Dysphagia pathophysiology: Difference between revisions

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===5.Medication induced===
===5.Medication induced===
A group of several medications can contribute to dysphagia by the following mechanism:
A group of several medications can contribute to dysphagia by the following mechanism:<ref name="pmid3606243">{{cite journal| author=Bonavina L, DeMeester TR, McChesney L, Schwizer W, Albertucci M, Bailey RT| title=Drug-induced esophageal strictures. | journal=Ann Surg | year= 1987 | volume= 206 | issue= 2 | pages= 173-83 | pmid=3606243 | doi= | pmc=1493104 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3606243  }} </ref><ref name="pmid8360134">{{cite journal| author=Philpott-Howard JN, Wade JJ, Mufti GJ, Brammer KW, Ehninger G| title=Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group. | journal=J Antimicrob Chemother | year= 1993 | volume= 31 | issue= 6 | pages= 973-84 | pmid=8360134 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8360134  }} </ref><ref name="pmid15778537">{{cite journal| author=Sagar R, Varghese ST, Balhara YP| title=Dysphagia due to olanzepine, an antipsychotic medication. | journal=Indian J Gastroenterol | year= 2005 | volume= 24 | issue= 1 | pages= 37-8 | pmid=15778537 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15778537  }} </ref><ref name="pmid2186626">{{cite journal| author=McCord GS, Clouse RE| title=Pill-induced esophageal strictures: clinical features and risk factors for development. | journal=Am J Med | year= 1990 | volume= 88 | issue= 5 | pages= 512-8 | pmid=2186626 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2186626  }} </ref>
*They decrease the strength of lower oesophageal sphincter relaxation.   
*They decrease the strength of lower oesophageal sphincter relaxation.   
*Reduction in lubrication by reduced saliva and impairment secondary peristalsis.
*Reduction in lubrication by reduced saliva and impairment secondary peristalsis.
*Compromise the airway patency and hence leading to the risk of aspiration. Finally, medications that have a local or systemic immunosuppressant effect can predispose to infective oesophagitis[60].  * Suppress the local and systemic immunity and predispose to infections.
*Compromise the airway patency and hence leading to the risk of aspiration. Finally, medications that have a local or systemic immunosuppressant effect can predispose to infective oesophagitis[60].  * Suppress the local and systemic immunity and predispose to infections.
Examples:
Examples:
*Antipsychotic, e.g., olanzapine, clozapine
*Antipsychotic, e.g., olanzapine, clozapine<ref name="pmid18615368">{{cite journal| author=Kohen I, Lester P| title=Quetiapine-associated dysphagia. | journal=World J Biol Psychiatry | year= 2009 | volume= 10 | issue= 4 Pt 2 | pages= 623-5 | pmid=18615368 | doi=10.1080/15622970802176495 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18615368  }} </ref>
*Tricyclic antidepressant, e.g., amitriptylin
*Tricyclic antidepressant, e.g., amitriptylin
*Anticholinergic,  
*Anticholinergic,  

Revision as of 19:20, 5 February 2018

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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

Anatomically, swallowing can be divided into three phases:[1][2][3][4]

  • Oral preparatory phase
  • Oral voluntary phase
  • Pharyngeal phase
  • Esophageal phase

(a)Oral preparatory phase:

  • This phase involves mastication and formation of a bolus in the oral cavity.

(b)Oral voluntary phase:

  • It is characterized by propelling the bolus into the pharyngeal phase.
  • It is controlled by the corticobulbar tracts and cranial nerves V(trigemenal),VII(facial)and XII(hypoglossal).

(c)Pharyngeal phase:

  • This phase is a reflex
  • It is controlled by the cranial nerves V(trigemenal),X(vagus)XI(accessory) and, XII(hypoglossal).

(d)Esophageal phase:

Pathogenesis of Dysphagia

The pathogenesis of dysphagia can be explained on the basis of etiology. It can be

  • Physiological
  • Pathological

{{#ev:youtube|X4ryV6wGK1Y}}

Effect of aging on swallowing mechanism

Physiological dysphagia

Normal aging results in following changes in the swallowing mechanism:[6][7][8][9][10]

  • Reduced lingual movement
  • Delayed onset of the pharyngeal swallow
  • Delayed upper esophageal sphincter manometric relaxation during swallowing
  • Diminished pharyngolaryngeal sensory discrimination
  • Cerebral atrophy
  • Decreased nerve function
  • Decline in muscle mass

Pathological dysphagia

Following mechanisms can lead to pathological dysphagia.

1.Luminal Stenosis

Esophageal lumen can be narrowed by the following factors:[11][12][13][14]

  • Stricture
  • Inflammation
  • Web
  • Malignancy

2.Non-obstructing gastro-esophageal disease

Many patients that describe dysphagia will have normal investigations including UGE and high-resolution manometry (HRM), suggesting that a dysfunction of the somatosensory as opposed to neuromuscular apparatus might be present[15]

3.Primary motility disorder

The pathophysiological process in primary motility disorder is:[16][17][18][19]

  • An imbalance between inhibitory and excitatory neurons of the myenteric plexus at the distal oesophageal sphincter.
  • There is a decrement in inhibitory innervation (nitrous oxide, or vasoactive intestinal peptide) leading to aperistalsis. [20]
  • Failure of relaxation of the lower oesophageal sphincter during swallowing.[21]

4.Rheumatological conditions

The underlying pathophysiological mechanism of dysphagia in rheumatological conditions is as follows:[22][23]

  • The smooth muscle of the mid and lower oesophagus is replaced by fibrous tissue secondary to the underlying autoimmune pathology leading to incompetence of the lower oesophageal sphincter (LOS) and subsequently to GORD and dysphagia.

Examples:

  • CREST syndrome[24]
  • Sjogren’s syndrome[25]
  • Systemic lupus erythematosus (SLE)
  • Mixed connective tissue disease (MCTD)
  • Rheumatoid arthritis

5.Medication induced

A group of several medications can contribute to dysphagia by the following mechanism:[26][27][28][29]

  • They decrease the strength of lower oesophageal sphincter relaxation.
  • Reduction in lubrication by reduced saliva and impairment secondary peristalsis.
  • Compromise the airway patency and hence leading to the risk of aspiration. Finally, medications that have a local or systemic immunosuppressant effect can predispose to infective oesophagitis[60]. * Suppress the local and systemic immunity and predispose to infections.

Examples:

  • Antipsychotic, e.g., olanzapine, clozapine[30]
  • Tricyclic antidepressant, e.g., amitriptylin
  • Anticholinergic,
  • Opioids
  • Iron supplements
  • Potassium supplements
  • NSAIDs
  • Tetracyclines
  • Macrolides
  • Bisphosphonates
  • Calcium channel blockers
  • Nitrates
  • Alcohol
  • Theophylline

6.Neurological disorders

The pathology of neurogenic causes of dysphagia is as follows:

  • Predominanlty affect the oropharyngeal phase.
  • There is 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.
  • The central, autonomic or peripheral nervous system is affected by several neurological diseases such as:
    • Parkinsons disease
    • Myasthenia gravis
    • Motor neuron disease
    • Cerebrovascular accident
    • Multiple sclerosis
  • Dysphagia is common after 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.


The following table summarizes the mechanism, genetic association, gross pathology features and microscopic findings of common causes of dysphagia.

Cause of dysphagia Type of food Type of progression Pathophysiological changes Genetic association Gross pathology features Microscopic findings
Oropharyngeal dysphagia Soilds Liquids Intermittent/Progressive
•Zenker's diverticulum

•Webs

Yes No Progressive •Zenker's diverticulum(ZD): Diverticulum or a sac is seen in the esophagus
•Webs
•Neoplasm Yes Yes Progressive •Neoplasm
Myogenic causes

•Myasthenia gravis

•Connective tissue disorder

•Myotonic dystrophy

Neurogenic causes

•ALS

•Parkinsonism

•Stroke

Yes Yes Progressive
Esophageal dysphagia
•Pill esophagitis

•Caustic injury

•Chemotherapy

Yes No
•Strictures

•Esophageal Cancer

Yes No Progressive Esophageal stricture is the result of:[31][32] The following genes can be involved:
  • CTC1
  • DKC1
  • NHP2
  • NOP10
  • RTEL1
  • TERC
  • WRAP53
On gross pathology, circumferential thickening of the lower esophageal wall are characteristic finding of esophageal stricture due to gastroesophageal reflux disease.[33] On microscopic histopathological analysis, characteristic findings of esophageal stricture due to gastroesophageal reflux disease are:[37]
•Esophageal Cancer:

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
Squamous cell carcinoma or adenocarcinoma of the esophagus may appear as:[39]
  • Polypoid lesion 

Nuclear atypia of malignancy:

•Rings

•Webs

Yes No Intermittent Rings:

Webs: Multiple theories have been found:

•Achalasia

•Diffuse esophageal spasm(DES)

Yes Yes Intermittent •Achalasia:
•Diffuse esophageal spasm(DES):
  • Impairment of inhibitory myenteric plexus neurons
  • Dysregulation of endogenous NO synthesis or/and degradation
There is a genetic association between DES and achalasia[44] Gross thickening of muscularis propria layer and lower esophageal sphincter (LES) due to hyperplasia are characteristic findings of DES There is degeneration of vagal fibres, inflammatory infiltration of myenteric plexus, and hyperplasia of smooth muscles are characteristic findings of DES
•Scleroderma Yes Yes Progressive

Gallery

Zenkers diverticulum

Zenkers diverticulumSource: Libre Pathology

Esophageal cancer

Esophageal squamous cell carcinoma by Nephron - Own work BY-SA 3.0
Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0

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[45]


References

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