Achalasia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pathophysiology

• Achalasia results from degeneration of neurons in the esophageal wall.

  • There is a decrease in the number of ganglion cells in the myenteric plexus, and the ganglion cells that remain, have been found to be associated with a lymphocytic inflammatory response.
  • The neurons that are destroyed are predominantly inhibitory neurons, which act via release of nitric oxide, with a relative sparing of the cholinergic neurons responsible for smooth muscle contraction.
  • It has also been shown that some patients have destruction of the dorsal motor nucleus of the vagus in the brainstem, as well as Wallerian degeneration of the vagal fibers that supply the esophagus.
  • The final result is an increase in LES tone and loss of normal peristalsis.

    • Patients with achalasia can also have incomplete relaxation of the UES and stomach.

• The etiology of achalasia is unknown.
• Theories include:

  • Autoimmune

    • Two-thirds of patients have auto-antibodies directed against DARP-32, a dopamine-carrying protein on the surface of cells in the myenteric plexus. Achalasia is also associated with HLA-DQw1.

  • Infection

    • Although some patients with achalasia have been found to have chronic HSV or measles infections, this association remains unconfirmed.

  • Several diseases have been associated with motor abnormalities similar or identical to those of achalasia and have been called pseudoachalasia.

    • Malignancy (especially gastric, lung, lymphoma and pancreatic) causes achalasia by either direct invasion of the esophageal neuronal plexus, or via the release of unidentified evil humors that act in a paraneoplastic function.
    • Chagas disease: Trypanosoma cruzi directly infects the esophagus.
    • Amyloidosis, sarcoidosis, eosinophilic gastroenteritis, neurofibromatosis, juvenile Sjögren’s, Ogilvie’s syndrome and Anderson-Fabry’s disease have also been associated with pseudoachalasia.

Gross Pathology

Pathological examination reveals a defect in the nerves that control the motility of the esophagus (the myenteric plexus). The esophagus is dilated and hypertrophied. In Chagas disease, the ganglion cells are destroyed by Trypanosoma cruzi, the causative parasite.