Special reports and reviewsThe pathogenesis of heartburn in nonerosive reflux disease: A unifying hypothesis
Section snippets
Nonerosive reflux disease
Our approach to examining the pathogenesis of heartburn in NERD first required that NERD be defined and that this definition be uniformly applied to clinical investigations to determine the applicability of their conclusions to the condition. The definition of NERD, as used herein, has 2 major requirements: (1) a history of āheartburnā in the absence of esophageal mucosal lesions on endoscopy and (2) supportive evidence that the symptom is acid-mediated, established by either prolonged ACT on
Esophageal visceral hypersensitivity
EVH is 1 of the 3 mechanisms proposed to explain the pathogenesis of heartburn in NERD. The term, itself, implies the presence of an esophageal neuronal defect at the periperal or central level that creates heightened perception of an esophageal stimulus.10, 11 EVH is recognized clinically by the presence of either allodynia or hyperalgesia. Allodynia is the perception of a stimulus at a level not perceived by a healthy subject and hyperalgesia is greater discomfort from a given stimulus than
Sustained esophageal contractions
SEC are another mechanism proposed to explain the pathogenesis of heartburn in NERD. SEC, which represent prolonged contractions of the esophageal longitudinal smooth muscle, can be detected in vivo in humans as an increase in wall thickness by high frequency endoscopic ultrasonography.17 The concept that SEC are the cause of heartburn in NERD evolved from observations in a dozen patients with GERD. GERD was diagnosed by a history of retrosternal burning in the absence of other identifiable
Abnormal tissue resistance
ATR is the third mechanism proposed to explain the pathogenesis of heartburn in NERD. In this context āabnormal tissue resistanceā refers specifically to āabnormal esophageal epithelial barrier function.ā In the esophagus, the main structural components of the barrier are the apical membranes and junctional complexes of the cells comprising the stratum corneum.22 These protect by preventing the diffusion of ingested and refluxed luminal contents from penetrating into the esophageal mucosa. In
Heartburn revisited
ATR as the proposed basis for reflux-associated heartburn in NERD effectively realigns it with the commonly accepted principles that form the basis for heartburn in erosive esophagitis. Consequently, heartburn in GERD can be viewed as the result of an acidic refluxate contacting a damaged esophageal epitheliumāwith heartburn in NERD being due more specifically to damage and ATR at the microscopic level and heartburn in erosive esophagitis being due to damage and ATR that has progressed to the
References (46)
Epidemiology and pathophysiology of symptomatic gastroesophageal reflux disease
Am J Gastroenterol
(2003)- et al.
Limitations of 24-hour intraesophageal pH monitoring in the hospital setting
Gastroenterology
(1985) Refractory heartburn
Gastroenterology
(2003)- et al.
Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease
Am J Gastroenterol
(2001) - et al.
Sensitization to painful distention and abnormal sensory perception in the esophagus
Gastroenterology
(1995) - et al.
A clinical test for esophagitis
Gastroenterology
(1958) - et al.
Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans
Gastroenterology
(1998) - et al.
Esophageal hypersensitvity may be a major cause of heartburn
Am J Gastroenterol
(1999) - et al.
Sustained esophageal contractionA marker of esophageal chest pain identified by intraluminal ultrasonography
Gastroenterology
(1999) - et al.
Barriers to paracellular permeability in rabbit esophageal epithelium
Gastroenterology
(1992)
The role of pepsin in acid injury to esophageal epithelium
Am J Gastroenterology
Dilated intercellular spacesA morphological feature of acid reflux-damaged human esophageal epithelium
Gastroenterology
Esophageal potential difference measurements in esophageal disease
Gastroenterology
Omeprazole and ultrastructural modifications occurring in reflux esophagitis
Gastroenterology
Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in humans
Neurosci Lett
Serosal bicarbonate protects against acid injury to rabbit esophagus
Gastroenterology
Intraesophageal acid perfusion sensitizes the esophagus to mechanical distensionA barostat study
Am J Gastroenterol
Identification and characterization of cerebral cortical response to esophageal mucosal acid exposure and distention
Gastroenterology
Food-induced heartburnEffect of osmolality
Gastroenterology
Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by laparoscopic fundoplication
Surgery
Reflux esophagitis
Epidemiology of oesophageal reflux disease
Scand J Gastroenterol
Ambulatory 24-hour pH-metry in the diagnosis of gastroesophageal reflux disease
Scand J Gastroenterol
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