Clarke, Alan T.
Studies of the luminal environment of the gastro-oesophageal junction.
MD thesis, University of Glasgow.
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The first chapter of my thesis “The Gastro-oesophageal Junction” discusses the histology of the gastro-oesophageal junction and the components integral to the function of the
anti-reflux barrier. It also discusses the pathology found at the gastro-oesophageal junction and describes the nitrite chemistry in this region thought to contribute to this pathology.
The second chapter “Mechanisms of Gastro-oesophageal Reflux” discusses the mechanisms of gastro-oesophageal reflux. This includes factors that reduce lower oesophageal pressure, the role of the hiatal hernia and the contribution of transient lower oesophageal sphincter relaxations. The relationship between obesity and reflux disease is also discussed.
The third chapter “Research into the Nature of the Acid Pocket” details previous research into the nature of the acid pocket, the primary focus of my own studies.
The fourth chapter “Severe Reflux Disease is Associated with Enlarged Unbuffered Proximal Gastric Acid Pocket” details my studies comparing the postprandial acid pocket
in healthy subjects and patients with severe reflux disease and my attempt to define its position relative to anatomical and manometric landmarks. 12 healthy subjects and 16 patients with severe reflux disease were studied. While fasted, a station pull-through was performed using a combined dual pH and manometry catheter. Position was confirmed by radiological visualisation of endoscopically-placed radio-opaque clips. The pullthrough study was repeated 15 minutes after a standardized fatty meal. Barium meal examination was performed before and following the meal. A region of unbuffered acid (pH≤2) immediately distal to the proximal gastric folds was more frequent in reflux patients (23/32 studies) than in healthy subjects (11/24) (p<0.05). This unbuffered acid pocket was longer in the reflux patients versus healthy subjects (median length 3cm, range 1cm to 15cm vs. 2 cm, range 1cm to 5cm; p<0.05). The acid pocket extended proximally as far as the proximal gastric folds in the patients but stopped a median of
1.1cm distal in healthy subjects (p=0.005). In healthy subjects the acid pocket occupied the distal portion of the sphincter which opened postprandially, whereas in reflux patients it corresponded to the proximal displacement of the gastric folds i.e. hiatus hernia.
The fifth chapter “Paradox Of Gastric Cardia – It Becomes More Acidic Following Meals While The Rest Of Stomach Becomes Less Acidic” details stationary pH studies
of the cardia in healthy subjects. The proximal cardia region of the stomach has a high incidence of inflammation, metaplasia and neoplasia. It demonstrates less acid buffering following meals than the more distal stomach. I employed novel high definition pHmetry to investigate acidity at the cardia under fasting conditions and in response to a meal. 15 healthy subjects were studied. A custom made 12 electrode pH catheter was clipped at
the squamo-columnar junction with 4 electrodes recording proximal to and 8 distal to the squamo-columnar junction. The most distal pH electrode was located at the catheter tip
and 9 electrodes in the region of the squamo-columnar junction were 11mm apart. The electrode situated in the cardia 5.5mm distal to the squamo-columnar junction differed
from all other intragastric electrodes during fasting in recording minimal acidity (pH<4 =2.2%) while all other intragastric electrodes recorded high intragastric acidity (pH<4 =>39.%) (p<0.05). The cardia also differed from the rest of the stomach showing a marked increase in acidity in response to the meal (from 2.2% fasting to 58.4% at 60-
70min after meal; p<0.05) while the electrodes distal to the cardia all showed a marked decrease in acidity (p<0.05). These changes in acidity at the cardia following the meal caused the gastric acidity to extend 10mm closer to the squamo-columnar junction.
The final discussion chapter discusses the results of our studies and my conclusions.
Papers concerning the acid pocket since my own work are also discussed.
My studies had full approval from the West Ethics Committee and North Glasgow Trust
(COREC Reference 04/50709/26).
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