with typical reflux symptoms (i.e., heartburn, regurgitation) have evidence of erosive esophagitis (Fig. 1) on upper endoscopy whereas the other 60-70 of patients even with troublesome reflux symptoms have no clear-cut esophageal mucosal abnormalities 2 - 7 . Thus, overall endoscopy is an insensitive test for diagnosing reflux disease. However, if detected, erosive esophagitis has a good positive predictive value for the diagnosis of GERD...

Transient lower esophageal relaxations

Compelling evidence exists that transient LES relaxations are the most frequent mechanism for reflux during periods of normal LES pressure gt 10 mmHg . Transient LES relaxations occur independently of swallowing, are not accompanied by peristalsis, are accompanied by crural diaphragmatic inhibition, and persist for longer periods than do swallow-induced LES relaxations gt 10 seconds 29 , 30 . The dominant stimulus for transient LES relaxation is distension of the proximal stomach, not...

Prokinetic agents

This class of agents targets the underlying motility dysfunction that causes GERD. Specifically, they increase lower esophageal sphincter pressure, accelerate gastric clearance, stimulate esophageal peristalsis, and increase the amplitude of esophageal contractions 73 . Each of these agents bethenechol, metoclopra-mide, domperidone, and cisapride is effective in improving symptoms and healing erosions. They are especially useful in the presence of dyspeptic symptoms such as nausea, vomiting,...

Lower esophageal sphincter

Phrenoesophageal Membrane

The LES is a 3-4 cm segment of tonically contracted smooth muscle in the distal esophagus. Among normal individuals basal LES tone varies from 1030 mmHg relative to intragastric pressure and exhibits substantial temporal variation. Studies utilizing concurrent fluoroscopy and manometry, localize the proximal aspect of the EGJ high-pressure zone 1-1.5 cm proximal to the SCJ and the distal aspect extending about 2 cm distal to it 1 Fig. 1 . Anatomical studies suggest that the EGJ component distal...

Introduction

The understanding of the pathophysiology of gastroesophageal reflux disease GERD has evolved in the last decade primarily by recognizing the multitude of factors that contribute to the emergence of the disorder Fig. 1 . These factors may overlap in some patients and differ in others. GERD is primarily considered a motility disorder, because dysfunction of the anti-reflux barrier is still considered as a prerequisite for the development of the disease. However, recent investigation into symptom...

Histamine2receptor blockers H2Bs

This class of medications indirectly suppresses gastric acid and pepsin secretion by occupying Histamine2 receptors. They suppress basal, nocturnal, and penta-gastrin secretion, as well as acid secretion induced by insulin, meals, and sham feeding 74 . These medications have no effect on LES pressure or esophageal clearance 31 . Acid suppression is incomplete in response to meals, thus these are less effective in people with advanced reflux disease 35 . The H2B's reduce nocturnal acid by 85-94...