• Esophageal mucosa resistance is directly related to the development of GERD. The esophagus has several components that form a protective barrier against harmful substances. These mechanisms include a weak pre-epithelial defense and a strong epithelial defense supported by a blood supply. The pre-epithelial layer consists of a small water layer that has a limited capacity when it comes to buffering. However, the buffering capacity is sufficient to maintain the surface pH values without activation of pepsin. When this mechanism fails, it is solely up to the epithelium itself to provide defense. This defense system is made of the cell membranes and intercellular junction complex, cellular and intercellular buffers, and cell membrane ion transporters. All of these defense mechanisms can be defeated by highly acidic reflux, or ingestion of smoke-derived chemicals, alcohol, or substances high in osmolality. When the esophageal defense mechanisms are overwhelmed, mucosal injury occurs. This then leads to acid and acid-pepsin attacking the intercellular junctions. Because of the damage to these junctions, there is an increase in paracellular permeability, and intracellular acidification occurs. This is present in the esophageal epithelium of those with GERD.