Wylie J. Dodds

Mechanisms of Gastroesophageal Reflux in Patients with Reflux Esophagitis

We evaluated the mechanisms of gastroesophageal reflux in 10 patients with reflux esophagitis and compared the results with findings from 10 controls. The patients had more episodes of reflux (35 +/- 15 in 12 hours, as compared with 9 +/- 8 in the controls) and a lower pressure of the lower esophageal sphincter (13 +/- 8 mm Hg as compared with 29 +/- 9 in the controls) (P less than 0.001). Reflux occurred by three different mechanisms: transient complete relaxation of the lower esophageal sphincter, a transient increase in intra-abdominal pressure, or spontaneous free reflux associated with a low resting pressure of the lower esophageal sphincter. In controls 94 per cent of reflux episodes were caused by transient sphincter sphincter relaxation. In the patients 65 per cent of episodes of reflux accompanied transient sphincter relaxation, 17 per cent accompanied a transient increase in intra-abdominal pressure, and 18 per cent occurred as spontaneous free reflux. The predominant reflux mechanism in individual patients varied: some had normal resting sphincter pressure and reflux that occurred primarily during transient sphincter relaxation, whereas others with low resting sphincter pressures had spontaneous free reflux or reflux that occurred during an increase in intra-abdominal pressure.

Esophageal Peristaltic Dysfunction in Peptic Esophagitis

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.

Effect of peristaltic dysfunction on esophageal volume clearance

Prolonged esophageal acid clearance, found in some patients with esophagitis, can be attributed in part to the peristaltic dysfunction observed in this population. In this study, we undertook to define the effect of commonly observed peristaltic dysfunction on volume clearance by obtaining concurrent videofluoroscopic and manometric recordings in patients with nonobstructive dysphagia or heartburn. Excellent correlation existed between the findings from the two studies. A single normal peristaltic wave resulted in 100% clearance of a barium bolus from the esophagus. At each recording site, luminal closure, as demonstrated by videofluoroscopy, coincided with the upstroke of the peristaltic pressure complex. Absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance from the involved segment. Regional hypotensive peristalsis was associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction. The regional peristaltic amplitude required to prevent retrograde escape of barium was greater in the distal compared with the proximal esophagus. The mean peristaltic amplitude associated with instances of retrograde escape was 25 mmHg in the distal esophagus compared with 12 mmHg in the proximal esophageal segments. Thus, the peristaltic dysfunction commonly seen in patients with esophagitis (failed and hypotensive peristalsis) likely leads to impaired volume clearance.

Pathogenesis of Reflux Esophagitis

During the past decade considerable new information has accrued about reflux esphagitis and the physiology of esophageal motor function. Although numerous reports review the clinical, diagnostic, and therapeutic aspects of reflux esophagitis (1-6), few reports (7) focus primarily on the pathophysiology of esophagitis production. Our purpose here is to: (a) review critically recent findings relevant to the pathophysiology of reflux esophagitis, (b) analyze factors that may contribute to the production of reflux esophagitis, and (c) identify appropriate questions that merit further investigation. Throughout the report we will endeavor to alert the reader when the manuscript reflects our own opinion, speculation, or scientific bias as opposed to established observations. For this report the term reflux esophagitis is defined as esophageal inflammation caused by refluxed material. On endoscopy reflux esophagitis may cause visible discoloration, friability, ulceration, exudate, or luminal narrowing. In active reflux esophagitis, histologic sections demonstrate an acute polymorphonuclear or a mixed polymorphonuclear and round cell infiltrate, generally accompanied by epithelial erosion or ulceration. These gross or histologic findings are necessary for a specific diagnosis of reflux esophagitis. In some patients with clinical complaints suggesting GE reflux, the esophagus appears normal at endoscopy and no evidence of inflammation is present on biopsy. Biopsies

Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis

We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1-5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10-40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 +/- 3 min (mean +/- SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 +/- 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called water brash when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.

Regional esophageal distribution and clearance of refluxed gastric acid

Regional differences in the esophageal distribution and clearance of refluxed gastric acid was studied in seven asymptomatic volunteers and seven patients with reflux esophagitis. Intraluminal pH was recorded for 3 postprandial hours from the distal, middle, and proximal esophagus on two separate occasions (with subjects in upright and supine positions). With the subjects in a supine position, about half of the acid reflux episodes reached the proximal esophagus in patients as well as in controls. This percentage decreased to 25% in patients and 29% in controls when they were upright. In both groups, the pH drops in the distal esophagus were significantly greater than in the proximal esophagus for both the supine and upright positions. In both patients and controls, a 4-5-fold greater acid exposure occurred in the distal esophagus, than in the proximal esophagus. In both patient and control groups, acid exposure time, as well as the number of reflux episodes in the distal esophagus, were significantly greater than that of the proximal esophagus (P less than 0.05). Spontaneous acid clearance time in the distal esophagus was significantly longer than that of the proximal esophagus in both positions (P less than 0.05) for both subject groups. In conclusion, regional differences exist in the exposure of the esophageal mucosa to refluxed gastric acid. These regional differences are more pronounced when subjects are upright than supine. Regional differences also exist in esophageal acid clearance, with clearance taking longer in the distal esophagus than in the proximal esophagus. The net effect of these phenomena is that acid exposure time in the distal esophagus is greater than that in the remainder of the esophagus.

Dysfunction of the belch reflex: A cause of incapacitating chest pain

We report a 25-yr-old woman who suffered incapacitating chest pain caused by upper esophageal sphincter (UES) dysfunction. She presented with a long history of severe episodic chest pain associated with gurgling noises in her chest and was unable to belch despite feeling a need to do so during pain episodes. Fluoroscopic and manometric studies confirmed that the patients chest pain and gurgling noise were associated with dysfunction of the belch reflex. Although reflux of gas from the stomach into the esophageal body occurred normally, the extreme esophageal distention resulting from the gas reflux failed to trigger UES relaxation. Consequently, there was no venting of gas across the UES. The gurgling noise was caused by the gastroesophageal reflux of gas and the pain was associated with profound esophageal distention. A manometric study of the UES revealed absent or incomplete UES relaxation in response to abrupt esophageal distention by gastroesophageal gas reflux, so that the nadir of UES pressure always exceeded esophageal body pressure. The distended esophagus was repeatedly cleared by secondary peristalsis. To our knowledge this is the first description of chest pain caused by dysfunction of the belch reflex. We speculate that the mechanism described in this patient may account for a subgroup of patients with chest pain of esophageal origin.