Aetiology
Inflammatory destruction of inhibitory nitrinergic neurons in the oesophageal myenteric (Auerbach) plexus results in loss of peristalsis and incomplete lower oesophageal sphincter relaxation. The exact cause of this inflammatory process is unknown, but possible triggers include infection, autoimmunity, and genetic factors.
Infection
Infectious diseases such as Chagas disease can manifest in a similar way to achalasia. Herpes and measles viruses have been associated with achalasia, and increased antibody titres against these viruses have been found in patients with achalasia, compared with healthy controls.[14] However, a causal relationship has not been established.
Autoimmunity
Patients with achalasia are more likely to suffer from autoimmune conditions.[15] This association is supported by the presence of myenteric plexus antibodies in many patients with achalasia, a T-cell infiltrate in the inflamed myenteric plexus, and increased prevalence of human leukocyte antigen class II antigens.[14]
Genetic factors
Familial achalasia is rare. However, a number of cases of achalasia have been reported among children of consanguineous couples.[16]
The triple-A (Allgrove) syndrome, characterised by achalasia, alacrima, and adrenocorticotrophic hormone-resistant adrenal insufficiency, is an autosomal recessive disorder that has been mapped to chromosome 12.[17][18]
The rs1799724 single nucleotide polymorphism (SNP) has been shown to be associated with the development of achalasia. This SNP is located between the lymphotoxin-alpha and tumour necrosis factor-alpha genes.[19]
Pathophysiology
The smooth muscle of the distal oesophageal wall and lower oesophageal sphincter are innervated by vagal pre-ganglionic fibres arising in the dorsal motor nucleus. These form synapses in the myenteric plexus ganglia with post-ganglionic fibres, consisting of cholinergic excitatory neurons, and inhibitory neurons releasing nitric oxide (NO) and vasoactive intestinal peptide.[20]
In achalasia, the loss of ganglion cells in the myenteric (Auerbach) plexus is accompanied by an inflammatory response, consisting of T lymphocytes, eosinophils, and mast cells, with neural fibrosis. The end result of these changes is a selective loss of post-ganglionic inhibitory neurons containing NO and vasoactive intestinal peptide. Stimulatory cholinergic neurons remain intact, resulting in a high basal lower oesophageal sphincter pressure and insufficient relaxation.
Aperistalsis is caused by loss of the latency gradient that normally permits sequential contractions along the oesophageal body, a process that is mediated by NO. Studies measuring NO synthase activity have confirmed loss of NO innervation in patients with achalasia, as have histological studies of oesophagectomy specimens from patients with achalasia.[21]
Use of this content is subject to our disclaimer