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Neurocardiogenic syncope pacemaker therapy

2012-05-17T13:34:30Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
Neurocardiogenic syncope is usually a self-limited episode of [[hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].<ref name="pmid15939833">{{cite journal |author=Grubb BP |title=Neurocardiogenic syncope and related disorders of orthostatic intolerance |journal=[[Circulation]] |volume=111 |issue=22 |pages=2997–3006 |year=2005 |month=June |pmid=15939833 |doi=10.1161/CIRCULATIONAHA.104.482018 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15939833 |accessdate=2012-05-17}}</ref><ref name="pmid8752825">{{cite journal |author=Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL |title=Tilt table testing for assessing syncope. American College of Cardiology |journal=[[Journal of the American College of Cardiology]] |volume=28 |issue=1 |pages=263–75 |year=1996 |month=July |pmid=8752825 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735109796002367 |accessdate=2012-05-17}}</ref>

[[Artificial pacemaker|Dual chamber pacing (DDD)]] is indicated only in patients with refractory neurocardiogenic syncope with significant [[bradycardia]] or [[asystole]]. In addition to cardiac pacing, adjunctive medical therapy may also be required as cardiac pacing alone has shown to be ineffective.

==Indications==
*Refractory neurocardiogenic syncope with significant [[bradycardia]] or [[asystole]].<ref name="pmid10899092">{{cite journal |author=Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, Moya A |title=Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators |journal=[[Circulation]] |volume=102 |issue=3 |pages=294–9 |year=2000 |month=July |pmid=10899092 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10899092 |accessdate=2012-05-17}}</ref><ref name="pmid11435337">{{cite journal |author=Ammirati F, Colivicchi F, Santini M |title=Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial |journal=[[Circulation]] |volume=104 |issue=1 |pages=52–7 |year=2001 |month=July |pmid=11435337 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11435337 |accessdate=2012-05-17}}</ref><ref name="pmid9935002">{{cite journal |author=Connolly SJ, Sheldon R, Roberts RS, Gent M |title=The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope |journal=[[Journal of the American College of Cardiology]] |volume=33 |issue=1 |pages=16–20 |year=1999 |month=January |pmid=9935002 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S073510979800549X |accessdate=2012-05-17}}</ref> Among patients with significant [[bradycardia]], despite the successful demonstration of permanent pacers to increase time to first syncopal episode and to reduce recurrent episodes by the VASIS study <ref name="pmid10899092">{{cite journal |author=Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, Moya A |title=Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators|journal=[[Circulation]] |volume=102 |issue=3 |pages=294–9 |year=2000 |month=July|pmid=10899092 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10899092 |accessdate=2012-05-17}}</ref> and the VPS study <ref name="pmid9935002">{{cite journal |author=Connolly SJ, Sheldon R, Roberts RS, Gent M |title=The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope |journal=[[Journal of the American College of Cardiology]] |volume=33 |issue=1 |pages=16–20 |year=1999 |month=January |pmid=9935002 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S073510979800549X |accessdate=2012-05-17}}</ref> respectively, the recent VPS-II study, did not demonstrate any reduction in the risk of recurrent syncopal events.<ref name="pmid12734133">{{cite journal |author=Connolly SJ, Sheldon R, Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, Morillo C, Gent M |title=Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=289 |issue=17 |pages=2224–9 |year=2003 |month=May |pmid=12734133 |doi=10.1001/jama.289.17.2224 |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.289.17.2224 |accessdate=2012-05-17}}</ref> Therefore, the use of cardiac pacing in such patient population still remains controversial.

*If cardiac pacing is indicated, [[Artificial pacemaker|dual chamber pacing]] is preferred following the demonstration of a strong positive [[tilt table test]]. Adjunctive medical therapy should be continued as it has shown to be more effective than pacing alone.

==ACC/AHA Guidelines- Permanent Pacing in Hypersensitive Carotid Sinus Syndrome and Neurocardiogenic Syncope (DO NOT EDIT)<ref name="pmid18483207">{{cite journal |author=Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW |title=ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=117 |issue=21 |pages=e350–408 |year=2008 |month=May |pmid=18483207 |doi=10.1161/CIRCUALTIONAHA.108.189742 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18483207 |accessdate=2012-05-17}}</ref>==
{{cquote|
===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]===
'''1.''' Permanent [[pacemaker|pacing]] is indicated for recurrent [[syncope]] caused by spontaneously occurring [[carotid sinus]] stimulation and [[carotid sinus]] pressure that induces [[ventricular asystole]] of more than 3 seconds.<ref name="pmid1561975">{{cite journal |author=Brignole M, Menozzi C, Lolli G, Bottoni N, Gaggioli G |title=Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome |journal=[[The American Journal of Cardiology]] |volume=69 |issue=12 |pages=1039–43 |year=1992 |month=April |pmid=1561975 |doi= |url= |accessdate=2012-05-17}}</ref><ref name="pmid1927916">{{cite journal |author=Brignole M, Menozzi C, Gianfranchi L, Oddone D, Lolli G, Bertulla A |title=Neurally mediated syncope detected by carotid sinus massage and head-up tilt test in sick sinus syndrome |journal=[[The American Journal of Cardiology]] |volume=68 |issue=10 |pages=1032–6 |year=1991 |month=October |pmid=1927916 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0002-9149(91)90491-3 |accessdate=2012-05-17}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]===
'''1.''' Permanent [[pacemaker|pacing]] is reasonable for [[syncope]] without clear, provocative events and with a hypersensitive cardioinhibitory response of 3 seconds or longer.<ref name="pmid1561975">{{cite journal |author=Brignole M, Menozzi C, Lolli G, Bottoni N, Gaggioli G |title=Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome |journal=[[The American Journal of Cardiology]] |volume=69 |issue=12 |pages=1039–43 |year=1992 |month=April |pmid=1561975 |doi= |url= |accessdate=2012-05-17}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]===
'''1.''' Permanent [[pacemaker|pacing]] may be considered for significantly symptomatic neurocardiogenic [[syncope]] associated with [[bradycardia]] documented spontaneously or at the time of tilt-table testing.<ref name="pmid11435337">{{cite journal |author=Ammirati F, Colivicchi F, Santini M |title=Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial |journal=[[Circulation]] |volume=104 |issue=1 |pages=52–7 |year=2001 |month=July |pmid=11435337 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11435337 |accessdate=2012-05-17}}</ref><ref name="pmid10899092">{{cite journal |author=Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, Moya A |title=Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators |journal=[[Circulation]] |volume=102 |issue=3 |pages=294–9 |year=2000 |month=July |pmid=10899092 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10899092 |accessdate=2012-05-17}}</ref><ref name="pmid12734133">{{cite journal |author=Connolly SJ, Sheldon R, Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, Morillo C, Gent M |title=Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=289 |issue=17 |pages=2224–9 |year=2003 |month=May |pmid=12734133 |doi=10.1001/jama.289.17.2224 |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.289.17.2224 |accessdate=2012-05-17}}</ref><ref name="pmid9591898">{{cite journal |author=Sheldon R, Koshman ML, Wilson W, Kieser T, Rose S |title=Effect of dual-chamber pacing with automatic rate-drop sensing on recurrent neurally mediated syncope |journal=[[The American Journal of Cardiology]] |volume=81 |issue=2 |pages=158–62 |year=1998 |month=January |pmid=9591898 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(97)00891-6 |accessdate=2012-05-17}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]]===
'''1.''' Permanent [[pacemaker|pacing]] is not indicated for a hypersensitive cardioinhibitory response to [[carotid sinus]] stimulation without symptoms or with vague symptoms. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

'''2.''' Permanent [[pacemaker|pacing]] is not indicated for situational vasovagal [[syncope]] in which avoidance behavior is effective and preferred. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''}}

==Guideline Resource==
[http://circ.ahajournals.org/content/117/21/e350.full.pdf The ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities] <ref name="pmid18483207">{{cite journal |author=Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW |title=ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=117 |issue=21 |pages=e350–408 |year=2008 |month=May |pmid=18483207 |doi=10.1161/CIRCUALTIONAHA.108.189742 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18483207 |accessdate=2012-05-17}}</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Cardiology]]

Neurocardiogenic syncope pacemaker therapy

2012-05-17T13:29:46Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
Neurocardiogenic syncope is usually a self-limited episode of [[hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].<ref name="pmid15939833">{{cite journal |author=Grubb BP |title=Neurocardiogenic syncope and related disorders of orthostatic intolerance |journal=[[Circulation]] |volume=111 |issue=22 |pages=2997–3006 |year=2005 |month=June |pmid=15939833 |doi=10.1161/CIRCULATIONAHA.104.482018 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15939833 |accessdate=2012-05-17}}</ref><ref name="pmid8752825">{{cite journal |author=Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL |title=Tilt table testing for assessing syncope. American College of Cardiology |journal=[[Journal of the American College of Cardiology]] |volume=28 |issue=1 |pages=263–75 |year=1996 |month=July |pmid=8752825 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735109796002367 |accessdate=2012-05-17}}</ref>

[[Artificial pacemaker|Dual chamber pacing (DDD)]] is indicated only in patients with refractory neurocardiogenic syncope with significant [[bradycardia]] or [[asystole]]. In addition to cardiac pacing, adjunctive medical therapy may also be required as cardiac pacing alone has shown to be ineffective.

==Indications==
*Refractory neurocardiogenic syncope with significant [[bradycardia]] or [[asystole]].<ref name="pmid10899092">{{cite journal |author=Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, Moya A |title=Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators |journal=[[Circulation]] |volume=102 |issue=3 |pages=294–9 |year=2000 |month=July |pmid=10899092 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10899092 |accessdate=2012-05-17}}</ref><ref name="pmid11435337">{{cite journal |author=Ammirati F, Colivicchi F, Santini M |title=Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial |journal=[[Circulation]] |volume=104 |issue=1 |pages=52–7 |year=2001 |month=July |pmid=11435337 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11435337 |accessdate=2012-05-17}}</ref><ref name="pmid9935002">{{cite journal |author=Connolly SJ, Sheldon R, Roberts RS, Gent M |title=The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope |journal=[[Journal of the American College of Cardiology]] |volume=33 |issue=1 |pages=16–20 |year=1999 |month=January |pmid=9935002 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S073510979800549X |accessdate=2012-05-17}}</ref> Among patients with significant [[bradycardia]], despite the successful demonstration of permanent pacers to increase time to first syncopal episode and to reduce recurrent episodes by the VASIS study <ref name="pmid10899092">{{cite journal |author=Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, Moya A |title=Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators|journal=[[Circulation]] |volume=102 |issue=3 |pages=294–9 |year=2000 |month=July|pmid=10899092 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10899092 |accessdate=2012-05-17}}</ref> and the VPS study <ref name="pmid9935002">{{cite journal |author=Connolly SJ, Sheldon R, Roberts RS, Gent M |title=The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope |journal=[[Journal of the American College of Cardiology]] |volume=33 |issue=1 |pages=16–20 |year=1999 |month=January |pmid=9935002 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S073510979800549X |accessdate=2012-05-17}}</ref> respectively, the recent VPS-II study, did not demonstrate any reduction in the risk of recurrent syncopal events.<ref name="pmid12734133">{{cite journal |author=Connolly SJ, Sheldon R, Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, Morillo C, Gent M |title=Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=289 |issue=17 |pages=2224–9 |year=2003 |month=May |pmid=12734133 |doi=10.1001/jama.289.17.2224 |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.289.17.2224 |accessdate=2012-05-17}}</ref> Therefore, the use of cardiac pacing in such patient population still remains controversial.

*If cardiac pacing is indicated, [[Artificial pacemaker|dual chamber pacing]] is preferred following the demonstration of a strong positive [[tilt table test]]. Adjunctive medical therapy should be continued as it has shown to be more effective than pacing alone.

==ACC/AHA Guidelines- Permanent Pacing in Hypersensitive Carotid Sinus Syndrome and Neurocardiogenic Syncope (DO NOT EDIT)<ref name="pmid18483207">{{cite journal |author=Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW |title=ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=117 |issue=21 |pages=e350–408 |year=2008 |month=May |pmid=18483207 |doi=10.1161/CIRCUALTIONAHA.108.189742 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18483207 |accessdate=2012-05-17}}</ref>==
{{cquote|
===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]===
'''1.''' Permanent [[pacemaker|pacing]] is indicated for recurrent [[syncope]] caused by spontaneously occurring [[carotid sinus]] stimulation and [[carotid sinus]] pressure that induces [[ventricular asystole]] of more than 3 seconds. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]===
'''1.''' Permanent [[pacemaker|pacing]] is reasonable for [[syncope]] without clear, provocative events and with a hypersensitive cardioinhibitory response of 3 seconds or longer. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]===
'''1.''' Permanent [[pacemaker|pacing]] may be considered for significantly symptomatic neurocardiogenic [[syncope]] associated with [[bradycardia]] documented spontaneously or at the time of tilt-table testing. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''

===[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]]===
'''1.''' Permanent [[pacemaker|pacing]] is not indicated for a hypersensitive cardioinhibitory response to [[carotid sinus]] stimulation without symptoms or with vague symptoms. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''

'''2.''' Permanent [[pacemaker|pacing]] is not indicated for situational vasovagal [[syncope]] in which avoidance behavior is effective and preferred. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''}}

==Guideline Resource==
[http://circ.ahajournals.org/content/117/21/e350.full.pdf The ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities] <ref name="pmid18483207">{{cite journal |author=Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW |title=ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=117 |issue=21 |pages=e350–408 |year=2008 |month=May |pmid=18483207 |doi=10.1161/CIRCUALTIONAHA.108.189742 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18483207 |accessdate=2012-05-17}}</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Cardiology]]

Artificial pacemaker

2012-05-17T13:21:40Z

Lakshmi Gopalakrishnan:

[[Image:Pacemaker GuidantMeridianSR.jpg|thumb|right|A pacemaker, scale in centimeters]]
[[Image:St Jude Medical pacemaker with ruler.jpg|right|thumb|An artificial pacemaker with electrode for transvenous insertion (from St. Jude Medical). The body of the device is about 4 centimeters long, the electrode measures between 50 and 60 centimeters.]]
{{SI}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==

A '''pacemaker''' (or '''artificial pacemaker''', so as not to be confused with the heart's natural [[cardiac pacemaker|pacemaker]]) is a medical device which uses electrical impulses, delivered by [[electrode]]s contacting the heart muscles, to regulate the beating of the [[heart]]. The primary purpose of a pacemaker is to maintain an adequate [[heart rate]], either because the heart's [[sinoatrial node|native pacemaker]] is not fast enough, or there is a block in the heart's [[electrical conduction system of the heart|electrical conduction system]]. Modern pacemakers are externally programmable and allow the [[cardiologist]] to select the optimum pacing modes for individual patients. Some combine a pacemaker and implantable [[implantable cardioverter-defibrillator|defibrillator]] in a single implantable device. Others have multiple electrodes stimulating differing positions within the heart to improve synchronisation of the [[ventricle (heart)|lower chambers]] of the heart.

== History of the artificial pacemaker ==
[[Image:CPI Pacemaker.jpg|thumb|left|World's first Lithium-iodide cell powered pacemaker. Cardiac Pacemakers Inc. 1972]] The preceding implantable devices all suffered from the unreliability and short lifetime of the available primary cell technology which was mainly that of the [[mercury battery]].
In '''1889''' J A McWilliam reported in the British Medical Journal of his experiments in which application of an electrical impulse to the human heart in [[asystole]] caused a [[ventricular]] contraction and that a heart rhythm of 60-70 beats per minute could be evoked by impulses applied at spacings equal to 60-70/minute.<ref>{{cite journal |author=McWilliam JA |year=1889 |month= |title=Electrical stimulation of the heart in man |journal=Br Med J |volume=1 |issue= |pages=348-50 |id= |url= |accessdate= 2007-10-24 |quote= }}. Partial quote in [http://www.hrsonline.org/News/ep-history/timeline/1800s.cfm#elec "Electrical Stimulation of the Heart in Man - 1889"], ''Heart Rhythm Society'', Accessed May 11, 2007.</ref>

In '''1928''' Dr Mark C Lidwell of the [[Royal Prince Alfred Hospital]] of Sydney, supported by physicist Edgar H Booth of the University of Sydney, devised a portable apparatus which "plugged into a lighting point" and in which "One pole was applied to a skin pad soaked in strong salt solution" while the other pole "consisted of a needle insulated except at its point, and was plunged into the appropriate cardiac chamber". "The pacemaker rate was variable from about 80 to 120 pulses per minute, and likewise the voltage variable from 1.5 to 120 volts" The apparatus was used to revive a stillborn infant at [[Crown Street Women's Hospital, Sydney]] whose heart continued "to beat on its own accord", "at the end of 10 minutes" of stimulation.<ref>Lidwell M C, "Cardiac Disease in Relation to Anaesthesia" in ''Transactions of the Third Session'', Australasian Medical Congress, Sydney, Australia, Sept. 2-7 1929, p 160.</ref><ref name="Mond_1982">{{cite journal |author=Mond H, Sloman J, Edwards R |title=The first pacemaker |journal=Pacing and clinical electrophysiology : PACE |volume=5 |issue=2 |pages=278-82 |year=1982 |pmid=6176970}}</ref>

In '''1932''' American physiologist [[Albert Hyman]], working independently, described an electro-mechanical instrument of his own, powered by a spring-wound hand-cranked motor. Hyman himself referred to his invention as an "artificial pacemaker", the term continuing in use to this day.<ref>Aquilina O, "[http://www.impaedcard.com/issue/issue27/aquilinao2/AquilinaO.htm A brief history of cardiac pacing]", ''Images Paediatr Cardiol'' 27 (2006), pp.17-81.</ref><ref>Furman S, Szarka G, Layvand D, "Reconstruction of Hyman's second pacemaker", Pacing Clin Electrophysiol.2005 May;28(5):446-453</ref>

An apparent [[hiatus]] in publication of research conducted between the early '''1930'''s and World War II may be attributed to the public perception of interfering with nature by 'reviving the dead'. For example, "Hyman did not publish data on the use of his pacemaker in humans because of adverse publicity, both among his fellow physicians, and due to newspaper reporting at the time. Lidwell may have been aware of this and did not proceed with his experiments in humans".<ref name="Mond_1982"/>

An external pacemaker was designed and built by the Canadian electrical engineer [[John Alexander Hopps|John Hopps]] in '''1950''' based upon observations by cardio-thoracic surgeon [[Wilfred Gordon Bigelow]] at [[Toronto General Hospital]] . A substantial external device using vacuum tube technology to provide [[transcutaneous pacing]], it was somewhat crude and painful to the patient in use and, being powered from an AC wall socket, carried a potential hazard of [[electrocution]] of the patient by inducing [[ventricular fibrillation]].

A number of innovators, including Paul Zoll, made smaller but still bulky [[transcutaneous pacing]] devices in the following years using a large rechargeable battery as the power supply.<ref>http://www.hno.harvard.edu/gazette/2001/04.19/12-zoll.html</ref>

In '''1957''' Dr. William L. Weirich published the results of research performed at the [[University of Minnesota]]. These studies demonstrated the restoration of heart rate, cardiac output and mean aortic pressures in animal subjects with complete [[heart block]] through the use of a [[myocardial]] electrode. This effective control of post surgical heart block proved to be a significant contribution to decreasing [[death|mortality]] of [[open heart surgery]] in this time period.<ref> Weirich W, Gott V, Lillehei C: The treatment of complete heart block by the combined use of a myocardial electrode and an artificial pacemaker. Surg. Forum 1957;8;360-363</ref>

The development of the transistor and its first commercial availability in '''1956''' was the pivotal event which led to rapid development of practical cardiac pacemaking.

In '''1957''' engineer Earl Bakken of Minneapolis, Minnesota, produced the first wearable external pacemaker for a patient of Dr. [[C. Walton Lillehei]]. This transistorized pacemaker, housed in a small plastic box, had controls to permit adjustment of pacing heart rate and output voltage and was connected to electrode leads which passed through the skin of the patient to terminate in electrodes attached to the surface of the [[myocardium]] of the heart.

The first clinical implantation into a human of a fully implantable pacemaker was in '''1958''' at the Karolinska University Hospital in Solna, Sweden, using a pacemaker designed by Rune Elmqvist and surgeon Åke Senning, connected to electrodes attached to the [[myocardium]] of the heart by [[thoracotomy]] . The device failed after three hours. A second device was then implanted which lasted for two days. The world's first implantable pacemaker patient, Arne Larsson, survived the first tests and died in 2001 after having received 22 different pacemakers during his lifetime.

In '''1959''' temporary [[transvenous pacing]] was first demonstrated by Furman et al in which the [[catheter]] electrode was inserted via the patient's [[basilic vein]].<ref> "Furman S, Schwedel JB" An intracardiac pacemaker for Stokes-Adams Seizures N Eng J Med 1959; 261:943-948" </ref>

In February,'''1960''', an improved version of the Swedish Elmqvist design was implanted in Montevideo, Uruguay in the Casmu Hospital by Doctors Fiandra and Rubio. That device lasted until the patient died of other ailments, 9 months later. The early Swedish-designed devices used rechargeable batteries, which were charged by an induction coil from the outside.

Implantable pacemakers constructed by engineer Wilson Greatbatch entered use in humans from April '''1960''' following extensive [[animal testing]]. The Greatbatch innovation varied from the earlier Swedish devices in using primary cells (mercury battery) as the energy source. The first patient lived for a further 18 months.

The first use of [[transvenous pacing]] in conjunction with an implanted pacemaker was by Parsonnet in the USA <ref> "Permanent Transvenous Pacing in 1962", Parsonnet V, PACE,1:285, 1978</ref><ref>"Preliminary Investigation of the Development of a Permanent Implantable Pacemaker Using an Intracardiac Dipolar Electrode", Parsonnet V, Zucker I R, Asa M M, Clin. Res., 10:391, 1962</ref>, Lageren in Sweden<ref> "How It Happened: My Recollection of Early Pacing", Lageren H, PACE: Pacing and Clinical Electrophysiology 1.1, Jan. 1978, pp 140-143</ref><ref> "Intracardiac Stimulation for Complete Heart Block", Lageren H, Acta. Chir. Sca., 125:562, 1963</ref> and Jean-Jaques Welti in France<ref>Jean Jaques Welti:Biography, Heart Rhythm Foundation</ref> in 1962-63.

The transvenous, or pervenous, procedure involved incision of a vein into which was inserted the [[catheter]] electrode lead under [[fluoroscopic]] guidance, until it was lodged within the [[trabeculae]] of the right ventricle. This method was to become the method of choice by the mid-'''1960s'''.

The preceding implantable devices all suffered from the unreliability and short lifetime of the available primary cell technology which was mainly that of the mercury battery.

In the late '''1960s''' several companies, including ARCO in the USA, developed isotope powered pacemakers, but this development was overtaken by the development in '''1970''' of the lithium-iodide cell by Wilson Greatbatch. Lithium-iodide or lithium anode cells became the standard for future pacemaker designs.

A further impediment to reliability of the early devices was the diffusion of water vapour from the body fluids through the [[epoxy]] resin encapsulation affecting the electronic circuitry. This phenomenon was overcome by encasing the pacemaker generator in an hermetically sealed metal case, initially by [[Telectronics]] of Australia in '''1969''' followed by Cardiac Pacemakers Inc of Minneapolis in '''1972'''. This technology, using titanium as the encasing metal, became the standard by the mid-'''1970s'''.

Others who contributed significantly to the technological development of the pacemaker in the pioneering years were Bob Anderson of Medtronic Minneapolis, J.G (Geoffrey) Davies of [[St George's Hospital]] London, [[Barouh Berkovits]] and Sheldon Thaler of American Optical, [[Geoffrey Wickham]] of Telectronics Australia, [[Walter Keller]] of Cordis Corp. of Miami, [[Hans Thornander]] who joined previously mentioned Rune Elmquist of Elema-Schonander in Sweden, [[Janwillem van den Berg]] of Holland and [[Anthony Adducci]] of Cardiac Pacemakers Inc.(Guidant)

== Applications ==
Artificial pacemakers can be used in order to help with and/or treat these conditions:
* [[Sick sinus syndrome|Sinus node dysfunction]] - when the [[sinoatrial node]] does not fire properly to contract the heart
* [[Bifascicular block]], [[trifascicular block]], or [[third degree AV block]].
*[[Stokes-Adams attack]] involving disruption of conduction between the [[sinoatrial node]] and the [[atrioventricular node]].

== Methods of pacing ==
=== Percussive Pacing ===
Percussive Pacing, also known as Transthoracic Mechanical Pacing, is the use of the closed fist, usually on the left lower edge of the sternum over the right ventricle, striking from a distance of 20 - 30 cm to induce a ventricular beat (the British Journal of Anesthesia suggests this must be done to raise the ventricular pressure 10 - 15mmhg to induce electrical activity). This is an old procedure used only as a life saving means until an electrical pacemaker is brought to the patient.<ref>(Cite_Journal)Percussion pacing in a three year-old girl with complete heart block during cardiac catheterization. C Eich, A Bleckmann and T. Paul, retrieved from http://bja.oxfordjournals.org/cgi/content/full/95/4/465</ref>

=== Transcutaneous pacing ===

{{main|Transcutaneous pacing}}

Transcutaneous pacing (TCP), also called external pacing, is recommended for the initial stabilization of hemodynamically significant [[bradycardia]]s of all types. The procedure is performed by placing two pacing pads on the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The rescuer selects the pacing rate, and gradually increases the pacing current (measured in mA) until electrical capture (characterized by a wide QRS complex with a tall, broad T wave on the [[electrocardiogram|ECG]]) is achieved, with a corresponding pulse. Pacing artifact on the [[electrocardiogram|ECG]] and severe muscle twitching may make this determination difficult. External pacing should not be relied upon for an extended period of time. It is an emergency procedure that acts as a bridge until transvenous pacing or other therapies can be applied.

=== Epicardial Pacing (temporary)===

{{Main|Epicardial}}
Temporary epicardial pacing is used during open heart surgery should the surgical procedure create atrio ventricular block. The electrodes are placed in contact with the outer wall of the ventricle (epicardium) to maintain satisfactory cardiac output until a temporary transvenous electrode has been inserted.

[[Image:Pacemaker dependent asystole.jpg|left|thumb|700px|ECG rhythm strip of a threshold determination in a patient with a temporary (epicardial) ventricular pacemaker. The epicardial pacemaker leads were placed after the patient collapsed during [[aortic valve]] surgery. In the first half of the tracing, pacemaker stimuli at 60 beats per minute result in a wide QRS complex with a [[right bundle branch block]] pattern. Progressively weaker pacing stimuli are administered, which results in [[asystole]] in the second half of the tracing. At the end of the tracing, distortion results from muscle contractions due to a (short) hypoxic [[seizure]]. Because decreased pacemaker stimuli do not result in a ventricular escape rhythm, the patient can be said to be pacemaker-dependent and needs a definitive pacemaker.]]
 

=== Transvenous pacing (temporary)===

{{main|Transvenous pacing}}

Transvenous pacing, when used for temporary pacing, is an alternative to transcutaneous pacing. A pacemaker wire is placed into a vein, under sterile conditions, and then passed into either the right atrium or right ventricle. The pacing wire is then connected to an external pacemaker outside the body. Transvenous pacing is often used as a bridge to permanent pacemaker placement. It can be kept in place until a permanent pacemaker is implanted or until there is no longer a need for a pacemaker and then it is removed.

=== Permanent pacing ===
[[Image:Fluoroscopy pacemaker leads right atrium ventricle.png|thumb|left|Right atrial and right ventricular leads as visualized under X-ray during a pacemaker implant procedure. The atrial lead is the curved one making a U shape in the upper left part of the figure.]]
Permanent pacing with an implantable pacemaker involves transvenous placement of one or more pacing electrodes within a chamber, or chambers, of the heart. The procedure is performed by incision of a suitable vein into which the electrode lead is inserted and passed along the vein, through the valve of the heart, until positioned in the chamber. The procedure is facilitated by [[fluoroscopy]] which enables the physician or cardiologist to view the passage of the electrode lead. After satisfactory lodgment of the electrode is confirmed the opposite end of the electrode lead is connected to the pacemaker generator.

The pacemaker generator is an hermetically sealed device containing a power source, usually a lithium battery, a sensing amplifier which processes the electrical manifestation of naturally occurring heart beats as sensed by the heart electrodes, the computer logic for the pacemaker and the output circuitry which delivers the pacing impulse to the electrodes.

Most commonly, the generator is placed below the subcutaneous fat of the chest wall, above the muscles and bones of the chest. However, the placement may vary on a case by case basis.

The outer casing of pacemakers is so designed that it will rarely be rejected by the body's [[immune system]]. It is usually made of [[titanium]], which is inert in the body.

== Basic pacemaker function ==
Modern pacemakers usually have multiple functions. The most basic form monitors the heart's native electrical rhythm. When the pacemaker doesn't sense a heartbeat within a normal beat-to-beat time period, it will stimulate the ventricle of the heart with a short low voltage pulse. This sensing and stimulating activity continues on a beat by beat basis.

The more complex forms include the ability to sense and/or stimulate both the atrial and ventricular chambers.

{| class="wikitable" style="margin: 1em auto 1em auto"
|+ '''The revised NASPE/BPEG generic code for antibradycardia pacing'''<ref>{{cite journal |author=Bernstein A, Daubert J, Fletcher R, Hayes D, Lüderitz B, Reynolds D, Schoenfeld M, Sutton R |title=The revised NASPE/BPEG generic code for antibradycardia, adaptive-rate, and multisite pacing. North American Society of Pacing and Electrophysiology/British Pacing and Electrophysiology Group |journal=Pacing Clin Electrophysiol |volume=25 |issue=2 |pages=260-4 |year=2002 |pmid=11916002}}</ref>
! I || II || III || IV || V
|-
| Chamber(s) paced || Chamber(s) sensed || Response to sensing || Rate modulation || Multisite pacing
|-
| O = None || O = None || O = None || O = None || O = None
|-
| A = Atrium || A = Atrium || T = Triggered || R = Rate modulation || A = Atrium
|-
| V = Ventricle || V = Ventricle || I = Inhibited || || V = Ventricle
|-
| D = Dual (A+V) || D = Dual (A+V) || D = Dual (T+I) || || D = Dual (A+V)
|-
|}

== Biventricular Pacing (BVP) ==

A biventricular pacemaker, also known as CRT (cardiac resynchronization therapy) is a type of pacemaker that can pace both the septal and lateral walls of the left ventricle. By pacing both sides of the left ventricle, the pacemaker can resynchronize a heart whose opposing walls do not contract in synchrony, which occurs in approximately 25-50 % of [[heart failure]] patients.

CRT devices have at least two leads, one in the right ventricle to stimulate the septum, and another inserted through the [[coronary sinus]] to pace the lateral wall of the left ventricle. Often, for patients in normal sinus rhythm, there is also a lead in the right atrium to facilitate synchrony with the atrial contraction. Thus, timing between the atrial and ventricular contractions, as well as between the septal and lateral walls of the left ventricle can be adjusted to achieve optimal cardiac function.

CRT devices have been shown to reduce mortality and improve quality of life in patients with heart failure symptoms; a LV ejection fraction less than or equal to 35% and QRS duration on EKG of 120 msec or greater.<ref>{{cite journal |author=Cleland JG, Daubert JC, Erdmann E, ''et al'' |title=The effect of cardiac resynchronization on morbidity and mortality in heart failure |journal=N. Engl. J. Med. |volume=352 |issue=15 |pages=1539–49 |year=2005 |pmid=15753115 |doi=10.1056/NEJMoa050496 |url=http://content.nejm.org/cgi/content/full/352/15/1539}}</ref><ref>{{cite journal |author=Bardy GH, Lee KL, Mark DB, ''et al'' |title=Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure |journal=N. Engl. J. Med. |volume=352 |issue=3 |pages=225–37 |year=2005 |pmid=15659722 |doi=10.1056/NEJMoa043399 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=15659722&promo=ONFLNS19}}</ref><ref name="pmid15753115">{{cite journal |author=Cleland J, Daubert J, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L |title=The effect of cardiac resynchronization on morbidity and mortality in heart failure |journal=N Engl J Med |volume=352 |issue=15 |pages=1539–49 |year=2005 |pmid=15753115 | doi=10.1056/NEJMoa050496}}</ref> CRT can be combined with an [[implantable cardioverter-defibrillator]] (ICD).<ref name="pmid15152059">{{cite journal |author=Bristow M, Saxon L, Boehmer J, Krueger S, Kass D, De Marco T, Carson P, DiCarlo L, DeMets D, White B, DeVries D, Feldman A |title=Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure |journal=N Engl J Med |volume=350 |issue=21 |pages=2140–50 |year=2004 |pmid=15152059 | doi=10.1056/NEJMoa032423}}</ref>

[[Image:Cardiac resynchronisation therapy.png|thumb|left|400px|Three leads can be seen in this example of a cardiac resynchronization device: a right atrial lead (solid black arrow), a right ventricular lead (dashed black arrow), and a coronary sinus lead (red arrow). The coronary sinus lead wraps around the outside of the left ventricle, enabling pacing of the left ventricle. Note that the right ventricular lead in this case has 2 thickened aspects that represent conduction coils and that the generator is larger than typical pacemaker generators, demonstrating that this device is both a pacemaker and a cardioverter-defibrillator, capable of delivering electrical shocks for dangerously fast abnormal ventricular rhythms.]]
 

== Advancements in pacemaker function ==
[[Image:Herzschrittmacher auf Roentgenbild.jpg|thumb|right|[[X-ray]] image of installed pacemaker showing wire routing]]
One unrealized advancement in pacemaker function could mimic nature by utilizing various bodily input parameters such as CO2 - O2 at in arterial-vein system, body temperature, ATP levels, Adrenaline, etc. Instead of producing a static, predetermined heart rate, or intermittent control, a Dynamic Pacemaker could compensate for both actual respiratory loading and potentially anticipated respiratory loading. A Dynamic Pacemaker would require sensory technology for which heart-rate regulation parameters must first be acutely identified. Dynamic Pacemaking technology could also be applied to future artificial hearts. Advances in transitional tissue welding would support this and other artificial organ/joint/tissue replacement efforts. Stem cells may or may not be of interest to transitional tissue welding.

When first invented, pacemakers controlled only the rate at which the heart's two largest chambers, the [[Ventricle (heart)|ventricle]]s, beat.

Many advancements have been made to enhance the control of the pacemaker once implanted. Many of these enhancements have been made possible by the transition to microprocessor controlled pacemakers. Pacemakers that control not only the ventricles but the [[Atrium (heart)|atria]] as well have become common. Pacemakers that control both the atria and ventricles are called dual-chamber pacemakers. Although these dual-chamber models are usually more expensive, timing the contractions of the atria to precede that of the ventricles improves the pumping efficiency of the heart and can be useful in congestive heart failure.

Rate responsive pacing allows the device to sense the physical activity of the patient and respond appropriately by increasing or decreasing the base pacing rate via rate response algorithms.

The DAVID trials<ref>{{cite journal |author=Wilkoff BL, Cook JR, Epstein AE, ''et al'' |title=Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial |journal=JAMA |volume=288 |issue=24 |pages=3115–23 |year=2002 |month=December |pmid=12495391 |doi= |url=http://jama.ama-assn.org/cgi/content/full/288/24/3115}}</ref> have shown that unnecessary pacing of the right ventricle can lead to [[heart failure]] and an increased incidence of atrial fibrillation. The newer dual chamber devices can keep the amount of right ventricle pacing to a minimum and thus prevent worsening of the heart disease.

== Other devices with pacemaker function ==

{{main|Implantable cardioverter-defibrillator}}

Sometimes devices resembling pacemakers, called ICDs ([[implantable cardioverter-defibrillator]]s) are implanted. These devices are often used in the treatment of patients at risk from sudden cardiac death. An ICD has the ability to treat many types of heart rhythm disturbances by means of pacing, [[cardioversion]], or [[defibrillation]].

{| class="wikitable" style="margin: 1em auto 1em auto"
|+ '''NASPE / BPEG Defibrillator (NBD) code - 1993'''<ref name=NASPE_defib_code>{{cite journal |author=Bernstein A, Camm A, Fisher J, Fletcher R, Mead R, Nathan A, Parsonnet V, Rickards A, Smyth N, Sutton R |title=North American Society of Pacing and Electrophysiology policy statement. The NASPE/BPEG defibrillator code |journal=Pacing Clin Electrophysiol |volume=16 |issue=9 |pages=1776-80 |year=1993 |pmid=7692407}}</ref>
! I || II || III || IV
|-
| Shock chamber || Antitachycardia pacing chamber || Tachycardia detection || Antibradycardia pacing chamber
|-
| O = None || O = None || E = Electrogram || O = None
|-
| A = Atrium || A = Atrium || H = Hemodynamic || A = Atrium
|-
| V = Ventricle || V = Ventricle || || V = Ventricle
|-
| D = Dual (A+V) || D = Dual (A+V) || || D = Dual (A+V)
|-
|}

{| class="wikitable" style="margin: 1em auto 1em auto"
|+ '''Short form of the NASPE/BPEG Defibrillator (NBD) code'''<ref name=NASPE_defib_code/>
| ICD-S || ICD with shock capability only
|-
| ICD-B || ICD with bradycardia pacing as well as shock
|-
| ICD-T || ICD with tachycardia (and bradycardia) pacing as well as shock
|-
|}

==Patient considerations ==

=== Insertion ===
[[Image:Pacemaker Wound.jpg|thumb|right|Wound left after a Pacemaker Implant]]
A pacemaker is typically inserted into the patient through a simple surgery using a [[local anesthetic]]. The patient is usually given a drug for relaxation. An incision is made in the left shoulder area below the collar bone where the pacemaker is actually housed in the patient's body. The lead or leads (the number of leads varies depending on the type of pacemaker) are fed into the heart through a large vein using a [[fluoroscope]] to monitor the progress of lead insertion. A temporary drain may be installed and removed the following day. The actual surgery may take about an hour.

The patient should exercise reasonable care about the wound as it heals.

Following surgery there is a followup session during which the pacemaker is checked using a "programmer" that can communicate with the device and allows a health care professional to evaluate the system's integrity and determine the settings such as pacing voltage output.
[[image:Pacemaker.NHLBI.jpg|left|350px|thumb|[http://www.nhlbi.nih.gov/health/dci/Diseases/pace/pace_howdoes.html Illustration of implanted pacemakers]]]
 
==== Pacemaker Patient Identification Card ====

International Pacemaker Patient Identification Cards carry information such as; patient data (between others, [[wikt:symptom|symptom]] primary, [[ECG]], [[aetiology]]), pacemaker center (doctor, hospital), IPG ([[rate]], [[mode]], date of implantation, MFG, type) and [[lead]] <ref>[http://www.xs4all.nl/~fbaart/aktueel/pm.htm European Pacemaker Patient Identification card]</ref> <ref>[http://www.eucomed.com/ Eucomed]</ref>.

=== Living with a pacemaker===

==== Periodic Pacemaker Checkups ====
[[Image:PaceMakerRemoteMonitoringDevicesTwoKinds.jpg|thumbnail|right|Two types of remote monitoring devices used by pacemaker patients.]]
Once the pacemaker is implanted, it is periodically checked to ensure the device is operational and performing appropriately. Depending on the frequency set by the following physician, the device can be checked as often as is necessary. Routine pacemaker checks are typically done in-office every six (6) months, though will vary depending upon patient/device status and remote monitoring availability.

At the time of in-office follow-up, the device will be interrogated to perform diagnostic testing. These tests include:

*Sensing: the ability of the device to "see" intrinsic cardiac activity (Atrial and ventricular depolarization).
*Impedance: A test to measure lead integrity. Large and/or sudden increases in impedance can be indicative of a lead fracture while large and/or sudden decreases in impedance can signify a breach in lead insulation.
*Threshold: this test confirms the minimum amount of energy (Both volts and pulse width) required to reliably depolarize (capture) the chamber being tested. Determining the threshold allows the Allied Professional, Representative, or Physician to program an output that recognizes an appropriate safety margin while optimizing device longevity.

As modern pacemakers are "on-demand", meaning that they only pace when necessary, device longevity is affected by how much it is utilized. Other factors affecting device longevity include programmed output and algorithms (features) causing a higher level of current drain from the battery.

An additional aspect of the in-office check is to examine any events that were stored since the last follow-up. These are typically stored based on specific criteria set by the physician and specific to the patient. Some devices have the availability to display intracardiac electrograms of the onset of the event as well as the event itself. This is especially helpful in diagnosing the cause or origin of the event and making any necessary programming changes.

==== Lifestyle Considerations ====

A patient's lifestyle is usually not modified to any great degree after insertion of a pacemaker. There are a few activities that are unwise such as full contact sports and activities that involve intense magnetic fields.

The pacemaker patient may find that some types of everyday actions need to be modified. For instance, the shoulder harness of a vehicle seatbelt may be uncomfortable if the harness should fall across the pacemaker insertion site.

Any kind of an activity that involves intense magnetic fields should be avoided. This includes activities such as [[arc welding]] possibly, with certain types of equipment<ref>
{{cite web
|url=http://www.ncbi.nlm.nih.gov/pubmed/1279591
|title=Testing of work environments for electromagnetic interference (Pacing Clin Electrophysiol. 1992) - PubMed Result
|publisher=www.ncbi.nlm.nih.gov
|accessdate=2008-11-10
|last=
|first=
}}
</ref>, or maintaining heavy equipment that may generate intense magnetic fields.

A 2008 U.S. study has found<ref>
{{cite web
|url=http://www.bidmc.org/News/InResearch/2008/November/MP3PlayerStudy.aspx
|title=MP3 Headphones Interfere With Implantable Defibrillators, Pacemakers - Beth Israel Deaconess Medical Center
|publisher=www.bidmc.org
|accessdate=2008-11-10
|last=
|first=
}}
</ref> that the magnets in some portable music player headphones may interfere with pacemakers when placed in close proximity.

Some medical procedures may require the use of [[antibiotic]]s to be administered before the procedure. The patient should inform all medical personnel that the patient does have a pacemaker. Some standard medical procedures such as the use of [[Magnetic resonance imaging]] (MRI) may be ruled out by the patient having a pacemaker.

=== Privacy and security ===

Security and privacy concerns have been raised with pacemakers that allow wireless communication. Unauthorized third parties may be able to read patient records contained in the pacemaker, or reprogram the devices, as has been demonstrated by a team of researchers.<ref name=ICD-Radio>{{cite conference|
year = 2008 | month = May |
title=Pacemakers and Implantable Cardiac Defibrillators: Software Radio Attacks and Zero-Power Defenses|
first=Daniel|
last=Halperin|
coauthors = Thomas S. Heydt-Benjamin, Benjamin Ransford, Shane S. Clark, Benessa Defend, Will Morgan, Kevin Fu, Tadayoshi Kohno, and William H. Maisel|
url=http://www.secure-medicine.org/icd-study/icd-study.pdf |
format = PDF |
conference=IEEE Symposium on Security and Privacy |
accessdate = 2008-08-10|
}}</ref> The demonstration worked at short range; they did not attempt to develop a long range antenna. The proof of concept exploit helps demonstrate the need for better security and patient alerting measures in remotely accessible medical implants.<ref name=ICD-Radio />

==EKG Findings==

[[Image:paced2.gif|left|350px|thumb|Ventricular paced rhythm shows ventricular pacemaker spikes]]
 

[[Image:ddd_paced_12lead.jpg|left|350px|thumb|DDD type pace rhythm]]
 

[[Image:Pacemaker2.jpg|left|350px|thumb|VVI pacemaker rhythm. Note the LBBB morphology with left axis deviation indicating the pacing lead in the right ventricular apex.]]
 

[[image:V19.ht23.jpg|left|350px|thumb|Ventricular paced rhythm]]
 

[[Image:DDDPM.jpg|left|350px|thumb|12 lead EKG: Dual chamber pacemaker ]]
 

==Related Chapters==
* [[Cardiology]]
* [[Electrical conduction system of the heart]]
* [[Transcutaneous pacing]]
* [[Pacemaker syndrome]]

==References==
{{Reflist|2}}

{{Electrocardiography}}

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[[fr:Stimulateur cardiaque]]
[[it:Pacemaker]]
[[he:קוצב לב]]
[[nl:Pacemaker]]
[[ja:心臓ペースメーカー]]
[[no:Pacemaker]]
[[nn:Pacemaker]]
[[pl:Stała elektrostymulacja serca]]
[[pt:Marcapasso]]
[[ru:Электрокардиостимулятор]]
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[[Category:Electrophysiology]]
[[Category:Cardiology]]

Neurocardiogenic syncope pacemaker therapy

2012-05-17T13:18:52Z

Lakshmi Gopalakrishnan:

Neurocardiogenic syncope symptoms

2012-05-17T12:56:09Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
The classic features of neurocardiogenic syncope include the presence of triggering stimuli with subsequent prodrome of [[nausea]] and [[diaphoresis]].

==History==
*Family history of syncope is almost always present.

==Triggers/Precipitating Factors==
*The sight of blood.
*Loss of blood.
*Sudden stressful or painful experiences.
*Surgical manipulation.
*Trauma.
*Pain.
*Anxiety.
*Stress.

==Prodrome==
*Prior to the syncopal episode, patients may complain of a prodome consisting of:
:*[[Nausea]],
:*[[Diaphoresis]] (absent in the elderly),
:*[[Lightheadedness]],
:*[[Blurred vision]],
:*[[Headache]],
:*[[Palpitations]],
:*[[Paraesthesia]],
:*[[Pallor]],

*The symptoms usually occur in the '''''upright position''''' and resolve almost immediately when the patient assumes the supine position. In the upright position there is '''''downward displacement of 300-800 cc of blood'''''.

==Recovery Phase==
* “Washed out” and [[tired feeling]].

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:48:07Z

Lakshmi Gopalakrishnan: /* Overview */

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually '''''self-limited''''' episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].<ref name="pmid15939833">{{cite journal |author=Grubb BP |title=Neurocardiogenic syncope and related disorders of orthostatic intolerance |journal=[[Circulation]] |volume=111 |issue=22 |pages=2997–3006 |year=2005 |month=June |pmid=15939833 |doi=10.1161/CIRCULATIONAHA.104.482018 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15939833 |accessdate=2012-05-17}}</ref><ref name="pmid8752825">{{cite journal |author=Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL |title=Tilt table testing for assessing syncope. American College of Cardiology |journal=[[Journal of the American College of Cardiology]] |volume=28 |issue=1 |pages=263–75 |year=1996 |month=July |pmid=8752825 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735109796002367 |accessdate=2012-05-17}}</ref>

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref> On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

The pathogenesis for [[syncope]] in patients with [[hypersensitive carotid sinus]] and [[neurocardiogenic syncope]] remain the same with the only difference being the receptor involved to stimulate the brainstem nucleus.

==Pathophysiology==
The underlying mechanism of exaggerated autonomic response to various stimuli in patients with neurocardiogenic stimuli remains unclear. However, the '''''activation of cardiac C-fibres''''' has been implicated in the pathogenesis of neurocardiogenic syncope.<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref>

Regardless of the triggers, the mechanism of [[syncope]] is similar among various [[vasovagal syncope]] syndromes.

Multiple triggering stimuli activate the [[nucleus tractus solitarius]] of the brainstem via the [[cardiac C fibres]], which then results in the simultaneous enhancement of the [[vagal tone|parasympathetic nervous system (vagal) tone]] and withdrawal of the [[sympathetic nervous system|sympathetic nervous system tone]].<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref><ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref><ref name="pmid11465961">{{cite journal |author=Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W |title=Guidelines on management (diagnosis and treatment) of syncope |journal=[[European Heart Journal]] |volume=22 |issue=15 |pages=1256–306 |year=2001 |month=August |pmid=11465961 |doi=10.1053/euhj.2001.2739 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11465961 |accessdate=2012-05-17}}</ref>

This results in a spectrum of hemodynamic responses:
:* On one end of the spectrum is the cardioinhibitory response caused by an '''''increased vagal tone''''' that is characterized by [[bradycardia]] and consequent [[hypotension]] that is significant enough to result in [[loss of consciousness]].

:*On the other end of the spectrum is the vasodepressor response, caused by a [[hypotension|drop in blood pressure]] without much change in [[heart rate]]. This phenomenon occurs due to '''''vasodilation''''' secondary to the withdrawal of [[sympathetic nervous system|sympathetic nervous system tone]].

As a result of increased [[vagal tone]] and [[vasodilation]], subsequent decrease in [[venous return]] and [[cardiac output]] is observed which is significant enough to cause [[syncope]] or [[loss of consciousness]].<ref name="pmid10678294">{{cite journal |author=White CM, Tsikouris JP |title=A review of pathophysiology and therapy of patients with vasovagal syncope |journal=[[Pharmacotherapy]] |volume=20 |issue=2 |pages=158–65 |year=2000 |month=February |pmid=10678294 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0277-0008&date=2000&volume=20&issue=2&spage=158 |accessdate=2012-05-17}}</ref><ref>Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.</ref>

====Neurocardiogenic Syncope====
Triggers such as pain, post-exercise stimulate the [[sympathetic nervous system]] causing an increase in the [[sympathetic nervous system|sympathetic tone]] ''([[tachycardia]] and increased [[cardiac contractility]])'' which then causes reflex-mediated activation of the cardiac C fibres and brainstem nucleus to counterbalance these effects and results in an [[vagal tone|increased vagal tone]] and [[bradycardia]].

====Hypersensitive Carotid Sinus====
Triggers such as carotid massage, rapid head turning cause stimulation of the [[carotid sinus]] and [[cardiopulmonary receptors]] which subsequently activate the brainstem nucleus to follow the common pathway of [[vagal tone|increased vagal tone]] and [[bradycardia]].

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:46:42Z

Lakshmi Gopalakrishnan: /* Overview */

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually '''''self-limited''''' episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].<ref name="pmid15939833">{{cite journal |author=Grubb BP |title=Neurocardiogenic syncope and related disorders of orthostatic intolerance |journal=[[Circulation]] |volume=111 |issue=22 |pages=2997–3006 |year=2005 |month=June |pmid=15939833 |doi=10.1161/CIRCULATIONAHA.104.482018 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15939833 |accessdate=2012-05-17}}</ref><ref name="pmid8752825">{{cite journal |author=Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL |title=Tilt table testing for assessing syncope. American College of Cardiology |journal=[[Journal of the American College of Cardiology]] |volume=28 |issue=1 |pages=263–75 |year=1996 |month=July |pmid=8752825 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735109796002367 |accessdate=2012-05-17}}</ref>

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref>

On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

==Pathophysiology==
The underlying mechanism of exaggerated autonomic response to various stimuli in patients with neurocardiogenic stimuli remains unclear. However, the '''''activation of cardiac C-fibres''''' has been implicated in the pathogenesis of neurocardiogenic syncope.<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref>

Regardless of the triggers, the mechanism of [[syncope]] is similar among various [[vasovagal syncope]] syndromes.

Multiple triggering stimuli activate the [[nucleus tractus solitarius]] of the brainstem via the [[cardiac C fibres]], which then results in the simultaneous enhancement of the [[vagal tone|parasympathetic nervous system (vagal) tone]] and withdrawal of the [[sympathetic nervous system|sympathetic nervous system tone]].<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref><ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref><ref name="pmid11465961">{{cite journal |author=Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W |title=Guidelines on management (diagnosis and treatment) of syncope |journal=[[European Heart Journal]] |volume=22 |issue=15 |pages=1256–306 |year=2001 |month=August |pmid=11465961 |doi=10.1053/euhj.2001.2739 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11465961 |accessdate=2012-05-17}}</ref>

This results in a spectrum of hemodynamic responses:
:* On one end of the spectrum is the cardioinhibitory response caused by an '''''increased vagal tone''''' that is characterized by [[bradycardia]] and consequent [[hypotension]] that is significant enough to result in [[loss of consciousness]].

:*On the other end of the spectrum is the vasodepressor response, caused by a [[hypotension|drop in blood pressure]] without much change in [[heart rate]]. This phenomenon occurs due to '''''vasodilation''''' secondary to the withdrawal of [[sympathetic nervous system|sympathetic nervous system tone]].

As a result of increased [[vagal tone]] and [[vasodilation]], subsequent decrease in [[venous return]] and [[cardiac output]] is observed which is significant enough to cause [[syncope]] or [[loss of consciousness]].<ref name="pmid10678294">{{cite journal |author=White CM, Tsikouris JP |title=A review of pathophysiology and therapy of patients with vasovagal syncope |journal=[[Pharmacotherapy]] |volume=20 |issue=2 |pages=158–65 |year=2000 |month=February |pmid=10678294 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0277-0008&date=2000&volume=20&issue=2&spage=158 |accessdate=2012-05-17}}</ref><ref>Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.</ref>

====Neurocardiogenic Syncope====
Triggers such as pain, post-exercise stimulate the [[sympathetic nervous system]] causing an increase in the [[sympathetic nervous system|sympathetic tone]] ''([[tachycardia]] and increased [[cardiac contractility]])'' which then causes reflex-mediated activation of the cardiac C fibres and brainstem nucleus to counterbalance these effects and results in an [[vagal tone|increased vagal tone]] and [[bradycardia]].

====Hypersensitive Carotid Sinus====
Triggers such as carotid massage, rapid head turning cause stimulation of the [[carotid sinus]] and [[cardiopulmonary receptors]] which subsequently activate the brainstem nucleus to follow the common pathway of [[vagal tone|increased vagal tone]] and [[bradycardia]].

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope epidemiology and demographics

2012-05-17T12:43:01Z

Lakshmi Gopalakrishnan: /* Overview */

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
Neurocardiogenic syncope is the most common cause of [[syncope]] in children and adults and accounts for approximately 10-40% of all syncopal episodes.

==Incidence==
The prevalence is 22% in the general population. Approximately 50%-66% of syncope cases are classified as due to vasovagal syncope.

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:41:23Z

Lakshmi Gopalakrishnan: /* Hyperactive Carotid Sinus */

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually '''''self-limited''''' episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref>

On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

==Pathophysiology==
The underlying mechanism of exaggerated autonomic response to various stimuli in patients with neurocardiogenic stimuli remains unclear. However, the '''''activation of cardiac C-fibres''''' has been implicated in the pathogenesis of neurocardiogenic syncope.<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref>

Regardless of the triggers, the mechanism of [[syncope]] is similar among various [[vasovagal syncope]] syndromes.

Multiple triggering stimuli activate the [[nucleus tractus solitarius]] of the brainstem via the [[cardiac C fibres]], which then results in the simultaneous enhancement of the [[vagal tone|parasympathetic nervous system (vagal) tone]] and withdrawal of the [[sympathetic nervous system|sympathetic nervous system tone]].<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref><ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref><ref name="pmid11465961">{{cite journal |author=Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W |title=Guidelines on management (diagnosis and treatment) of syncope |journal=[[European Heart Journal]] |volume=22 |issue=15 |pages=1256–306 |year=2001 |month=August |pmid=11465961 |doi=10.1053/euhj.2001.2739 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11465961 |accessdate=2012-05-17}}</ref>

This results in a spectrum of hemodynamic responses:
:* On one end of the spectrum is the cardioinhibitory response caused by an '''''increased vagal tone''''' that is characterized by [[bradycardia]] and consequent [[hypotension]] that is significant enough to result in [[loss of consciousness]].

:*On the other end of the spectrum is the vasodepressor response, caused by a [[hypotension|drop in blood pressure]] without much change in [[heart rate]]. This phenomenon occurs due to '''''vasodilation''''' secondary to the withdrawal of [[sympathetic nervous system|sympathetic nervous system tone]].

As a result of increased [[vagal tone]] and [[vasodilation]], subsequent decrease in [[venous return]] and [[cardiac output]] is observed which is significant enough to cause [[syncope]] or [[loss of consciousness]].<ref name="pmid10678294">{{cite journal |author=White CM, Tsikouris JP |title=A review of pathophysiology and therapy of patients with vasovagal syncope |journal=[[Pharmacotherapy]] |volume=20 |issue=2 |pages=158–65 |year=2000 |month=February |pmid=10678294 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0277-0008&date=2000&volume=20&issue=2&spage=158 |accessdate=2012-05-17}}</ref><ref>Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.</ref>

====Neurocardiogenic Syncope====
Triggers such as pain, post-exercise stimulate the [[sympathetic nervous system]] causing an increase in the [[sympathetic nervous system|sympathetic tone]] ''([[tachycardia]] and increased [[cardiac contractility]])'' which then causes reflex-mediated activation of the cardiac C fibres and brainstem nucleus to counterbalance these effects and results in an [[vagal tone|increased vagal tone]] and [[bradycardia]].

====Hypersensitive Carotid Sinus====
Triggers such as carotid massage, rapid head turning cause stimulation of the [[carotid sinus]] and [[cardiopulmonary receptors]] which subsequently activate the brainstem nucleus to follow the common pathway of [[vagal tone|increased vagal tone]] and [[bradycardia]].

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:32:28Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually '''''self-limited''''' episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref>

On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

==Pathophysiology==
The underlying mechanism of exaggerated autonomic response to various stimuli in patients with neurocardiogenic stimuli remains unclear. However, the '''''activation of cardiac C-fibres''''' has been implicated in the pathogenesis of neurocardiogenic syncope.<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref>

Regardless of the triggers, the mechanism of [[syncope]] is similar among various [[vasovagal syncope]] syndromes.

Multiple triggering stimuli activate the [[nucleus tractus solitarius]] of the brainstem via the [[cardiac C fibres]], which then results in the simultaneous enhancement of the [[vagal tone|parasympathetic nervous system (vagal) tone]] and withdrawal of the [[sympathetic nervous system|sympathetic nervous system tone]].<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref><ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref><ref name="pmid11465961">{{cite journal |author=Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W |title=Guidelines on management (diagnosis and treatment) of syncope |journal=[[European Heart Journal]] |volume=22 |issue=15 |pages=1256–306 |year=2001 |month=August |pmid=11465961 |doi=10.1053/euhj.2001.2739 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11465961 |accessdate=2012-05-17}}</ref>

This results in a spectrum of hemodynamic responses:
:* On one end of the spectrum is the cardioinhibitory response caused by an '''''increased vagal tone''''' that is characterized by [[bradycardia]] and consequent [[hypotension]] that is significant enough to result in [[loss of consciousness]].

:*On the other end of the spectrum is the vasodepressor response, caused by a [[hypotension|drop in blood pressure]] without much change in [[heart rate]]. This phenomenon occurs due to '''''vasodilation''''' secondary to the withdrawal of [[sympathetic nervous system|sympathetic nervous system tone]].

As a result of increased [[vagal tone]] and [[vasodilation]], subsequent decrease in [[venous return]] and [[cardiac output]] is observed which is significant enough to cause [[syncope]] or [[loss of consciousness]].<ref name="pmid10678294">{{cite journal |author=White CM, Tsikouris JP |title=A review of pathophysiology and therapy of patients with vasovagal syncope |journal=[[Pharmacotherapy]] |volume=20 |issue=2 |pages=158–65 |year=2000 |month=February |pmid=10678294 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0277-0008&date=2000&volume=20&issue=2&spage=158 |accessdate=2012-05-17}}</ref><ref>Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.</ref>

====Neurocardiogenic Syncope====
Triggers such as pain, post-exercise stimulate the [[sympathetic nervous system]] causing an increase in the [[sympathetic nervous system|sympathetic tone]] ''([[tachycardia]] and increased [[cardiac contractility]])'' which then causes reflex-mediated activation of the cardiac C fibres and brainstem nucleus to counterbalance these effects and results in an [[vagal tone|increased vagal tone]] and [[bradycardia]].

====Hyperactive Carotid Sinus====
Triggers such as carotid massage, rapid head turning cause stimulation of the [[carotid sinus]] and [[cardiopulmonary receptors]] which subsequently activate the brainstem nucleus to follow the common pathway of [[vagal tone|increased vagal tone]] and [[bradycardia]].

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:14:02Z

Lakshmi Gopalakrishnan: /* Pathophysiology */

{{Neurocardiogenic syncope}}
{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually '''''self-limited''''' episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref>

On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

==Pathophysiology==
The underlying mechanism of exaggerated autonomic response to various stimuli in patients with neurocardiogenic stimuli remains unclear. However, the '''''activation of cardiac C-fibres''''' has been implicated in the pathogenesis of neurocardiogenic syncope.<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref>

Regardless of the triggers, the mechanism of [[syncope]] is similar among various [[vasovagal syncope]] syndromes.

Multiple triggering stimuli activate the [[nucleus tractus solitarius]] of the brainstem via the [[cardiac C fibres]], which then results in the simultaneous enhancement of the [[vagal tone|parasympathetic nervous system (vagal) tone]] and withdrawal of the [[sympathetic nervous system|sympathetic nervous system tone]].<ref>Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999</ref><ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref><ref name="pmid11465961">{{cite journal |author=Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W |title=Guidelines on management (diagnosis and treatment) of syncope |journal=[[European Heart Journal]] |volume=22 |issue=15 |pages=1256–306 |year=2001 |month=August |pmid=11465961 |doi=10.1053/euhj.2001.2739 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11465961 |accessdate=2012-05-17}}</ref>

This results in a spectrum of hemodynamic responses:
:* On one end of the spectrum is the cardioinhibitory response caused by an '''''increased vagal tone''''' that is characterized by [[bradycardia]] and consequent [[hypotension]] that is significant enough to result in [[loss of consciousness]].

:*On the other end of the spectrum is the vasodepressor response, caused by a [[hypotension|drop in blood pressure]] without much change in [[heart rate]]. This phenomenon occurs due to '''''vasodilation''''' secondary to the withdrawal of [[sympathetic nervous system|sympathetic nervous system tone]].

As a result of increased [[vagal tone]] and [[vasodilation]], subsequent decrease in [[venous return]] and [[cardiac output]] is observed which is significant enough to cause [[syncope]] or [[loss of consciousness]].<ref name="pmid10678294">{{cite journal |author=White CM, Tsikouris JP |title=A review of pathophysiology and therapy of patients with vasovagal syncope |journal=[[Pharmacotherapy]] |volume=20 |issue=2 |pages=158–65 |year=2000 |month=February |pmid=10678294 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0277-0008&date=2000&volume=20&issue=2&spage=158 |accessdate=2012-05-17}}</ref><ref>Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.</ref>

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope pathophysiology

2012-05-17T12:11:46Z

Lakshmi Gopalakrishnan: /* Pathophysiology */

Neurocardiogenic syncope pathophysiology

2012-05-17T12:02:30Z

Lakshmi Gopalakrishnan:

Neurocardiogenic syncope pathophysiology

2012-05-17T11:30:28Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
[[Neurocardiogenic syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually self-limited episode of [[Hypotension|systemic hypotension]] characterized by both [[bradycardia]] (asystole or relative bradycardia) and [[vasodilation|peripheral vasodilation]].

It is caused by an abnormal or '''''exaggerated autonomic response''''' to various stimuli, commonly standing and emotion.<ref name="pmid12270863">{{cite journal |author=Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W |title=Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing |journal=[[Circulation]] |volume=106 |issue=13 |pages=1684–9 |year=2002 |month=September |pmid=12270863 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12270863 |accessdate=2012-05-17}}</ref><ref name="pmid14623807">{{cite journal |author=Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D |title=Water ingestion as prophylaxis against syncope |journal=[[Circulation]] |volume=108 |issue=21 |pages=2660–5 |year=2003 |month=November |pmid=14623807 |doi=10.1161/01.CIR.0000101966.24899.CB |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=14623807 |accessdate=2012-05-17}}</ref> The underlying mechanism for this exaggerate autonomic response remains unclear; however, the activation of cardiac C fibres has shown to play role which subsequently causes reflex-mediated changes in the vascular tone and heart rate.<ref name="pmid11117979">{{cite journal |author=Kapoor WN |title=Syncope |journal=[[The New England Journal of Medicine]] |volume=343 |issue=25 |pages=1856–62 |year=2000 |month=December |pmid=11117979 |doi=10.1056/NEJM200012213432507 |url=http://www.nejm.org/doi/abs/10.1056/NEJM200012213432507?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-05-17}}</ref>

On the contrary, '''''failure of autonomic reflex response''''' results in [[orthostatic hypotension]].

==Pathophysiology==

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic syncope

2012-05-17T02:42:12Z

Lakshmi Gopalakrishnan: /* Diagnosis */

'''For patient information on this page, click [[Neurocardiogenic syncope (patient information)|here]]'''

{{Neurocardiogenic syncope}}
{{CMG}}

==[[Neurocardiogenic syncope overview|Overview]]==

==[[Neurocardiogenic syncope pathophysiology|Pathophysiology]]==

==[[Neurocardiogenic syncope epidemiology and demographics|Epidemiology & Demographics]]==

==[[Neurocardiogenic syncope risk factors|Risk Factors]]==

==[[Neurocardiogenic syncope causes|Causes]]==

==[[Neurocardiogenic syncope natural history|Natural History, Prognosis & Complication]]==

==[[Neurocardiogenic syncope differentiating from other diseases|Differentiating Neurocardiogenic Syncope From Other Diseases]]==

==Diagnosis==
[[Neurocardiogenic syncope symptoms|History & Symptoms]] | [[Neurocardiogenic syncope physical examination|Physical Examination]] | [[Neurocardiogenic syncope electrocardiogram|Electrocardiogram]] | [[Neurocardiogenic syncope chest x-ray|Chest X-Ray]] | [[Tilt table test]] | [[Neurocardiogenic syncope echocardiography|Echocardiography]] | [[Neurocardiogenic syncope cardiac catheterization|Cardiac Catheterization]]

==Treatment==
====[[Neurocardiogenic syncope medical treatment|Medical Therapy]]====

====[[Neurocardiogenic syncope pacemaker therapy|Pacemaker Therapy]]====

==Related Chapters==
*[[Vasovagal syncope]]
*[[Postural orthostatic tachycardia syndrome]]
*[[Dysautonomia]]

==Additional Resources==
# Neurocardiogenic syncope. Carol Chen-Scarabelli, Tiziano M Scarabelli. BMJ 2004;329:336–41
# Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al for the Task Force on Syncope, European Society of Cardiology.Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001;22:1256-306.
# Vasovagal Syncope. Alexis M. Fenton, MD; Stephen C. Hammill, MD; Robert F. Rea, MD; Phillip A. Low, MD; and Win-Kuang Shen, MD. Ann Intern Med. 2000;133:714-725.
# Connolly SJ, Sheldon R, Thorpe KE, et al. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA. 2003;289:2224-9.

[[Category:Disease]]
[[Category:Cardiology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Neurocardiogenic syncope

2012-05-17T02:36:19Z

Lakshmi Gopalakrishnan: /* Additional Resources */

'''For patient information on this page, click [[Neurocardiogenic syncope (patient information)|here]]'''

{{Neurocardiogenic syncope}}
{{CMG}}

==[[Neurocardiogenic syncope overview|Overview]]==

==[[Neurocardiogenic syncope pathophysiology|Pathophysiology]]==

==[[Neurocardiogenic syncope epidemiology and demographics|Epidemiology & Demographics]]==

==[[Neurocardiogenic syncope risk factors|Risk Factors]]==

==[[Neurocardiogenic syncope causes|Causes]]==

==[[Neurocardiogenic syncope natural history|Natural History, Prognosis & Complication]]==

==[[Neurocardiogenic syncope differentiating from other diseases|Differentiating Neurocardiogenic Syncope From Other Diseases]]==

==Diagnosis==
[[Neurocardiogenic syncope symptoms|History & Symptoms]] | [[Neurocardiogenic syncope physical examination|Physical Examination]] | [[Neurocardiogenic syncope electrocardiogram|Electrocardiogram]] | [[Neurocardiogenic syncope chest x-ray|Chest X-Ray]] | [[Neurocardiogenic syncope echocardiography|Echocardiography]] | [[Neurocardiogenic syncope cardiac catheterization|Cardiac Catheterization]]

==Treatment==
====[[Neurocardiogenic syncope medical treatment|Medical Therapy]]====

====[[Neurocardiogenic syncope pacemaker therapy|Pacemaker Therapy]]====

==Related Chapters==
*[[Vasovagal syncope]]
*[[Postural orthostatic tachycardia syndrome]]
*[[Dysautonomia]]

==Additional Resources==
# Neurocardiogenic syncope. Carol Chen-Scarabelli, Tiziano M Scarabelli. BMJ 2004;329:336–41
# Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al for the Task Force on Syncope, European Society of Cardiology.Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001;22:1256-306.
# Vasovagal Syncope. Alexis M. Fenton, MD; Stephen C. Hammill, MD; Robert F. Rea, MD; Phillip A. Low, MD; and Win-Kuang Shen, MD. Ann Intern Med. 2000;133:714-725.
# Connolly SJ, Sheldon R, Thorpe KE, et al. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA. 2003;289:2224-9.

[[Category:Disease]]
[[Category:Cardiology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Postural orthostatic tachycardia syndrome

2012-05-17T02:35:29Z

Lakshmi Gopalakrishnan:

{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = |
Caption = |
DiseasesDB = |
ICD10 = |
ICD9 = |
ICDO = |
OMIM = |
MedlinePlus = |
eMedicineSubj = |
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{{SI}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

'''''Synonyms and Keywords:''''' postural tachycardia syndrome, POTS

==Overview==
'''Postural orthostatic tachycardia syndrome''' is a condition of [[dysautonomia]], and more specifically, [[orthostatic intolerance]], in which a change from the [[supine position]] to an upright position causes an abnormally large increase in heart rate, called [[tachycardia]]. This is often, but not always, accompanied by a fall in blood pressure. Patients with POTS have problems maintaining homeostasis when changing position, i.e. moving from one chair to another or reaching above their heads. Many patients also experience symptoms when stationary or even while lying down. Symptoms present in various degrees of severity depending on the patient. POTS is a serious, though non-life threatening, medical condition that can be severely disabling and debilitating. Many patients are unable to attend school or work, and especially severe cases can completely incapacitate the patient.

==History==
POTS was first named and identified by Schondorf and Low in 1993, however the syndrome has been described in medical studies dating back to at least 1940. Hypertension associated with POTS has been previously described as the "hyperadrenergic syndrome" by Streeten and "idiopathic hypovolemia" by Fouad. Hypotension associated with POTS has been previously described as the "neurally mediated hypotension" form of POTS

==Symptoms==
The hallmark symptom of POTS is an increase in heart rate from the supine to upright position of more than 30 beats per minute or to a heart rate greater than 120 beats per minute within 10 minutes of head-up tilt. This tachycardic response is often accompanied by a profound decrease in blood pressure and a wide variety of symptoms associated with hypotension including:

*[[lightheadedness]], sometimes called pre-syncope (pre-fainting) [[dizziness]] (but not [[Vertigo (medical)|vertigo]], which is also called dizziness)
*exercise intolerance
*extreme [[fatigue (physical)|fatigue]]
*[[Fainting|syncope]] (fainting)

Chronic or acute hypoperfusion of tissues and organs in the upper parts of the body are thought to cause the following symptoms:

*[[cold extremities]]
*[[chest pain]] and discomfort
*[[disorientation]]
*[[dyspnea]]
*[[headache]]
*[[muscle weakness]]
*[[tremulousness]]
*visual disturbances

Autonomic [[dysfunction]] is thought to cause additional gastrointestinal symptoms:
*[[abdominal pain]] or discomfort
*[[bloating]]
*[[constipation]]
*[[diarrhea]]
*[[nausea]]
*[[vomiting]]

Cerebral [[hypoperfusion]] can cause cognitive and emotive difficulties:
*brain fog
*[[burnout (psychology)|burnout]]
*decreased mental stamina
*[[depression (mood)|depression]]
*difficulty finding the right word
*impaired concentration
*[[sleep disorders]]

Inappropriate levels of [[epinephrine]] and [[norepinephrine]] lead to anxiety-like symptoms:
*[[chills]]
*feelings of fear
*[[Flushing (physiology)|flushing]]
*[[hyperthermia|overheating]]
*[[nervousness]]
*over-stimulation

Symptoms of POTS overlap considerably with those of [[generalized anxiety disorder]], and a misdiagnosis of an anxiety disorder is not uncommon.

==Associated Conditions==
*POTS is often accompanied by [[vasovagal syncope]], also called "neurally mediated hypotension" (NMH) or "neurocardiogenic syncope" (NCS). Vasovagal syncope is a fainting reflex due to a profound drop in blood pressure. Autonomic disfunction that occurs with these disorders causes blood to inappropriately pool in the limbs away from the heart, lungs, and brain. The combination of misdirected bloodflow and hypotension will invoke syncope. Tachycardia associated with POTS may be a cardiac response to restore cerebral hypoperfusion.
*POTS may be a cause of [[chronic fatigue syndrome]] in patients that exhibit signs of [[orthostatic intolerance]]. Treating POTS will greatly improve or even eliminate disabling fatigue for these patients.
*Some patients with [[fibromyalgia]] complain of dysautonomia-related symptoms. Treating these patients for POTS will often improve myofascial and neuropathic pain.
*Autonomic dysfunction is most likely responsible for [[irritable bowel syndrome]] in many patients as well.
*Patients with [[Ehlers-Danlos Syndrome]] (EDS) often develop POTS as a secondary condition.
*Some POTS patients experience symptoms associated with [[Restless Leg Syndrome]], or RLS. Treating POTS should also relieve RLS symptoms in these patients.

==Causes==
The causes of POTS are not fully known. Most patients develop symptoms in their teenage years during a period of rapid growth and see gradual improvement into their mid-twenties. Others develop POTS after a viral or bacterial infection such as [[mononucleosis]] or [[pneumonia]]. Some patients develop symptoms after experiencing some sort of trauma such as a car accident or injury. Women can also develop POTS during or after [[pregnancy]]. These patients generally have a poorer prognosis. In one large test, 12.5% of 152 patients with POTS reported a family history of orthostatic intolerance, suggesting that there is a genetic inheritance associated with POTS. <ref>Thieben, MJ, Sandroni, P, Sletten, DM, et. al Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc 2007; 82:308.</ref>

==Diagnosis==
POTS can be difficult to diagnose. A routine physical examination and standard blood tests will not indicate POTS. A [[tilt table test]] is vital to diagnosing POTS, although all symptoms must be considered before a final diagnosis is made. Tests to rule out [[Addison's Disease]], [[pheochromocytoma]], electrolyte imbalance, [[Lyme Disease]], [[Celiac Disease]], [[Ehlers-Danlos Syndrome]], and various food allergies are usually performed. A blood test may be performed to verify abnormally high levels of [[norepinephrine]] present in some POTS patients.

Between 75 and 80 percent of POTS patients are female and of the [[menstruating]] age. Most male patients develop POTS in their early to mid-teens during a [[growth spurt]] or following a viral or bacterial infection. Some women also develop POTS symptoms during or after [[pregnancy]].

==Prognosis==
Most POTS patients will see symptom improvement over the course of several years. Those who develop POTS in their early to mid teens during a period of rapid growth will most likely see complete symptom resolution by their mid twenties. Patients with post-viral POTS will also usually improve greatly or see a full symptom resolution. Adults who develop POTS, especially women during or after pregnancy, usually see milder improvement and can be plagued with their condition for life. Rarely, a teenager who develops POTS will gradually worsen overtime and have lifelong symptoms. Patients with secondary POTS as a consequence of [[Ehlers-Danlos Syndrome]] will also usually struggle with symptoms for life.

Recovered individuals do complain of occasional, non-debilitating recurrence of symptoms associated with autonomic dysfunction including dizzy spells, lightheadedness, flushing, transient syncope, and symptoms of irritable bowel syndrome.

==Treatment==
There is at this time only one drug approved by the [[Food and Drug Administration|FDA]] to treat [[orthostatic intolerance]], however several classes of drugs often provide symptom control and relief. Treatments must be carefully tested due to medication sensitivity often associated with POTS patients, and each patient will respond to different therapies in different ways. Most patients will respond to some form of treatment.

===Fludrocortisone===
The first line of treatment for POTS is usually [[fludrocortisone]], or Florinef, a [[corticosteroid]] used to increase sodium retention and thus increase blood volume and blood pressure. An increase in sodium and water intake must coincide with fludrocortisone therapy for effective treatment. Dietary increases in sodium and sodium supplements are often used. [[Gatorade]] is also effective in providing both sodium and fluid.

===Beta Blockers===
[[Beta blockers]] such as [[atenolol]] and [[propanolol]] are often prescribed to treat POTS. These medications work by blocking the effects of [[epinephrine]] and [[norepinephrine]] released by the autonomic nervous system. Beta blockers also reduce sympathetic activity by blocking sympathetic impulses.

===Midodrine===
[[Midodrine]] (Proamatine), is approved by the U.S. [[FDA]] to treat [[orthostatic hypotension]], a condition related to POTS. It is a stimulant that causes [[vasoconstriction]] and thereby increases [[blood pressure]] and allows more blood to return to the upper parts of the body. Use of midodrine is often discontinued due to intolerable side-effects, and it is known to cause supine hypertension (high blood pressure when lying down).

===Antidepressants===
Antidepressants, especially [[selective serotonin reuptake inhibitors]] (SSRIs) such as [[Prozac]], [[Zoloft]], [[Celexa]], [[Lexapro]], and [[Paxil]], can be extremely effective in re-regulating the autonomic nervous system and raising blood pressure. Some studies indicate that [[serotonin-norepinephrine reuptake inhibitor]]s (SNRIs) such as [[Effexor]] and [[Cymbalta]] are even more effective. [[Tricyclic antidepressants]], tetracyclic antidepressants, and [[monoamine oxidase inhibitors]] are also occasionally, but rarely, prescribed. A combination of two antidepressants, usually an [[SSRI]] or [[SNRI]] with [[Wellbutrin]] or [[Remeron]], is also shown to be very effective.

===Stimulants===
Medications used to treat [[attention deficit disorder|ADD]] and [[attention deficit hyperactivity disorder|ADHD]] such as [[Ritalin]] and [[Adderall]] are used to balance dopamine levels, increase vasoconstriction, and increase blood pressure.

===Anxiolytics===
Anti-anxiety medications, such as [[Xanax]], [[Ativan]], and [[Klonopin]], can be used to combat imbalances of [[adrenaline]] usually seen with POTS patients.

===Other Medications===
*[[Angiotensin converting enzyme inhibitors]], or ACE inhibitors, are used to increase [[vasoconstriction]], cardiac output, and sodium and water retention.
*[[Clonidine]] can work in patients with reduced sympathetic activity. Ironically an anti-hypertensive drug, Clonidine promotes production and release of [[epinephrine]] and [[norepinephrine]].
*[[Disopyramide]], or Norpace, is an antiarrhythmic medication that inhibits the release of [[epinephrine]] and [[norepinephrine]].
*[[Erythropoietin]], used to treat anemia via [[intravenous infusion]], is very effective at increasing blood volume. It is seldom used, however, due to the dangers of increasing the [[hematocrit]], the inconvenience of intravenous infusion, and its prohibitively expensive cost.
*[[Pregabalin]], or Lyrica, an [[anticonvulsant]] drug, has been shown to be especially effective in treating [[neuropathic pain]] associated with POTS. In fact, Lyrica is currently the only prescription drug approved by the FDA to treat [[fibromyalgia]]. Some POTS patients also report improvement in concentration and energy while on Lyrica.
*[[Pseudoephedrine]] and [[phenylephrine]], over the counter [[decongestants]], increase [[vasoconstriction]] by promoting the release of [[norepinephrine]].
*[[Pyridostigmine]], or Mestinon, inhibits the breakdown of [[acetylcholine]], promoting autonomic nervous system activity. It is especially effective in patients who exhibit symptoms of excessive sympathetic activity.
*[[Theophylline]], a drug used to treat respiratory diseases such as [[COPD]] and [[asthma]], is occasionally prescribed at low doses for POTS patients. Theophylline increases cardiac output, increases blood pressure, and stimulates [[epinephrine]] and [[norepinephrine]] production. Due to its very narrow [[therapeutic index]], Theophylline is known to cause a wide variety of side-effects and even [[toxicity]].
*Women who report a worsening of symptoms during [[menstruation]] will often use combined (containing both estrogen and progestin) forms of [[hormonal contraception]] to prevent hormonal changes and an aggravation of their condition.

===Dietary Changes===
*[[Alcohol]] has been shown to drastically exacerbate all types of [[orthostatic intolerance]] due to its [[vasodilation]] and [[dehydration]] properties. It should be avoided whenever possible because of its adverse effects and its [[interactivity]] with many of the medications prescribed to POTS patients.
*[[Caffeine]] helps some POTS patients due to its stimulative effects, however, other patients report a worsening of symptoms with caffeine intake. Each patient should experiment to determine whether caffeine helps or hurts his or her condition.
*Diets high in [[carbohydrates]] have been connected to impaired vasoconstrictive action. Eating foods with lower carbohydrate levels can mildly improve POTS symptoms.
*Eating frequent, small meals can reduce gastrointestinal symptoms associated with POTS by requiring the diversion of less blood to the abdomen.
*Patients diagnosed with POTS will usually be advised to maintain a high sodium diet in order to augment the effects of their medication regimen, especially if that regimen includes [[fludrocortisone]]. Patients should also drink plenty of fluids, with a recommended intake of at least two liters per day and as much as 500 milliliters every two hours throughout the day.

===Physical Therapy===
POTS symptoms can be worsened by postural asymmetries, restrictions in mobility, and areas of adverse mechanical tension in the nervous system. These physical abnormalities can be relieved with gentle manual therapies including neural mobilization (or neural tension work), myofascial release, and cranio-sacral therapy.

===External Body Pressure===
Pressure garments can reduce symptoms associated with [[orthostatic intolerance]] by constricting blood pressures with external body pressure. Compression hose and anti-embolism stockings, both knee and thigh-high, provide relief for many patients. For especially severe cases, military anti-shock trousers and anti-gravity suits, or g-suits can be helpful but also limiting.

===Exercise===
Exercise is very important for maintaining muscle strength and avoiding [[deconditioning]]. Though many POTS patients report difficulty exercising, some form of exercise is essential to controlling symptoms and eventually, improving the condition.

==References==
*Schondorf R, Low PA. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysdautonomia? Neurology. 1993;43:132-137. [http://www.neurology.org/cgi/content/abstract/43/1_Part_1/132 (PMID: 8423877)]
*Fouad FM, Tadena-Thome L, Braro EL et al: Idiopathic hypovolemia. Ann Intern Med. 1986; 104:298-303. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3511818 (PMID: 3511818)]
*Grubb, BP. The Postural Tachycardia Syndrome: a Brief Review of Etiology, Diagnosis and Treatment. Hellenic J Cardiol. 2002;43:47-52.
*Raj, SR. The Postural Tachycardia Syndrome (POTS): Pathophysiology, Diagnosis & Management. Indian Pacing and Electrophysiology Journal (ISSN 0972-6292). 2006; 6(2): 84-99. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16943900 online]
*Newton et al: Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM 2007 Aug;100(8):519-26 Epub 2007 Jul 7

==Resources==
*[http://www.ndrf.org National Dysautonomia Research Foundation (NDRF)]
*[http://www.dynakids.org Dysautonomia Youth Network of America, Inc.]
*[http://www.potsplace.com/ Dysautonomia Information Network (aka POTS Place)]
*[http://home.att.net/~potsweb/POTS.html POTS, Patient's Report (aka POTSweb)]

{{Electrocardiography}}
{{Circulatory system pathology}}

[[Category:Cardiology]]
[[Category:Neurology]]
[[Category:Endocrinology]]
[[Category:Syndromes]]
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Template:Neurocardiogenic syncope

2012-05-17T02:24:18Z

Lakshmi Gopalakrishnan:

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Neurocardiogenic syncope

2012-05-17T02:22:01Z

Lakshmi Gopalakrishnan:

'''For patient information on this page, click [[Neurocardiogenic syncope (patient information)|here]]'''

{{Neurocardiogenic syncope}}
{{CMG}}

==[[Neurocardiogenic syncope overview|Overview]]==

==[[Neurocardiogenic syncope pathophysiology|Pathophysiology]]==

==[[Neurocardiogenic syncope epidemiology and demographics|Epidemiology & Demographics]]==

==[[Neurocardiogenic syncope risk factors|Risk Factors]]==

==[[Neurocardiogenic syncope causes|Causes]]==

==[[Neurocardiogenic syncope natural history|Natural History, Prognosis & Complication]]==

==[[Neurocardiogenic syncope differentiating from other diseases|Differentiating Neurocardiogenic Syncope From Other Diseases]]==

==Diagnosis==
[[Neurocardiogenic syncope symptoms|History & Symptoms]] | [[Neurocardiogenic syncope physical examination|Physical Examination]] | [[Neurocardiogenic syncope electrocardiogram|Electrocardiogram]] | [[Neurocardiogenic syncope chest x-ray|Chest X-Ray]] | [[Neurocardiogenic syncope echocardiography|Echocardiography]] | [[Neurocardiogenic syncope cardiac catheterization|Cardiac Catheterization]]

==Treatment==
====[[Neurocardiogenic syncope medical treatment|Medical Therapy]]====

====[[Neurocardiogenic syncope pacemaker therapy|Pacemaker Therapy]]====

==Additional Resources==
# Neurocardiogenic syncope. Carol Chen-Scarabelli, Tiziano M Scarabelli. BMJ 2004;329:336–41
# Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al for the Task Force on Syncope, European Society of Cardiology.Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001;22:1256-306.
# Vasovagal Syncope. Alexis M. Fenton, MD; Stephen C. Hammill, MD; Robert F. Rea, MD; Phillip A. Low, MD; and Win-Kuang Shen, MD. Ann Intern Med. 2000;133:714-725.
# Connolly SJ, Sheldon R, Thorpe KE, et al. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA. 2003;289:2224-9.

[[Category:Disease]]
[[Category:Cardiology]]

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Neurocardiogenic syncope pathophysiology

2012-05-17T02:14:44Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
[[Neurocardiogenic Syncope]] is defined as a syndrome in which triggering of a neural reflex results in a usually self-limited episode of systemic hypotension characterized by both bradycardia (asystole or relative bradycardia) and peripheral [[vasodilation]]. It is caused by an abnormal or exaggerated autonomic response to various stimuli which results from excessive autonomic reflex activity, which shows as abnormal vascular tone and heart rate. In contrast, [[Orthostatic Hypotension]] is a failure of the autonomic reflex response.

==References==
{{reflist|2}}

[[Category:Cardiology]]

{{WH}}
{{WS}}

Neurocardiogenic Syncope pacemaker therapy

2012-05-17T02:14:01Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope pacemaker therapy to Neurocardiogenic syncope pacemaker therapy

#REDIRECT [[Neurocardiogenic syncope pacemaker therapy]]

Neurocardiogenic syncope pacemaker therapy

2012-05-17T02:14:01Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope pacemaker therapy to Neurocardiogenic syncope pacemaker therapy

__NOTOC__
{{Neurocardiogenic syncope}}

==ACC / AHA Guidelines- Permanent Pacing in Hypersensitive Carotid Sinus Syndrome and Neurocardiogenic Syncope (DO NOT EDIT) <ref name="Epstein"> Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008; 117: 2820–2840. PMID 18483207 </ref>==
{{cquote|
===Class I===
1. Permanent [[pacemaker|pacing]] is indicated for recurrent [[syncope]] caused by spontaneously occurring [[carotid sinus]] stimulation and [[carotid sinus]] pressure that induces [[ventricular asystole]] of more than 3 seconds. ''(Level of Evidence: C)''

===Class IIa===
1. Permanent [[pacemaker|pacing]] is reasonable for [[syncope]] without clear, provocative events and with a hypersensitive cardioinhibitory response of 3 seconds or longer. ''(Level of Evidence: C)''

===Class IIb===
1. Permanent [[pacemaker|pacing]] may be considered for significantly symptomatic neurocardiogenic [[syncope]] associated with [[bradycardia]] documented spontaneously or at the time of tilt-table testing. ''(Level of Evidence: B)''

===Class III===
1. Permanent [[pacemaker|pacing]] is not indicated for a hypersensitive cardioinhibitory response to [[carotid sinus]] stimulation without symptoms or with vague symptoms. ''(Level of Evidence: C)''

2. Permanent [[pacemaker|pacing]] is not indicated for situational vasovagal [[syncope]] in which avoidance behavior is effective and preferred. ''(Level of Evidence: C)''}}

==Sources==
* The ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities <ref name="Epstein"> Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008; 117: 2820–2840. PMID 18483207 </ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

Neurocardiogenic syncope medical treatment

2012-05-17T02:13:50Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Treatment==
*Infrequent episodes of [[vasovagal syncope]] that are preceded by a warning prodrome probably do not require any intervention besides counseling and observation. Attention to hydration and salt intake may suffice.

*[[Beta blockers]] are preferred as initial treatment but have not been demonstrated as effective in a randomized clinical trial. The [[Prevention of Syncope Trial]] showed that [[metoprolol]] was overall ineffective in preventing [[syncope]].

*In patients with borderline [[hypotension|low blood pressure]] who may be subject to symptomatic [[orthostasis]], [[fludrocortisone]], [[midodrine]], and compression hose are often used initially.
**[[Midodrine]] (ProAmantine 2.5-10 TID), an alpha agonist has been shown to be effective in several randomized controlled clinical trials. Side effects include nausea and supine hypertension.
**[[Fludrocortisone]] 0.1 mg/ Day, a mineralocorticoid that promotes renal reabsorption of sodium to cause increased blood volume has been used in the treatment of vasodepressor syncope in both children and adults. Caution is needed in elderly patients because they poorly tolerate the drug and there is a risk of [[hypertension]], [[cardiac failure]], and [[edema]].

*[[Scopolamine]], an anticholinergic agent, has central nervous system depressant effects and has been used successfully in some patients with syncope.

*[[SSRIs|Selective serotonin reuptake inhibitors]] ([[Paxil]] 20mg/ Day) selectively block serotonin, which has been shown to induce vagally mediated [[bradycardia]] and blood pressure lowering.

*[[Pyridostigmine]] (Mestinon 60mg po BID), an acetylcholinesterase inhibitor which increases acetylcholine levels at the autonomic ganglia. It prevents a drop in blood pressure without causing supine hypertension. Demonstrated to be effective in POTS and orthostatic hypotension. Can be used in conjuction with Midrodrine.

*In regards to pacing, in the '''VPS II Study''', 100 patients whoo were > 19 years of age who had a history of recurrent vasovagal syncope with 6 episodes of syncope ever or 3 episodes in the past 2 years, and a positive result on the head-up tilt table test (TTT) with a heart rate × blood pressure product < 6000/min × mm Hg were randomized to receive dual chamber pacing with rate drop. The results demonstrated that fewer patients in the DDD group than the ODO group had syncope during follow-up, but the difference did not reach statistical significance. Compared with ODO, the relative risk reduction in time to syncope with DDD was 30% (95% CI −33% to 63%). The number of pacemaker complications was similar between the DDD and ODO groups (10 vs 9 complications).

==References==
{{reflist|2}}

[[Category:Cardiology]]

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Neurocardiogenic Syncope medical treatment

2012-05-17T02:10:55Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope medical treatment to Neurocardiogenic syncope medical treatment

#REDIRECT [[Neurocardiogenic syncope medical treatment]]

Neurocardiogenic syncope medical treatment

2012-05-17T02:10:55Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope medical treatment to Neurocardiogenic syncope medical treatment

{{Neurocardiogenic syncope}}
{{CMG}}

==Treatment==

*Infrequent episodes of vasovagal syncope that are preceded by a warning prodrome probably do not require any intervention besides counseling and observation. Attention to hydration and salt intake may suffice.
*Beta blockers are preferred as initial treatment but have not been demonstrated as effective in a RCT. The [[Prevention of Syncope Trial]] showed that metoprolol was overall ineffective in preventing syncope.
*In patients with borderline low blood pressure who may be subject to symptomatic orthostasis, fludrocortisone, midodrine, and compression hose are often used initially.
**Midodrine (ProAmantine 2.5-10 TID), an alpha agonist has been shown to be effective in several randomized controlled clinical trials. Side effects include nausea and supine hypertension.
**Fludrocortisone 0.1 mg/ Day, a mineralocorticoid that promotes renal reabsorption of sodium to cause increased blood volume has been used in the treatment of vasodepressor syncope in both children and adults. Caution is needed in elderly patients because they poorly tolerate the drug and there is a risk of hypertension, cardiac failure, and edema.
*Scopolamine, an anticholinergic agent, has central nervous system depressant effects and has been used successfully in some patients with syncope
*Selective serotonin reuptake inhibitors (Paxil 20mg/ Day) selectively block serotonin, which has been shown to induce vagally mediated bradycardia and blood pressure lowering.
*Pyridostigmine (Mestinon 60mg po BID), an acetylcholinesterase inhibitor which increases acetylcholine levels at the autonomic ganglia. It prevents a drop in blood pressure without causing supine hypertension. Demonstrated to be effective in POTS and orthostatic Hypotension. Can be used in conjuction with Midrodrine.
*In regards to pacing, in the '''VPS II Study''', 100 patients whoo were > 19 years of age who had a history of recurrent vasovagal syncope with 6 episodes of syncope ever or 3 episodes in the past 2 years, and a positive result on the head-up tilt table test (TTT) with a heart rate × blood pressure product < 6000/min × mm Hg were randomized to receive dual chamber pacing with rate drop. The results demonstrated that fewer patients in the DDD group than the ODO group had syncope during follow-up, but the difference did not reach statistical significance. Compared with ODO, the relative risk reduction in time to syncope with DDD was 30% (95% CI −33% to 63%). The number of pacemaker complications was similar between the DDD and ODO groups (10 vs 9 complications).

Neurocardiogenic syncope physical examination

2012-05-17T02:10:35Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
The physical examination is unremarkable in 50% of patients.

==References==
{{reflist|2}}

[[Category:Cardiology]]

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Neurocardiogenic Syncope physical examination

2012-05-17T02:10:14Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope physical examination to Neurocardiogenic syncope physical examination

#REDIRECT [[Neurocardiogenic syncope physical examination]]

Neurocardiogenic syncope physical examination

2012-05-17T02:10:14Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope physical examination to Neurocardiogenic syncope physical examination

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
The physical examination is unremarkable in 50% of patients.

Neurocardiogenic syncope symptoms

2012-05-17T02:09:58Z

Lakshmi Gopalakrishnan: /* Recovery Phase */

__NOTOC__
{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==

==Triggers==
Vasovagal syncope may be precipitated by:
*The sight of blood
*Loss of blood
*Sudden stressful or painful experiences
*Surgical manipulation
*Trauma

==Prodrome==
Prior to the syncopal episode, patients may complain of a prodome consisting of:
*[[Nausea]]
*[[Diaphoresis]]
*[[Lightheadedness]]
*[[Blurred vision]]
*[[Headache]]
*[[Palpitations]]
*[[Paraesthesia]]
*[[Pallor]]

The symptoms usually occur in the upright position and resolve almost immediately when the patient assumes the supine position. In the upright position there is "downward" displacementof 300-800 cc of blood.

==Recovery Phase==
* “Washed out” and [[tired feeling]]

==References==
{{reflist|2}}

[[Category:Cardiology]]

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Neurocardiogenic Syncope symptoms

2012-05-17T02:09:35Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope symptoms to Neurocardiogenic syncope symptoms

#REDIRECT [[Neurocardiogenic syncope symptoms]]

Neurocardiogenic syncope symptoms

2012-05-17T02:09:35Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope symptoms to Neurocardiogenic syncope symptoms

Neurocardiogenic syncope differentiating from other diseases

2012-05-17T02:09:18Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
Neurocardiogenic syncope must be distinguished from situational syncope ([[cough syncope]], [[defecation syncope]], [[micturation syncope]], [[neurally mediated syncope]] and [[carotid sinus hypersensitivity]].

==Situational Syncope==
The syncope comes on after [[cough syncope|cough]], [[defecation syncope|defecation]], or [[micturation syncope|micturation]]

==Neurally Mediated Syncope==
This form of syncope occurs in the context of severe throat or facial pain as occurs in [[glossopharyngeal neuralgia]] or [[trigeminal neuralgia]].

==Neurocardiogenic Syncope==
Syncope following exposure to a noxious stiumulus, fear, or pain is consistent with neurocardiogenic syncope.

==Carotid Sinus Syncope==
Carotid sinus syncope may occur with rotation or turning of the head or pressure on the carotid sinus (for example, carotid massage, shaving, tight collars or neckwear, or tumour compression).

==References==
{{reflist|2}}

[[Category:Cardiology]]

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Neurocardiogenic Syncope differentiating from other diseases

2012-05-17T02:08:53Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope differentiating from other diseases to Neurocardiogenic syncope differentiating from other diseases

#REDIRECT [[Neurocardiogenic syncope differentiating from other diseases]]

Neurocardiogenic syncope differentiating from other diseases

2012-05-17T02:08:53Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope differentiating from other diseases to Neurocardiogenic syncope differentiating from other diseases

__NOTOC__
{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
Neurocardiogenic syncope must be distinguished from situational syncope ([[cough syncope]], [[defecation syncope]], [[micturation syncope]], [[neurally mediated syncope]] and [[carotid sinus hypersensitivity]].

==Situational Syncope==
The syncope comes on after [[cough syncope|cough]], [[defecation syncope|defecation]], or [[micturation syncope|micturation]]

==Neurally Mediated Syncope==
This form of syncope occurs in the context of severe throat or facial pain as occurs in [[glossopharyngeal neuralgia]] or [[trigeminal neuralgia]].

==Neurocardiogenic Syncope==
Syncope following exposure to a noxious stiumulus, fear, or pain is consistent with neurocardiogenic syncope.

==Carotid Sinus Syncope==
Carotid sinus syncope may occur with rotation or turning of the head or pressure on the carotid sinus (for example, carotid massage, shaving, tight collars or neckwear, or tumour compression).

Neurocardiogenic syncope epidemiology and demographics

2012-05-17T02:08:36Z

Lakshmi Gopalakrishnan:

{{Neurocardiogenic syncope}}
{{CMG}}

==Overview==
Neurocardiogenic syncope is the most common cause of syncope in children and adults.

==Incidence==
The prevalence is 22% in the general population. Approximately 50%-66% of syncope cases are classified as due to vasovagal syncope.

==References==
{{reflist|2}}

[[Category:Cardiology]]

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Neurocardiogenic Syncope epidemiology and demographics

2012-05-17T02:07:47Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope epidemiology and demographics to Neurocardiogenic syncope epidemiology and demographics

#REDIRECT [[Neurocardiogenic syncope epidemiology and demographics]]

Neurocardiogenic syncope epidemiology and demographics

2012-05-17T02:07:47Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope epidemiology and demographics to Neurocardiogenic syncope epidemiology and demographics

{{SI}}
{{CMG}}

==Overview==
Neurocardiogenic syncope is the most common cause of syncope in children and adults.

==Incidence==
The prevalence is 22% in the general population. Approximately 50%-66% of syncope cases are classified as due to vasovagal syncope.

Neurocardiogenic Syncope pathophysiology

2012-05-17T02:07:02Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope pathophysiology to Neurocardiogenic syncope pathophysiology

#REDIRECT [[Neurocardiogenic syncope pathophysiology]]

Neurocardiogenic syncope pathophysiology

2012-05-17T02:07:02Z

Lakshmi Gopalakrishnan: moved Neurocardiogenic Syncope pathophysiology to Neurocardiogenic syncope pathophysiology

Hypercalciuria

2012-05-08T18:49:19Z

Lakshmi Gopalakrishnan: /* See also */

{{Infobox_Disease
| Name = {{PAGENAME}}
| Image =
| Caption =
| DiseasesDB = 6220
| ICD10 = {{ICD10|E|83|5|e|70}}
| ICD9 = {{ICD9|791.9}}
| ICDO =
| OMIM =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| eMedicine_mult = |
| MeshID = D053565
}}

{{CMG}}; {{AOEIC}} {{LG}}

==Overview==
Hypercalciuria refers to elevated [[calcium]] in the urine. Chronic hypercalciuria may lead to impairment
of renal function, [[nephrocalcinosis]], and [[renal insufficiency]].

== Differential Diagnosis of Causes of {{PAGENAME}} ==
===By Organ System===
{|height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Vitamin D]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| [[hypoparathyroidism|Autosomal dominant hypoparathyroidism]], [[Hypophosphatasia]], [[hyperparathyroidism|Neonatal severe primary hyperparathyroidism]], [[Cushing syndrome]], [[Primary hyperparathyroidism]], [[Hyperthyroidism]], [[Pituitary tumour]] (growth hormone secreting)
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| [[Zero gravity]]
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Wilson disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[hypoparathyroidism|Autosomal dominant hypoparathyroidism]], [[chondrodysplasia|Metaphyseal chondrodysplasia, Jansen type]], [[Hypophosphatasia]], [[hyperparathyroidism|Neonatal severe primary hyperparathyroidism]], [[Wilson disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[chondrodysplasia|Metaphyseal chondrodysplasia, Jansen type]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| [[Bone metastases]]
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"| [[Wilson disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"| [[Dent disease]], [[X-linked recessive nephrolithiasis type 1]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Sarcoidosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Hypokalaemic distal renal tubular acidosis]], [[Idiopathic hypercalciuria]], [[Immobility]], [[Paget disease of bone]], [[Proximal renal tubular acidosis]]
|-
|}

===In alphabetical order===
*Autosomal dominant [[hypoparathyroidism]]
*[[Bone metastases]]
*[[Cushing syndrome]]
*[[Dent disease]]
*[[Hyperparathyroidism]], primary
*[[Hyperthyroidism]]
*Hypokalaemic distal [[renal tubular acidosis]]
*[[Hypophosphatasia]]
*Idiopathic hypercalciuria
*Immobility
*[[Metaphyseal chondrodysplasia]], Jansen type
*Neonatal severe [[primary hyperparathyroidism]]
*[[Paget disease]] of bone
*[[Pituitary tumour]] (growth hormone secreting)
*Proximal [[renal tubular acidosis]]
*[[Sarcoidosis]]
*[[Vitamin D]]
*[[Wilson disease]]
*X-linked recessive [[nephrolithiasis]] type 1
*Zero gravity

==Related Chapters==
* [[Hypercalcaemia]]

{{WH}}
{{WikiDoc Sources}}

Proximal renal tubular acidosis

2012-05-08T18:47:09Z

Lakshmi Gopalakrishnan: ←Redirected page to Renal tubular acidosis

#redirect [[renal tubular acidosis]]

Paget disease of bone

2012-05-08T18:46:39Z

Lakshmi Gopalakrishnan: ←Redirected page to Paget's disease of bone

#redirect [[Paget's disease of bone]]

Idiopathic hypercalciuria

2012-05-08T18:32:35Z

Lakshmi Gopalakrishnan: ←Redirected page to Hypercalciuria

#redirect [[Hypercalciuria]]

Hypokalaemic distal renal tubular acidosis

2012-05-08T18:32:18Z

Lakshmi Gopalakrishnan: ←Redirected page to Renal tubular acidosis

#redirect [[Renal tubular acidosis]]

Renal tubular acidosis

2012-05-08T18:32:01Z

Lakshmi Gopalakrishnan:

{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = Nephrocalcinosis.jpg|
Caption = Significant [[bilateral]] [[nephrocalcinosis]] (calcification of the kidneys) on a [[frontal]] [[X-ray]] (radiopacities (white) in the right upper and left upper quadrant of the image), as seen in distal renal tubular acidosis.|
DiseasesDB = 11687 |
DiseasesDB_mult = {{DiseasesDB2|11673}} {{DiseasesDB2|11705}} |
ICD10 = {{ICD10|N|25|8|n|25}} |
ICD9 = {{ICD9|588.89}} |
ICDO = |
OMIM = 179800 |
MedlinePlus = |
eMedicineSubj = |
eMedicineTopic = |
MeshID = D000141 |
}}

{{Search infobox}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
'''Renal tubular acidosis''' ('''RTA''') is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately [[wiktionary:acidify|acidify]] the [[urine]].<ref name=laing>{{cite journal |quotes= |last=Laing |first=C M |authorlink= |coauthors= |year=2005 |month=Jun |title=Renal tubular acidosis: developments in our understanding of the molecular basis. |journal=Int J Biochem Cell Biol |volume=37 |issue= 6|pages= 1151-61|id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15778079&dopt=Citation}}</ref> When blood is filtered by the kidney, the [[wiktionary:liquid or solution that has passed through a filter|filtrate]] passes through the tubules of the [[nephron]], allowing for exchange of salts, acid equivalents, and other [[wiktionary:solutes|solutes]] before it drains into the [[urinary bladder|bladder]] as [[urine]]. The [[metabolic acidosis]] that results from RTA may be caused either by failure to recover sufficient ([[alkaline]]) [[bicarbonate]] ions from the filtrate in the early portion of the nephron ([[proximal tubule]]) or by insufficient secretion of ([[acid]]) hydrogen ions into the latter portions of the nephron ([[distal tubule]]). Although a metabolic acidosis also occurs in those with [[renal insufficiency]], the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes.

The word ''[[acidosis]]'' refers to the tendency for RTA to lower the blood's pH. When the blood pH is below normal (7.35), this is called ''acidemia''. The metabolic acidosis caused by RTA is a [[normal anion gap acidosis]].

==Type I-Distal RTA==
[[Image:XrayRicketsLegssmall.jpg|thumb|left|200px|Radiograph of a [[rickets]] sufferer, a complication of distal RTA.]] 
Distal RTA ('''dRTA''') is the most common and also the classical form of RTA, being the first described. It has a number of causes which cause a common underlying problem, which is a failure of acid secretion by the alpha intercalated [[cell (biology)|cell]]s of the [[cortical collecting duct]] of the [[distal]] [[nephron]].
This leads to a failure acidify the urine to a [[pH]] of less than 5.3 even if the blood is too acidic (ie there is systemic acidemia), and consequently there is a tendency towards acidemia.
This leads to the clinical features of dRTA;<ref name=laing/>
*Variable [[metabolic acidosis]]/acidemia
*[[Hypokalemia]] (which may be severe)
*[[kidney stone|Urinary stone]] formation
*[[Nephrocalcinosis]] (deposition of [[calcium]] in the substance of the kidney)
*[[Bone]] demineralisation (causing [[rickets]] in children and [[osteomalacia]] in adults)

The acidosis is variable, and one may have dRTA with alpha intercalated cell failure without necessarily being acidemic, this is termed ''incomplete dRTA''. The diagnosis of dRTA can be made by the observation of a urinary [[pH]] of greater than 5.3 in the face of a systemic acidemia (usually taken to be a serum bicarbonate of 20 mmol/l or less). In the case of an incomplete dRTA, failure to acidify the urine following an oral acid loading challenge is often used as a test. The test usually performed is ''the short [[ammonium chloride]] test'',<ref>{{cite journal |quotes= |last=Wrong |first= O|authorlink= |coauthors=Davies HEF |year= 1959|month= |title=The Excretion of Acid in Renal Disease |journal=QJM |volume= 28|issue= |pages=259-313 |id= |url= |accessdate= }}</ref> in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described. <ref>{{cite journal |last=Walsh |first=S B |authorlink= |coauthors= |year=2007 |month=Apr |title=Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride. |journal=Kidney International |volume= |issue= |pages= |id= |url=http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17410104&dopt=Citation |accessdate= |quote= }}</ref>

The symptoms and sequelae of dRTA are variable and ranging from being completely [[asymptomatic]], through [[loin]] pain and [[hematuria]] from [[kidney stones]] to [[failure to thrive]] and severe [[rickets]] in childhood forms as well as possible [[renal failure]] and even [[death]].

Interestingly, dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.<ref>{{cite journal | author = Lewis D | title = What was wrong with Tiny Tim? | journal = Am J Dis Child | volume = 146 | issue = 12 | pages = 1403-7 | year = 1992 | id = PMID 1340779}}</ref><ref>http://www.time.com/time/magazine/article/0,9171,977391,00.html</ref>

===Causes===
[[Image:Alpha Intercalated Cell Cartoon.jpg|thumb|left|200px|Cartoon of the alpha intercalated cell, showing the apical proton pump and the basolateral band 3 (kAE1)]] 
*[[Autoimmune disease]]. Classically [[Sjögren's syndrome]], but it is also associated with [[systemic lupus erythematosus]], [[rheumatoid arthritis]] and even [[hypergammaglobulinemia]]. Hypokalaemia is often severe in these cases.<ref>{{cite journal |quotes= |last=Wrong |first=OM |authorlink= |coauthors= |year=1993 |month= |title=Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis |journal=QJM |volume=86 |issue=8 |pages=513-542 |id= |url=http://qjmed.oxfordjournals.org/cgi/content/abstract/86/8/513 |accessdate= }}</ref>
*Hereditary causes include mutations of [[Band 3]]<ref>{{cite journal |quotes= |last=Bruce |first= L J|authorlink= |coauthors= |year=1997 |month= |title=Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene |journal=J Clin Invest |volume=100 |issue= |pages=1693-1707 |id= |url=http://www.jci.org/cgi/content/abstract/100/7/1693 |accessdate= }}</ref> the basolateral bicarbonate transporter of the intercalated cell, which may transmit in an [[autosomal dominant]] fashion in western European cases, or in an [[autosomal recessive]] fashion in South East Asian cases. The South East Asian cases are associated with more severe hypokaemia.<ref>{{cite journal |quotes= |last=Bruce |first=L J |authorlink= |coauthors= |year=2000 |month= |title=Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells |journal=Biochem J |volume=350 |issue= |pages=41-51 |id= |url=http://www.biochemj.org/bj/350/0041/bj3500041.htm |accessdate= }}</ref> Other Hereditary causes include mutations of subunits of the [[apical_membrane|apical]] [[proton pump]] vH+-ATPase,<ref>{{cite journal|last=Wagner|first=CA |year=2004 |month=Oct|title=Renal Vacuolar H+-ATPase|journal=Physiological Reviews|volume=84 |issue=4 |pages=1263-314|url=http://physrev.physiology.org/cgi/content/full/84/4/1263}}</ref> which transmit in an autosomal recessive fashion, and may be associated with sensorineural [[deafness]].<ref>{{cite journal |quotes= |last=Karet |first=F E |authorlink= |coauthors= |year=1999 |month= |title=Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness |journal=Nature Genetics |volume=21 |issue= |pages=81-90 |id= |url=http://www.nature.com/ng/journal/v21/n1/abs/ng0199_84.html |accessdate= }}</ref>
*Liver [[cirrhosis]].
*Nephrocalcinosis. While it is a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the [[cortical collecting duct]].
*[[Renal transplantation]].
*[[Sickle cell anemia]].
*Toxins, including [[ifosfamide]],<ref>{{cite journal |last=Skinner |first=R|authorlink= |coauthors= |year=1996 |month=Aug |title=Risk factors for ifosfamide nephrotoxicity in children |journal=Lancet |volume=348(9027) |issue= |pages=578-80 |id= |url=http://cat.inist.fr/?aModele=afficheN&cpsidt=3189518 |accessdate= }}</ref> [[toluene]],<ref>{{cite journal |last=Battle |first=DC |authorlink= |coauthors= |year=1988 |month= |title=On the mechanism of toluene-induced renal tubular acidosis |journal=Nephron |volume=49 |issue=3 |pages=210-8 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3135502&dopt=Citation |accessdate= }}</ref> [[lithium carbonate]]<ref>{{cite journal |last=Boton |first=R |authorlink= |coauthors= |year=1987 |month=Nov |title=Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy |journal=Am J Kidney Dis |volume=10 |issue=5 |pages=329-45 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3314489&dopt=Abstract |accessdate= }}</ref> and [[amphotericin B]].<ref>{{cite journal |last=McCurdy |first=DK |authorlink= |coauthors= |year=1968 |month=Jan |title=Renal tubular acidosis due to amphotericin B |journal=NEJM |volume=278 |issue=3 |pages=124-30 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=5634966 |accessdate= }}</ref>
*Chronic urinary tract obstruction.

===Treatment===
This is relatively straightforward. It involves correction of the acidemia with oral [[sodium bicarbonate]] or [[sodium citrate]]. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with [[potassium citrate]] tablets which not only replace potassium but won't increase calcium excretion and thus exacerbate stone disease as sodium bicarbonate or citrate may do.<ref>{{cite journal |quotes= |last=Morris |first= R C|authorlink= |coauthors= |year=2002 |month= |title=Alkali Therapy In Renal Tubular Acidosis: Who Needs It? |journal=J Am Soc Nephrol |volume=13 |issue= |pages=2186–2188 |id= |url=http://jasn.asnjournals.org/cgi/reprint/13/8/2186.pdf |accessdate= }}</ref>

==Type 2-Proximal RTA==
Proximal RTA ('''pRTA''') is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3.<ref>{{cite journal |last=Rodriguez |first=Soriano J |authorlink= |coauthors= |year=1967 |month=Mar |title=Proximal renal tubular acidosis. A defect in bicarbonate reabsorption with normal urinary acidification. |journal=Paedatr Res |volume=1 |issue=2 |pages=81-98 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=6029811 |accessdate= |quote= }}</ref> pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalised dysfunction of the proximal tubular cells called [[Fanconi's syndrome]] where there is also phosphaturia, [[glycosuria]], aminoaciduria, uricosuria and tubular [[proteinuria]].
The principle feature of Fanconi's syndrome is bone demineralisation due to phosphate wasting.

===Causes===
Familial disorders
*[[Cystinosis]]<ref>{{cite journal |last=Gahl |first=William |authorlink= |coauthors= |year=2002 |month=July |title=Cystinosis |journal=NEJM |volume=347 |issue= |pages=111-121 |id= |url=http://content.nejm.org/cgi/content/extract/347/2/111 |accessdate= |quote= }}</ref>
*[[Galactosemia]]<ref>{{cite journal |last=Golberg |first=L |authorlink= |coauthors= |year=1956 |month=Aug |title=A clinical and biochemical study of galactosaemia; a possible explanation of the nature of the biochemical lesion |journal=Arch Dis Child |volume=31 |issue=158 |pages=254-64 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=13363463&dopt=Citation |accessdate= |quote= }}</ref>
*[[Glycogen storage disease]] (type I)<ref>{{cite journal |last=Matsuo |first=N |authorlink= |coauthors= |year=1986 |month=Mar |title=Proximal renal tubular acidosis in a child with type 1 glycogen storage disease. |journal=Acta Paediatr Scand |volume=75 |issue=2 |pages=332-5 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3457521&dopt=Citation |accessdate= |quote= }}</ref>
*[[Hereditary fructose intolerance]]<ref>{{cite journal |last=Morris |first=Curtis |authorlink= |coauthors= |year=1968 |month=July |title=An experimental renal acidification defect in patients with hereditary fructose intolerance |journal=J Clin Invest |volume=47 |issue=6 |pages=1389–1398 |id= |url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=297294&blobtype=pdf |accessdate= |quote= }}</ref>
*[[Oculocerebrorenal syndrome|Lowe's syndrome]]<ref>{{cite journal |last=Hodgson |first=SV |authorlink= |coauthors= |year=1986 |month=Mar |title=A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome. |journal=Am J Med Genet |volume=23 |issue=3 |pages=837-47 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3953680&dopt=Citation |accessdate= |quote= }}</ref>
*[[Tyrosinemia]]
*[[Wilson's disease]]<ref>{{cite journal |last=Weibers |first=DO |authorlink= |coauthors= |year=1979 |month=Aug |title=Renal stones in Wilson's disease |journal=Am J Med |volume=67 |issue=2 |pages=249-54 |id= |url=http://www.md-journal.com/pt/re/medicine/abstract.00005792-200005000-00002.htm;jsessionid=GJqhJ2BT5PpykNC8TdC42PFLB1RXHMtrf2YyZLnQWhD0G8p6zxML!1888299356!-949856144!8091!-1 |accessdate= |quote= }}</ref>

Acquired disorders
*[[Amyloidosis]]<ref>{{cite journal |last=Rochman |first=J |authorlink= |coauthors= |year=1980 |month=Oct |title=Adult Fanconi's syndrome with renal tubular acidosis in association with renal amyloidosis: occurrence in a patient with chronic lymphocytic leukemia |journal=Arch Int Med |volume=140 |issue=10 |pages= |id= |url=http://archinte.ama-assn.org/cgi/content/abstract/140/10/1361 |accessdate= |quote= }}</ref>
*[[Multiple myeloma]]<ref>{{cite journal |last= Messiaen |first=Thierry |authorlink= |coauthors= |year=2000 |month=May |title=Adult Fanconi Syndrome Secondary to Light Chain Gammopathy: Clinicopathologic Heterogeneity and Unusual Features in 11 Patients. |journal=Medicine |volume=79 |issue=3 |pages=135-154 |id= |url=http://www.md-journal.com/pt/re/medicine/abstract.00005792-200005000-00002.htm;jsessionid=GJqhJ2BT5PpykNC8TdC42PFLB1RXHMtrf2YyZLnQWhD0G8p6zxML!1888299356!-949856144!8091!-1 |accessdate= |quote= }}</ref>
*[[Paroxysmal nocturnal hemoglobinuria]]<ref>{{cite journal |last=Riley |first=AL |authorlink= |coauthors= |year=1977 |month=Jan |title=Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria |journal=Am J Med |volume=62 |issue=1 |pages=125-9 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=13653&dopt=Citation |accessdate= |quote= }}</ref>
*Toxins, such as [[HAART]], [[ifosfamide]],<ref>{{cite journal |last=Skinner |first=R |authorlink= |coauthors= |year=2003 |month=July |title=Chronic ifosfamide nephrotoxicity in children |journal=Medical and Pediatric Oncology |volume=41 |issue=3 |pages=190-197 |id= |url=http://www3.interscience.wiley.com/cgi-bin/abstract/104546256/ABSTRACT?CRETRY=1&SRETRY=0}}</ref> [[lead]], and [[cadmium]]

===Treatment===
Again this depends on oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate [[diuresis]]. The amount of bicarbonate given may have to be very large, to stay ahead of the urinary losses. Correction with oral [[bicarbonate]] may exacerbate urinary potassium losses and precipitate [[hypokalemia]].<ref>{{cite journal |last=Rodriguez |first=Soriano J |authorlink= |coauthors= |year=2002 |month=Aug |title=Renal tubular acidosis: the clinical entity |journal=J Am Soc Nephrol |volume=13 |issue=8 |pages=2160-70 |id= |url=http://jasn.asnjournals.org/cgi/reprint/13/8/2160.pdf |accessdate= |quote= }}</ref>As with dRTA, reversal of the chronic acidosis should reverse bone demineralisation.<ref>{{cite journal |quotes= |last=McSherry |first=E |authorlink= |coauthors= |year=1981 |month= |title=Renal tubular acidosis in childhood |journal=Kidney International |volume=20 |issue= |pages=799 |id= |url= |accessdate= }}</ref>

==Type 3 RTA==
This was previously used to designate a rare and transient mixed dRTA and pRTA of uncertain [[aetiology]]. Now it is used to describe a genetic defect in type 2 [[carbonic anhydrase]] (CA2), which is found in both the proximal and distal tubular cells, as well in bone. As a result it causes;
*proximal renal tubular acidosis
*distal renal tubular acidosis
*[[osteopetrosis]]
*cerebral [[calcification]] and subsequent mental impairment;
It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb region of North Africa, possibly due to the high prevalence of [[consanguinity]] there.<ref>{{cite journal |last=Fathallah |first=D. M. |authorlink= |coauthors= |year=1997 |month= |title=Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for founder effect and genomic recombination at the CA II locus |journal=Human Genetics |volume= |issue=99 |pages=634-637 |id=10.1007/s004390050419 |url=http://www.springerlink.com/content/7fvlgeehvxf5d5rt/fulltext.pdf |accessdate= }}</ref>
The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.

==Type 4 RTA ([[Hypoaldosteronism]])==
Type 4 RTA is not actually a tubular disorder at all, and nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a ''physiological'' reduction in distal tubular ammonium excretion, which is secondary to [[hypoaldosteronism]].
Its cardinal feature is [[hyperkalemia]], and measured urinary acidification is normal.

[[Image:Aldosteron.svg|thumb|300px|left|Aldosterone molecule]] 

===Causes===
*'''[[Aldosterone]] deficiency-Primary (rare)'''
#Primary [[adrenal insufficiency]]
#[[Congenital adrenal hyperplasia]]
#[[Aldosterone synthase]] deficiency
#Potassium sparing diuretics

*'''Hyporeninemic hypoaldosteronism''' (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)<ref name="hypoaldosteronism">{{cite journal |last=DeFronzo, RA |first= |authorlink= |coauthors= |year=1980 |month= |title=Hyperkalemia in hyporeninemic hypoaldosteronism |journal=Kidney International |volume= |issue=17 |pages=118. |id= |url= |accessdate= }}</ref>
#Renal dysfunction-most commonly [[diabetic nephropathy]]
#[[HIV]] infection
#[[ACE inhibitors]]
#[[NSAID]]s
#[[Ciclosporin]]

*'''Aldosterone resistance'''
#Drugs ([[Amiloride]], [[Spironolactone]],[[Trimethoprim]], [[Pentamidine]])
#[[Pseudohypoaldosteronism]]

===Treatment===
*Aldosterone deficiency should be treated with a [[mineralocorticoid]] (such as fludrocortisone), as well as possibly a [[glucocorticoid]] for [[cortisol]] deficiency, if present.
*Hyporeninemic hypoaldosteronism is ammenable to [[fludrocortisone]] treatment,<ref name="hypoaldosteronism"/> but the accompanying [[hypertension]] and [[edema]] can prove a problem in these patients, so often a [[diuretic]] (such as the [[thiazide]] diuretic, bendrofluazide,or a [[loop diuretic]], such as [[furosemide]]) is used to control the [[hyperkalemia]].<ref>{{cite journal |last=Sebastian |first=A |authorlink= |coauthors= |year=1984 |month= |title=Amelioration of hyperchloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal tubular acidosis |journal=Am J Nephrol |volume=4 |issue=5 |pages=287-300 |id= |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6524600&dopt=Citation |accessdate= }}</ref>

==Related Chapetsr==
*[[Hyperchloremic acidosis]]
*[[Hypokalemia]]
*[[Kidney stone]]

==References==
{{reflist|2}}

{{Nephrology}}

[[Category:Kidney diseases]]

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{{WikiDoc Sources}}

X-linked recessive nephrolithiasis type 1

2012-05-08T18:29:15Z

Lakshmi Gopalakrishnan: ←Redirected page to Nephrolithiasis

#redirect [[Nephrolithiasis]]

Dent's disease

2012-05-08T18:27:02Z

Lakshmi Gopalakrishnan:

{{Infobox Anatomy |
Name = {{PAGENAME}} |
Latin = |
GraySubject = 253 |
GrayPage = 1221 |
Image = Gray1128.png |
Caption = Nephron of the kidney without [[juxtaglomerular apparatus]] |
Image2 = Nefron.png |
Caption2 = Nephron. Diagram is labeled in [[Polish language|Polish]], but flow can still be identified. |
Precursor = [[Metanephric blastema]] |
System = |
Artery = |
Vein = |
Nerve = |
Lymph = |
MeshName = Nephrons |
MeshNumber = |
DorlandsPre = |
DorlandsSuf = |
}}
{{Search infobox}}
{{SCC}}

==Overview==

'''Dent's disease''' (or '''Dent disease''') is a rare [[X-linked recessive]] inherited condition that affects the [[kidney]]. It is one cause of [[Fanconi syndrome]], and is characterized by tubular proteinuria, [[hypercalciuria]], [[calcium nephrolithiasis]], [[nephrocalcinosis]] and [[chronic renal failure]].

"Dent's disease" is often used to describe an entire group of familial disorders, including X-linked recessive [[nephrolithiasis]] with renal failure, X-linked recessive hypophosphataemic rickets, and both Japanese and idiopathic low molecular weight proteinuria.<ref>Mayo Clinic, Division of Nephrology and Hypertension, [http://mayoresearch.mayo.edu/mayo/research/nephrology/renal_stone_disease.cfm Mineral Metabolism and Stone Disease]</ref>

== History ==

Dent's disease was first described by Dent, C. E. and Friedman, M in 1964 when they reported 2 unrelated British boys with [[rickets]] associated with renal tubular damage characterized by [[hypercalciuria]], [[hyperphosphaturia]], [[proteinuria]], and [[aminoaciduria]].<ref>Dent CE, Friedman M. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=14169453&dopt=Abstract Hypercalciuric rickets associated with renal tubular damage]</ref> This is a genetic disorder caused by the [[genetic mutations]] in the renal [[chloride channel]] [http://www.gene.ucl.ac.uk/nomenclature/data/get_data.php?gd_app_sym=CLCN5 ClCN5] which encodes a kidney-specific voltage gated [[chloride channel]] and a 746 amino acid protein (CLC-5), with 12 to 13 transmembrane domains; it manifests itself through low molecular weight proteinuria, hypercalciuria, aminoaciduria and hypophosphataemia. Because of its rather rare occurrence, Dent's disease is often diagnosed as [[idiopathic]] [[hypercalciuria]] (IH), i.e. excess calcium in urine with undetermined causes.

== Symptoms ==

Dent's disease often produces symptoms of:

* Extreme thirst combined with [[dehydration]] which leads to frequent urination
* [[Nephrolithiasis]] (kidney stones)
* [[Hypercalciuria]] (high urine calcium - ''>300 mg/d or >4 mg/kg per d'') with normal levels blood/serum calcium)

Dent's disease ''may'' also be associated with:
* [[Aminoaciduria]] ([[amino acids]] in urine)
* [[Phosphaturia]] (phosphate in urine)
* [[Glycosuria]] (glucose in urine)
* [[Kaliuresis]] (potassium in urine)
* [[Uricosuria]] (excessive amounts of uric acid in the urine.)
* Impaired urinary acidification
* [[Rickets]]

In a very large study of patients with Dent's disease, 9 out of 15 men, and 1 out of 10 women suffered [[end-stage renal failure]] by the age of 47.<ref>Helen K Burgess, Satishkumar A Jayawardene and Nestor Velasco [http://ndt.oxfordjournals.org/cgi/content/full/16/7/1512 Dent's disease: can we slow its progression?]</ref>

== Genetics ==
[[Image:XlinkRecessive.jpg|thumb|left|100px|X-linked recessive inheritance.]]
Because it is an X-linked recessive disorder, only males are affected with the disease, whereas females are asymptomatic carriers. The males are prone to manifesting symptoms in early adulthood with symptoms of calculi, rickets or even with renal failure in more severe cases.

In humans, gene CLCN5 is located on chromosome Xp11.22 and has a 2238-bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746 amino acid protein.<ref>Fisher SE, Black GC, Lloyd SE, Hatchwell E, Wrong O, Thakker RV, Craig IW: [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=8575751&dopt=AbstractPlus Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis). Hum Mol Genet3 : 2053-2059,1994]</ref>

CLCN5 belongs to the family of voltage-gated chloride channel genes (CLCN1-CLCN7, and CLCKa and CLCKb) that have approximately 12 transmembrane domains. These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly cell volume.<ref>Jentsch TJ, Friedrich T, Schriever A, Yamada H: [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10370055&dopt=AbstractPlus The CLC chloride channel family. Pflügers Arch 437:783 -795, 1999]</ref>

The mechanisms by which CLC-5 dysfunction results in hypercalciuria and the other features of Dent's disease remain to be elucidated. The identification of additional CLCN5 mutations may help in these studies, and we have pursued such studies in patients with Dent's disease.<ref>Katsusuke Yamamoto, [http://jasn.asnjournals.org/cgi/content/full/11/8/1460 Characterization of Renal Chloride Channel (CLCN5) Mutations in Dent's Disease, J Am Soc Nephrol 11:1460-1468, 2000]</ref>
 

== Treatment ==

As of today, there is no agreed-upon treatment of Dent's disease and no therapy has been formally accepted. Most treatment measures are mostly supportive in nature and they include:

* [[Thiazide]] [[diuretics]] which have been used with success in reducing the calcium output in urine, but they are also known to cause [[hypokalemia]].
** In rats with [[diabetes insipidus]] thiazide diuretics inhibit the NaCl co-transporter in the renal distal convoluted tubule leading indirectly to less water and solutes being delivered to the distal tubule.<ref>Johannes Loffing, JASN, [http://jasn.asnjournals.org/cgi/content/full/15/11/2948 Paradoxical Antidiuretic Effect of Thiazides in Diabetes Insipidus: Another Piece in the Puzzle]</ref>
* [[Amiloride]] which also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria.
** A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dent's patients, however urine pH was "significantly higher in patients with Dent’s disease than in those with idiopathic hypercalciuria (P < 0.03), and supersaturation for uric acid was consequently lower (P < 0.03)."<ref>JASN, [http://jasn.asnjournals.org/cgi/content/full/13/12/2938 Responsiveness of Hypercalciuria to Thiazide in Dent’s Disease]</ref>
* For patients with [[osteomalacia]], [[Vitamin D]] or derivatives have been employed, apparently with success.
* Some lab tests on mice with CLC-5 related tubular damage showed that a high [[citrate]] diet preserved renal function and delayed progress of renal disease.<ref>Johns Hopkins University School of Medicine, [http://cat.inist.fr/?aModele=afficheN&cpsidt=17008604 High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease]</ref>

==Resources==
* [http://ndt.oxfordjournals.org/cgi/content/full/16/7/1512 Dent's disease: can we slow its progression?]
* [http://jasn.asnjournals.org/cgi/content/full/16/3/729#R5 Genetic Hypercalciuria]
* [http://jasn.asnjournals.org/cgi/content/full/13/12/2938 Responsiveness of Hypercalciuria to Thiazide in Dent’s Disease]
* [http://cat.inist.fr/?aModele=afficheN&cpsidt=17008604 High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease]
* [http://www.orpha.net/static/GB/dent_disease.html Dent disease on Orphanet]

== References ==
{{reflist|2}}

{{WH}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Kidney diseases]]
[[Category:Urinary system]]
[[Category:Urology]]

Wilson's disease

2012-05-08T18:25:30Z

Lakshmi Gopalakrishnan:

'''For patient information click [[Wilson's disease (patient information)|here]]'''
{{Infobox_Disease |
Name = Wilson disease |
Image = PBB Protein ATP7B image.jpg |
Caption = Mutations in the ''[[ATP7B]]'' gene are present in the majority of patients with Wilson's disease. |
DiseasesDB = 14152 |
ICD10 = {{ICD10|E|83|0|e|70}} |
ICD9 = {{ICD9|275.1}} |
OMIM = 277900 |
MedlinePlus = 000785 |
eMedicineSubj = |
eMedicineTopic = |
eMedicine_mult = |
MeshID = D006527 |
}}
{{SI}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
'''Wilson's disease''' or '''hepatolenticular degeneration''' is an [[autosomal recessive]] [[genetic disorder]] in which [[copper]] accumulates in [[biological tissue|tissues]]; this manifests as [[neurology|neurological]] or [[psychiatry|psychiatric]] symptoms and [[liver]] disease. It is treated with [[medication]] that reduces copper absorption or removes the excess copper from the body, but occasionally a [[liver transplantation|liver transplant]] is required.<ref name=Ala/>

The condition is due to [[mutation]]s in the [[Wilson disease protein]] (ATP7B) [[gene]]. A single abnormal copy of the gene is present in 1 in 100 people, who do not develop any symptoms (they are [[Genetic carrier|carrier]]s). If a child inherits the gene from both parents, they may develop Wilson's disease. Symptoms usually appear between the ages of 6 and 20 years, but cases in much older patients have been described. Wilson's disease occurs in 1 to 4 per 100,000 people.<ref name=Ala/> Wilson's disease is named after Dr [[Samuel Alexander Kinnier Wilson]] (1878-1937), the British neurologist who first described the condition in 1912.<ref name=Wilson1912/>

==History==

The disease bears the name of the British physician Dr [[Samuel Alexander Kinnier Wilson]] (1878-1937), a [[Neurology|neurologist]] who described the condition, including the pathological changes in the brain and liver, in 1912.<ref name=Wilson1912>{{cite journal| author=Kinnier Wilson SA | title=Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver | journal=Brain | year=1912 | volume=34 | issue=1 | pages=295–507 | doi=10.1093/brain/34.4.295 | url=http://brain.oxfordjournals.org/cgi/reprint/34/4/295 | format=PDF}}</ref> Wilson's work had been predated by, and drew on, reports from the German neurologist Dr [[Carl Friedrich Otto Westphal|Carl Westphal]] (in 1883), who termed it "pseudosclerosis", by the British neurologist Dr [[William Richard Gowers|William Gowers]] (in 1888), and by Dr [[Adolph Strümpell]] (in 1898), who noted hepatic cirrhosis.<ref name=Robertson>{{cite journal |author=Robertson WM |title=Wilson's disease |journal=Arch. Neurol. |volume=57 |issue=2 |pages=276–7 |year=2000 |month=February |pmid=10681092 |url=http://archneur.ama-assn.org/cgi/content/full/57/2/276 |doi=10.1001/archneur.57.2.276}}</ref> Prof John N. Cumings made the link with copper accumulation in both the liver and the brain in 1948.<ref name="pmid18124738">{{cite journal |author=Cumings JN |title=The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration |journal=Brain |volume=71 |issue=Dec |pages=410–5 |year=1948 |pmid=18124738 | doi=10.1093/brain/71.4.410 | url=http://brain.oxfordjournals.org/cgi/reprint/71/4/410 |format=PDF}}</ref> The occurrence of hemolysis was noted in 1967.<ref>{{cite journal |author=McIntyre N, Clink HM, Levi AJ, Cumings JN, Sherlock S |title=Hemolytic anemia in Wilson's disease |journal=N. Engl. J. Med. |volume=276 |issue=8 |pages=439–44 |year=1967 |month=February |pmid=6018274}}</ref>

Cumings, and simultaneously the New Zealand neurologist Dr Derek Denny-Brown, working in the USA, first reported effective treatment with metal chelator [[dimercaprol|British anti-Lewisite]] in 1951.<ref>{{cite journal |author=Cumings JN |title=The effects of B.A.L. in hepatolenticular degeneration |journal=Brain |volume=74 |issue=1 |pages=10–22 |year=1951 |month=March |pmid=14830662 |doi=10.1093/brain/74.1.10}}</ref><ref>{{cite journal |author=Denny-Brown D, Porter H |title=The effect of BAL (2,3-dimercaptopropanol) on hepatolenticular degeneration (Wilson's disease) |journal=N. Engl. J. Med. |volume=245 |issue=24 |pages=917–25 |year=1951 |month=December |pmid=14882450}}</ref> This treatment had to be injected but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose but had few treatments available.<ref name=Robertson/><ref>{{cite journal |author=Vilensky JA, Robertson WM, Gilman S |title=Denny-Brown, Wilson's disease, and BAL (British antilewisite [2,3-dimercaptopropanol]) |journal=Neurology |volume=59 |issue=6 |pages=914–6 |year=2002 |month=September |pmid=12297577}}</ref> The first effective oral chelation agent, [[penicillamine]], was discovered in 1956 by the British neurologist Dr John Walshe.<ref name=Walshe1956>{{cite journal |author=Walshe JM |title=Wilson's disease; new oral therapy |journal=Lancet |volume=267 |issue=6906 |pages=25–6 |year=1956 |month=January |pmid=13279157 |doi=10.1016/S0140-6736(56)91859-1}}</ref> In 1982, Walshe also introduced trientine,<ref>{{cite journal |author=Walshe JM |title=Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride |journal=Lancet |volume=1 |issue=8273 |pages=643–7 |year=1982 |month=March |pmid=6121964 |doi=10.1016/S0140-6736(82)92201-2}}</ref> and was the first to develop tetrathiomolybdate for clinical use.<ref>{{cite journal |author=Harper PL, Walshe JM |title=Reversible pancytopenia secondary to treatment with tetrathiomolybdate |journal=Br. J. Haematol. |volume=64 |issue=4 |pages=851–3 |year=1986 |month=December |pmid=3801328 |doi=10.1111/j.1365-2141.1986.tb02250.x}}</ref> Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by Brewer and colleagues at the University of Michigan.<ref name=Walshe1996/><ref>{{cite journal |author=Brewer GJ |title=Recognition, diagnosis, and management of Wilson's disease |journal=Proc. Soc. Exp. Biol. Med. |volume=223 |issue=1 |pages=39–46 |year=2000 |month=January |pmid=10632959 |url=http://www.ebmonline.org/cgi/content/full/223/1/39 |doi=10.1046/j.1525-1373.2000.22305.x}}</ref>

The genetic basis of Wilson's disease and linkage to ATP7B mutations was elucidated in the 1980s and 1990s by several research groups.<ref name="pmid8298641">{{cite journal |author=Tanzi RE, Petrukhin K, Chernov I, ''et al'' |title=The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene |journal=Nat. Genet. |volume=5 |issue=4 |pages=344–50 |year=1993 |pmid=8298641 |doi=10.1038/ng1293-344}}</ref><ref name="pmid8298639">{{cite journal |author=Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW |title=The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene |journal=Nat. Genet. |volume=5 |issue=4 |pages=327–37 |year=1993 |pmid=8298639 |doi=10.1038/ng1293-327}}</ref>

==Pathophysiology==
[[Image:Brain structure.gif|left|framed|Location of the basal ganglia, the part of the brain affected by Wilson's disease]]
Copper is needed by the body for a [[Copper#Biological_role|number of functions]], predominantly as a [[Cofactor (biochemistry)|cofactor]] for a number of enzymes such as ceruloplasmin, [[cytochrome c oxidase]], [[dopamine beta hydroxylase|dopamine β-hydroxylase]], [[superoxide dismutase]] and [[tyrosinase]].<ref name=deBie2007/>

Copper enters the body through the [[Gastrointestinal tract|digestive tract]]. A transporter protein on the [[enterocyte|cells of the small bowel]], [[SLC31A1|copper membrane transporter 1]] (CMT1), carries copper inside the cells, where some is bound to [[metallothionein]] and part is carried by [[ATOX1]] to an organelle known as the [[Golgi apparatus|trans-Golgi network]]. Here, in response to rising concentrations of copper, an enzyme called [[ATP7A]] releases copper into the [[portal vein]] to the liver. Liver cells also carry the CMT1 protein, and metallothionein and ATOX1 bind it inside the cell, but here it is ATP7B that links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into [[bile]]. Both functions of ATP7B are impaired in Wilson's disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apoceruloplasmin) and rapidly degraded in the bloodstream.<ref name=deBie2007/>

When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage through a process known as [[Fenton's reagent|Fenton chemistry]]; this damage eventually leads to [[hepatitis|chronic active hepatitis]], [[fibrosis]] (deposition of connective tissue) and [[cirrhosis]]. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body but particularly in the kidneys, eyes and brain. In the brain, most copper is deposited in the [[basal ganglia]], particularly in the [[putamen]] and [[globus pallidus]] (together called the ''[[lenticular nucleus]]''); these areas normally participate in the coordination of movement as well as playing a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilson's disease.<ref name=deBie2007/>

[[Image:Copper metabolism.png|center|framed|Normal absorption and distribution of copper. Cu = copper, CP = ceruloplasmin, green = ATP7B carrying copper.]]

It is not clear why Wilson's disease causes hemolysis, but various lines of evidence suggest that high levels of free (non-ceruloplasmin bound) copper have a direct effect on either oxidation of [[hemoglobin]], inhibition of energy-supplying enzymes in the [[red blood cell]], or direct damage to the [[cell membrane]].<ref>{{cite book |last=Lee |first=GR |editor=Lee GR, Foerster J, Lukens J ''et al'' |title=Wintrobe's clinical hematology |edition=10th |volume=vol 1 |year=1999 |publisher=Williams & Wilkins |isbn=0-683-18242-0 |pages=1298 |chapter=Chapter 48: acquired hemolytic anaemias resulting from direct effects of infectious, chemical or physical agents }}</ref>

==Signs and symptoms==
The main sites of copper accumulation are the [[liver]] and the [[brain]], and consequently liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis.<ref name=Ala>{{cite journal |author=Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML |title=Wilson's disease |journal=Lancet |volume=369 |issue=9559 |pages=397–408 |year=2007 |pmid=17276780 |doi=10.1016/S0140-6736(07)60196-2}}</ref> Patients with liver problems tend to come to medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their twenties or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these patients, when tested, turn out to have been experiencing symptoms of the condition but haven't received a diagnosis.<ref name=Merle2007>{{cite journal |author=Merle U, Schaefer M, Ferenci P, Stremmel W |title=Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study |journal=Gut |volume=56 |issue=1 |pages=115–20 |year=2007 |pmid=16709660 |doi=10.1136/gut.2005.087262 | url=http://gut.bmj.com/cgi/content/full/56/1/115}}</ref>

===Liver disease===

Liver disease may present as [[tiredness]], increased bleeding tendency or confusion (due to [[hepatic encephalopathy]]) and [[portal hypertension]]. The latter, a condition in which the pressure on the [[portal vein]] is markedly increased, leads to [[esophageal varices]] (blood vessels in the [[esophagus]]) that may bleed in a life-threatening fashion, [[splenomegaly]] (enlargement of the spleen) and [[ascites]] (accumulation of fluid in the abdominal cavity). On examination, signs of chronic liver disease such as [[spider angioma|spider naevi]] (small distended blood vessels, usually on the chest) may be observed. [[Chronic active hepatitis]] has caused [[cirrhosis]] of the liver in most patients by the time they develop symptoms. While most people with cirrhosis have an increased risk of [[hepatocellular carcinoma]] (liver cancer), this risk is relatively very low in Wilson's disease.<ref name=Ala/>

About 5% of all patients are diagnosed only when they develop fulminant [[acute liver failure]], often in the context of a [[hemolytic anemia]] (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by deranged [[coagulation]]) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products such as [[ammonia]] in the bloodsteam. When these irritate the [[brain]], the patient develops [[hepatic encephalopathy]] (confusion, coma, seizures and finally life-threatening [[Cerebral edema|swelling of the brain]]).<ref name=Ala/>

===Neuropsychiatric symptoms===

About half the patients with Wilson's have neurological or psychiatric problems. Most patients initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms then follow, often in the form of [[parkinsonism]] (increased rigidity and slowing of routine movements) with or without a typical hand [[tremor]], [[ataxia]] (lack of coordination) or [[dystonia]] (twisting and repetitive movements of part of the body). [[Seizure]]s and [[migraine]] appear to be more common in Wilson's disease.<ref name=Ala/>

Psychiatric problems due to Wilson's disease may include behavioral changes, [[clinical depression|depression]], [[anxiety]] and [[psychosis]].<ref name=Ala/>

===Other organ systems===
[[Image:Kayser-Fleischer ring.jpg|left|thumb|200px|A Kayser-Fleischer ring in a patient with symptoms suggestive of Wilson's disease]]
Various medical conditions have been linked with copper accumulation in Wilson's disease:
* Eyes: ''[[Kayser-Fleischer ring]]s'' (KF rings) may be visible around the iris. They are due to copper deposition in [[Descemet's membrane]] of the [[cornea]]. They do not occur in all patients and may only be visible on [[slit lamp]] examination. Wilson's disease is also associated with sunflower [[cataract]]s, brown or green pigmentation of the anterior and posterior lens capsule. Neither cause significant visual loss.<ref name=Ala/> KF rings occur in 66% of cases, more often in those with neurological than with liver problems.<ref name=Merle2007/>
* Kidneys: [[renal tubular acidosis#Type 2-Proximal RTA|renal tubular acidosis]], a disorder of [[bicarbonate]] handling by the [[proximal tubule]]s leads to [[nephrocalcinosis]] (calcium accumulation in the kidneys), weakening of the bone (due to calcium and phosphate loss) and occasionally [[aminoaciduria]] (loss of [[amino acid]]s, needed for protein synthesis).<ref name=Ala/>
* Heart: [[cardiomyopathy]] (weakness of the heart muscle) is a rare but recognized problem in Wilson's disease; it may lead to [[heart failure]] (fluid accumulation due to decreased pump function) and [[cardiac arrhythmia]]s (episodes of irregular and/or abnormally fast or slow heart beat).<ref name=Ala/>
* Hormones: [[hypoparathyroidism]] (failure of the [[parathyroid gland]]s, leading to low calcium levels), [[infertility]] and [[habitual abortion]].<ref name=Ala/>

==Diagnosis==

Wilson's disease may be suspected on the basis of any of the symptoms mentioned above, or when a close relative has been found to have Wilson's. Most patients have slightly abnormal [[liver function tests]] such as a raised [[aspartate transaminase]], [[alanine transaminase]] and [[bilirubin]] level. If the liver damage is significant, [[albumin]] may be decreased due to an inability of damaged liver cells to produce this protein; likewise, the [[prothrombin time]] (a test of [[coagulation]]) may be prolonged as the liver is unable to produce proteins known as clotting factors.<ref name=Ala/> [[Alkaline phosphatase]] levels are relatively low in patients with Wilson's-related acute liver failure.<ref name="pmid3758940">{{cite journal |author=Shaver WA, Bhatt H, Combes B |title=Low serum alkaline phosphatase activity in Wilson's disease |journal=Hepatology |volume=6 |issue=5 |pages=859–63 |year=1986 |pmid=3758940 |doi=10.1002/hep.1840060509}}</ref> If there are neurological symptoms, [[magnetic resonance imaging]] (MRI) of the brain is usually performed; this shows hyperintensities in the part of the brain called the [[basal ganglia]] in the [[spin-spin relaxation time|T2]] setting.<ref name=Roberts>{{cite journal| author=Roberts EA, Schilsky ML |title=A practice guideline on Wilson disease |journal=Hepatology |year=2003 |volume=37 |issue=6 |pages=1475–92 |pmid=12774027 |doi=10.1053/jhep.2003.50252 |url=http://www3.interscience.wiley.com/cgi-bin/fulltext/106595824/PDFSTART |format=PDF}}</ref>

There is no totally reliable test for Wilson's disease, but levels of [[ceruloplasmin]] and copper in the blood, as well of the amount of copper excreted in urine during a 24 hour period, are together used to form an impression of the amount of copper in the body. The [[gold standard (test)|gold standard]] or most ideal test is a [[liver biopsy]].<ref name=Ala/>

===Ceruloplasmin===
[[Image:PBB Protein CP image.jpg|left|thumb|80px|Ceruloplasmin]]
Levels of [[ceruloplasmin]] are abnormally low (<0.2 gram/liter) in 80-95% of cases.<ref name=Ala/>

It can, however, be present at normal levels in people with ongoing [[inflammation]] as it is an [[acute phase protein]].

Low ceruloplasmin is also found in [[Menkes disease]] and [[aceruloplasminemia]], which are related to, but much rarer than, Wilson's disease.<ref name=Ala/><ref name=Roberts/>

The combination of neurological symptoms, Kayser-Fleisher rings and a low ceruloplasmin level is considered sufficient for the diagnosis of Wilson's disease. In many cases, however, further tests are needed.<ref name=Roberts/>

===Serum and urine copper===

Serum copper and more importantly urine copper are elevated in Wilson's disease. Urine is collected for 24 hours in a bottle with a copper-free liner. Levels above 100 μg/24h (1.6 μmol/24h) confirm Wilson's disease, and levels above 40 μg/24h (0.6 μmol/24h) are strongly indicative.<ref name=Ala/> High urine copper levels are not unique to Wilson's disease; they are sometimes observed in [[autoimmune hepatitis]] and in [[cholestasis]] (any disease obstructing the flow of bile from the liver to the small bowel).<ref name=Roberts/>

In children, the [[penicillamine]] test may be used. A 500 mg oral dose of penicillamine is administered, and urine collected for 24 hours. If this contains more than 1600 μg (25 μmol), it is a reliable indicator of Wilson's disease. This test has not been validated in adults.<ref name=Roberts/>

===Liver biopsy===
Once other investigations have indicated Wilson's disease, the ideal test is the removal of a small amount of liver tissue through a [[liver biopsy]]. This is assessed microscopically for the degree of [[steatosis]] and [[cirrhosis]], and [[histochemistry]] and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 [[microgram|μg]] of copper per gram of dried liver tissue confirms Wilson's disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilson's.<ref name=Ala/>

In the earlier stages of the disease, the biopsy typically shows [[fatty liver|steatosis]] (deposition of fatty material), increased [[glycogen]] in the [[Cell nucleus|nucleus]], and areas of [[necrosis]] (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by [[inflammation|inflammatory]] cells, piecemeal necrosis and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis.<ref name=Roberts/>

===Genetic testing===
Mutation analysis of the ''ATP7B'' gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, it is possible to screen family members for the disease as part of [[clinical genetics]] family counselling.<ref name=Ala/>

==Genetics==
[[Image:autorecessive.svg|thumb|left|Wilson's disease has an autosomal recessive pattern of inheritance.]]
{{main|ATP7B}}
The Wilson's disease gene (''ATP7B'') has been mapped to [[chromosome 13]] (13q14.3) and is expressed primarily in the liver, [[kidney]], and [[placenta]]. The gene codes for a [[P-ATPase|P-type]] (cation transport enzyme) [[ATPase]] that transports copper into [[bile]] and incorporates it into [[ceruloplasmin]].<ref name=Ala/> Mutations can be detected in 90% of patients. Most (60%) are [[homozygous]] for ''ATP7B'' mutations (two abnormal copies), and 30% have only one abnormal copy. 10% have no detectable mutation.<ref name=Merle2007/>

Although 300 mutations of ''ATP7B'' have been described, in most populations the cases of Wilson's disease are due to a small number of mutations specific for that population. For instance, in Western populations the H1069Q mutation (replacement of a [[histidine]] by a [[glutamine]] at position 1069 in the gene) is present in 37-63% of cases, while in China this mutation is very uncommon and R778L ([[arginine]] to [[leucine]] at 778) is found more often. Relatively little is known about the relative impact of various mutations, although the H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies.<ref name=Ala/><ref name=deBie2007>{{cite journal |author=de Bie P, Muller P, Wijmenga C, Klomp LW |title=Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes |journal=J. Med. Genet. |volume=44 |issue=11 |pages=673–88 |year=2007 |month=November |pmid=17717039 |doi=10.1136/jmg.2007.052746 |url=http://jmg.bmj.com/cgi/content/full/44/11/673}}</ref>

A normal variation in the ''[[PRNP]]'' gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces [[prion protein]], which is active in the brain and other tissues and also appears to be involved in transporting copper.<ref>{{cite journal |author=Grubenbecher S, Stüve O, Hefter H, Korth C |title=Prion protein gene codon 129 modulates clinical course of neurological Wilson disease |journal=Neuroreport |volume=17 |issue=5 |pages=549–52 |year=2006 |pmid=16543824 |doi=10.1097/01.wnr.0000209006.48105.90}}</ref> A role for the ''[[Apolipoprotein E|ApoE]]'' gene was initially suspected but could not be confirmed.<ref name=deBie2007/>

The condition is inherited in an autosomal recessive pattern, which means both copies of the gene have mutations. In order to inherit it, both of the parents of an individual must carry an affected gene. Most patients have no family history of the condition.<ref name=deBie2007/> People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism.<ref name=Roberts/>

Wilson's disease is the most common of a group of hereditary diseases that cause copper overload in the liver. All can cause cirrhosis at a young age. The other members of the group are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. These are not related to ''ATP7B'' mutations, but ICC has been linked to mutations in the ''[[Keratin 8|KRT8]]'' and the ''[[Keratin 18|KRT18]]'' gene.<ref name=deBie2007/>

== Treatment ==
===Medical treatment===
Various treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet. In general, a diet low in copper-containing foods ([[mushroom]]s, [[nut (fruit)|nuts]], [[chocolate]], dried [[fruit]], liver, and shellfish) is recommended.<ref name=Ala/>

Generally, [[penicillamine]] is the first treatment used. This binds copper ([[chelation]]) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems: about 20% of patients experience a side effect or complicaton of penicillamine treatment, such as drug-induced [[systemic lupus erythematosus|lupus]] (causing joint pains and a skin rash) or [[myasthenia gravis|myasthenia]] (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is also observed in other treatments for Wilson's, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment.<ref name=Ala/><ref name=Roberts/> Patients intolerant to penicillamine may instead be commenced on [[trientine hydrochloride]], which also has chelating properties. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive.<ref name=Roberts/> A further agent with known activity in Wilson's disease is [[tetrathiomolybdate]]. This is still regarded as experimental,<ref name=Roberts/> although some studies have shown a beneficial effect.<ref name=Ala/>

Once all results have returned to normal, [[zinc]] (usually in the form of [[zinc acetate]]) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates [[metallothionein]], a protein in gut cells that binds copper and prevents their absorption and transport to the liver. Zinc therapy is continued unless symptoms recur, or if the urinary excretion of copper increases.<ref name=Roberts/>

In rare cases where none of the oral treatments are effective, especially in severe neurological disease, [[dimercaprol]] (British anti-Lewisite) is still occasionally necessary. This treatment is injected [[Intramuscular injection|intermuscularly]] (into a muscle) every few weeks, and has a number of unpleasant side effects such as pain.<ref name=Walshe1996>{{cite journal |author=Walshe JM |title=Treatment of Wilson's disease: the historical background |journal=QJM |volume=89 |issue=7 |pages=553–5 |year=1996 |month=July |pmid=8759497}}</ref>

People who are [[asymptomatic]] (for instance those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. It is unclear whether these people are best treated with penicillamine or zinc acetate.<ref name=Roberts/>

===Liver transplantation===
[[Liver transplantation]] is the only cure for Wilson's disease, but is used only in particular scenarios because of the numerous risks and complications associated with the procedure. It is used mainly in patients with fulminant liver failure who fail to respond to medical treatment, or in patients with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated.<ref name=Ala/><ref name=Roberts/>

==Other species==
Hereditary copper accumulation has been described in Bedlington Terriers,<ref>{{cite journal |author=Sternlieb I, Twedt DC, Johnson GF, ''et al'' |title=Inherited copper toxicity of the liver in Bedlington terriers |journal=Proc. R. Soc. Med. |volume=70 Suppl 3 |issue= |pages=8–9 |year=1977 |pmid=122681}}</ref> where it generally only affects the liver. It is due to mutations in the ''[[COMMD1]]'' (or ''MURR1'') gene.<ref>{{cite journal |author=van De Sluis B, Rothuizen J, Pearson PL, van Oost BA, Wijmenga C |title=Identification of a new copper metabolism gene by positional cloning in a purebred dog population |journal=Hum. Mol. Genet. |volume=11 |issue=2 |pages=165–73 |year=2002 |pmid=11809725 |url=http://hmg.oxfordjournals.org/cgi/content/full/11/2/165 |doi=10.1093/hmg/11.2.165}}</ref> In patients with non-Wilsonian copper accumulation states (such as Indian childhood cirrhosis), no ''COMMD1'' mutations could be detected to explain their genetic origin.<ref>{{cite journal |author=Müller T, van de Sluis B, Zhernakova A, ''et al'' |title=The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis |journal=J. Hepatol. |volume=38 |issue=2 |pages=164–8 |year=2003 |pmid=12547404 |doi=10.1016/S0168-8278(02)00356-2}}</ref>

==Pathological Findings==

[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]

<div align="left">
<gallery heights="175" widths="175">
Image:Wilson.jpg|Liver cirrhosis and enlarged gall bladder in Wilson's disease.
Image:Wilson 2.jpg|Liver cirrhosis and enlarged gall bladder in Wilson's disease.
Image:Wilson 3.jpg|Lung, hemorrhagic bronchopneumonia, Wilson's disease
Image:Wilson 4.jpg|Spleen, congestion. Wilson's disease
</gallery>
</div>

==Resources==
* {{WhoNamedIt|synd|1818|Wilson's disease}}
* {{NLM|wilsondisease|Wilson disease}}
* {{GeneTests|wilson|Wilson Disease}}

==References==
{{reflist|2}}

{{Mineral metabolic pathology}}

[[Category:Disease]]

[[Category:Neurological disorders]]
[[Category:Hepatology]]
[[Category:Gastroenterology]]
[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Rare diseases]]
[[Category:Mature chapter]]

{{Link FA|de}}

[[ar:مرض ويلسون]]
[[ca:Malaltia de Wilson]]
[[de:Morbus Wilson]]
[[es:Enfermedad de Wilson]]
[[fr:Maladie de Wilson]]
[[it:Malattia di Wilson]]
[[he:מחלת וילסון]]
[[lb:Wilson-Krankheet]]
[[hu:Wilson-kór]]
[[nl:Ziekte van Wilson]]
[[ja:肝レンズ核変性症]]
[[pl:Choroba Wilsona]]
[[pt:Doença de Wilson]]
[[ru:Болезнь Вильсона — Коновалова]]
[[fi:Wilsonin tauti]]
[[zh:肝豆狀核變性]]

{{WH}}
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Zero gravity

2012-05-08T18:24:46Z

Lakshmi Gopalakrishnan: Created page with "{{SI}} {{CMG}} ==Zero Gravity== Condition in which no acceleration, whether due to gravity or any other force, can be detected by an observer within a system. It also means t..."

{{SI}}
{{CMG}}

==Zero Gravity==
Condition in which no acceleration, whether due to gravity or any other force, can be detected by an observer within a system. It also means the absence of weight or the absence of the force of gravity acting on a body. Microgravity, gravitational force between 0 and 10 -6 g, is included here. ''(From NASA Thesaurus, 1988)''

==References==
{{reflist|2}}

{{WH}}
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Pituitary tumour

2012-05-08T18:23:49Z

Lakshmi Gopalakrishnan:

{{SI}}
{{CMG}}

==Pituitary tumour==
*The anterior [[pituitary]] secretes a number of [[hormones]] including:
:*[[Growth hormone]] (GH)
:*[[Prolactin]] (PRL)
:*[[Thyroid-stimulating hormone]] (TSH)
:*[[Adrenocorticotropic hormone]] (ACTH)
:*[[Melanocyte-stimulating hormone]] (MSH)
:*[[Follicle stimulating hormone]] (FSH)
:*[[Luteinizing hormone]] (LH)

*Although theoretically a tumour could secrete any of these hormones, the common tumours secrete ''growth hormone'' (see [[acromegaly]]), ''prolactin'' (see [[prolactinoma]] and [[hyperprolactinaemia]]), mixed secretions or no secretion at all.

==Diagnosis==
*Once tumours were categorised by their light microscopic appearance but now tumours are more reliably categorised by [[immunoperoxidase]] studies.

*Blood tests for the hormones are important diagnostic tools.

*CT scans, MRI and other imaging techniques are important for determining size (and seriousness of tumours), growth over time and treatment options.

==Treatment==
Treatment includes:
* [[Bromocriptine]]
* Surgical removal
* Ablation by [[radiotherapy]]

==Prognosis==
Most tumours are benign but are quite serious because of their position close to important brain structures.

==References==
{{reflist|2}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Types of cancer]]

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