Upper Gastrointestinal Tract Figure 1: Sir Thomas Willis 1621–1675
resumes resting pressure. Relaxation is mediated mainly by vasoactive intestinal polypeptide and nitric oxide (NO). The LES also has a periodic relaxation called transient LES relaxation, not triggered by swallowing. Causes of these relaxations are unknown and are the relaxations that are the most common cause of gastroesophageal reflux disease (GERD). Conversely, failure of relaxation of this sphincter leads to achalasia.8
Pathophysiology
The resultant denervation and reduction of post-ganglionic nerve fibers have been postulated to be related to the hypertensive or non-relaxing LES in patients with achalasia.37
Misiewicz et al.
demonstrated a quantitative marked decrease in the density of ganglion cells.38
With permission from The College of Optometrists.
2–4cm of the esophagus lies below the diaphragm; it is otherwise a predominantly thoracic structure. Muscle fibers of the esophagus are arranged into inner circular and outer longitudinal layers. The upper one third of the esophagus is composed of striated skeletal muscle. The lower two thirds is made up of smooth muscle. Blood supply to the upper esophagus is provided by branches of the inferior thyroid arteries. The thoracic segment is supplied directly from the aorta and by bronchial arteries. When the esophagus enters the abdomen the blood supply is mainly from esophageal branches of the left gastric artery and the left inferior phrenic artery. Venous drainage of the esophagus is variable and complex. Importantly, venous drainage of the lower segment occurs with direct communication of the portal system. This becomes clinically evident if portal hypertension or obstruction occurs, resulting in blood being shunted though the esophageal venous plexus. Subsequent engorgement of the esophageal veins may produce varices, which can result in upper gastrointestinal bleeding.
The normal mucosal lining of the esophagus is made up of stratified squamous epithelial cells that contain mucosal glands. The esophagus does not have a serosal layer, which distinguishes it from the rest of the GI tract.
Physiology
The physiological motor function of the esophagus is mainly achieved by coordination of the UES, the esophageal body, and the LES. The upper sphincter is under the motor innervation of the nucleus ambiguus in the brain and maintains a constant state of tonic contraction with a resting pressure of about 100mmHg. It prevents passage of air from the pharynx to the stomach and reflux of esophageal contents into the pharynx. This anatomical sphincter prevents food regurgitation and aspiration. Primary esophageal peristalsis moves a bolus at 3–4cm/second and reaches mean amplitude of 14.87mmHg ± 5.14 standard deviation (SD) in the distal esophagus. Primary peristalsis then elicits a secondary peristaltic wave that aids emptying. The LES mean resting pressure is between 15 and 24mmHg.7
Normally the LES relaxes at the time of swallowing for about 5–10 seconds, to allow food passage to the stomach, then
12
At the cellular level, degeneration or absence of myenteric ganglion cells is seen in most patients with symptoms. The most marked cell losses are encountered in the dilated segment of the esophagus; cells were present in the narrowed distal segment of the esophagus though reduced in numbers by approximately 50%. When studied with the electron microscope, esophageal smooth muscle cells showed three principal types of cellular changes consistent with denervation atrophy: myofilament detachment from surface membranes, cellular atrophy, and cellular hypertrophy.21
The term “pseudoachalasia” or secondary achalasia is an achalasia-like picture secondary to malignant tumors at the gastroesophageal junction (GEJ), usually originating at the gastric fundus or cardia or, less commonly, by malignant spread of tumors originating in the esophagus, lung, breast, pancreas, uterus, ovary, colon, or prostate.22,23
Other
non-neoplastic causes of secondary achalasia include Chagas’ disease and, rarely, amyloidosis. In some cases Nissen fundoplication may cause secondary achalasia.24,25
Etiology
Multiple theories have been postulated to explain the etiology of achalasia: viral infection and genetic disorders have been described in the literature; however, the cause remains unknown. Severe trauma, emotional or physical, and drastic weight loss are other suggested etiologies of this condition. In addition, studies have described an autoimmune cause of achalasia following human herpes virus-1 (HSV-1) with cytotoxic CD8+ T-cells infiltrating the LES destroying the neurons carrying the “foreign” antigen.18
Chagas disease, a cause of secondary achalasia, is a parasitic infection found in South America and caused by the organism Trypanosoma cruzii. It causes destruction of the smooth muscle ganglion cells of the myenteric plexus resulting in motor dysfunction and progressive dilation. Chagas disease may also affect the colon, ureters, and other viscera.10,15
Clinical Presentation
Progressive dysphagia, of both liquids and solids, is the cardinal symptom of achalasia. Emotional stress and ingestion of cold fluids
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
Achalasia is classified as primary or secondary. Primary or idiopathic achalasia results from the degeneration of ganglion cells in the myenteric plexus in the esophageal wall. In 1927, Rake defined achalasia as a neurologic disturbance whose morphologic correlate is a loss of ganglion cells in Auerbach’s plexus of smooth esophageal muscle.10
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