Pathogenesis of achalasia cardia

World J Gastroenterol. 2012 Jun 28;18(24):3050-7. doi: 10.3748/wjg.v18.i24.3050.


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: Esophageal sphincter; Esophagus; Motility disorder; Motor dysphagia; Peristalsis.

Publication types

  • Review

MeSH terms

  • Deglutition
  • Deglutition Disorders / etiology*
  • Deglutition Disorders / genetics
  • Deglutition Disorders / immunology
  • Deglutition Disorders / physiopathology
  • Disease Progression
  • Esophageal Achalasia / etiology*
  • Esophageal Achalasia / genetics
  • Esophageal Achalasia / immunology
  • Esophageal Achalasia / physiopathology
  • Esophagus / innervation*
  • Ganglia / physiopathology*
  • Genetic Predisposition to Disease
  • Humans
  • Phenotype
  • Prognosis
  • Risk Assessment
  • Risk Factors