Pathogenesis Of Reflux Esophagitis Research Articles

Corpus gastritis is protective against reflux oesophagitis

BACKGROUNDGastric acid is important in the pathogenesis of reflux oesophagitis. Acid production by the gastric corpus is reduced in corpus gastritis.AIMSTo determine whether corpus gastritis protects against reflux oesophagitis.METHODSPatients presenting...

Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis.

In a prospective study of consecutive patients with reflux esophagitis and/or hiatal hernia and Barrett's esophagus, the prevalence of Helicobacter pylori was assessed. Antral biopsy specimens were studied and a serum sample for detection of IgG antibodies against Helicobacter pylori was taken. As a reference group patients presenting with a normal esophagus, stomach, and duodenum were taken. Reflux esophagitis was diagnosed in 118 patients, hiatal hernia without esophageal inflammation in 109, and Barrett's esophagus in 13. Helicobacter pylori was present in 74 (30%) of these patients and in 204 (51%) of the reference group. Prevalence of Helicobacter pylori was significantly lower in all groups compared with the reference group (P < 0.001). There was no difference when patients with esophagitis, Barrett's esophagus, or hiatal hernia were compared. Patients with esophagitis and Helicobacter pylori in their antrum are significantly older than esophagitis patients without concomitant Helicobacter infection, 61.5 (SD, 17) versus 53 (SD, 17) years (P < 0.001). It is concluded that the prevalence of Helicobacter pylori infection in patients with gastroesophageal reflux disease is significantly lower than in the reference group, irrespective of the severity of esophagitis. Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis.

Role of salivary and seric epidermal growth factor in pathogenesis of reflux esophagitis in chronic alcoholics and nondrinkers.

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Reflux oesophagitis and Helicobacter pylori infection in elderly patients.

Helicobacter pylori is associated with gastritis, peptic ulcers and gastric malignancies. Little attention has been paid to the possibility that it may also have a role in the pathogenesis of reflux oesophagitis. This is especially true in elderly patients who have life-long infection and provide an ideal group to study the mucosal changes associated with the organism. The aim of this study was to determine if H pylori is associated with reflux oesophagitis in elderly patients. Consecutive gastroscopy patients were recruited. Multiple biopsies were taken from oesophagus, stomach, antrum and duodenum for histology and rapid urease tests. Patients also had IgG ELISA antibodies and 13C-urea breath tests performed. Patients with macroscopic or microscopic evidence of reflux oesophagitis were compared to patients with macroscopically normal upper gastrointestinal tracts and no microscopic evidence of reflux. A total of 114 patients were recruited, average age 78.9 years (+/- 5.4). There were 37 refluxers and 33 non-refluxers. We found no evidence for an association between the presence of H pylori and reflux oesophagitis in elderly patients. The high prevalence of H pylori in patients with reflux oesophagitis can be explained by the presence of incidental gastritis.

Ambulatory esophageal pressure and pH monitoring in patients with high-grade reflux esophagitis

Using conventional manometry and 24-hr ambulatory pressure and pH monitoring, we investigated esophageal motility and the esophageal motor response to reflux in 11 patients with reflux esophagitis Savary-Miller grade III and IV, and an age- and sex-matched group of 11 healthy controls. The patients had a significantly increased esophageal acid exposure. Conventional manometry showed a significantly decreased LES pressure and distal peristaltic amplitude in patients. The 24-hr monitoring yielded a significant decrease in peristaltic contraction duration and peristaltic propagation velocity in the patient group. Distal peristaltic amplitude was not decreased. Analysis of the contractions occurring in the 2-min period after each reflux episode showed a reduced number of contractions during the upright period, caused by a significantly decreased number of peristaltic contractions. During the supine period, there was a trend towards an increased number of contractions. It is concluded that esophageal motor activity and the response to reflux are impaired in patients with high-grade reflux esophagitis. However, the abnormalities found are only minor and are unlikely to play an important role in the pathogenesis of reflux esophagitis.

Roles of Gastric Acid and pH in the Pathogenesis of Gastro-Oesophageal Reflux Disease

In recent years, gastric acid has been shown to play a major role in the pathogenesis of reflux oesophagitis, though it remains possible that defective oesophageal mucosal resistance may also play some part. Abnormally prolonged and/or frequent exposure of the distal oesophagus to a pH of less than 4 is the major defect; this results from frequent gastro-oesophageal reflux, the impact of which is magnified in about half of the patients by slow oesophageal acid clearance. Abnormal oesophageal acid exposure increases in severity from endoscopy-negative reflux disease through worsening grades of reflux oesophagitis. Pepsin activity has been shown to be a major determinant of the aggressiveness of refluxate and, in turn, the full activity of gastric pepsin requires a pH below 3. Thus, gastric acid probably exerts a predominantly indirect effect on the pathogenesis of reflux oesophagitis by determining peptic activity. Although bile and other components of small intestinal juice can injure the oesophageal mucosa, these factors are apparently important only in the exceptional patient with very severe reflux disease. Gastric acid hypersecretion is probably also unimportant in the majority of patients. Peptic activity, and hence the aggressiveness of refluxate, are reduced markedly between pH 3 and 4. Achievement of this threshold, pH 3-4, in the daytime is important as, contrary to traditional beliefs, daytime reflux, triggered by food intake, is of the greatest importance in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

What has the surgeon to know about pathophysiology of reflux disease?

Much has been learned about the pathophysiology of gastro-esophageal reflux (GER) since it was initially described by Asher Winkelstein in 1935. With the development and refinement of esophageal function tests in the past decades, the diagnostic modalities have become available for a deliberate and systematic evaluation of antireflux mechanisms. Some of the newer concepts of the pathogenesis of reflux esophagitis are reviewed in this article.

Bile acids and trypsin are unimportant in alkaline esophageal reflux.

We recorded esophageal alkaline exposure time (AET) in 52 patients with gastroesophageal reflux and in 20 control subjects to determine whether esophageal pH monitoring can measure reflux of bile acids and trypsin from the duodenum. Patients underwent a further 16-h study (divided into 2-h periods) in which AET was correlated with bile acid and trypsin concentrations in esophageal aspirates. Patients had greater nocturnal AET than controls (22.7 versus 0.9%, p = 0.005). Patients with a stricture had a greater AET than patients with erosive esophagitis (25.2 versus 13%, p less than 0.05). There was no relationship between esophageal bile acid concentrations and AET, and total bile acid concentrations were similar regardless of whether a 2-h period contained alkaline episodes. Esophageal bile acid concentrations were no different, in patients with a normal esophagus, esophagitis, stricture, or Barrett's esophagus. Trypsin was found in only 5% of aspirates, and could not be predicted by AET. We conclude that measurement of AET is not useful in the clinical evaluation of duodeno-esophageal bile reflux, and bile acids and trypsin are not important in the pathogenesis of reflux esophagitis.

Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis.

Nocturnal gastro-oesophageal reflux may be important in the pathogenesis of reflux oesophagitis. This study aimed to determine whether: (1) gastro-oesophageal reflux occurs during sleep in patients with reflux oesophagitis and, if so, to explore the mechanism, and (2) the sleep pattern of patients with oesophagitis is different from that of control subjects. After a standard evening meal, simultaneous manometric, oesophageal pH, and polysomnographic recordings were obtained in 11 patients with endoscopic oesophagitis and 11 control subjects. Patients with gastrooesophageal reflux disease had significantly more total reflux episodes throughout the nocturnal monitoring period than control subjects (105 v 6). Ninety two of 105 episodes of gastro-oesophageal reflux in patients occurred during the awake state and 10 during sleep stage II. A number of reflux episodes occurred during brief periods of arousal from the various sleep stages. Of the 105 reflux events recorded in patients, 42 were induced by transient lower oesophageal sphincter relaxation, 20 by stress reflux, 22 by free reflux mechanisms, and in 21 the mechanism was unclear. The sleep pattern and the time spent in each sleep stage was not different between the two groups. It is concluded that the awake state is crucial for the occurrence of nocturnal reflux episodes in normal subjects as well as in patients with reflux oesophagitis and that the difference between the frequency of gastro-oesophageal reflux between normal subjects and patients cannot be explained by different sleep patterns.

Sucralfate versus cimetidine in the treatment of reflux esophagitis, with special reference to the esophageal motor function

Sixty patients entered a double-blind clinical trial comparing the effect of 1 g of sucralfate granulate given four times daily and cimetidine, 400 mg twice daily. Twenty-six patients treated with sucralfate and 26 treated with cimetidine were examined with short-term pH monitoring before and after 12 weeks of treatment. Thirty patients, 19 treated with cimetidine and 11 treated with sucralfate, had esophageal motility studied by a radionuclide test before and after 12 weeks of treatment. The efficacy of the treatments was judged by symptoms and endoscopic response after 4, 8, and 12 weeks of treatment. The endpoint healing rate was approximately 60% in both groups and symptoms were relieved in half of the patients in both groups (difference not significant). The effect of the treatments on pH and number of spikes reflected the different pharmacodynamic profiles of the drugs, whereas the mean transit time (MTT) was not changed by the treatments. The residual activity after radionuclide transit in the sitting position was significantly increased after treatment with cimetidine. The data support the hypothesis that primary dysmotility might be involved in the pathogenesis of reflux esophagitis in about 33% of the patients. Possibilities for a combination therapy with sucralfate and cimetidine are stressed.

Does body posture affect the incidence and mechanism of gastro-oesophageal reflux?

We studied eight patients with gastro-oesophageal reflux disease to compare the frequency and mechanism of reflux in the upright and supine positions. Simultaneous oesophageal manometry and pH studies were performed on two separate days in each subject in the fasting and postprandial periods. The frequency of reflux tended to be higher in the upright position. The most prevalent mechanism of reflux in either position was transient relaxation of the lower oesophageal sphincter. The frequency of transient lower oesophageal sphincter relaxation was higher in the upright than in the supine position. There was no difference in the total reflux time, acid clearance time, and number of reflux episodes lasting longer than five minutes in the two positions. We suggest that daytime reflux (upright) may be as important as night time (supine) reflux in the pathogenesis of reflux oesophagitis and needs to be considered when treating patients with reflux disease.

ＦＯＹ‐３０５の術後逆流性食道炎に対する作用 （第２報） 胃全摘後のラット逆流性食道炎発生機序の解析

Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The purpose of this study is to clarify the effect of FOY-305 on these factors in the esophagitis. We initially produced esophagitis in rats with total gastrectomy followed by an end-to-side esophago-jejunostomy (Billroth-II). After treatment of FOY-305 on post-operative day 7 in this model, esophageal washout samples were analyzed for increases in activity of trypsin and total bile acid concentration. FOY-305 completely inhibited increases of trypsin activity in 2 and 4 hr, and it significantly (P less than 0.05) reduced bile acid concentration in 4 hr after initiating treatment. In addition, we evaluated the injurious effect of trypsin and sodium taurocholate (Tc-Na) on isolated esophagus of rats by measuring released tyrosine in the medium and used it as an index of the degree of injury. Tc-Na (3-fold of enteral bile acid concentration) inflicted only a slight injurious effect with negligible tyrosine release increases, and it did not show synergistic action when concomitantly used with trypsin. However, trypsin clearly induced increased tyrosine release from the esophageal mucosa, and this effect was significantly (P less than 0.001) inhibited by FOY-305 (50 microM). These results indicate that trypsin is one of the important factors in the pathogenesis of reflux esophagitis after total gastrectomy, and FOY-305 exerts a therapeutic effect by eliciting an inhibitory action against trypsin activity.

Pathogenesis of reflux esophagitis in relation to the characteristic difference between acid-pepsin and bile as an aggressive factor

Pathogenesis of reflux esophagitis in relation to the characteristic difference between acid-pepsin and bile as an aggressive factor

Role of lipase in the pathogenesis of experimental esophagitis in the rabbit.

The role of lipase in the pathogenesis of reflux esophagitis was investigated in an experimental model in which an in situ isolated segment of rabbit esophagus was perfused (at pH 7) with a solution containing lipase in concentrations of 2 and 10 mg/ml. The severity of mucosal damage was assessed using the following indicators of mucosal integrity: transmucosal potential difference, net flux of sodium, and mucosal permeability to erythritol labeled with carbon 14, a neutral molecule with a greatest molecular diameter of 8.2 nm. Furthermore, the morphologic characteristics of esophageal damage were studied by light and scanning electron microscopy. The results suggest that lipase significantly decreased transmucosal potential difference and increased mucosal permeability to sodium and erythritol labeled with carbon 14. Morphologically, lipase induced cytoplasmatic vesiculation and widening of intercellular spaces within the basal cell layer. The epithelial cell layers were also often seen to be sloughed off with consequent exposure of the subepithelial connective tissue at the mucosal surface. The findings suggest that lipase has an adverse effect on the esophageal mucosa that may have pathogenetic significance in clinical reflux esophagitis.

Morphology of lysolecithin-induced damage on esophageal mucosa. An experimental light and scanning electron microscopical study

The morphology of the esophageal mucosal damage induced by lysolecithin was investigated in an experimental model, where an isolated segment of rabbit esophagus was purfused in situ with lysolecithin, alone or in combination with HCl. The results indicate that lysolecithin alone causes no morphological damage to the esophageal mucosa. However, when combined with HCl, lysolecithin causes widening of intercellular spaces and detachment of superficial cells leading ultimately to disclosure of denuded submucosal collagen bundles. This suggests that, in clinical situations lysolecithin refluxed from the duodenum into the stomach and further to esophagus may have importance in the pathogenesis of reflux esophagitis when gastric acid is present, too. In contrast, under unacidic conditions (i.e., in the pathogenesis of alkaline reflux esophagitis) lysolecithin seems to be of minor importance.

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 (≤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.

Clinical relevance of gastroduodenal dysfunction in reflux esophagitis.

This review critically evaluates the gastroduodenal factors that may play a clinically relevant role in the pathogenesis of reflux esophagitis. The gastroesophageal pressure gradient is of obvious importance, but the role of gastric contraction/relaxation is poorly understood. The intragastric volume, as well as the factors that influence it, could theoretically play a role in gastroesophageal reflux (GER). For example, suppression of gastric emptying and gastric motility would be expected to increase GER, and treatment with gastrokinetic agents appears to provide symptomatic improvement. However, only a fraction of patients with GER have delayed gastric emptying, and there is no correlation between either subjective epigastric fullness or esophagitis on one hand and gastric emptying on the other hand. Gastric acid and pepsin, and possibly the hypersecretion of acid, play a pivotal role in reflux esophagitis, as demonstrated by the efficacy of the treatment with histamine H2 antagonists and antacids. Other important factors in experimental esophagitis are duodenogastric reflux, the presence of bile acids in the gastric contents, as well as trypsin if the pH is alkaline. It is suggested that these important findings may lead to novel therapeutic approaches of reflux esophagitis.

Medical management of reflux esophagitis.

Esophageal reflux should be treated only if symptoms are severe enough for patients to seek therapy or if esophagitis results. One study found that the number of reflux episodes lasting more than 5 min was the best indicator of esophagitis. Factors such as efficiency of the antireflux barrier, esophageal clearing, and aggressive power of refluxed material impact on the pathogenesis of reflux esophagitis. Therapy should be aimed at these factors and depends on severity of disease. Dietary measures, postural measures, and drug therapy can be used to alleviate symptoms and/or improve healing of esophageal lesions, with surgery recommended only in rare cases. Antacids, Gaviscon, and motor-stimulating drugs (metoclopramide, domperidone, bethanechol) may be sufficient to treat pathologic reflux without esophagitis. Once erosive or ulcerative lesions have developed, more rigorous medical treatment including H2 receptor blockers is mandatory.

Acid clearance during sleep in the pathogenesis of reflux esophagitis.

Impaired esophageal clearing of refluxed gastric contents during sleep has been implicated in the pathogenesis of reflux esophagitis. To more directly evaluate this hypothesis, 13 symptomatic patients with esophagitis and 13 normal controls had 15 ml of 0.1 N HCl instilled into the esophagus in the recumbent position while awake and during polygraphically monitored sleep. When sleep was maintained for the majority of the acid-clearing duration, the clearance times for both patients and controls were significantly prolonged when compared to those while awake (P less than 0.01). However, when sleep was maintained for less than 50% of the acid-clearing interval, the patients showed significantly longer acid clearance times. The swallowing rate did not differentiate the two groups under any condition. These data show that sleep impairs esophageal acid clearance. Acid clearance occurred predominantly in association with arousals from sleep. The defective acid clearance found in patients with esophagitis probably plays a major role in the pathogenesis of this disorder.