Dysphagia pathophysiology: Difference between revisions

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{{Dysphagia}}
{{Dysphagia}}


{{CMG}}{{AE}}{{FT}}
{{CMG}};{{AE}}{{FT}}
==Overview==
==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.
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.
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==Pathophysiology==
==Pathophysiology==
=== Physiology of normal swallowing ===
=== Physiology of normal swallowing ===
Anatomically, swallowing can be divided into three phases:<ref name="CookKahrilas1999">{{cite journal|last1=Cook|first1=Ian J.|last2=Kahrilas|first2=Peter J.|title=AGA technical review on management of oropharyngeal dysphagia|journal=Gastroenterology|volume=116|issue=2|year=1999|pages=455–478|issn=00165085|doi=10.1016/S0016-5085(99)70144-7}}</ref><ref name="pmid24772045">{{cite journal| author=Aslam M, Vaezi MF| title=Dysphagia in the elderly. | journal=Gastroenterol Hepatol (N Y) | year= 2013 | volume= 9 | issue= 12 | pages= 784-95 | pmid=24772045 | doi= | pmc=3999993 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24772045  }} </ref><ref name="pmid21915488">{{cite journal| author=Cassiani RA, Santos CM, Parreira LC, Dantas RO| title=The relationship between the oral and pharyngeal phases of swallowing. | journal=Clinics (Sao Paulo) | year= 2011 | volume= 66 | issue= 8 | pages= 1385-8 | pmid=21915488 | doi= | pmc=3161216 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21915488  }} </ref><ref name="pmid2333995">{{cite journal| author=Dantas RO, Kern MK, Massey BT, Dodds WJ, Kahrilas PJ, Brasseur JG et al.| title=Effect of swallowed bolus variables on oral and pharyngeal phases of swallowing. | journal=Am J Physiol | year= 1990 | volume= 258 | issue= 5 Pt 1 | pages= G675-81 | pmid=2333995 | doi=10.1152/ajpgi.1990.258.5.G675 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2333995  }} </ref>
Normal physiology of swallowing can be discussed under three phases:<ref name="CookKahrilas1999">{{cite journal|last1=Cook|first1=Ian J.|last2=Kahrilas|first2=Peter J.|title=AGA technical review on management of oropharyngeal dysphagia|journal=Gastroenterology|volume=116|issue=2|year=1999|pages=455–478|issn=00165085|doi=10.1016/S0016-5085(99)70144-7}}</ref><ref name="pmid24772045">{{cite journal| author=Aslam M, Vaezi MF| title=Dysphagia in the elderly. | journal=Gastroenterol Hepatol (N Y) | year= 2013 | volume= 9 | issue= 12 | pages= 784-95 | pmid=24772045 | doi= | pmc=3999993 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24772045  }} </ref><ref name="pmid21915488">{{cite journal| author=Cassiani RA, Santos CM, Parreira LC, Dantas RO| title=The relationship between the oral and pharyngeal phases of swallowing. | journal=Clinics (Sao Paulo) | year= 2011 | volume= 66 | issue= 8 | pages= 1385-8 | pmid=21915488 | doi= | pmc=3161216 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21915488  }} </ref><ref name="pmid2333995">{{cite journal| author=Dantas RO, Kern MK, Massey BT, Dodds WJ, Kahrilas PJ, Brasseur JG et al.| title=Effect of swallowed bolus variables on oral and pharyngeal phases of swallowing. | journal=Am J Physiol | year= 1990 | volume= 258 | issue= 5 Pt 1 | pages= G675-81 | pmid=2333995 | doi=10.1152/ajpgi.1990.258.5.G675 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2333995  }} </ref>
* 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:'''
* The [[esophagus]] is a part of the [[gastrointestinal tract]] which is responsible of moving [[Food|the food]] from the [[mouth]] to the [[rectum]].<ref name="pmid1606845">{{cite journal| author=Stein HJ, DeMeester TR| title=Outpatient physiologic testing and surgical management of foregut motility disorders. | journal=Curr Probl Surg | year= 1992 | volume= 29 | issue= 7 | pages= 413-555 | pmid=1606845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1606845  }}</ref>
* The esophagus has anti-reflux barrier which prevents the return of the [[acidic]] contentof the [[stomach]] back to the [[esophagus]]. The anti-reflux barrier consists of the [[lower esophageal sphincter]] (LES) and the related part of the [[diaphragm]]. 
* The [[lower esophageal sphincter]] is contracting [[smooth muscle]] at the end of the [[esophagus]] responsible for the food passage to the [[stomach]]. LES has high pressure tone which helps keeping it a strong barrier between the [[esophagus]] and the [[stomach]].
[[Image:GERD.png|250px|thumb|center|Source by:BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=44923646|]]


===Pathogenesis of Dysphagia===
==== '''<u>Oral phase</u>''' ====
The pathogenesis of dysphagia can be explained on the basis of etiology. It can be
* '''Preparatory phase:'''
* Physiological
** Preparatory phase involves [[mastication]] and formation of a [[bolus]] in the [[oral cavity]].
* Pathological
* '''Voluntary phase:'''
** Voluntary phase is characterized by propelling the bolus into the pharyngeal phase.
{{#ev:youtube|X4ryV6wGK1Y}}
** Voluntary phase is controlled by
*** [[Corticobulbar tract|Corticobulbar tracts]]
*** Cranial nerves [[Trigeminal nerve|V]], [[Facial Nerve|VII]], and [[Hypoglossal nerve|XII]].


===Effect of aging on swallowing mechanism===
==== '''<u>Pharyngeal phase:</u>''' ====
'''Physiological dysphagia'''
* Pharyngeal phase is a reflex mechanism and is controlled by the cranial nerves [[Trigeminal nerve|V]], [[Vagus nerve|X]], [[Glossopharyngeal nerve|XI]], and [[Hypoglossal nerve|XII]].


Normal aging results in following changes in the swallowing mechanism:<ref name="pmid3541821">{{cite journal| author=Masoro EJ| title=Biology of aging. Current state of knowledge. | journal=Arch Intern Med | year= 1987 | volume= 147 | issue= 1 | pages= 166-9 | pmid=3541821 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3541821  }} </ref><ref name="pmid25590391">{{cite journal| author=Carucci LR, Turner MA| title=Dysphagia revisited: common and unusual causes. | journal=Radiographics | year= 2015 | volume= 35 | issue= 1 | pages= 105-22 | pmid=25590391 | doi=10.1148/rg.351130150 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25590391  }} </ref><ref name="pmid8023945">{{cite journal| author=Cook IJ, Weltman MD, Wallace K, Shaw DW, McKay E, Smart RC et al.| title=Influence of aging on oral-pharyngeal bolus transit and clearance during swallowing: scintigraphic study. | journal=Am J Physiol | year= 1994 | volume= 266 | issue= 6 Pt 1 | pages= G972-7 | pmid=8023945 | doi=10.1152/ajpgi.1994.266.6.G972 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8023945  }} </ref><ref name="pmid7900799">{{cite journal| author=Shaw DW, Cook IJ, Gabb M, Holloway RH, Simula ME, Panagopoulos V et al.| title=Influence of normal aging on oral-pharyngeal and upper esophageal sphincter function during swallowing. | journal=Am J Physiol | year= 1995 | volume= 268 | issue= 3 Pt 1 | pages= G389-96 | pmid=7900799 | doi=10.1152/ajpgi.1995.268.3.G389 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7900799  }} </ref><ref name="EasterlingRobbins2008">{{cite journal|last1=Easterling|first1=Caryn S.|last2=Robbins|first2=Elizabeth|title=Dementia and Dysphagia|journal=Geriatric Nursing|volume=29|issue=4|year=2008|pages=275–285|issn=01974572|doi=10.1016/j.gerinurse.2007.10.015}}</ref>
==== '''<u>Esophageal phase:</u>''' ====
* Reduced lingual movement
* Once the bolus reaches esophageal phase, [[esophagus]] is responsible for moving the bolus along the [[upper gastrointestinal tract]] to initiate the process of [[digestion]] by delivering it to [[stomach]].<ref name="pmid1606845">{{cite journal| author=Stein HJ, DeMeester TR| title=Outpatient physiologic testing and surgical management of foregut motility disorders. | journal=Curr Probl Surg | year= 1992 | volume= 29 | issue= 7 | pages= 413-555 | pmid=1606845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1606845 }}</ref>
* Delayed onset of the pharyngeal swallow
* The [[esophagus]] has anti-reflux barrier which prevents the return of the [[acidic]] contents of the [[stomach]] back to the [[esophagus]].  
* Delayed upper esophageal sphincter manometric relaxation during swallowing
* The anti-reflux barrier is formed by the [[lower esophageal sphincter]] (LES) and a part of the [[diaphragm]].
* Diminished pharyngolaryngeal sensory discrimination
* The [[lower esophageal sphincter]] is contracting [[smooth muscle]] located at the end of the [[esophagus]].
* Cerebral atrophy
* Due to it's high pressure tone LES, acts as a strong barrier between the [[esophagus]] and the [[stomach]] contents.
* Decreased nerve function
[[Image:GERD.png|250px|thumb|center|Source by:BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=44923646|]]
* Decline in muscle mass
 
===Pathological dysphagia===
Following mechanisms can lead to pathological dysphagia.
 
===Luminal Stenosis===
Esophageal lumen can be narrowed by the following factors:<ref name="pmid23943072">{{cite journal| author=Starmer HM, Riley LH, Hillel AT, Akst LM, Best SR, Gourin CG| title=Dysphagia, short-term outcomes, and cost of care after anterior cervical disc surgery. | journal=Dysphagia | year= 2014 | volume= 29 | issue= 1 | pages= 68-77 | pmid=23943072 | doi=10.1007/s00455-013-9482-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23943072  }} </ref><ref name="pmid27840183">{{cite journal| author=Inayat F, Hussain Q, Shafique K| title=Dysphagia Caused by Extrinsic Esophageal Compression From Mediastinal Lymphadenopathy in Patients With Sarcoidosis. | journal=Clin Gastroenterol Hepatol | year= 2017 | volume= 15 | issue= 7 | pages= e119-e120 | pmid=27840183 | doi=10.1016/j.cgh.2016.11.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27840183  }} </ref><ref name="pmid16187198">{{cite journal| author=Oda K, Iwakiri R, Hara M, Watanabe K, Danjo A, Shimoda R et al.| title=Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor. | journal=Dig Dis Sci | year= 2005 | volume= 50 | issue= 10 | pages= 1921-6 | pmid=16187198 | doi=10.1007/s10620-005-2962-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16187198  }} </ref><ref name="pmid25341679">{{cite journal| author=Roman S, Kahrilas PJ| title=The diagnosis and management of hiatus hernia. | journal=BMJ | year= 2014 | volume= 349 | issue= | pages= g6154 | pmid=25341679 | doi=10.1136/bmj.g6154 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341679 }} </ref>
* Stricture
* Inflammation
* Web
* Malignancy
 
===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<ref name="pmid24990069">{{cite journal| author=Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR| title=Risk factors for eosinophilic esophagitis. | journal=Clin Exp Allergy | year= 2014 | volume= 44 | issue= 8 | pages= 1012-9 | pmid=24990069 | doi=10.1111/cea.12363 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24990069  }} </ref>
 
===Primary motility disorder===
The pathophysiological process in primary motility disorder is:
*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
*Failure of relaxation of the lower oesophageal sphincter during swallowing.
 
===Rheumatological conditions===
The underlying pathophysiological mechanism of dysphagia in rheumatological conditions is as follows:
*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.
 
===Medication induced===
===Neurological disorders===
 
The following table summarizes the mechanism, genetic association, gross pathology features and microscopic findings of each cause.  
{| class="wikitable"
!Cause of dysphagia
! colspan="2" |Type of food
!Type of progression
! rowspan="2" |Pathophysiological changes
! rowspan="2" |Genetic association
! rowspan="2" |Gross pathology features
! rowspan="2" |Microscopic findings
|-
|'''Oropharyngeal dysphagia'''
|'''Soilds'''
|'''Liquids'''
|'''Intermittent/Progressive'''
|-
| rowspan="2" |•Zenker's diverticulum
 
•Webs
| rowspan="2" |Yes
| rowspan="2" |No
| rowspan="2" |Progressive
|'''•Zenker's diverticulum(ZD):'''
* It is the result of [[Motor control|motor]] abnormalities of the [[esophagus]]


* [[Zenker's diverticulum|ZD]] is a defect over the [[Killian's dehiscence|Killian's triangle]], a point of [[Muscle weakness|weakness]] in the [[muscular]] wall of the [[hypopharynx]]
===Pathogenesis of physiological dysphagia===
* [[Killian's dehiscence|Killian's triangle]] is surrounded by the [[Cricopharyngeal muscle|cricopharyngeal]] [[sphincter]] and [[oblique]] fibers of the [[Inferior constrictor muscle|inferior constrictor]] of the [[pharyngeal]] [[muscle]]. 
Physiological dysphagia occurs as a result of normal aging. Normal aging results in certain changes that affect the swallowing mechanism which include:<ref name="pmid3541821">{{cite journal| author=Masoro EJ| title=Biology of aging. Current state of knowledge. | journal=Arch Intern Med | year= 1987 | volume= 147 | issue= 1 | pages= 166-9 | pmid=3541821 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3541821  }} </ref><ref name="pmid25590391">{{cite journal| author=Carucci LR, Turner MA| title=Dysphagia revisited: common and unusual causes. | journal=Radiographics | year= 2015 | volume= 35 | issue= 1 | pages= 105-22 | pmid=25590391 | doi=10.1148/rg.351130150 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25590391  }} </ref><ref name="pmid8023945">{{cite journal| author=Cook IJ, Weltman MD, Wallace K, Shaw DW, McKay E, Smart RC et al.| title=Influence of aging on oral-pharyngeal bolus transit and clearance during swallowing: scintigraphic study. | journal=Am J Physiol | year= 1994 | volume= 266 | issue= 6 Pt 1 | pages= G972-7 | pmid=8023945 | doi=10.1152/ajpgi.1994.266.6.G972 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8023945  }} </ref><ref name="pmid7900799">{{cite journal| author=Shaw DW, Cook IJ, Gabb M, Holloway RH, Simula ME, Panagopoulos V et al.| title=Influence of normal aging on oral-pharyngeal and upper esophageal sphincter function during swallowing. | journal=Am J Physiol | year= 1995 | volume= 268 | issue= 3 Pt 1 | pages= G389-96 | pmid=7900799 | doi=10.1152/ajpgi.1995.268.3.G389 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7900799  }} </ref><ref name="EasterlingRobbins2008">{{cite journal|last1=Easterling|first1=Caryn S.|last2=Robbins|first2=Elizabeth|title=Dementia and Dysphagia|journal=Geriatric Nursing|volume=29|issue=4|year=2008|pages=275–285|issn=01974572|doi=10.1016/j.gerinurse.2007.10.015}}</ref>
* ZD should be considered a pseudodiverticulum as it includes only [[Mucous membrane|mucosa]] and [[submucosa]].
* Reduced [[lingual]] movement.
|
* Delayed onset of the [[Pharynx|pharyngeal]] swallow.
|Diverticulum or a sac is seen in the esophagus
* Delayed [[upper esophageal sphincter]] relaxation during swallowing.
|
* Diminished [[Pharynx|pharyngo]]-[[Larynx|laryngeal]] response.
* Pseudo [[diverticulum]]
* Decreased [[Nerve|nerve function]].
* Only [[mucosa]] and [[submucosa]] present
* Decline in [[muscle mass]].
* [[Chronic]] [[submucosal]] [[inflammation]]
* [[Epithelial]] [[atypia]] or [[dysplasia]]
|-
|'''•Webs'''
|
|
|
|-
|•Neoplasm
|Yes
|Yes
|Progressive
|'''•Neoplasm'''
|
|
|
|-
|'''Myogenic causes'''
•Myasthenia gravis


•Connective tissue disorder
===Pathogenesis of pathological dysphagia===
Pathological dysphagia can occur as a result of the following mechanisms.


•Myotonic dystrophy
=====1. Luminal Stenosis=====
* Esophageal lumen can be narrowed by the following factors:<ref name="pmid23943072">{{cite journal| author=Starmer HM, Riley LH, Hillel AT, Akst LM, Best SR, Gourin CG| title=Dysphagia, short-term outcomes, and cost of care after anterior cervical disc surgery. | journal=Dysphagia | year= 2014 | volume= 29 | issue= 1 | pages= 68-77 | pmid=23943072 | doi=10.1007/s00455-013-9482-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23943072  }} </ref><ref name="pmid27840183">{{cite journal| author=Inayat F, Hussain Q, Shafique K| title=Dysphagia Caused by Extrinsic Esophageal Compression From Mediastinal Lymphadenopathy in Patients With Sarcoidosis. | journal=Clin Gastroenterol Hepatol | year= 2017 | volume= 15 | issue= 7 | pages= e119-e120 | pmid=27840183 | doi=10.1016/j.cgh.2016.11.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27840183  }} </ref><ref name="pmid16187198">{{cite journal| author=Oda K, Iwakiri R, Hara M, Watanabe K, Danjo A, Shimoda R et al.| title=Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor. | journal=Dig Dis Sci | year= 2005 | volume= 50 | issue= 10 | pages= 1921-6 | pmid=16187198 | doi=10.1007/s10620-005-2962-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16187198  }} </ref><ref name="pmid25341679">{{cite journal| author=Roman S, Kahrilas PJ| title=The diagnosis and management of hiatus hernia. | journal=BMJ | year= 2014 | volume= 349 | issue=  | pages= g6154 | pmid=25341679 | doi=10.1136/bmj.g6154 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341679  }} </ref>
** [[Stricture]]
** [[Inflammation]]
** [[Esophageal webs]]
** [[Esophageal cancer|Malignancy]]


'''Neurogenic causes'''
=====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.<ref name="pmid24990069">{{cite journal| author=Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR| title=Risk factors for eosinophilic esophagitis. | journal=Clin Exp Allergy | year= 2014 | volume= 44 | issue= 8 | pages= 1012-9 | pmid=24990069 | doi=10.1111/cea.12363 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24990069  }} </ref>
* Non-obstructive causes of dysphagia include:
** Motility disorders of esophagus
** Rheumatological conditions
** Medication induced dysphagia
** Neurological disorders


•ALS
===== Motility disorders of esophagus=====
* Motility disorder of esophagus occurs when there is an imbalance between inhibitory and excitatory neurons of the [[myenteric plexus]] at the [[Lower esophageal sphincter|distal esophageal sphincter]].<ref name="pmid24513804">{{cite journal| author=Xiao Y, Kahrilas PJ, Nicodème F, Lin Z, Roman S, Pandolfino JE| title=Lack of correlation between HRM metrics and symptoms during the manometric protocol. | journal=Am J Gastroenterol | year= 2014 | volume= 109 | issue= 4 | pages= 521-6 | pmid=24513804 | doi=10.1038/ajg.2014.13 | pmc=4120962 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24513804  }} </ref><ref name="pmid21480936">{{cite journal| author=Enestvedt BK, Williams JL, Sonnenberg A| title=Epidemiology and practice patterns of achalasia in a large multi-centre database. | journal=Aliment Pharmacol Ther | year= 2011 | volume= 33 | issue= 11 | pages= 1209-14 | pmid=21480936 | doi=10.1111/j.1365-2036.2011.04655.x | pmc=3857989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21480936  }} </ref><ref name="pmid1398223">{{cite journal| author=Howard PJ, Maher L, Pryde A, Cameron EW, Heading RC| title=Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh. | journal=Gut | year= 1992 | volume= 33 | issue= 8 | pages= 1011-5 | pmid=1398223 | doi= | pmc=1379432 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1398223  }} </ref><ref name="pmid25965233">{{cite journal| author=Pandolfino JE, Gawron AJ| title=Achalasia: a systematic review. | journal=JAMA | year= 2015 | volume= 313 | issue= 18 | pages= 1841-52 | pmid=25965233 | doi=10.1001/jama.2015.2996 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25965233  }} </ref>
*This imbalance results in a decrement of inhibitory innervation leading to [[Peristalsis|aperistalsis]].<ref name="pmid12850684">{{cite journal| author=Gockel I, Lord RV, Bremner CG, Crookes PF, Hamrah P, DeMeester TR| title=The hypertensive lower esophageal sphincter: a motility disorder with manometric features of outflow obstruction. | journal=J Gastrointest Surg | year= 2003 | volume= 7 | issue= 5 | pages= 692-700 | pmid=12850684 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12850684  }} </ref>
*Reduced inhibitory innervation also leads to failure of relaxation of the [[lower esophageal sphincter]] resulting in difficulty in swallowing ([[dysphagia]]).<ref name="pmid23877351">{{cite journal| author=Vaezi MF, Pandolfino JE, Vela MF| title=ACG clinical guideline: diagnosis and management of achalasia. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 8 | pages= 1238-49; quiz 1250 | pmid=23877351 | doi=10.1038/ajg.2013.196 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23877351  }} </ref>


•Parkinsonism
=====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.<ref name="pmid25796576">{{cite journal| author=Bredenoord AJ| title=Minor Disorders of Esophageal Peristalsis: Highly Prevalent, Minimally Relevant? | journal=Clin Gastroenterol Hepatol | year= 2015 | volume= 13 | issue= 8 | pages= 1424-5 | pmid=25796576 | doi=10.1016/j.cgh.2015.03.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25796576  }} </ref><ref name="pmid9009125">{{cite journal| author=Anselmino M, Zaninotto G, Costantini M, Ostuni P, Ianniello A, Boccú C et al.| title=Esophageal motor function in primary Sjögren's syndrome: correlation with dysphagia and xerostomia. | journal=Dig Dis Sci | year= 1997 | volume= 42 | issue= 1 | pages= 113-8 | pmid=9009125 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9009125  }} </ref>


•Stroke
* Most common rheumatological conditions associated with dysphagia include:
|Yes
**[[CREST syndrome]]<ref name="pmid25475597">{{cite journal| author=Carlson DA, Hinchcliff M, Pandolfino JE| title=Advances in the evaluation and management of esophageal disease of systemic sclerosis. | journal=Curr Rheumatol Rep | year= 2015 | volume= 17 | issue= 1 | pages= 475 | pmid=25475597 | doi=10.1007/s11926-014-0475-y | pmc=4343525 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25475597  }} </ref>
|Yes
**[[Sjögren's syndrome|Sjogren’s syndrome]]<ref name="pmid22590983">{{cite journal| author=Tang DM, Pathikonda M, Harrison M, Fisher RS, Friedenberg FK, Parkman HP| title=Symptoms and esophageal motility based on phenotypic findings of scleroderma. | journal=Dis Esophagus | year= 2013 | volume= 26 | issue= 2 | pages= 197-203 | pmid=22590983 | doi=10.1111/j.1442-2050.2012.01349.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22590983  }} </ref>
|Progressive
**[[Systemic lupus erythematosus]] ([[SLE]])
|
**[[Mixed connective tissue disease]] [[Mixed connective tissue disease|(MCTD]])
|
**[[Rheumatoid arthritis]]
|
|
|-
|'''Esophageal dysphagia'''
|
|
|
|
|
|
|
|-
|•Pill esophagitis
•Caustic injury


•Chemotherapy
=====Medication induced=====
|Yes
* Medications can contribute to dysphagia by making peristalsis difficult either by:<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>
|No
** Decreasing the strength of lower esophageal sphincter relaxation.
|
** Reducing the lubrication of esophageal lumen by decreasing the salivary secretions.
|
* Some medications also have a local or systemic immunosuppressant effect can predispose to infective oesophagitis.  
|
** [[Antipsychotics]],<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]]
|
**[[Anticholinergics|Anticholinergic]]
|-
**[[Opioids]]
| rowspan="2" |•Strictures
**[[Iron supplements]]
•Esophageal Cancer
**[[Potassium chloride|Potassium supplements]]
| rowspan="2" |Yes
**[[NSAIDs]]
| rowspan="2" |No
**[[Tetracyclines]]
| rowspan="2" |Progressive
**[[Macrolides]]
|Esophageal stricture is the result of:<ref name=":0">{{cite book | last = Holzheimer | first = R | title = Surgical treatment : evidence-based and problem-oriented | publisher = Zuckschwerdt | location = München New York | year = 2001 | isbn = 3-88603-714-2 }}</ref><ref name="pmid24640761">{{cite journal |vauthors=Belevich VL, Ovchinnikov DV |title=[Treatment of benign esophageal stricture] |language=Russian |journal=Vestn. Khir. Im. I. I. Grek. |volume=172 |issue=5 |pages=111–4 |year=2013 |pmid=24640761 |doi= |url=}}</ref>
**[[Bisphosphonates]]
*Lower pressure of [[esophageal sphincter]] in [[gastroesophageal reflux disease]]
**[[Calcium channel blocker|Calcium channel blockers]]
**[[Nitrates]]
**[[Alcohol]]
**[[Theophylline]]


*[[Esophageal]] motor disorders
=====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.<ref name="pmid26970760">{{cite journal| author=Takizawa C, Gemmell E, Kenworthy J, Speyer R| title=A Systematic Review of the Prevalence of Oropharyngeal Dysphagia in Stroke, Parkinson's Disease, Alzheimer's Disease, Head Injury, and Pneumonia. | journal=Dysphagia | year= 2016 | volume= 31 | issue= 3 | pages= 434-41 | pmid=26970760 | doi=10.1007/s00455-016-9695-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26970760  }} </ref><ref name="pmid16269630">{{cite journal| author=Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R| title=Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. | journal=Stroke | year= 2005 | volume= 36 | issue= 12 | pages= 2756-63 | pmid=16269630 | doi=10.1161/01.STR.0000190056.76543.eb | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16269630  }} </ref><ref name="pmid10594255">{{cite journal| author=Martino R, Pron G, Diamant N| title=Screening for oropharyngeal dysphagia in stroke: insufficient evidence for guidelines. | journal=Dysphagia | year= 2000 | volume= 15 | issue= 1 | pages= 19-30 | pmid=10594255 | doi=10.1007/s004559910006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10594255  }} </ref>
*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:
** [[Parkinson's disease|Parkinsons disease]]
** [[Myasthenia gravis]]
** [[Motor neuron disease]]
** [[Cerebrovascular accident]]
** [[Multiple sclerosis]]


*[[Inflammation]] and [[fibrosis]] due to intrinsic diseases of [[esophagus]], such as[[neoplasia]]
== Genetics ==
The following genes can be involved in the development of dysphagia subsequent to different pathologies:
* ''[[ACD (gene)|ACD]]''


*Surgical esophageal [[anastomosis]]
* ''CTC1''


*[[Esophageal]] compression by other organs
* ''DKC1 ''
|The following genes can be involved:
*''[[ACD (gene)|ACD]]''


*''CTC1''
* ''NHP2''


*''DKC1 ''
* ''NOP10''


*''NHP2''
* ''[[PARN]]''


*''NOP10''
* ''RTEL1''


*''[[PARN]]''
* ''TERC''


*''RTEL1''
* ''[[TERT]]''


*''TERC''
* ''[[TINF2]]''


*''[[TERT]]''
* ''WRAP53''
 
*''[[TINF2]]''
 
*''WRAP53 ''
|On [[gross pathology]], circumferential thickening of the lower [[esophageal]] wall are characteristic finding of esophageal stricture due to [[gastroesophageal reflux disease]].<ref name="YamasakiOzawa2016">{{cite journal|last1=Yamasaki|first1=Yasushi|last2=Ozawa|first2=Soji|last3=Oguma|first3=Junya|last4=Kazuno|first4=Akihito|last5=Ninomiya|first5=Yamato|title=Long peptic strictures of the esophagus due to reflux esophagitis: a case report|journal=Surgical Case Reports|volume=2|issue=1|year=2016|issn=2198-7793|doi=10.1186/s40792-016-0190-1}}</ref>
*Pale [[mucosa]] with white [[exudate]] in [[lymphocytic]] [[esophagitis]]<ref name="MaejimaUno2016">{{cite journal|last1=Maejima|first1=Ryuhei|last2=Uno|first2=Kaname|last3=Iijima|first3=Katsunori|last4=Fujishima|first4=Fumiyoshi|last5=Noguchi|first5=Tetsuya|last6=Ara|first6=Nobuyuki|last7=Asano|first7=Naoki|last8=Koike|first8=Tomoyuki|last9=Imatani|first9=Akira|last10=Shimosegawa|first10=Tooru|title=A Japanese case of lymphocytic esophagitis|journal=Digestive Endoscopy|volume=28|issue=4|year=2016|pages=476–480|issn=09155635|doi=10.1111/den.12578}}</ref>
 
*[[Swelling]] and [[hemorrhagic]] [[congestion]] in [[caustic]] ingestion<ref name="Contini2013">{{cite journal|last1=Contini|first1=Sandro|title=Caustic injury of the upper gastrointestinal tract: A comprehensive review|journal=World Journal of Gastroenterology|volume=19|issue=25|year=2013|pages=3918|issn=1007-9327|doi=10.3748/wjg.v19.i25.3918}}</ref>
 
*Multiple yellow [[plaque]]<nowiki/>s in infectious [[esophagitis]] due to ''Candida''<ref name="pmid24719600">{{cite journal |vauthors=Wilcox CM |title=Overview of infectious esophagitis |journal=Gastroenterol Hepatol (N Y) |volume=9 |issue=8 |pages=517–9 |year=2013 |pmid=24719600 |pmc=3980995 |doi= |url=}}</ref>
 
*Ulceration of the [[esophagus]] in [[viral]] [[esophagitis]]
|On [[microscopic]] [[histopathological]] analysis, characteristic findings of esophageal stricture due to [[gastroesophageal reflux disease]] are:<ref name="urlEsophageal stricture - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/Esophageal_stricture |title=Esophageal stricture - Libre Pathology |format= |work= |accessdate=}}</ref>
* Intraepithelial [[lymphocyte|lymphocytosi]]s
* [[Basal cell]] [[hyperplasia]]
* [[Ulceration]] <ref name="YamasakiOzawa20162" />
|-
|•Esophageal Cancer:
|
Mutations in the following genes can cause esophageal cancer:
Mutations in the following genes can cause esophageal cancer:
* Chromosomal losses (4q, 5q, 9p, and 18q)
* Chromosomal losses (4q, 5q, 9p, and 18q)
Line 222: Line 132:
* [[P53 (protein)|PT53]] genes and [[P16 (gene)|P16]] genes 
* [[P53 (protein)|PT53]] genes and [[P16 (gene)|P16]] genes 
* Variants in ADH and/or ALDH2 genes
* Variants in ADH and/or ALDH2 genes
|[[Squamous cell carcinoma]] or [[adenocarcinoma]] of the [[esophagus]] may appear as:<ref>{{cite book | last = Sugarbaker | first = David | title = Adult chest surgery | publisher = McGraw-Hill Education | location = New York | year = 2015 | isbn = 0071781897 }}</ref>
*Flat and irregular [[plaque]]


*Polypoid lesion 
* HLA class II molecules
* [[Vasoactive intestinal peptide]]
* [[CD117|KIT]]
* [[Interleukin]] 23 receptor
 
== Associated Conditions ==
Common conditions associated with dysphagia include:
*[[Stricture|Peptic stricture]]
*Esophageal rings and webs
*[[Esophageal cancer]]
*[[Achalasia]]
*Spastic motility disorders
*[[Diffuse esophageal spasm]]
*[[Nutcracker esophagus]]
*Hypertensive lower esophageal sphincter
*Nonspecific spastic esophageal motility disorders
 
== 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:


*[[Ulcer|Ulcerating]], fungating mass.
'''Zenkers diverticulum:'''
*Location:
* Diverticulum or a sac is seen in the esophagus
*[[Squamous cell carcinoma]] is usually found in the mid-third of the [[esophagus]].
'''Esophageal stricture:'''
*[[Adenocarcinoma]] is usually found in the lower third of the [[esophagus]] near the gastric opening.
* Pale [[mucosa]] with white [[exudate]] in [[lymphocytic]] [[esophagitis]]
|


====Nuclear [[atypia]] of malignancy:====
* [[Swelling]] and [[hemorrhagic]] [[congestion]] in [[caustic]] ingestion
*Found in both types:<ref>{{Cite web | title =Squamous cell carcinoma of the esophagus| url =http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_esophagus }}</ref>
*[[Poikilocytosis|Poikilocytosis]]
*[[Anisocytosis|Anisocytosis]]
*[[Staining|Staining variation]]
*[[Mitosis|Mitotic activity]]
|-
|•Rings
•Webs
|Yes
|No
|Intermittent
|'''Rings:'''
'''Webs:''' Multiple theories have been found:
* Webs may form due to the chronic damage to the [[Mucosa|esophageal mucosa]]
* Or due to failure of the [[esophagus]] to recanalize.
|
|
|
|-
| rowspan="2" |•Achalasia


•Diffuse esophageal spasm(DES)
* Multiple yellow [[plaque]]<nowiki/>s in infectious [[esophagitis]] due to ''Candida''
| rowspan="2" |Yes
| rowspan="2" |Yes
| rowspan="2" |Intermittent
|'''•Achalasia''':
*[[Pathology|Pathological]] examination reveals a defect in the nerves that control the motility of the esophagus (the [[myenteric plexus]]). 


*The esophagus is dilated and [[hypertrophy|hypertrophied]].
* Ulceration of the [[esophagus]] in [[viral]] [[esophagitis]]
|
'''Esophageal cancer:'''
* HLA class II molecules[[Vasoactive intestinal peptide]]<ref name="pmid19309439">{{cite journal| author=Paladini F, Cocco E, Cascino I, Belfiore F, Badiali D, Piretta L et al.| title=Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene. | journal=Neurogastroenterol Motil | year= 2009 | volume= 21 | issue= 6 | pages= 597-602 | pmid=19309439 | doi=10.1111/j.1365-2982.2009.01284.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19309439  }} </ref>
 
* [[CD117|KIT]]<ref name="pmid21951831">{{cite journal| author=Alahdab YO, Eren F, Giral A, Gunduz F, Kedrah AE, Atug O et al.| title=Preliminary evidence of an association between the functional c-kit rs6554199 polymorphism and achalasia in a Turkish population. | journal=Neurogastroenterol Motil | year= 2012 | volume= 24 | issue= 1 | pages= 27-30 | pmid=21951831 | doi=10.1111/j.1365-2982.2011.01793.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21951831  }} </ref>
[[Squamous cell carcinoma]] or [[adenocarcinoma]] of the [[esophagus]] may appear as:
* [[Interleukin]] 23 receptor<ref name="pmid20367798">{{cite journal| author=de León AR, de la Serna JP, Santiago JL, Sevilla C, Fernández-Arquero M, de la Concha EG et al.| title=Association between idiopathic achalasia and IL23R gene. | journal=Neurogastroenterol Motil | year= 2010 | volume= 22 | issue= 7 | pages= 734-8, e218 | pmid=20367798 | doi=10.1111/j.1365-2982.2010.01497.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20367798  }} </ref>|
* Flat and irregular [[plaque]]
|
 
* Polypoid lesion 
 
* [[Ulcer|Ulcerating]], fungating mass.
* Location:
* [[Squamous cell carcinoma]] is usually found in the mid-third of the [[esophagus]].
* [[Adenocarcinoma]]<nowiki/>is usually found in the lower third of the [[esophagus]] near the gastric opening.
'''Achalasia:'''
* There is defect in the nerves that control the motility of the esophagus (the [[myenteric plexus]]). 
* There is defect in the nerves that control the motility of the esophagus (the [[myenteric plexus]]). 
* The esophagus is dilated and [[Hypertrophy|hypertrophied]].
* The esophagus is dilated and [[Hypertrophy|hypertrophied]].
|-
'''Diffuse esophageal spasm(DES):'''
|'''•Diffuse esophageal spasm(DES):'''
* Impairment of inhibitory myenteric plexus neurons


* Dysregulation of endogenous NO synthesis or/and degradation
Gross thickening of muscularis propria layer and lower esophageal sphincter (LES) due to hyperplasia are characteristic findings of DES.
|There is a genetic association between DES and achalasia<ref name="pmid3061886">{{cite journal| author=Frieling T, Berges W, Borchard F, Lübke HJ, Enck P, Wienbeck M| title=Family occurrence of achalasia and diffuse spasm of the oesophagus. | journal=Gut | year= 1988 | volume= 29 | issue= 11 | pages= 1595-602 | pmid=3061886 | doi= | pmc=1433819 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3061886  }}</ref>
|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===


[[File:Micro Zenker.jpg|thumb|none|372x372px|Zenkers diverticulum[https://librepathology.org/wiki/File:Pharyngoesophageal_diverticulum_-_alt_--_very_low_mag.jpg Source: Libre Pathology]]]
== Microscopic Pathology ==


===Esophageal cancer===
[[Image:ssc.jpg|thumb|centre|1000px|Esophageal squamous cell carcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31284085]]
[[Image:Ac.jpg|thumb|centre|1000px|Esophageal adenocarcinoma by Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12475495]]
===Esophagitis===
===Esophagitis===
[[Image:Eosinophilic esophagiits path.jpg|thumb|centre|150px|[[H&E]] stain of [[esophagus]] [[biopsy]] showing eosinophilic esophagitis, manifested by an infiltration of [[eosinophils]] in the [[lamina propria]]]]
[[Image:Eosinophilic esophagiits path.jpg|thumb|left|150px|[[H&E]] stain of [[esophagus]] [[biopsy]] showing eosinophilic esophagitis, manifested by an infiltration of [[eosinophils]] in the [[lamina propria]]]]
<br clear="left" />
 
===Esophageal stricture===
===Esophageal stricture===
[[File:Esophagus path.jpg|300px|thumb|centre|Esophageal stricture <"https://commons.wikimedia.org/wiki/File%3ATinci%C3%B3n_hematoxilina-eosina.jpg"> via Wikimedia Commons<nowiki></ref></nowiki>]]
[[File:Esophagus path.jpg|300px|thumb|left|Esophageal stricture <"https://commons.wikimedia.org/wiki/File%3ATinci%C3%B3n_hematoxilina-eosina.jpg"> via Wikimedia Commons<nowiki></ref></nowiki>]]
[[File:Esophageal stricture due to GERD.png|300px|thumb|centre|Esophageal stricture due to GERD, via wikipedia.org<ref>From en.wikipedia.org, Public Domain, <"https://commons.wikimedia.org/w/index.php?curid=1931423"></ref>]]
<br clear="left" />
 
[[File:Esophageal stricture due to GERD.png|300px|thumb|left|Esophageal stricture due to GERD, via wikipedia.org<ref>From en.wikipedia.org, Public Domain, <"https://commons.wikimedia.org/w/index.php?curid=1931423"></ref>]]
<br clear="left" />


==References==
==References==
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Latest revision as of 21:30, 29 July 2020

Dysphagia Microchapters

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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

  1. Cook, Ian J.; Kahrilas, Peter J. (1999). "AGA technical review on management of oropharyngeal dysphagia". Gastroenterology. 116 (2): 455–478. doi:10.1016/S0016-5085(99)70144-7. ISSN 0016-5085.
  2. Aslam M, Vaezi MF (2013). "Dysphagia in the elderly". Gastroenterol Hepatol (N Y). 9 (12): 784–95. PMC 3999993. PMID 24772045.
  3. Cassiani RA, Santos CM, Parreira LC, Dantas RO (2011). "The relationship between the oral and pharyngeal phases of swallowing". Clinics (Sao Paulo). 66 (8): 1385–8. PMC 3161216. PMID 21915488.
  4. Dantas RO, Kern MK, Massey BT, Dodds WJ, Kahrilas PJ, Brasseur JG; et al. (1990). "Effect of swallowed bolus variables on oral and pharyngeal phases of swallowing". Am J Physiol. 258 (5 Pt 1): G675–81. doi:10.1152/ajpgi.1990.258.5.G675. PMID 2333995.
  5. Stein HJ, DeMeester TR (1992). "Outpatient physiologic testing and surgical management of foregut motility disorders". Curr Probl Surg. 29 (7): 413–555. PMID 1606845.
  6. Masoro EJ (1987). "Biology of aging. Current state of knowledge". Arch Intern Med. 147 (1): 166–9. PMID 3541821.
  7. Carucci LR, Turner MA (2015). "Dysphagia revisited: common and unusual causes". Radiographics. 35 (1): 105–22. doi:10.1148/rg.351130150. PMID 25590391.
  8. Cook IJ, Weltman MD, Wallace K, Shaw DW, McKay E, Smart RC; et al. (1994). "Influence of aging on oral-pharyngeal bolus transit and clearance during swallowing: scintigraphic study". Am J Physiol. 266 (6 Pt 1): G972–7. doi:10.1152/ajpgi.1994.266.6.G972. PMID 8023945.
  9. Shaw DW, Cook IJ, Gabb M, Holloway RH, Simula ME, Panagopoulos V; et al. (1995). "Influence of normal aging on oral-pharyngeal and upper esophageal sphincter function during swallowing". Am J Physiol. 268 (3 Pt 1): G389–96. doi:10.1152/ajpgi.1995.268.3.G389. PMID 7900799.
  10. Easterling, Caryn S.; Robbins, Elizabeth (2008). "Dementia and Dysphagia". Geriatric Nursing. 29 (4): 275–285. doi:10.1016/j.gerinurse.2007.10.015. ISSN 0197-4572.
  11. Starmer HM, Riley LH, Hillel AT, Akst LM, Best SR, Gourin CG (2014). "Dysphagia, short-term outcomes, and cost of care after anterior cervical disc surgery". Dysphagia. 29 (1): 68–77. doi:10.1007/s00455-013-9482-9. PMID 23943072.
  12. Inayat F, Hussain Q, Shafique K (2017). "Dysphagia Caused by Extrinsic Esophageal Compression From Mediastinal Lymphadenopathy in Patients With Sarcoidosis". Clin Gastroenterol Hepatol. 15 (7): e119–e120. doi:10.1016/j.cgh.2016.11.010. PMID 27840183.
  13. Oda K, Iwakiri R, Hara M, Watanabe K, Danjo A, Shimoda R; et al. (2005). "Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor". Dig Dis Sci. 50 (10): 1921–6. doi:10.1007/s10620-005-2962-5. PMID 16187198.
  14. Roman S, Kahrilas PJ (2014). "The diagnosis and management of hiatus hernia". BMJ. 349: g6154. doi:10.1136/bmj.g6154. PMID 25341679.
  15. Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR (2014). "Risk factors for eosinophilic esophagitis". Clin Exp Allergy. 44 (8): 1012–9. doi:10.1111/cea.12363. PMID 24990069.
  16. Xiao Y, Kahrilas PJ, Nicodème F, Lin Z, Roman S, Pandolfino JE (2014). "Lack of correlation between HRM metrics and symptoms during the manometric protocol". Am J Gastroenterol. 109 (4): 521–6. doi:10.1038/ajg.2014.13. PMC 4120962. PMID 24513804.
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  27. Philpott-Howard JN, Wade JJ, Mufti GJ, Brammer KW, Ehninger G (1993). "Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group". J Antimicrob Chemother. 31 (6): 973–84. PMID 8360134.
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  34. From en.wikipedia.org, Public Domain, <"https://commons.wikimedia.org/w/index.php?curid=1931423">

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