The fundamental pathologic abnormality in achalasia is thought to be

A. absent cholinergic fibers to the motor end plate receptors of the lower esophageal sphincter.
B. atrophy of esophageal smooth muscle.
C. hypertrophy of the lower esophageal sphincter.
D. loss of nonadrenergic noncholinergic neurons in the myenteric plexus of the lower esophagus.

Answer D

The cause of achalasia is still unknown. A loss of control at the postganglionic level of nonadrenergic and noncholinergic inhibitory nerves seems to be the basic defect. The intrinsic motor neurons of Auerbach's plexus between the inner circular and outer longitudinal muscular layers are either reduced in number or absent. Changes are most prominent in the distal portion of the esophagus and lower esophageal sphincter. Histopathologic changes also exist in the preganglionic nerve axons and the brain stem nuclei. Although the esophageal smooth muscle shows variable and nonspecific changes, the gross appearance of the distal esophageal muscle and lower esophageal sphincter is usually normal.

Pasricha PJ, Kalloo AN. Recent advances in the treatment of achalasia. Gastroint Endo Clin N Am 1997;7:191-206.
Achalasia is a disorder of the esophagus characterized by aperistalsis and failure of the lower esophageal sphincter to relax. This article discusses traditional and new therapies directed against the sphincter muscle. Because limitations of these treatments do exist, alternatives to sphincter destruction are presented.

Sugarbaker DJ, Kearney DJ, Richards WG. Esophageal physiology and pathophysiology. Surg Clin N Am 1993;73:1101-18.
This article presents the normal physiology of esophageal peristalsis. It discusses current approaches to the diagnosis and treatment of primary disorders of the esophagus, including achalasia, nutcracker esophagus, diffuse esophageal spasm, as well as the secondary disorder, scleroderma.

Verne GN, Sallustio JE, Eaker EY. Anti-myenteric antibodies in patients with achalasia. A prospective study. Dig Dis Sci 1997;42:307-13.
Achalasia is a motility disorder of the esophagus characterized by the loss of inhibitory neurons in the distal esophagus. Although idiopathic in nature, autoimmune mechanisms have been proposed, and we set out to determine the presence of myenteric neuronal antibodies. We prospectively studied 18 patients with well-characterized achalasia (by clinical, x-ray, and manometric evidence), nine with gastroesophageal reflux disease, and analyzed the sera from 22 disease-free controls. Using double-label, indirect immunofluorescence techniques, rat esophageal and intestinal sections were double-labeled with sera (dilutions of 1:50 to 1:400) from the three groups and with neurofilament antibody to localize neurons. Seven of 18 achalasia patients had sera that stained the majority of neurons within plexi in the esophageal and intestinal sections, including both NADPH diaphorase (nitric oxide synthase) -positive and -negative neurons. None of the gastroesophageal reflux patients or the controls showed staining. Neuronal antibodies in achalasia provide an attractive hypothesis to explain this diffuse, possibly immune-based disorder.