Achalasia pathophysiology

Achalasia Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Achalasia from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Achalasia pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Achalasia pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Achalasia pathophysiology
CDC on Achalasia pathophysiology
Achalasia pathophysiology in the news
Blogs on Achalasia pathophysiology
Directions to Hospitals Treating Achalasia
Risk calculators and risk factors for Achalasia pathophysiology

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

Pathophysiology

Achalasia is a motility disorder characterized by insufficiently relaxed lower esophageal sphincter and absent peristalsis. Esophageal motility is coordinated by enteric neurons, hence their degeneration results in above mentioned esophageal motility abnormalities. Mostly the inhibitory neurons which cause LES relaxation by producing nitric oxide are degenerated. Relative sparing of cholinergic neurons results in increased LES tone. Cause of enteric neuron degeneration is still unknown, however, following theories have been suggested: Immune ganglionitis:

• • 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.