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World J Gastroenterol. Jun 28, 2012; 18(24): 3050-3057
Published online Jun 28, 2012. doi: 10.3748/wjg.v18.i24.3050
Pathogenesis of achalasia cardia
Uday C Ghoshal, Sunil B Daschakraborty, Renu Singh
Uday C Ghoshal, Sunil B Daschakraborty, Renu Singh, Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226104, India
Author contributions: Ghoshal UC made substantial contributions to conception, drafting and revising the manuscript critically for important intellectual content; Daschakraborty SB and Singh R made substantial contributions during writing of the first draft of the paper; all authors approved the version to be published.
Correspondence to: Uday C Ghoshal, MD, DNB, DM, FACG, Additional Professor, Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.
Telephone: +91-522-2494405 Fax: +91-522-2668017
Received: June 25, 2011
Revised: October 11, 2011
Accepted: April 28, 2012
Published online: June 28, 2012

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

Keywords: Esophagus, Motor dysphagia, Motility disorder, Peristalsis, Esophageal sphincter