Fibromuscular dysplasia pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(40 intermediate revisions by 2 users not shown)
Line 2: Line 2:
{{Fibromuscular dysplasia}}
{{Fibromuscular dysplasia}}


 
{{CMG}}; {{AE}} {{M.B}}
{{CMG}}; {{AE}} Shantanu Sinha, MD,FACC


==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
In Fibromuscular dysplasia, the proliferation of [[vascular smooth muscle]] of one or more small or medium-sized [[arteries]] undergo [[dysplasia]] and cause [[stenosis]]. this [[abnormal]] [[cellular]] [[development]] is characterized by [[fibrous]] thickening of the [[Tunica intima|intima]], [[Tunica media|media]], or [[adventitia]] of the involved arteries; which ultimately lead to arterial narrowing. Despite numerous [[genetic]], [[hormonal]] and mechanical factors have been proposed, the [[etiology]] of fibromuscular dysplasia remains unknown.  


OR
==Pathophysiology==
In Fibromuscular dysplasia, [[the proliferation]] of [[vascular smooth muscle]] of one or more small or medium-sized [[arteries]] undergo [[dysplasia]] and cause [[stenosis]]. this [[abnormal]] [[cellular]] [[development]] is characterized by [[fibrous]] thickening of the [[tunica intima|intima]], [[tunica media|media]], or [[adventitia]] of the involved arteries; which ultimately lead to arterial narrowing.


It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
===Pathogenesis===
Despite numerous [[genetic]], [[hormonal]] and mechanical factors have been proposed, the [[etiology]] of fibromuscular dysplasia remains unknown. A variety of factors have been implicated. These include:
* Cigarette smoking and a history of [[hypertension]]<ref>{{Cite journal
| author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
| title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
| journal = [[Hypertension (Dallas, Tex. : 1979)]]
| volume = 14
| issue = 5
| pages = 472–479
| year = 1989
| month = November
| pmid = 2680961
}}</ref>
* Genetic factors, with a reported [[autosomal mode]] of [[inheritance]] in some families.<ref>{{Cite journal
| author = [[J. Perdu]], [[P. Boutouyrie]], [[C. Bourgain]], [[N. Stern]], [[B. Laloux]], [[E. Bozec]], [[M. Azizi]], [[C. Bonaiti-Pellie]], [[P.-F. Plouin]], [[S. Laurent]], [[A.-P. Gimenez-Roqueplo]] & [[X. Jeunemaitre]]
| title = Inheritance of arterial lesions in renal fibromuscular dysplasia
| journal = [[Journal of human hypertension]]
| volume = 21
| issue = 5
| pages = 393–400
| year = 2007
| month = May
| doi = 10.1038/sj.jhh.1002156
| pmid = 17330059
}}</ref>


OR
*Some studies suggest fibromuscular dysplasia is a systemic disease with altered [[TGF-β]] expression and [[connective tissue]] features.


[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
* Hormonal influence, The increased incidence of FMD in women as compared with men suggests a possible hormonal given the predominance in women of childbearing age but no association has been found      between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones.<ref>{{Cite journal
| author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
| title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
| journal = [[Hypertension (Dallas, Tex. : 1979)]]
| volume = 14
| issue = 5
| pages = 472–479
| year = 1989
| month = November
| pmid = 2680961
}}</ref>


OR
* Some authors have proposed the sex difference to be related to immune system functioning, but overt inflammation, as is observed in most classic autoimmune diseases, is histologically lacking.
* Mechanical factors due to  stretching of [[smooth muscle cells]] and microtrauma to the vessel wall.
* [[Ischemia]] due to fibrotic occlusion of the [[vasa vasorum]].


Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
==Genetics==
*[[Genetic predisposition]] may play a role in the [[development]] of fibromuscular dysplasia. Owing to, FMD is more common among the first-degree relatives of patients with this condition.


OR
*Some studies showed an [[autosomal dominant]] transmission pattern for fibromuscular dysplasia; however, as of yet, no etiologic genes have been identified for this disease. Applying [[molecular genetics]] investigations will reveal information about FMD [[pathogenesis]], and family-based studies, evaluating [[genome]] of candidates, and wide [[genome]] studies can help to recognize [[pathophysiology]] of FMD.


*In the US Registry, about eight percent of patients report a confirmed diagnosis of FMD in one or more in first- or second-degree family members. However, the high prevalence of aneurysms, sudden death, and stroke among first- and second-degree family members in the US Registry shows that FMD may be associated with systemic arteriopathy with a great diversity of clinical phenotype traits. It is hypothesized that FMD may have common features with vascular connective tissue diseases, such as [[Loeys-Dietz syndrome]] or the vascular type of [[Ehlers-Danlos syndrome]].


[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*Increased level of [[TGF-β]]1 and 2 secreted by [[fibroblasts]] in patients with FMD in comparison to matched 
FMD patients also had elevated plasma levels of circulating [[TGF-β]]1 and [[TGF-β]]2 relative to matched controls. The potential involvement of TGF-b pathways in the [[pathogenesis]] of FMD is an area for future investigation, especially as this pathway could provide a potential target for disease-modifying medical therapies.<ref>{{Cite journal
| author = [[Santhi K. Ganesh]], [[Rachel Morissette]], [[Zhi Xu]], [[Florian Schoenhoff]], [[Benjamin F. Griswold]], [[Jiandong Yang]], [[Lan Tong]], [[Min-Lee Yang]], [[Kristina Hunker]], [[Leslie Sloper]], [[Shinie Kuo]], [[Rafi Raza]], [[Dianna M. Milewicz]], [[Clair A. Francomano]], [[Harry C. Dietz]], [[Jennifer Van Eyk]] & [[Nazli B. McDonnell]]
| title = Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-beta expression and connective tissue features
| journal = [[FASEB journal : official publication of the Federation of American Societies for Experimental Biology]]
| volume = 28
| issue = 8
| pages = 3313–3324
| year = 2014
| month = August
| doi = 10.1096/fj.14-251207
| pmid = 24732132
}}</ref>
   
*[[Polymorphisms]] of angiotensin-converting–enzyme allele ACE-I among patients with multifocal renal arterial fibromuscular
dysplasia has been investigated.<ref>{{Cite journal
| author = [[A. Bofinger]], [[C. Hawley]], [[P. Fisher]], [[N. Daunt]], [[M. Stowasser]] & [[R. Gordon]]
| title = Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia
| journal = [[Journal of human hypertension]]
| volume = 15
| issue = 3
| pages = 185–190
| year = 2001
| month = March
| doi = 10.1038/sj.jhh.1001144
| pmid = 11317203
}}</ref>


OR
*In some case reports, the association of FMD with neurofibromatosis, Alport syndrome, and pheochromocytoma have been considered; And [[mutations]] in [[collagen]], and with [[alpha1-antitrypsin deficiency]] have also been suggested.<ref>{{Cite journal
| author = [[David P. Slovut]] & [[Jeffrey W. Olin]]
| title = Fibromuscular dysplasia
| journal = [[The New England journal of medicine]]
| volume = 350
| issue = 18
| pages = 1862–1871
| year = 2004
| month = April
| doi = 10.1056/NEJMra032393
| pmid = 15115832
}}</ref><ref>{{Cite journal
| author = [[G. Tromp]], [[Y. Wu]], [[D. J. Prockop]], [[S. L. Madhatheri]], [[C. Kleinert]], [[J. J. Earley]], [[J. Zhuang]], [[O. Norrgard]], [[R. C. Darling]] & [[W. M. Abbott]]
| title = Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms
| journal = [[The Journal of clinical investigation]]
| volume = 91
| issue = 6
| pages = 2539–2545
| year = 1993
| month = June
| doi = 10.1172/JCI116490
| pmid = 8514866
}}</ref><ref>{{Cite journal
| author = [[W. I. Schievink]], [[F. B. Meyer]], [[J. E. Parisi]] & [[E. F. Wijdicks]]
| title = Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency
| journal = [[Neurosurgery]]
| volume = 43
| issue = 2
| pages = 229–233
| year = 1998
| month = August
| pmid = 9696074
}}</ref>


The progression to [disease name] usually involves the [molecular pathway].
==Associated Conditions==
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
 
==Pathophysiology==
In individuals with FMD, the walls of one or more arteries undergo [[dysplasia]].  Due to this abnormal cellular development, the vessels may become [[stenosis|stenosed]].  A sufficient decrease in blood flow through the artery can cause symptoms.  Fibromuscular dysplasia is characterized by fibrous thickening of the [[tunica intima|intima]], [[tunica media|media]], or [[adventitia]] of the [[renal artery]]. Up to 75% of all patients with FMD will have disease in the renal arteries. The lesions cause narrowing of the artery [[lumen (anatomy)|lumen]]. The second most common artery affected is the [[carotid]] artery, which is found in the neck and supplies the brain with blood.  Less commonly, FMD affects the arteries in the abdomen (supplying the [[liver]], [[spleen]] and [[intestines]]) and extremities (legs and arms).  More than one artery may have evidence of FMD in 28% of people with this disease. All arteries should be checked if FMD is found in one vascular bed. As a result of renal artery stenosis, the kidney's [[afferent arteriole|afferent arteriolar]] pressure falls.  The [[renin-angiotensin system]] is activated, causing fluid retention and [[hypertension]].


===Pathogenesis===
*The underlying [[connective tissue]] problem among [[arteries]] with FMD, causes weakening of [[arterial wall]] and leads to [[vessel]] [[dilatation]].The combined prevalence of aneurysms and FMD is estimated to be about 8%.
*The exact pathogenesis of [disease name] is not fully understood.
OR
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Genetics==
*FMD is a predisposing factor  for spontaneous [[cervical carotid]], or renal artery  [[dissections]]. [[Dissection]] through the weakening of the arterial wall, in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.
*[Disease name] is transmitted in [mode of genetic transmission] pattern.
*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
*The development of [disease name] is the result of multiple genetic mutations.
 
==Associated Conditions==


==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On gross pathology, focal, irregular, thickening in medium and large muscular arteries are characteristic findings of FMD.


==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, circumferential or eccentric deposition of collagen in intima but no lipid or inflammatory component are characteristic findings of FMD.
[[File:FMD..jpg||none|600px|thumb|Microscopic pathology Source:Librepathology]]


==References==
==References==

Latest revision as of 18:56, 30 August 2018

Fibromuscular dysplasia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Fibromuscular dysplasia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiorgram

X-ray

CT

MRI

Arteriography

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Management Guidelines

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

ASA/ACCF/AHA Guideline Recommendations

Management of Patients With Fibromuscular Dysplasia of the Extracranial Carotid Arteries

Case Studies

Case #1

Fibromuscular dysplasia pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Fibromuscular dysplasia pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Fibromuscular dysplasia pathophysiology

CDC on Fibromuscular dysplasia pathophysiology

Fibromuscular dysplasia pathophysiology in the news

Blogs on Fibromuscular dysplasia pathophysiology

Directions to Hospitals Treating Fibromuscular dysplasia

Risk calculators and risk factors for Fibromuscular dysplasia pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohsen Basiri M.D.

Overview

In Fibromuscular dysplasia, the proliferation of vascular smooth muscle of one or more small or medium-sized arteries undergo dysplasia and cause stenosis. this abnormal cellular development is characterized by fibrous thickening of the intima, media, or adventitia of the involved arteries; which ultimately lead to arterial narrowing. Despite numerous genetic, hormonal and mechanical factors have been proposed, the etiology of fibromuscular dysplasia remains unknown.

Pathophysiology

In Fibromuscular dysplasia, the proliferation of vascular smooth muscle of one or more small or medium-sized arteries undergo dysplasia and cause stenosis. this abnormal cellular development is characterized by fibrous thickening of the intima, media, or adventitia of the involved arteries; which ultimately lead to arterial narrowing.

Pathogenesis

Despite numerous genetic, hormonal and mechanical factors have been proposed, the etiology of fibromuscular dysplasia remains unknown. A variety of factors have been implicated. These include:

  • Some studies suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.
  • Hormonal influence, The increased incidence of FMD in women as compared with men suggests a possible hormonal given the predominance in women of childbearing age but no association has been found between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones.[3]
  • Some authors have proposed the sex difference to be related to immune system functioning, but overt inflammation, as is observed in most classic autoimmune diseases, is histologically lacking.
  • Mechanical factors due to stretching of smooth muscle cells and microtrauma to the vessel wall.
  • Ischemia due to fibrotic occlusion of the vasa vasorum.

Genetics

  • Genetic predisposition may play a role in the development of fibromuscular dysplasia. Owing to, FMD is more common among the first-degree relatives of patients with this condition.
  • Some studies showed an autosomal dominant transmission pattern for fibromuscular dysplasia; however, as of yet, no etiologic genes have been identified for this disease. Applying molecular genetics investigations will reveal information about FMD pathogenesis, and family-based studies, evaluating genome of candidates, and wide genome studies can help to recognize pathophysiology of FMD.
  • In the US Registry, about eight percent of patients report a confirmed diagnosis of FMD in one or more in first- or second-degree family members. However, the high prevalence of aneurysms, sudden death, and stroke among first- and second-degree family members in the US Registry shows that FMD may be associated with systemic arteriopathy with a great diversity of clinical phenotype traits. It is hypothesized that FMD may have common features with vascular connective tissue diseases, such as Loeys-Dietz syndrome or the vascular type of Ehlers-Danlos syndrome.
  • Increased level of TGF-β1 and 2 secreted by fibroblasts in patients with FMD in comparison to matched

FMD patients also had elevated plasma levels of circulating TGF-β1 and TGF-β2 relative to matched controls. The potential involvement of TGF-b pathways in the pathogenesis of FMD is an area for future investigation, especially as this pathway could provide a potential target for disease-modifying medical therapies.[4]

  • Polymorphisms of angiotensin-converting–enzyme allele ACE-I among patients with multifocal renal arterial fibromuscular

dysplasia has been investigated.[5]

Associated Conditions

  • FMD is a predisposing factor for spontaneous cervical carotid, or renal artery dissections. Dissection through the weakening of the arterial wall, in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.

Gross Pathology

  • On gross pathology, focal, irregular, thickening in medium and large muscular arteries are characteristic findings of FMD.

Microscopic Pathology

  • On microscopic histopathological analysis, circumferential or eccentric deposition of collagen in intima but no lipid or inflammatory component are characteristic findings of FMD.
Microscopic pathology Source:Librepathology

References

  1. ↑ C. N. Sang, P. K. Whelton, U. M. Hamper, M. Connolly, S. Kadir, R. I. White, R. Sanders, K. Y. Liang & W. Bias (1989). "Etiologic factors in renovascular fibromuscular dysplasia. A case-control study". Hypertension (Dallas, Tex. : 1979). 14 (5): 472–479. PMID 2680961. Unknown parameter |month= ignored (help)
  2. ↑ J. Perdu, P. Boutouyrie, C. Bourgain, N. Stern, B. Laloux, E. Bozec, M. Azizi, C. Bonaiti-Pellie, P.-F. Plouin, S. Laurent, A.-P. Gimenez-Roqueplo & X. Jeunemaitre (2007). "Inheritance of arterial lesions in renal fibromuscular dysplasia". Journal of human hypertension. 21 (5): 393–400. doi:10.1038/sj.jhh.1002156. PMID 17330059. Unknown parameter |month= ignored (help)
  3. ↑ C. N. Sang, P. K. Whelton, U. M. Hamper, M. Connolly, S. Kadir, R. I. White, R. Sanders, K. Y. Liang & W. Bias (1989). "Etiologic factors in renovascular fibromuscular dysplasia. A case-control study". Hypertension (Dallas, Tex. : 1979). 14 (5): 472–479. PMID 2680961. Unknown parameter |month= ignored (help)
  4. ↑ Santhi K. Ganesh, Rachel Morissette, Zhi Xu, Florian Schoenhoff, Benjamin F. Griswold, Jiandong Yang, Lan Tong, Min-Lee Yang, Kristina Hunker, Leslie Sloper, Shinie Kuo, Rafi Raza, Dianna M. Milewicz, Clair A. Francomano, Harry C. Dietz, Jennifer Van Eyk & Nazli B. McDonnell (2014). "Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-beta expression and connective tissue features". FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 28 (8): 3313–3324. doi:10.1096/fj.14-251207. PMID 24732132. Unknown parameter |month= ignored (help)
  5. ↑ A. Bofinger, C. Hawley, P. Fisher, N. Daunt, M. Stowasser & R. Gordon (2001). "Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia". Journal of human hypertension. 15 (3): 185–190. doi:10.1038/sj.jhh.1001144. PMID 11317203. Unknown parameter |month= ignored (help)
  6. ↑ David P. Slovut & Jeffrey W. Olin (2004). "Fibromuscular dysplasia". The New England journal of medicine. 350 (18): 1862–1871. doi:10.1056/NEJMra032393. PMID 15115832. Unknown parameter |month= ignored (help)
  7. ↑ G. Tromp, Y. Wu, D. J. Prockop, S. L. Madhatheri, C. Kleinert, J. J. Earley, J. Zhuang, O. Norrgard, R. C. Darling & W. M. Abbott (1993). "Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms". The Journal of clinical investigation. 91 (6): 2539–2545. doi:10.1172/JCI116490. PMID 8514866. Unknown parameter |month= ignored (help)
  8. ↑ W. I. Schievink, F. B. Meyer, J. E. Parisi & E. F. Wijdicks (1998). "Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency". Neurosurgery. 43 (2): 229–233. PMID 9696074. Unknown parameter |month= ignored (help)

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Fibromuscular_dysplasia_pathophysiology&oldid=1492735"