What is the relation between acid reflux, esophageal glycoconjugate (mucin) secretion, and viscosity?
M. Marcinkiewicz, T. Zbroch,
Z. Namiot, J. Sarosiek (Kansas City),
The integrity of the esophageal mucosa depends upon an equilibrium between aggressive factors and protective mechanisms. Aggressive factors are represented by components of gastric (acid and pepsin) and duodenal (bile acids, trypsin, chymotrypsin, potentially phospholipase A2 and lysolecithin) secretions [1-4]. Protective mechanisms are operating within three overlapping dimensions: 1) pre-epithelial barrier, 2) epithelial barrier, and 3) post-epithelial barrier [1, 2, 5].
Although protective role of epithelial and postepithelial barriers has been well explored in an experimental setting, it is hard to address their role in humans due to daunting technical challenges [5-11]. Therefore, in humans only the role of pre-epithelial defense mechanisms can be adequately explored [2, 5, 12-17].
There are two major components of pre-epithelial defense in humans: 1) protective factors secreted by the salivary glands and, 2) protective factors elaborated within the esophageal mucosa and submucosal mucous glands. Since aggressive components of the gastroesophageal refluxate act always on the luminal aspect of the esophageal mucosa, the mucus-bicarbonate barrier on the surface of the esophageal mucosa, generated by combined salivary and esophageal mucosal protective components, is the vanguard of mucosal protection [2, 3, 5, 13, 14, 16-18].
We have recently demonstrated that the esophageal mucosal exposure to saline resulted in a continuous release of esophageal glycoconjugate (predominantly mucin) into the perfusate [13]. This indicates a steady rate of glycoconjugate secretion from submucosal mucous glands and deposition on the surface of the mucosa. Mucus layer components, including glycoconjugate, were subsequently released into the perfusing solution [13]. Lowering the intraluminal pH to 2.1 resulted in inhibition of the rate glycoconjugate release into the perfusate solution suggesting inhibition of glycoconjugate secretion from submucosal glands or inhibition of its luminal release from the mucus layer.
Subsequent exposure of the esophageal mucosa to HCl/pepsin, mimicking the natural GER scenario, resulted in a significant increase in the rate of glycoconjugate release into the perfusing solution [13]. This was accompanied by a significant decline of esophageal secretion viscosity from its value of 137 ± 21 to 93 ± 15 [13]. Since the content of glycoconjugate in the esophageal perfusate during the mucosal exposure to HCl/pepsin increased and its viscosity declined, this indicates that the released glycoconjugates were partially degraded by proteolytically active pepsin. Therefore, the decline of the viscosity of the esophageal secretion was observed.
In patients with grade II reflux esophagitis (RE) the basal rate of esophageal glycoconjugate (mucin) release was similar to corresponding values recorded in controls [14]. This rate, however, was significantly lower during the mucosal exposure to HCl/pepsin solution which suggests decline of its content within the mucus layer. This hypothesis has been confirmed by a significant decline of esophageal glycoconjugate secretion both in basal conditions and after mucosal exposure to HCl/pepsin in patients with grade III RE [14]. This impairment in the rate of release of the esophageal glycoconjugate persisted even after healing of endoscopic changes implying that the esophageal glycoconjugate deficiency is a preexisting condition and may facilitate the development of RE.
The measurement of esophageal secretion viscosity in patients with RE revealed their significantly lower values than in controls, especially during the mucosal exposure to HCl/pepsin (117 ± 8 vs 182 ± 28 centipoises, p < 0.05, unpublished results).
These data indicate that the viscosity of the esophageal secretion is strictly related to the content of its major component, esophageal glycoconjugate, predominantly mucin, and that its value may also be decisive in determining the protective potential of the mucus layer covering the esophageal mucosa.
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