Dysphagia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Overview

Dysphagia can result from propulsive failure, motility disorders, structural disorders, intrinsic or extrinsic compression of the oropharynx or esophagus. Propulsive failure can result from dysfunction of the central nervous system control mechanisms, intrinsic musculature, or peripheral nerves. Structural abnormalities may result from surgery, neoplasm, caustic injury, or congenital anomalies.

Pathophysiology

Physiology of normal swallowing

Normal physiology of swallowing can be discussed under three phases:[1][2][3][4]

Oral phase

  • Preparatory phase:
  • Voluntary phase:
    • Voluntary phase is characterized by propelling the bolus into the pharyngeal phase.
    • Voluntary phase is controlled by

Pharyngeal phase:

  • Pharyngeal phase is a reflex mechanism and is controlled by the cranial nerves V, X, XI, and XII.

Esophageal phase:

Pathogenesis of physiological dysphagia

Physiological dysphagia occurs as a result of normal aging. Normal aging results in certain changes that affect the swallowing mechanism which include:[6][7][8][9][10]

Pathogenesis of pathological dysphagia

Pathological dysphagia can occur as a result of the following mechanisms.

1. Luminal Stenosis
2. Non-obstructing gastro-esophageal disease
  • Majority of the patients that present with dysphagia will have normal investigation findings.
  • Normal findings suggests a somato-sensory dysfunction rather than neuro-muscular cause of dysphagia.[15]
  • Non-obstructive causes of dysphagia include:
    • Motility disorders of esophagus
    • Rheumatological conditions
    • Medication induced dysphagia
    • Neurological disorders
Motility disorders of esophagus
Rheumatological conditions
  • The smooth muscle of the mid and lower esophagus is replaced by fibrous tissue secondary to the underlying autoimmune pathology leading to incompetence of the lower esophageal sphincter (LES) and subsequently to GERD and dysphagia.[22][23]
Medication induced
Neurological disorders
  • Neurological disorders predominanlty affect the oropharyngeal phase. However, pharyngeal phase of swallowing can also be involved in cases of stroke affecting the basal ganglia and the cortex, as it affects the ability to initiate the swallow and decrement in bolus transit between pharynx and esophagus.[31][32][33]
  • Neurological deficits can cause weakness of the oral musculature and tongue movements resulting in failure to form a intact food bolus and decreased sensitivity of the pharyngeal receptors, subsequent to neurological compromise leading to dysphagia.
  • The central, autonomic or peripheral nervous system is affected by several neurological diseases such as:

Genetics

The following genes can be involved in the development of dysphagia subsequent to different pathologies:

  • CTC1
  • DKC1 
  • NHP2
  • NOP10
  • RTEL1
  • TERC
  • WRAP53

Mutations in the following genes can cause esophageal cancer:

  • Chromosomal losses (4q, 5q, 9p, and 18q)
  • Chromosomal gains (8q, 17q, and 20q)
  • Gene amplifications (7, 8, and 17q)
  • PT53 genes and P16 genes 
  • Variants in ADH and/or ALDH2 genes

Associated Conditions

Common conditions associated with dysphagia include:

Gross Morphology

The gross morphology of dysphagia depends on the underlying pathologic condition. Following are the gross morphologic features of some important causes of dysphagia:

Zenkers diverticulum:

  • Diverticulum or a sac is seen in the esophagus

Esophageal stricture:

Esophageal cancer:

Squamous cell carcinoma or adenocarcinoma of the esophagus may appear as:

  • Polypoid lesion 

Achalasia:

Diffuse esophageal spasm(DES):

Gross thickening of muscularis propria layer and lower esophageal sphincter (LES) due to hyperplasia are characteristic findings of DES.

Microscopic Pathology

Esophagitis

H&E stain of esophagus biopsy showing eosinophilic esophagitis, manifested by an infiltration of eosinophils in the lamina propria


Esophageal stricture

Esophageal stricture <"https://commons.wikimedia.org/wiki/File%3ATinci%C3%B3n_hematoxilina-eosina.jpg"> via Wikimedia Commons</ref>


Esophageal stricture due to GERD, via wikipedia.org[34]


References

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  34. From en.wikipedia.org, Public Domain, <"https://commons.wikimedia.org/w/index.php?curid=1931423">

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