The junctions between the squamous epithelial cells lining the esophagus are quite different from the junctions between epithelial cells in other regions of the gastrointestinal tract, where tight junctions link the luminal ends of columnar epithelial cells by a functional “belt” comprising specialized membrane and intracellular proteins such as occludin and Zoo-1. Such tight junctions can be classified based on the number of strands into “tight” and “leaky” tight junctions. The gastric epithelium has “tight” tight junctions with as many as 15 adhesive strands of protein. At best, the tight junctions visualized in the first layer of the esophageal epithelium contain two or so strands and must be extremely leaky. In the stratified squamous epithelium of the esophagus, adjacent epithelial cells are joined more loosely by desmosomes (gap junctions) connected by intracellular intermediate filaments. The barrier function of the cells lining the esophagus is therefore normally dependent not on tight junctions but on the multiplicity of cell layers comprising the stratified epithelium and the intercellular spaces between these cell layers. The esophagus may be considered as analogous to “wet skin” and in this respect even behave in a similar fashion when damaged.

In GERD, the spaces between squamous epithelial cells enlarge, thereby perhaps allowing luminal contents more access to the submucosa. Whether enlargement of the intercellular space is the primary event or secondary to cell shrinkage is not entirely clear and remains to be determined.