Abstract
Gastroesophageal reflux disease (GERD) is likely the most prevalent condition afflicting the GI tract in the USA. However, most GERD patients do not have esophagitis, and as esophagitis has become less of a problem, largely because of more effective treatments, the issue of symptom control has become a more substantial one. From a pathophysiological viewpoint, GERD results from the excessive reflux of gastric contents into the esophagus which is normally prevented as a function of the esophagogastric junction (EGJ), the integrity of which is dependent upon both physiological and anatomical factors, inclusive of, but not limited to, hiatus hernia. The net result is of an increased number of reflux events, an increasing diversity of potential mechanisms of reflux. Once reflux has occurred, the duration of resultant esophageal acid exposure is determined by the effectiveness of esophageal acid clearance, the dominant determinants of which are peristalsis, salivation, and, again, the anatomical integrity of the EGJ. About half of GERD patients have abnormal acid clearance and the major contributor to this is hiatus hernia. Abnormalities of acid clearance are probably the major determinant of developing esophagitis as opposed to symptomatic GERD. In summary, GERD is a multifactorial disease involving both physiological and anatomical abnormalities.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20.
El-Serag HB, Petersen NJ, Carter J, et al. Gastroesophageal reflux among different racial groups in the United States. Gastroenterology. 2004;126:1692–9.
DeMeester TR, Wang CI, Wernly JA, et al. Technique, indications, and clinical use of 24 hour esophageal pH monitoring. J Thorac Cardiovasc Surg. 1980;79:656–70.
Wienbeck M, Barnert J. Epidemiology of reflux disease and reflux esophagitis. Scand J Gastroenterol Suppl. 1989;156:7–13.
Bainbridge ET, Temple JG, Nicholas SP, Newton JR, Boriah V. Symptomatic gastro-oesophageal reflux in pregnancy. A comparative study of white Europeans and Asians in Birmingham. Br J Clin Pract. 1983;37:53–7.
El-Serag HB, Sonnenberg A. Opposing time trends of peptic ulcer and reflux disease. Gut. 1998;43:327–33.
Pandolfino JE, Howden CW, Kahrilas PJ. H. Pylori and GERD: is less more? Am J Gastroenterol. 2004;99:1222–5.
Abe Y, Ohara S, Koike T, et al. The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett’s esophagus in Japan. Am J Gastroenterol. 2004;99:1213–21.
Dent J, Dodds WJ, Friedman RH, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest. 1980;65:256–67.
Goyal RK, Rattan S. Nature of the vagal inhibitory innervation to the lower esophageal sphincter. J Clin Invest. 1975;55:1119–26.
Yamato S, Saha JK, Goyal RK. Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. Life Sci. 1992;50:1263–72.
Kahrilas PJ. Anatomy and physiology of the gastroesophageal junction. Gastroenterol Clin North Am. 1997;26:467–86.
Liebermann-Meffert D, Allgower M, Schmid P, Blum AL. Muscular equivalent of the lower esophageal sphincter. Gastroenterology. 1979;76:31–8.
Brasseur JG, Ulerich R, Dai Q, et al. Pharmacological dissection of the human gastro-oesophageal segment into three sphincteric components. J Physiol. 2007;580:961–75.
Thor KB, Hill LD, Mercer DD, Kozarek RD. Reappraisal of the flap valve mechanism in the gastroesophageal junction. A study of a new valvuloplasty procedure in cadavers. Acta Chir Scand. 1987;153:25–8.
Hill LD, Kozarek RA, Kraemer SJ, et al. The gastroesophageal flap valve: in vitro and in vivo observations. Gastrointest Endosc. 1996;44:541–7.
De Troyer A, Sampson M, Sigrist S, Macklem PT. Action of costal and crural parts of the diaphragm on the rib cage in dog. J Appl Physiol. 1982;53:30–9.
Altschuler SM, Boyle JT, Nixon TE, Pack AI, Cohen S. Simultaneous reflex inhibition of lower esophageal sphincter and crural diaphragm in cats. Am J Physiol. 1985;249:G586–91.
Mittal RK, Fisher M, McCallum RW, et al. Human lower esophageal sphincter pressure response to increased intra-abdominal pressure. Am J Physiol. 1990;258:G624–30.
Klein WA, Parkman HP, Dempsey DT, Fisher RS. Sphincterlike thoracoabdominal high pressure zone after esophagogastrectomy. Gastroenterology. 1993;105:1362–9.
van Herwaarden MA, Samsom M, Smout AJ. Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations. Gastroenterology. 2000;119:1439–46.
Bredenoord AJ, Weusten BL, Timmer R, Smout AJ. Intermittent spatial separation of diaphragm and lower esophageal sphincter favors acidic and weakly acidic reflux. Gastroenterology. 2006;130:334–40.
Mittal RK, Holloway RH, Penagini R, Blackshaw LA, Dent J. Transient lower esophageal sphincter relaxation. Gastroenterology. 1995;109:601–10.
Sifrim D, Holloway R. Transient lower esophageal sphincter relaxations: how many or how harmful? Am J Gastroenterol. 2001;96:2529–32.
Sifrim D, Holloway R, Silny J, et al. Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings. Gastroenterology. 2001;120:1588–98.
Wyman JB, Dent J, Heddle R, Dodds WJ, Toouli J, Downton J. Control of belching by the lower oesophageal sphincter. Gut. 1990;31:639–46.
Kahrilas PJ, Shi G, Manka M, Joehl RJ. Increased frequency of transient lower esophageal sphincter relaxation induced by gastric distention in reflux patients with hiatal hernia. Gastroenterology. 2000;118:688–95.
Zagorodnyuk VP, Chen BN, Brookes SJ. Intraganglionic laminar endings are mechano-transduction sites of vagal tension receptors in the guinea-pig stomach. J Physiol. 2001;534:255–68.
Zagorodnyuk VP, Chen BN, Costa M, Brookes SJ. Mechanotransduction by intraganglionic laminar endings of vagal tension receptors in the guinea-pig oesophagus. J Physiol. 2003;553:575–87.
Martin CJ, Dodds WJ, Liem HH, et al. Diaphragmatic contribution to gastroesophageal competence and reflux in dogs. Am J Physiol. 1992;263:G551–7.
Pandolfino JE, Zhang Q, Ghosh SK, Han A, Boniquit C, Kahrilas PJ. tLESRs and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology. 2006;131:1725–33.
Martin CJ, Patrikios J, Dent J. Abolition of gas reflux and transient lower esophageal sphincter relaxation by vagal blockade in the dog. Gastroenterology. 1986;91:890–6.
Kahrilas PJ, Boeckxstaens G. Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients? Gut. 2012;61:1501–9.
Sloan S, Rademaker AW, Kahrilas PJ. Determinants of gastroesophageal junction incompetence: hiatal hernia, lower esophageal sphincter, or both? Ann Intern Med. 1992;117:977–82.
Kahrilas PJ, Lin S, Chen J, Manka M. The effect of hiatus hernia on gastro-oesophageal junction pressure. Gut. 1999;44:476–82.
Marchand P. The surgery for hiatus hernia: is vagotomy rational? S Afr Med J. 1970;44:35–9.
Michelson E, Siegel C. The role of the phrenico-esophageal ligament in the lower esophageal sphincter. Surg Gynecol Obstet. 1964;118:1291–4.
Kahrilas PJ, Lin S, Manka M, Shi G, Joehl RJ. Esophagogastric junction pressure topography after fundoplication. Surgery. 2000;127:200–8.
Contractor QQ, Akhtar SS, Contractor TQ. Endoscopic esophagitis and gastroesophageal flap valve. J Clin Gastroenterol. 1999;28:233–7.
Pandolfino JE, Bianchi L, Lee TJ, Hirano I, Kahrilas PJ. Esophagogastric junction morphology predicts susceptibility to exercise-induced reflux. Am J Gastroenterol. 2004;99:1430–6.
Roy S, Fox MR, Curcic J, Schwizer W, Pal A. The gastro-esophageal reflux barrier: biophysical analysis on 3D models of anatomy from magnetic resonance imaging. Neurogastroenterol Motil. 2012;24:616–25.
Pandolfino JE, Shi G, Trueworthy B, Kahrilas PJ. Esophagogastric junction opening during relaxation distinguishes nonhernia reflux patients, hernia patients, and normal subjects. Gastroenterology. 2003;125:1018–24.
Helm JF, Dodds WJ, Riedel DR, et al. Determinants of esophageal acid clearance in normal subjects. N Engl J Med. 1984;310:284–8.
Stanciu C, Bennett JR. Oesophageal acid clearing: one factor in the production of reflux oesophagitis. Gut. 1974;15:852–7.
Kahrilas PJ, Dodds WJ, Hogan WJ. Effect of peristaltic dysfunction on esophageal volume clearance. Gastroenterology. 1988;94:73–80.
Kahrilas PJ, Dodds WJ, Hogan WJ, et al. Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology. 1986;91:897–904.
Mittal RK, Lange RC, McCallum RW. Identification and mechanism of delayed esophageal acid clearance in subjects with hiatus hernia. Gastroenterology. 1987;92:130–5.
Sloan S, Kahrilas PJ. Impairment of esophageal emptying with hiatal hernia. Gastroenterology. 1991;100:596–605.
Korsten MA, Rosman AS, Fishbein S, et al. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. Am J Med. 1991;90:701–6.
Kahrilas PJ, Gupta RR. The effect of cigarette smoking on salivation and esophageal acid clearance. J Lab Clin Med. 1989;114:431–8.
Acknowledgements
This work was supported by grant R01 DC00646 (PJK) from the Public Health Service.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag London
About this chapter
Cite this chapter
Kahrilas, P.J., Pandolfino, J.E. (2014). Pathophysiology of Gastroesophageal Reflux Disease. In: Fisichella, P., Soper, N., Pellegrini, C., Patti, M. (eds) Surgical Management of Benign Esophageal Disorders. Springer, London. https://doi.org/10.1007/978-1-4471-5484-6_2
Download citation
DOI: https://doi.org/10.1007/978-1-4471-5484-6_2
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-5483-9
Online ISBN: 978-1-4471-5484-6
eBook Packages: MedicineMedicine (R0)