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PathophysiologyofhypertensionWikipedia,thefreeencyclopedia

Pathophysiologyofhypertension
FromWikipedia,thefreeencyclopedia

Thepathophysiologyofhypertensionisanareawhichattemptstoexplain
mechanisticallythecausesofhypertension,whichisachronicdisease
characterizedbyelevationofbloodpressure.Hypertensioncanbeclassifiedby
causeaseitheressentialorsecondary.Essentialhypertensionindicatesthatno
specificmedicalcausecanbefoundtoexplainthehypertension.About9095%
ofhypertensionisessentialhypertension.[1][2][3][4]Secondaryhypertension
indicatesthatthehypertensionisaresultofaspecificunderlyingconditionwith
awellknownmechanism,suchaschronickidneydisease,narrowingofthe
aortaorkidneyarteries,orendocrinedisorderssuchasexcessaldosterone,
cortisol,orcatecholamines.Persistenthypertensionisamajorriskfactorfor
hypertensiveheartdisease,coronaryarterydisease,stroke,aorticaneurysm,
peripheralarterydisease,andchronickidneydisease.[5]Thepathophysiologyof
essentialhypertensionremainsanareaofactiveresearch,withmanytheories
thatarenotmutuallyexclusive.

Adiagramexplainingfactorsaffectingarterialpressure

Cardiacoutputandperipheralresistancearethetwodeterminantsofarterialpressure.[6]Cardiacoutputisdeterminedbystrokevolumeandheartratestroke
volumeisrelatedtomyocardialcontractilityandtothesizeofthevascularcompartment.Peripheralresistanceisdeterminedbyfunctionalandanatomicchanges
insmallarteriesandarterioles.

Contents
1
2
3
4
5

Genetics
Autonomicnervoussystem
Reninangiotensinaldosteronesystem
Endothelialdysfunction
References

Genetics
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SinglegenemutationscancauseMendelianformsofhighbloodpressure[7]tengeneshavebeenidentifiedwhichcausethesemonogenicformsof
hypertension.[7][8]Thesemutationsaffectbloodpressurebyalteringrenalsalthandling.[9][10]Thereisgreatersimilarityinbloodpressurewithinfamiliesthan
betweenfamilies,whichindicatesaformofinheritance,[11]andthisisnotduetosharedenvironmentalfactors.[12]Withtheaidofgeneticanalysistechniques,a
statisticallysignificantlinkageofbloodpressuretoseveralchromosomalregions,includingregionslinkedtofamilialcombinedhyperlipidemia,was
found.[13][14][15][16][17]Thesefindingssuggestthattherearemanygeneticloci,inthegeneralpopulation,eachwithsmalleffectsonbloodpressure.Overall,
however,identifiablesinglegenecausesofhypertensionareuncommon,consistentwithamultifactorialcauseofessentialhypertension.[2][10][18][19]

Autonomicnervoussystem
Theautonomicnervoussystemplaysacentralroleinmaintainingcardiovascularhomeostasisviapressure,volume,andchemoreceptorsignals.Itdoesthisby
regulatingtheperipheralvasculature,andkidneyfunction,whichinturnaffectcardiacoutput,vascularresistance,andfluidretention.Excessactivityofthe
sympatheticnervoussystemincreasesbloodpressureandcontributestohypertension.[20][21][22][22][23][24]
Themechanismsofincreasedsympatheticnervoussystemactivityinhypertensioninvolvealterationsinbaroreflexandchemoreflexpathwaysatbothperipheral
andcentrallevels.Arterialbaroreceptorsareresettoahigherpressureinhypertensivepatients,andthisperipheralresettingrevertstonormalwhenarterial
pressureisnormalized.[25][26][27]Furthermore,thereiscentralresettingoftheaorticbaroreflexinhypertensivepatients,resultinginsuppressionofsympathetic
inhibitionafteractivationofaorticbaroreceptornerves.Thisbaroreflexresettingseemstobemediated,atleastpartly,byacentralactionofangiotensin
II.[28][29][30]Additionalsmallmoleculemediatorsthatsuppressbaroreceptoractivityandcontributetoexaggeratedsympatheticdriveinhypertensioninclude
reactiveoxygenspeciesandendothelin.[31][32]Somestudiesshownthathypertensivepatientsmanifestgreatervasoconstrictorresponsestoinfusednorepinephrine
thannormotensivecontrols.[33]Andthathypertensivepatientsdonotshowthenormalresponsetoincreasedcirculatingnorepinephrinelevelswhichgenerally
inducesdownregulationofnoradrenergicreceptor,anditisbelievedthatthisabnormalresponseisgeneticallyinherited.[34]
Exposuretostressincreasessympatheticoutflow,andrepeatedstressinducedvasoconstrictionmayresultinvascularhypertrophy,leadingtoprogressiveincreases
inperipheralresistanceandbloodpressure.[2]Thiscouldpartlyexplainthegreaterincidenceofhypertensioninlowersocioeconomicgroups,sincetheymust
enduregreaterlevelsofstressassociatedwithdailyliving.Personswithafamilyhistoryofhypertensionmanifestaugmentedvasoconstrictorandsympathetic
responsestolaboratorystressors,suchascoldpressortestingandmentalstress,thatmaypredisposethemtohypertension.Thisisparticularlytrueofyoung
AfricanAmericans.Exaggeratedstressresponsesmaycontributetotheincreasedincidenceofhypertensioninthisgroup.[35]

Reninangiotensinaldosteronesystem
Anothersystemmaintainingtheextracellularfluidvolume,peripheralresistance,andthatifdisturbedmayleadtohypertension,isthereninangiotensin
aldosteronesystem.Reninisacirculatingenzymethatparticipatesinmaintainingextracellularvolumeandarterialvasoconstriction,thereforecontributingto
regulationofbloodpressure.Itperformsthisfunctionbybreakingdown(hydrolyzing)angiotensinogen,secretedfromtheliver,intothepeptideangiotensinI.
AngiotensinIisfurthercleavedbyanenzymethatislocatedprimarilybutnotexclusivelyinthepulmonarycirculationboundtoendotheliumthatenzymeis
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angiotensinconvertingenzyme(ACE).ThiscleavageproducesangiotensinII,themostvasoactivepeptide.[36][37]AngiotensinIIisapotentconstrictorofallblood
vessels.Itactsonthemusculatureofarteries,raisingperipheralresistanceandtherebyelevatingbloodpressure.AngiotensinIIalsocausestheadrenalglandsto
releasealdosterone,whichstimulatestheepithelialcellsofthekidneystoincreasereabsorptionofsaltandwater,leadingtoraisedbloodvolumeandraisedblood
pressure.Soelevatedreninlevelsintheblood(normally1.982.46ng/mlintheuprightposition)[38]leadstohypertension.[2][39]
Recentstudiesclaimthatobesityisariskfactorforhypertensionbecauseofactivationofthereninangiotensinsystem(RAS)inadiposetissue,[40][41]andalso
linkedreninangiotensinsystemwithinsulinresistance,andclaimsthatanyonecancausetheother.[42]LocalproductionofangiotensinIIinvarioustissues,
includingthebloodvessels,heart,adrenals,andbrain,iscontrolledbyACEandotherenzymes,includingtheserineproteasechymase.Theactivityoflocalrenin
angiotensinsystemsandalternativepathwaysofangiotensinIIformationmaymakeanimportantcontributiontoremodelingofresistancevesselsandthe
developmentoftargetorgandamage(i.e.leftventricularhypertrophy,congestiveheartfailure,atherosclerosis,stroke,endstagekidneydisease,myocardial
infarction,andarterialaneurysm)inhypertensivepersons.[39]

Endothelialdysfunction
Theendotheliumofbloodvesselsproducesanextensiverangeofsubstancesthatinfluencebloodflowand,inturn,isaffectedbychangesinthebloodandthe
pressureofbloodflow.Forexample,localnitricoxideandendothelin,whicharesecretedbytheendothelium,arethemajorregulatorsofvasculartoneandblood
pressure.Inpatientswithessentialhypertension,thebalancebetweenthevasodilatorsandthevasoconstrictorsisupset,whichleadstochangesintheendothelium
andsetsupaviciouscyclethatcontributestothemaintenanceofhighbloodpressure.Inpatientswithhypertension,endothelialactivationanddamagealsolead
tochangesinvasculartone,vascularreactivity,andcoagulationandfibrinolyticpathways.Alterationsinendothelialfunctionareareliableindicatoroftarget
organdamageandatheroscleroticdisease,aswellasprognosis.[43]
Evidencesuggeststhatoxidantstressaltersmanyfunctionsoftheendothelium,includingmodulationofvasomotortone.Inactivationofnitricoxide(NO)by
superoxideandotherreactiveoxygenspecies(ROS)seemstooccurinconditionssuchashypertension.[44][45][46]Normallynitricoxideisanimportantregulator
andmediatorofnumerousprocessesinthenervous,immuneandcardiovascularsystems,includingsmoothmusclerelaxationthusresultinginvasodilationofthe
arteryandincreasingbloodflow,suppressorofmigrationandproliferationofvascularsmoothmusclecells.[2]IthasbeensuggestedthatangiotensinIIenhances
formationoftheoxidantsuperoxideatconcentrationsthataffectbloodpressureminimally.[47]
Endothelinisapotentvasoactivepeptideproducedbyendothelialcellsthathasbothvasoconstrictorandvasodilatorproperties.Circulatingendothelinlevelsare
increasedinsomehypertensivepatients,[48][49]particularlyAfricanAmericansandpersonswithhypertension.[48][50][51][52]

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