Motor Disorders of the Thoracic Esophagus and Lower Esophageal Sphincter (LES)

In humans, thoracic and abdominal parts of the esophagus including the LES are composed of
smooth muscles and are affected by different diseases from those affecting the cervical
esophagus. When used without qualification, the term esophagus implies the thoracic (smooth
muscle part) esophagus. Motor disorders of the esophagus generally affect both the esophageal
body and the LES; however, either the body or the sphincter may be predominantly affected.
Based on pathophysiology, motor disorders of the smooth muscle portion of the esophagus and
the LES can be due to defects in the inhibitory nerves, excitatory nerves or smooth muscles.
Disorders of inhibitory innervation include achalasia, diffuse esophageal spasm, and transient
lower esophageal sphincter relaxation (TLESR). Increased function of excitatory innervation
includes hypertensive peristalsis and hypertensive and hypercontracting LES, and decreased
function of excitatory innervation of the smooth muscle includes hypotensive peristalsis,
hypotensive LES, and decreased reflex LES contraction.
Achalasia

Achalasia is due to deficiency of inhibitory neural influence that involves both the
esophageal body and the LES. It is characterized by nonperistaltic contractions in the
smooth muscle segment of the esophagus and absent, incomplete, or abnormally timed
LES relaxation in response to swallowing. These abnormalities result from loss of
deglutitive inhibition that is responsible for the peristaltic sequence of esophageal
contractions and relaxation of the LES, due to defective inhibitory nerves. Resting LES
pressures may also be elevated due to unopposed action of the excitatory nerves.
Impaired relaxation of the LES causes functional obstruction and progressive esophageal
dilation, stasis of food, and secondary elevation in basal intraesophageal pressures.

Achalasia is usually caused by degeneration of the postganglionic inhibitory nitric

oxide/vasoactive intestinal peptide neurons in the myenteric plexus. Postganglionic
excitatory neurons may also be affected in advanced cases. The etiology of the majority
of cases seen in the United States is not known; therefore, these cases are labeled as
primary or idiopathic. There are many causes of secondary achalasia. In South America,
the parasite Trypanosoma cruzi is endemic and it causes achalasia by destroying
myenteric neurons with immunoinflammation (Chagas disease). The
termpseudoachalasia should be reserved for cases that may appear like achalasia but lack
the basic pathology of achalasia, for example, extrinsic compression at the
gastroesophageal junction by tumors or inflammatory masses.

The main symptom of achalasia is dysphagia that is often to both liquids and solids.
Dysphagia is mainly localized to the lower chest but sometimes it may also be localized
to the neck. Regurgitation of food retained in the esophagus without gastric acid is also
frequent. In advanced cases nocturnal regurgitation may lead pulmonary aspiration.

Weight loss also occurs in advanced cases. Many patients also complain of chest pain,
and heartburn-like symptoms may occur. Chest pain may be due to esophageal distention
or excessive muscle contraction. Heartburn may be due to lactic acid formed by
fermentation of stagnant food in the esophagus, esophageal distention, or esophageal
muscle contraction. Gastroesophageal reflux does not occur in the presence of achalasia.

Diagnosis of achalasia is often suspected by clinical symptoms. The chest x-ray may
reveal a widened mediastinum and air-fluid level in the esophagus due retained food,
fluid, and air. The barium swallow shows a dilated esophagus with a fluid level and
characteristic bird-beak-like narrowing of the gastroesophageal junction. Administration
of a smooth muscle relaxant such as sublingual nitroglycerin causes relaxation of the LES
and may help distinguish achalasia from pseudoachalasia due to mechanical causes.
Esophageal motility studies show nonperistaltic contractions and impaired relaxation of
the LES. Basal esophageal body and LES pressure may be elevated.

Treatment of achalasia is directed at removing the functional obstruction caused by

nonrelaxing LES. Drugs that relax the LES (e.g., calcium channel blockers, nitrates,
phosphodiesterase inhibitors, and anticholinergics) may alleviate symptoms in a small
subset of patients. Injection of botulinum toxin into the LES has also been demonstrated
to be efficacious, although this needs to be repeated periodically and is generally reserved
for elderly patients with comorbidities. Rupture of the LES muscle by pneumatic dilation
is a commonly used treatment. It is successful in alleviated dysphagia and improving
esophageal emptying in the majority of patients, although repeat dilation may be required
to achieve the highest success rate. Surgical incision of the LES (Heller myotomy)
performed laparoscopically has replaced that performed by open surgery. The surgical
procedure is effective and is often performed when pneumatic dilation fails.
Gastroesophageal reflux disease may complicate successful surgery or even pneumatic
dilation.

Diffuse Esophageal Spasm

Diffuse esophageal spasm (DES) is characterized by replacement of normal peristaltic

contraction by nonperistaltic contractions. Nonperistaltic contractions are not effective in
causing normal esophageal transit. It is due to loss of deglutitive inhibition associated
with the impairment of inhibitory nerve function that is localized to the esophageal body.
The LES relaxation is normal. The impairment is usually mild, particularly in early cases.
Some cases of DES may progress to achalasia. The cause of the impairment is not found
in many cases (idiopathic), but it is suspected that a large number of disorders, including
stress, may cause inhibitory nerve dysfunction.

Dysphagia to solids and liquids and chest pain are the usual presenting symptoms. The
barium swallow may be normal or show nonpropagated contractions (also called tertiary

contractions). In advanced cases the barium swallow may reveal a corkscrew esophagus
and pseudodiverticula. The diagnosis is best made by an esophageal motility study. A
diagnosis of DES is made when greater than 20% swallow-induced contractions are
nonperistaltic. Occasional nonperistaltic contraction can occur normally. The amplitude
of the nonperistaltic contractions may be increased or normal or even decreased.
Sometimes contractions are multipeaked, and spontaneous contractions unassociated with
swallowing may be present. Management involves reassurance and the use of smooth
muscle relaxants.
Hypertensive Peristalsis, Hypercontracting LES, and Hypertensive LES

These are manometric diagnoses without clear clinical correlates. They are
diagnosed when the amplitude of peristaltic contractions, after-contraction of the LES, or
basal LES pressure exceeds the normal values. These disorders may result from
overactivity of the excitatory nerves. Stress may cause hypertensive peristaltic
contractions. Hypertensive peristalsis is the most frequent manometric finding in patients
referred for evaluation of noncardiac, angina-like chest pain. Esophageal transit is
normal. These patients, however, are often found to have esophageal hypersensitivity.
Treatment with nitrates and calcium channel blockers has been used but with no proven
benefit.

Inappropriate Transient LES Relaxation

Swallowing is associated with transient LES relaxation and esophageal peristaltic

contraction. Transient LES relaxation also normally occurs during the belching reflex, but
may also occur without obvious belching. Such episodes of inappropriate transient LES
relaxation may be associated with gastroesophageal reflux. The reflex transient LES
relaxation is mediated by inhibitory motor nerves, and its increased frequency may lead
to gastroesophageal reflux disease (GERD). Diagnosis of transient LES relaxation can
only be made on long-term manometric recordings that are usually employed in research
but not in clinical practice.

Hypotensive Esophagus

Hypotensive esophagus is characterized by reduced basal LES pressure and reduced force
of the esophageal peristaltic contractions. It may be caused by muscle atrophy and
diseases or impairment of cholinergic input or both these factors. Reduced force of the
peristaltic contractions results in ineffective transport of the swallowed food, resulting in
dysphagia to solids. Liquids may move by gravity in the upright position but may cause
difficulty in the recumbent position. Reduced LES basal tone promotes gastroesophageal
reflux leading to GERD. Often LES hypotension exists without hypotensive esophageal
peristaltic contractions. The precise etiology of hypotensive esophagus or

hypotensive LES remains unknown in most cases. Important secondary causes are
esophageal involvement in scleroderma and other connective tissue diseases, and the use
of drugs with anticholinergic properties. Esophageal involvement is common in patients
with scleroderma. This may occur even in the absence of obvious skin and joint
involvement, although in such cases Raynauds phenomenon is usually present.
Microvessel disease and fibrosis in scleroderma and other connective tissue disorders
may lead to intramural neuronal dysfunction and muscle atrophy.
Ineffective Esophageal Clearance

Ineffective esophageal clearance of food or other contents can occur with

hypotensive contractions or nonperistaltic contractions (diffuse esophageal spasm) or
absence of peristaltic contraction due to loss of the swallowing reflex. Ineffective
esophageal clearance can be documented by proper videofluoroscopic examination of the
esophagus. Recently, esophageal impedance studies have been shown to provide similar
information. Peristaltic contractions of amplitude <30 mmHg are ineffective in propelling
esophageal contents. Increased frequency ( 30%) of low-amplitude (<30 mmHg)
peristaltic contractions or nonperistaltic contractions in the distal esophagus following
wet swallows may be associated with symptoms of dysphagia. However, they are
common manometric abnormalities found in patients with reflux esophagitis, and can
also be found in patients without evidence of reflux disease.

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease occurs as a complication of ineffective

antireflux barriers at the gastroesophageal junction. The ineffective antireflux barriers
may be compromised because of the hypotension and increased frequency of transient
LES relaxation. Dislocation of the LES in the thorax and hiatus hernia may also impair
LES competence. Impaired esophageal clearance of the refluxed gastric contents due to
hypotensive or nonperistaltic contractions may worsen the esophageal mucosal injury
caused by acid reflux. Gastroesophageal reflux disease is associated with symptoms of
heartburn and regurgitation. Some cases have symptoms due to pharyngeal and laryngeal
factors, and pulmonary symptoms due to gastric acid injury. In severe cases, esophageal
bleeding, peptic stricture, and intestinal metaplasia with its associated complications may
occur.

Heartburn and Esophageal Chest Pain

The symptom of heartburn is characteristic of reflux esophagitis, and esophageal chest

pain resembling cardiac pain (noncardiac chest pain) occurs in achalasia and diffuse
esophageal spasm. Many patients with heartburn or noncardiac chest pain have no or

minimal esophageal motility abnormality. In these cases the symptoms may be due to
hypersensitivity of esophageal nociceptive mechanisms