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As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD.<\/jats:p>","DOI":"10.1111\/nyas.14501","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T02:59:21Z","timestamp":1601866761000},"page":"3-14","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid"],"prefix":"10.1111","volume":"1486","author":[{"given":"Priya","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Medicine University of California San Diego School of Medicine La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-2033","authenticated-orcid":false,"given":"Rena","family":"Yadlapati","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of California San Diego School of Medicine, Center for Esophageal Diseases La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00630.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.11622\/smedj.2016167"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02238.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.09.047"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110246"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.4.451"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00160.2010"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2003.07303.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.132"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000439"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12239"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.133470"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(91)90107-O"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(94)90068-X"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(97)90327-5"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-005-1282-0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.44.5.598"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520701245645"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.240"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"e13919","DOI":"10.1111\/nmo.13919","article-title":"Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance","author":"Bortoli N.","year":"2020","journal-title":"Neurogastroenterol. 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