Figure 1.

Concepts on the Pathogenesis of Reflux Esophagitis. (A) The traditional concept has been that reflux esophagitis results from a caustic (acid) burn. When esophageal squamous epithelium is exposed to reflux, acid and pepsin are thought to damage the junctions between the cells, making the epithelium permeable and allowing acid to seep into the epithelium and injure the epithelial cells. This acid burn causes cell death, which triggers the infiltration of neutrophils and eosinophils into the epithelium. The death of surface cells is also assumed to induce a proliferative response leading to basal cell and papillary hyperplasia to repair the injured epithelium. (B) The alternative concept that we propose is that reflux esophagitis develops as a cytokine-mediated inflammatory injury (i.e. cytokine sizzle). In this model, the reflux of acid and bile salts doesn’t destroy epithelial cells directly, but rather induces them to secrete pro-inflammatory cytokines, which attract T lymphocytes first. These cytokines also induce basal cell proliferation. Ultimately, it is inflammatory cells that mediate the epithelial injury, not the direct acid burn.