Acid inhibition and gastroesophageal reflux disease.

Malfunction of the lower esophageal sphincter results in acid reflux into the esophagus. Reflux is mostly episodic so that the esophagus is not often presented with a continuous acid load. Prediction of esophageal disease related to reflux takes into account the pH of the refluxate and the duration of reflux. Expulsion of the refluxate back into the stomach shortens the time of exposure. The volume of reflux is also an important parameter for estimation of the acid load on the esophageal epithelium. It is the magnitude of this acid load that determines the presence or absence of pathology or symptoms. Intraesophageal pH monitoring provides an approximate measure of the acid load to the lower esophagus [2, 3] The human esophageal epithelium is a multi-layered, stratified squamous epithelium. Afferent nerves are present, reaching into the superficial layers of the mucosa. With incompetence of the lower esophageal sphincter (LES)b, acid reflux results with pain and damage to the epithelium depending on the pH of the refluxate. Rather than being protected by a continuous tight junction, this epithelium has largely regional cell-to-cell contact via desmosomes but, being multi-layered, provides a winding path for proton diffusion into the epithelium. It is nevertheless significantly more acid sensitive than the gastric epithelium that is provided with "tight" tight junctions. The threshold of acidity for damage and pain may be different. A higher acidity is likely needed for damage to the epithelial cells compared to the acidity required for stimulation of the pain fibers. This is probably because the epithelial cells have acid recovery mechanisms (such as Na/H or anion exchange) mostly absent in the pain fibers. Dependent on the location of the pain fibers and the access thereto of H+, different individuals will have different sensitivities to luminal acidity. These thoughts raise the question as to the therapeutic aims of acid control, elevation of mean diurnal pH for healing of erosions or prevention of acidic excursions for symptom relief or both.