Pathophysiology of achalasia

Abstract

Achalasia is a rare esophageal motor disorder characterized by selective loss of esophageal inhibitory neuronal function, particularly at the lower esophageal sphincter (LES), where unopposed contractile tone leads to incomplete LES relaxation following swallows. Involvement of the esophageal body nerves leads to abnormal sequencing of contraction in some variants and aperistalsis in others. These motor abnormalities result in obstruction of food passage from the esophagus to the stomach and manifest clinically as symptoms such as dysphagia or chest pain. The gravity of the clinical presentation has spurred centuries of investigation into the disorder and its potential therapies. The modern diagnosis of achalasia hinges on demonstration of abnormal LES relaxation in conjunction with a non-peristaltic esophageal body on high resolution manometry (HRM). The pathophysiologic basis is hypothesized to be initiated by an environmental trigger, probably a viral infection, in genetically predisposed individuals. Given similar antigenic structure and an associated mimicry, antibodies formed against the environmental trigger cause inflammation and damage to esophageal neurons and ganglia. If this process results in neuronal death, classic achalasia features develop, with esophageal body aperistalsis and loss of LES relaxation. Alternatively, if inflammation is profound without neuronal death, an imbalance of esophageal excitation and inhibition ensues, and esophageal body contraction may be maintained, albeit exaggerated and/or premature, producing non-classic achalasia subtypes. Caution should be exercised as structural and mechanical obstructive processes can occur at the esophagogastric junction and can mimic idiopathic achalasia. Both local and distant neoplasia as well as Chagas disease can also result in an achalasia like motor pattern, from mechanisms that are not completely understood. From the days of whalebone dilatations to modern individualized surgical interventions, much has been learned about the pathophysiology of achalasia; however, it remains just as captivating as it ever was.