Catecholaminergic polymorphic ventricular tachycardia pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
* | *[[CPVT]] is primarily due to the [[voltage-gated ion channel]] [[mutation]] which intermittently causes the [[heart]] to develop [[polymorphic ventricular tachycardia]] in response to the natural release of [[catecholamines]]. | ||
*The [[genes]] encoding [[ryanodine receptor 2|cardiac ryanodine-calcium release channel]] [[ryanodine receptor 2|RyR2]] or, infrequently, [[Calsequestrin|cardiac calsequestrin]] [[Calsequestrin|CASQ2]] are involved in the release of [[calcium]] from the [[sarcoplasmic reticulum]]. | |||
* | *[[Mutations]] in the [[genes]] encoding [[ryanodine receptor 2|cardiac ryanodine-calcium release channel]] [[ryanodine receptor 2|RyR2]] or [[Calsequestrin|cardiac calsequestrin]] [[Calsequestrin|CASQ2]] or other related genes, therein result in inappropriate [[calcium]] leak from the [[sarcoplasmic reticulum]] during electrical [[diastole]], with a subsequent increase in the [[cell|cytosolic]] [[calcium]] concentration.<ref name="JiangXiao2004">{{cite journal|last1=Jiang|first1=D.|last2=Xiao|first2=B.|last3=Yang|first3=D.|last4=Wang|first4=R.|last5=Choi|first5=P.|last6=Zhang|first6=L.|last7=Cheng|first7=H.|last8=Chen|first8=S. R. W.|title=RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR)|journal=Proceedings of the National Academy of Sciences|volume=101|issue=35|year=2004|pages=13062–13067|issn=0027-8424|doi=10.1073/pnas.0402388101}}</ref><ref name="di BarlettaViatchenko-Karpinski2006">{{cite journal|last1=di Barletta|first1=Marina Raffaele|last2=Viatchenko-Karpinski|first2=Serge|last3=Nori|first3=Alessandra|last4=Memmi|first4=Mirella|last5=Terentyev|first5=Dmitry|last6=Turcato|first6=Federica|last7=Valle|first7=Giorgia|last8=Rizzi|first8=Nicoletta|last9=Napolitano|first9=Carlo|last10=Gyorke|first10=Sandor|last11=Volpe|first11=Pompeo|last12=Priori|first12=Silvia G.|title= | ||
Clinical Phenotype and Functional Characterization of | |||
* | CASQ2 | ||
Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia | |||
*The | |journal=Circulation|volume=114|issue=10|year=2006|pages=1012–1019|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.106.623793}}</ref><ref name="LehnartWehrens2004">{{cite journal|last1=Lehnart|first1=Stephan E.|last2=Wehrens|first2=Xander H.T.|last3=Laitinen|first3=Päivi J.|last4=Reiken|first4=Steven R.|last5=Deng|first5=Shi-Xiang|last6=Cheng|first6=Zhenzhuang|last7=Landry|first7=Donald W.|last8=Kontula|first8=Kimmo|last9=Swan|first9=Heikki|last10=Marks|first10=Andrew R.|title=Sudden Death in Familial Polymorphic Ventricular Tachycardia Associated With Calcium Release Channel (Ryanodine Receptor) Leak|journal=Circulation|volume=109|issue=25|year=2004|pages=3208–3214|issn=0009-7322|doi=10.1161/01.CIR.0000132472.98675.EC}}</ref> | ||
*The [[cytosolic]] [[calcium]] overload activates the [[sodium-calcium exchanger]], leading to a transient inward current, and delayed [[after-depolarizations]] that in turn can lead to triggered [[arrhythmias]], particularly under conditions of high [[adrenergic|β-adrenergic]] tone.<ref name="CerroneNoujaim2007">{{cite journal|last1=Cerrone|first1=Marina|last2=Noujaim|first2=Sami F.|last3=Tolkacheva|first3=Elena G.|last4=Talkachou|first4=Arkadzi|last5=O’Connell|first5=Ryan|last6=Berenfeld|first6=Omer|last7=Anumonwo|first7=Justus|last8=Pandit|first8=Sandeep V.|last9=Vikstrom|first9=Karen|last10=Napolitano|first10=Carlo|last11=Priori|first11=Silvia G.|last12=Jalife|first12=José|title=Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation Research|volume=101|issue=10|year=2007|pages=1039–1048|issn=0009-7330|doi=10.1161/CIRCRESAHA.107.148064}}</ref><ref name="Knollmann2006">{{cite journal|last1=Knollmann|first1=B. C.|title=Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia|journal=Journal of Clinical Investigation|year=2006|issn=0021-9738|doi=10.1172/JCI29128}}</ref> | |||
==Genetics== | ==Genetics== |
Revision as of 06:22, 23 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
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].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Physiology
The normal physiology of [name of process] can be understood as follows:
Pathogenesis
- CPVT is primarily due to the voltage-gated ion channel mutation which intermittently causes the heart to develop polymorphic ventricular tachycardia in response to the natural release of catecholamines.
- The genes encoding cardiac ryanodine-calcium release channel RyR2 or, infrequently, cardiac calsequestrin CASQ2 are involved in the release of calcium from the sarcoplasmic reticulum.
- Mutations in the genes encoding cardiac ryanodine-calcium release channel RyR2 or cardiac calsequestrin CASQ2 or other related genes, therein result in inappropriate calcium leak from the sarcoplasmic reticulum during electrical diastole, with a subsequent increase in the cytosolic calcium concentration.[1][2][3]
- The cytosolic calcium overload activates the sodium-calcium exchanger, leading to a transient inward current, and delayed after-depolarizations that in turn can lead to triggered arrhythmias, particularly under conditions of high β-adrenergic tone.[4][5]
Genetics
[Disease name] is transmitted in [mode of genetic transmission] pattern.
OR
Genes involved in the pathogenesis of [disease name] include:
- [Gene1]
- [Gene2]
- [Gene3]
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Associated Conditions
Conditions associated with [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ Jiang, D.; Xiao, B.; Yang, D.; Wang, R.; Choi, P.; Zhang, L.; Cheng, H.; Chen, S. R. W. (2004). "RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR)". Proceedings of the National Academy of Sciences. 101 (35): 13062–13067. doi:10.1073/pnas.0402388101. ISSN 0027-8424.
- ↑ di Barletta, Marina Raffaele; Viatchenko-Karpinski, Serge; Nori, Alessandra; Memmi, Mirella; Terentyev, Dmitry; Turcato, Federica; Valle, Giorgia; Rizzi, Nicoletta; Napolitano, Carlo; Gyorke, Sandor; Volpe, Pompeo; Priori, Silvia G. (2006). "Clinical Phenotype and Functional Characterization of
CASQ2
Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 114 (10): 1012–1019. doi:10.1161/CIRCULATIONAHA.106.623793. ISSN 0009-7322. line feed character in
|title=
at position 54 (help) - ↑ Lehnart, Stephan E.; Wehrens, Xander H.T.; Laitinen, Päivi J.; Reiken, Steven R.; Deng, Shi-Xiang; Cheng, Zhenzhuang; Landry, Donald W.; Kontula, Kimmo; Swan, Heikki; Marks, Andrew R. (2004). "Sudden Death in Familial Polymorphic Ventricular Tachycardia Associated With Calcium Release Channel (Ryanodine Receptor) Leak". Circulation. 109 (25): 3208–3214. doi:10.1161/01.CIR.0000132472.98675.EC. ISSN 0009-7322.
- ↑ Cerrone, Marina; Noujaim, Sami F.; Tolkacheva, Elena G.; Talkachou, Arkadzi; O’Connell, Ryan; Berenfeld, Omer; Anumonwo, Justus; Pandit, Sandeep V.; Vikstrom, Karen; Napolitano, Carlo; Priori, Silvia G.; Jalife, José (2007). "Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation Research. 101 (10): 1039–1048. doi:10.1161/CIRCRESAHA.107.148064. ISSN 0009-7330.
- ↑ Knollmann, B. C. (2006). "Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia". Journal of Clinical Investigation. doi:10.1172/JCI29128. ISSN 0021-9738.