Achalasia

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Achalasia

• Dan Imler
• Morning Report

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Definition

• A Greek term that means "does not relax
• Normally
• The act of swallowing (deglutition) normally
  initiates a peristaltic wave that propels
  ingested material down the esophagus.
• Deglutition also triggers relaxation of the lower
  esophageal sphincter (LES), a process that allows
  the swallowed material to enter the stomach.

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Definition

• Achalasia is a disease of unknown cause in which
  there is a loss of peristalsis in the distal
  esophagus (whose musculature is comprised
  predominantly of smooth muscle) and a failure of
  LES relaxation.

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Definition

• Although both of these abnormalities impair
  esophageal emptying, the symptoms and signs of
  achalasia (eg, dysphagia and chest pain) are due
  primarily to the defect in LES relaxation.

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Definition

• The relentless LES contraction in achalasia
  causes functional obstruction of the esophagus
  that persists until the hydrostatic pressure of
  the retained material exceeds the pressure
  generated by the sphincter muscle.

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Pathophysiology

• Achalasia results from the degeneration of
  neurons in the esophageal wall.
• Histologic examination reveals decreased numbers
  of neurons (ganglion cells) in the myenteric
  plexuses, and the ganglion cells that remain
  often are surrounded by lymphocytes and, less
  prominently, by eosinophils.
• This inflammatory degeneration preferentially
  involves the nitric oxide-producing, inhibitory
  neurons that effect the relaxation of esophageal
  smooth muscle.
• However the cholinergic neurons that contribute
  to LES tone by causing smooth muscle contraction
  are relatively spared.

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Pathophysiology

• The disordered motility that characterizes
  achalasia appears to result primarily from the
  loss of inhibitory neurons within the wall of the
  esophagus itself.
• Loss of inhibitory innervation in the LES causes
  the basal sphincter pressure to rise, and renders
  the sphincter muscle incapable of normal
  relaxation.
• In the smooth muscle portion of the esophageal
  body, the loss of inhibitory neurons results in
  aperistalsis.

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Cholecystokinin (CCK) test

• In normal individuals, the intravenous
  administration of CCK octapeptide stimulates both
  the contraction of smooth muscle cells in the
  LES, and the release of inhibitory
  neurotransmitters from ganglion cells in the wall
  of the esophagus.
• Thus, the weak, direct stimulatory effect of CCK
  on the sphincter muscle is opposed by the
  CCK-induced release of inhibitory
  neurotransmitters.
• The inhibitory effects predominate, and the net
  result is a fall in LES pressure.
• In contrast, when CCK octapeptide is administered
  to patients with achalasia, the direct
  stimulatory effect of the hormone on smooth
  muscle is unopposed and LES pressure rises.

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• In addition to the LES dysfunction there may also
  be a subtle defect in reflex relaxation of the
  upper esophageal sphincter (UES).
• The abrupt esophageal distention that results
  when gas from the stomach suddenly enters the
  esophagus normally triggers a reflex relaxation
  of the UES, thereby allowing the gas to escape
  through the mouth in the form of a belch.
• The UES belch reflex can be demonstrated
  experimentally by injecting air into the
  esophagus.
• In normal subjects, esophageal air injection
  causes UES relaxation that is accompanied by an
  audible belch.
• In patients with achalasia, however, air injected
  into the esophagus frequently causes a
  paradoxical increase in UES pressure without a
  belch.
• This abnormal reflex presumably results from the
  loss of inhibitory neurons, although the precise
  neural pathways that effect the reflex are not
  clear.
• The inability to burp in some patients with
  achalasia may contribute to the esophageal
  distention and chest pain that often accompany
  the disease.

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Etiology

• The cause of the inflammatory degeneration of
  neurons in achalasia is not known.
• The observations that achalasia is associated
  with HLA-DQw1 and that affected patients often
  have circulating antibodies to enteric neurons
  suggest that achalasia may be an autoimmune
  disorder.
• Some investigators have proposed that achalasia
  may result from chronic infections with herpes
  zoster or measles viruses, but modern studies
  have not confirmed an association between
  achalasia and any recognized viral disease.

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Etiology

• Malignancy the most common cause of
  pseudoachalasia in most populations. In one
  series, for example, six patients with
  pseudoachalasia and 161 patients with primary
  idiopathic achalasia were seen over a 14 year
  period.
• Chagas' disease seen in Central and South
  America, esophageal infection with the protozoan
  parasite Trypanosoma cruzi can result in a loss
  of intramural ganglion cells leading to
  aperistalsis and incomplete LES relaxation.
• Other causes A variety of other diseases have
  been associated with achalasia-like motor
  abnormalities. These include amyloidosis,
  sarcoidosis, neurofibromatosis, eosinophilic
  gastroenteritis, multiple endocrine neoplasia
  type 2B, juvenile Sjögren's syndrome, chronic
  idiopathic intestinal pseudo-obstruction, and
  Fabry disease.

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Epidemiology

• Achalasia has an annual incidence of
  approximately 1 case per 100,000.
• Men and women are affected with equal frequency.
• The disease can occur at virtually any age, but
  onset before adolescence is decidedly unusual.
• Achalasia is usually diagnosed in patients who
  are between the ages of 25 and 60 years.

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Clinical Manifestations

• Dysphagia for solids (91 percent) and liquids (85
  percent) is the primary clinical feature of
  achalasia.
• Although dysphagia for liquids can occur in
  patients with other esophageal motility disorders
  this symptom is most characteristic of achalasia
  and strongly suggests the diagnosis.

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Clinical Manifestations

• Difficulty belching is present in approximately
  85 percent of patients, although few describe
  this symptom spontaneously (ie, without specific
  prompting from the physician).
• Weight loss usually in the range of 5 to 10 kg
• Regurgitation of material retained in the flaccid
  esophagus may occur, especially during recumbency
  at night, and may result in aspiration.
• Chest pain is more common in younger patients,
  and tends to diminish over the course of several
  years.
• Affected patients may eat more slowly and adopt
  specific maneuvers such as lifting the neck or
  throwing the shoulders back in order to enhance
  esophageal emptying.
• Globus sensation (a lump in the throat) has been
  reported as a presenting symptom.
• Hiccups are common and probably result from
  obstruction of the distal esophagus

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Diagnosis

• The symptoms of achalasia often are insidious in
  onset and gradual in progression.
• As a result, patients typically experience
  symptoms for years before seeking medical
  attention.
• In one series of 87 consecutive patients with
  newly diagnosed achalasia, the mean duration of
  symptoms was 4.7 years.
• The delay in diagnosis was due to
  misinterpretation of typical findings by
  physicians rather than atypical clinical
  manifestations.
• Many patients are treated for other disorders
  such as gastroesophageal reflux disease before
  the diagnosis of achalasia is made.

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Radiographic studies

• A barium swallow is the primary screening test
  when achalasia is suspected on clinical grounds.
• The diagnostic accuracy of barium swallow for
  achalasia is approximately 95 percent.
• The barium swallow typically shows a dilated
  esophagus that terminates in a beak-like
  narrowing caused by the persistently contracted
  lower esophageal sphincter (LES).
• In some cases, the dilation is so profound that
  the esophagus assumes a sigmoid shape.

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Manometry

• Although clinical and radiographic findings may
  strongly suggest the diagnosis of achalasia, a
  manometric examination is required for
  confirmation in virtually all cases.
• Elevated resting LES pressure In the LES, the
  loss of inhibitory neurons typically causes LES
  pressures to rise to hypertensive levels.
• Incomplete LES relaxation Normally, there is
  complete relaxation of the LES after a swallow
  in contrast, LES relaxation in response to a
  swallow may be incomplete or absent in achalasia.
  

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Endoscopy

• Endoscopic evaluation is generally recommended
  for most patients with achalasia primarily to
  exclude malignancies at the esophagogastric
  junction that can mimic primary achalasia
  clinically, radiographically, and manometrically.
• Thus recommended for people with symptoms
• Duration of symptoms less than six months
• Presentation after age 60
• Excessive weight loss in relation to the duration
  of symptoms
• Difficult passage of the endoscope through the
  gastroesophageal junction

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Medical Therapy

• No treatment reliably restores function in the
  body of the esophagus, although the return of
  peristaltic activity has been observed
  occasionally after the administration of
  therapies designed solely to decrease LES
  pressure.
• Nitrates and calcium channel blockers relax the
  smooth muscle of the LES both in normal
  individuals and in patients with achalasia, and
  these agents have been used to treat the disorder
  with limited success.
• The drugs usually are taken sublingually 10 to 30
  minutes before meals.

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Dilation of the LES

• Despite the many variations in technique, most
  studies describe good to excellent short-term
  results in 60 to 85 percent of patients with
  achalasia who are treated with a single session
  of pneumatic dilation.
• Approximately 50 percent of patients with
  achalasia who are treated initially with a single
  pneumatic dilation will require further therapy
  within five years, and that subsequent pneumatic
  dilations are progressively less likely to result
  in a sustained remission.
• Esophageal perforation is the most common serious
  complication of pneumatic dilation, occurring in
  most large series of experienced endoscopists in
  2 to 6 percent of cases

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Surgical Myotomy

• Surgical myotomy via the modified Heller approach
  results in good to excellent relief of symptoms
  in 70 to 90 percent of patients with few serious
  complications.
• The surgeon weakens the LES by cutting its muscle
  fibers.
• The mortality rate (approximately 0.3 percent) is
  similar to that reported for pneumatic dilation.

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Botulinum Toxin

• Botulinum toxin injected into the LES of patients
  with achalasia poisons the excitatory
  (acetylcholine-releasing) neurons that increase
  LES smooth muscle tone, thereby producing a
  therapeutic decrease in LES pressure.
• A number of studies have demonstrated the
  efficacy of botulinum toxin injection for
  producing short-term symptomatic improvement in
  patients with achalasia.
• The long-term safety and efficacy remain
  uncertain.

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References

• Uptodate.com
• Clinical manifestations and diagnosis of
  achalasia
• Pathophysiology and etiology of achalasia
• Overview of the treatment of achalasia