**4.2 Etiology and pathophysiology of LPRD**

The pathophysiology of LPR is still incompletely understood. In the contrast to GERD, as we have already noted, LPR is never physiological, and mucosa of the upper respiratory tract is not resistant to gastric content. Although dysfunction of any previously mentioned barrier can cause LPR, the pathophysiology of LPR is primarily attributed to failure or dysfunction of the upper esophageal sphincter. The retrograde flow of gastric acid and pepsin induces mucosal inflammatory reaction and overall cell damage. Tripsin makes role in LES abnormalities and heat sensitivity disturbing barrier function. Furthermore, stress and autonomic nerve dysfunction by increasing the opening of LES and UES are probably involved in the development of LPR. In some studies, it has been hypothesized that gas refluxes carry aerosolized droplets containing hydrogen and pepsin into the proximal esophagus and upper respiratory space. Microaspiration of acid droplets is a very important mechanism for the development of mucosal inflammation [15].
