Esophageal Motility Disorders

Introduction

Background

The esophagus functions solely to deliver food from the mouth to the stomach where the process of digestion can begin. Efficient transport by the esophagus requires a coordinated, sequential motility pattern that propels food from above and clears acid and bile reflux from below. Disruption of this highly integrated muscular motion limits delivery of food and fluid, as well as causes a bothersome sense of dysphagia and chest pain. Disorders of esophageal motility are referred to as primary or secondary esophageal motility disorders and categorized according to their abnormal manometric patterns.

Anatomy

The tubular esophagus is a muscular organ, approximately 25 cm in length, and has specialized sphincters at proximal and distal ends. The upper esophageal sphincter (UES) is comprised of several striated muscles, creating a tonically closed valve and preventing air from entering into the gastrointestinal tract. The lower esophageal sphincter (LES) is composed entirely of smooth muscle and maintains a steady baseline tone to prevent gastric reflux into the esophagus.

The body of the esophagus is similarly composed of 2 muscle types. The proximal esophagus is predominantly striated muscle, while the distal esophagus and the remainder of the GI tract contain smooth muscle. The mid esophagus contains a graded transition of striated and smooth muscle types. The muscle is oriented in 2 perpendicular opposing layers: an inner circular layer and an outer longitudinal layer, known collectively as the muscularis propria. The longitudinal muscle is responsible for shortening the esophagus, while the circular muscle forms lumen-occluding ring contractions.

Esophageal peristalsis

The coordination of these simultaneously contracting muscle layers produces the motility pattern known as peristalsis. Peristalsis is a sequential, coordinated contraction wave that travels the entire length of the esophagus, propelling intraluminal contents distally to the stomach. The LES relaxes during swallows and stays opened until the peristaltic wave travels through the LES, then contracts and redevelops resting basal tone. Low peristaltic amplitudes normally occur at the transition zone between the striated and smooth muscle portions; however, the peristalsis is uninterrupted.

Primary peristalsis is the peristaltic wave triggered by the swallowing center. The peristaltic contraction wave travels at a speed of 2 cm/s and correlates with manometry-recorded contractions. The relationship of contraction and food bolus is more complex because of intrabolus pressures from above (contraction from above) and the resistance from below (outflow resistance).

The secondary peristaltic wave is induced by esophageal distension from the retained bolus, refluxed material, or swallowed air. The primary role is to clear the esophagus of retained food or any gastroesophageal refluxate.

Tertiary contractions are simultaneous, isolated, dysfunctional contractions. These contractions are nonperistaltic, have no known physiologic role, and are observed with increased frequency in elderly people. Radiographic description of this phenomenon has been called presbyesophagus.

Esophageal motility disorders

Esophageal motility disorders are not uncommon in gastroenterology. The spectrum of these disorders ranges from the well-defined primary esophageal motility disorders (PEMDs) to very nonspecific disorders that may play a more indirect role in reflux disease and otherwise be asymptomatic. Esophageal motility disorders may occur as manifestations of systemic diseases, referred to as secondary motility disorders.

Esophageal motility disorders are less common than mechanical and inflammatory diseases affecting the esophagus, such as reflux esophagitis, peptic strictures, and mucosal rings. The clinical presentation of a motility disorder is varied, but, classically, dysphagia and chest pain are reported. In 80% of patients, the cause of a patient's dysphagia can be suggested from the history, including dysmotility of the esophagus. Before entertaining a diagnosis of a motility disorder, first and foremost, the physician must evaluate for a mechanical obstructing lesion.

Esophageal motility disorders discussed in this article include the following:

• Achalasia
• Spastic esophageal motility disorders, including diffuse esophageal spasm (DES), nutcracker esophagus, and hypertensive LES
• Nonspecific esophageal motility disorder (inefficient esophageal motility disorder)
• Secondary esophageal motility disorders related to scleroderma, diabetes mellitus, alcohol consumption, psychiatric disorders, and presbyesophagus

Pathophysiology

The pathophysiology of the primary esophageal motility disorders is poorly defined, with the exception of achalasia. The underlying cause of all the primary motility disorders remains elusive. The secondary motility disorders, such as scleroderma esophagus or esophageal motility disorder of diabetes, are better understood from the standpoint of the preexisting underlying disorders.

Achalasia

Achalasia is the best defined primary motility disorder and the only one with an established pathology. The predominant neuropathologic process of achalasia involves the loss of ganglion cells from the wall of the esophagus, starting at the LES and developing proximally. The degree of ganglion cell loss parallels the disease duration such that, at 10 years, ganglion cells are likely completely absent. At the LES, the loss of inhibitory nerves is demonstrated by loss of nitric oxide synthase and vasoactive intestinal peptide (VIP) immunohistochemistry staining. Variable amounts of inflammatory cells have been described within the myenteric plexus along with the disappearing nerves. In the peristaltic esophageal body, achalasia is characterized by a loss of intrinsic acetylcholine-containing nerves. Extrinsic nerves may also be affected, characterized by Wallerian degeneration of the axoplasm and myelin sheaths within the vagus nerve and dorsal motor nucleus. Anatomically, the circular muscle layer at the

LES is thickened, but, microscopically, individual muscle cells are grossly normal.

The physiologic process of achalasia is correlated most directly to the loss of the inhibitory nerves at the sphincter, resulting in failure of the LES to completely relax and causing relative obstruction. Manometry may reveal elevated LES pressure greater than 40 mm Hg in more than 60% of patients; however, hypertensive LES is not universal or required for the manometric diagnosis. The loss of nerves along the esophageal body causes aperistalsis, leading to stasis of ingested food and subsequent dilation of the esophagus. Nonperistaltic isolated contractions or low-amplitude simultaneous contractions of the esophageal body may be observed. If high-amplitude (>60 mm Hg) simultaneous contractions occur, the entity is categorized as vigorous achalasia, which may represent an early stage of classic achalasia. Physiologic characteristics of achalasia are additionally useful in assisting with establishing the diagnosis through chemical challenge testing.

With the partial ganglion cell loss in patients with achalasia, edrophonium (acetylcholine esterase inhibitor) increases LES pressure while atropine (muscarinic antagonist) decreases LES pressure. This characteristic likely explains why the botulinum toxin (acetylcholine release inhibitor) may have therapeutic benefit in patients with achalasia.

Spastic motility disorders of the esophageal body

No documented abnormalities exist regarding the distribution of myenteric neurons in patients diagnosed with spastic motility disorders of the esophageal body, but diffuse fragmentation of vagal filaments, increased endoneural collagen, and mitochondrial fragmentation are described. There appears to be a functional imbalance between excitatory and inhibitory postganglionic pathways, disrupting the coordinated components of peristalsis. In DES, muscular hypertrophy or hyperplasia has been described in the distal two thirds of the esophagus. Muscle wall thickening has been described in patients who are asymptomatic and, conversely, has been absent in some patients with typical symptoms and manometric findings. This controversial finding causes difficulty in attributing symptoms or manometric abnormalities to muscle structure changes. In addition, anxiety states may also play a role in some patients.

Scleroderma esophagus

In scleroderma, the primary defect in this systemic process is related to smooth muscle atrophy and fibrosis. Esophageal dysmotility develops as the smooth muscle of the esophagus is replaced by scar tissue, gradually leading to progressive loss of peristalsis and a weakening of LES. Motility is preserved at the proximal striated muscle portion of the esophagus.

Frequency

United States

Esophageal motility disorders, excluding achalasia, lack population-based studies. The 2 best-characterized motility disorders, achalasia and DES, represent only a small percentage of diagnosed motility disorders. The incidence of achalasia is 1-3 case per 100,000 population per year. As with any other chronic illness, prevalence exceeds incidence significantly. Familial clustering is observed, but a genetic relationship is not established. Nutcracker esophagus is the most common motility disorder (>40% of all motility disorders diagnosed), but it is the most controversial in significance.

International

In Europe, the incidence of achalasia is similar to that of the United States.

Mortality/Morbidity

• Achalasia is associated with significant and progressive symptomatic discomfort. When advanced, this condition can lead to such severe dysphagia that malnutrition, weight loss, and dehydration can develop. Increased incidence of both esophageal squamous cell and adenocarcinoma is observed in patients with long-standing achalasia. Therapeutic procedures and operations are associated with a small but significant risk of mortality and morbidity.
• Spastic esophageal motility disorders are associated with symptomatic discomfort but do not lead to the severity of dysphagia observed in patients with achalasia. Chest pain is, in fact, a more common complaint that may precipitate emergency room visits and cardiologic evaluations.
• Scleroderma esophagus is associated with severe and progressive acid reflux symptoms and complications. Associated complications, including strictures, Barrett esophagus, and adenocarcinoma of the esophagus, are the concern.

Race

Racial and environmental differences in the incidence of achalasia and other esophageal motility disorders might be present; however, because of the low incidence of disease and underdiagnosis in developing countries, these differences have not been demonstrated. Racial differences in the incidence of achalasia and other esophageal motility disorders have not been established.

Sex

Achalasia affects both sexes in equal numbers. No reliable information for other motility disorders exists.

Age

Achalasia commonly presents in the fifth decade but rarely may develop in children as well as in elderly persons.