Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pathophysiology and etiology of achalasia

Stuart J Spechler, MD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


The act of swallowing (deglutition) normally initiates a peristaltic wave that propels ingested material down the esophagus. Deglutition also triggers relaxation of the lower esophageal sphincter (LES), a process that allows the swallowed material to enter the stomach.

Achalasia (a Greek term that means "does not relax") is a disease of unknown cause in which there is a loss of peristalsis in the distal esophagus (whose musculature is comprised predominantly of smooth muscle) and a failure of LES relaxation. Although both of these abnormalities impair esophageal emptying, the symptoms of achalasia (eg, dysphagia and regurgitation) are due primarily to the defect in LES relaxation. The relentless LES contraction in achalasia causes functional obstruction of the esophagus (picture 1) that persists until the hydrostatic pressure of the retained material exceeds the pressure generated by the sphincter muscle.

The pathophysiology and etiology of achalasia will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Achalasia: Pathogenesis, clinical manifestations, and diagnosis" and "Overview of the treatment of achalasia".)


Achalasia results from the degeneration of neurons in the esophageal wall (figure 1) [1]. Histologic examination reveals decreased numbers of neurons (ganglion cells) in the myenteric plexuses, and the ganglion cells that remain often are surrounded by lymphocytes and, less prominently, by eosinophils [2,3]. This inflammatory degeneration preferentially involves the nitric oxide-producing, inhibitory neurons that effect the relaxation of esophageal smooth muscle; the cholinergic neurons that contribute to lower esophageal sphincter (LES) tone by causing smooth muscle contraction may be relatively spared [4].

In some patients, degenerative changes are also found in the ganglion cells of the dorsal motor nucleus of the vagus in the brainstem, and Wallerian degeneration has been observed in the vagal fibers that supply the esophagus (figure 1) [5]. However, the disordered motility that characterizes achalasia appears to result primarily from the loss of inhibitory neurons within the wall of the esophagus itself. Loss of inhibitory innervation in the LES causes the basal sphincter pressure to rise, and renders the sphincter muscle incapable of normal relaxation. In the smooth muscle portion of the esophageal body, the loss of inhibitory neurons results in aperistalsis.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 12, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Reynolds JC, Parkman HP. Achalasia. Gastroenterol Clin North Am 1989; 18:223.
  2. Goldblum JR, Whyte RI, Orringer MB, Appelman HD. Achalasia. A morphologic study of 42 resected specimens. Am J Surg Pathol 1994; 18:327.
  3. Goldblum JR, Rice TW, Richter JE. Histopathologic features in esophagomyotomy specimens from patients with achalasia. Gastroenterology 1996; 111:648.
  4. Holloway RH, Dodds WJ, Helm JF, et al. Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia. Gastroenterology 1986; 90:924.
  5. Qualman SJ, Haupt HM, Yang P, Hamilton SR. Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease. Gastroenterology 1984; 87:848.
  6. Dodds WJ, Dent J, Hogan WJ, et al. Paradoxical lower esophageal sphincter contraction induced by cholecystokinin-octapeptide in patients with achalasia. Gastroenterology 1981; 80:327.
  7. Massey BT, Hogan WJ, Dodds WJ, Dantas RO. Alteration of the upper esophageal sphincter belch reflex in patients with achalasia. Gastroenterology 1992; 103:1574.
  8. Mearin F, Papo M, Malagelada JR. Impaired gastric relaxation in patients with achalasia. Gut 1995; 36:363.
  9. Wong RK, Maydonovitch CL, Metz SJ, Baker JR Jr. Significant DQw1 association in achalasia. Dig Dis Sci 1989; 34:349.
  10. Verne GN, Sallustio JE, Eaker EY. Anti-myenteric neuronal antibodies in patients with achalasia. A prospective study. Dig Dis Sci 1997; 42:307.
  11. Verne GN, Hahn AB, Pineau BC, et al. Association of HLA-DR and -DQ alleles with idiopathic achalasia. Gastroenterology 1999; 117:26.
  12. Niwamoto H, Okamoto E, Fujimoto J, et al. Are human herpes viruses or measles virus associated with esophageal achalasia? Dig Dis Sci 1995; 40:859.
  13. Birgisson S, Galinski MS, Goldblum JR, et al. Achalasia is not associated with measles or known herpes and human papilloma viruses. Dig Dis Sci 1997; 42:300.
  14. Facco M, Brun P, Baesso I, et al. T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens. Am J Gastroenterol 2008; 103:1598.
  15. de Oliveira RB, Rezende Filho J, Dantas RO, Iazigi N. The spectrum of esophageal motor disorders in Chagas' disease. Am J Gastroenterol 1995; 90:1119.
  16. Kahrilas PJ, Kishk SM, Helm JF, et al. Comparison of pseudoachalasia and achalasia. Am J Med 1987; 82:439.
  17. Campos CT, Ellis FH Jr, LoCicero J 3rd. Pseudoachalasia: a report of two cases with comments on possible causes and diagnosis. Dis Esophagus 1997; 10:220.
  18. Costigan DJ, Clouse RE. Achalasia-like esophagus from amyloidosis. Successful treatment with pneumatic bag dilatation. Dig Dis Sci 1983; 28:763.
  19. Dufresne CR, Jeyasingham K, Baker RR. Achalasia of the cardia associated with pulmonary sarcoidosis. Surgery 1983; 94:32.
  20. Foster PN, Stewart M, Lowe JS, Atkinson M. Achalasia like disorder of the oesophagus in von Recklinghausen's neurofibromatosis. Gut 1987; 28:1522.
  21. Cuthbert JA, Gallagher ND, Turtle JR. Colonic and oesophageal disturbance in a patient with multiple endocrine neoplasia, type 2b. Aust N Z J Med 1978; 8:518.
  22. Similä S, Kokkonen J, Kaski M. Achalasia sicca--juvenile Sjögren's syndrome with achalasia and gastric hyposecretion. Eur J Pediatr 1978; 129:175.
  23. Schuffler MD. Chronic intestinal pseudo-obstruction syndromes. Med Clin North Am 1981; 65:1331.
  24. Roberts DH, Gilmore IT. Achalasia in Anderson-Fabry's disease. J R Soc Med 1984; 77:430.