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CARDIOVASCULARPATHOPHYSIOLOGYHypertension
- Sustainedincreaseofsystemicarterial(particularlysystolic)bloodpressure
Clinicalmanifestation§ Silentdiseaseinearlyhypertensioni.e.nosignsorsymptoms§ Othershaveanatomicandphysiologicaldamagetobrain,eyes,kidney,vessels,heart
Diastolic(mmHg)
Systolic(mmHg)
Normal <80 <120
HighNormal 80-89 120-139
Grade1(mild) 90-99 140-159
Grade2(moderate) 100-109 160-179
Grade3(severe) >110 >180
§ MeanarterialBP=cardiacoutputxperipheralresistance
o MAP=COxTPVR§ IncreaseBPdueto:
o Increasedcardiacoutput(=HRxstrokevolume)o Increasedperipheralresistance(reducedvesseldiameterandincreasedviscosity)
§ Peripheralresistance-oppositiontoflowthatbloodencountersinvesselsawayfromtheheart.Dependsontwovariables:
o Bloodviscosity“thickness”§ RBCcountandalbuminconcentrationelevateviscositythemost§ Decreasedviscositywithanemiaandhypoproteinemiaspeedflow§ Increasedviscositywithpolycythemiaanddehydrationslowflow§ Smokingincreaseviscosity
o Vesselradius–mostpowerfulinfluenceoverflow§ Vasomotion-changeinvesselradius
• Vasoconstriction-bymusculareffortthatresultsinsmoothmusclecontraction
• Vasodilation-byrelaxationofsmoothmuscle§ Twomajortypesofbaroreceptors
o Arterialorhighpressurebaroreceptors-fastresponse–regulatesheartrateandbloodvesseldiameter–locatedincarotidsinusandaorticarch
o Lowpressurebaroreceptors-slowerresponse–respondstochangeinbloodvolume–locatedinwallsofmajorveinsandrightatriumoftheheartwhichreceivesdeoxygenatedbloodfromtheblood
§ VolumedecreaseàSignalssenttohypothalamusleadingtoADHreleaseandwaterreabsorption
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§ Volumeincreaseàsecretionofatrialnatriureticpeptide(ANP)whichpromoteswaterandsodiumexcretionthroughtheurine
Juxtaglomerularapparatus
§ ifGFRrises:o flowoftubularfluid
increasesandmoreNaClisreabsorbedbythePCT
o maculadensastimulatesJGcellswithaparacrineo JGcellscontractwhichconstrictsafferentarteriole,reducingGFRtonormalOR
§ Mesangialcellsmaycontract,constrictingthecapillariesandreducingfiltration
§ IfGFRfalls:o Macularelaxesafferentarteriolesandmesangialcellso BloodflowincreasesandGFRrisesbacktonormalo ReleaseofreninfromJGcells
§ Myogenicresponse:intrinsicabilityofvascularsmoothmuscletorespondtopressurechanges
Renin-angiotensin-aldosteronepathway
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Atrialnatriureticpeptides
Arterial(HighPressure)Baroreceptors§ Mechanoreceptorthatdetectsthepressure
ofbloodflowingthroughthem,cansendmessagestoCNStoincreaseordecreasetotalperipheralresistanceandcardiacoutput
§ Thefrequencyofafferentimpulsesincreaseswhenthepressureisrisingduringsystoleanddecreaseswhenthepressureisfallingduringdiastole
Controlcentreàmedullaofbrainstem
§ Cardiostimulatorycentre:makestheheartbeatfasterandstrongeràincreasingbloodpressure
§ Cardioinhibitorycentre:slowstheheartdownàdecreasingbloodpressure
§ Vasomotorcentre:clusterofsympatheticneuronsinthemedullathatoverseeschangesinbloodvesseldiameter
o Maintainsbloodvesseltonebyinnervatingsmoothmusclesofbloodvessels,especiallyarterioles
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EtiologyofHypertension§ Primary:diagnosisofprimaryhypertensionisoneofexclusion-ifnosecondarycauses
foundo Multipleriskfactors:
§ Obesity,smoking,genetics(aging,hyperlipidaemia,sleepapnoea),increasebloodviscosity(increasesaltintake,oralcontraceptives)
§ Secondary:duetosystemicdiseasethatraisesperipheralresistanceo Renaldisease-decreasedurineformation,retentionofsodiumandwatero Renovascularhypertension-renalarterystenosis-reducedrenalbloodflowwhich
triggersrenin-angiotensin-aldosteronemechanismo Adrenalglandtumours-excessivealdosteroneproduction-increaseinwaterand
sodiumretentiono Pheochromocytoma-increaseadrenalineo Coarctationoftheaorta-narrowingoftheaorticarch–LVmustgenerategreater
pressureso Drugs-oralcontraceptives,corticosteroids
§ Malignant:morecommoninyoungeradults,esp.AfricanAmericanmen,duringpregnancyandpeoplewithkidneydisordersorcollagenvasculardisorders
o Intensespasmofarteriese.g.cerebralarteries,retinalvessels-swellingofopticnerves
o Suddenandrapiddevelopmentofextremelyhighbloodpressureàmedicalemergency
§ TreatmentofunderlyingcausereversehypertensionHealthconsequences
§ Bloodvessels§ Heart§ Kidneys§ Brain§ Eyes
§ Unmodifiableriskfactors:age,
genetics,gender,race,pregnancy§ Modifiableriskfactors:
§ Diet:reducesodiumintake§ Obesity:loseweight§ Stopsmoking§ Oralcontraceptives-previousstudiesshowedastrongassociationwithriskofstroke§ Treatment-medicationse.g.diuretics,ACEinhibitors,Cachannelblockers,betablockers
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Atherosclerosis§ Progressivedisease-thickeningandhardeningofarteriescausedbyformationoffibrofatty
plaquesthathardenwithtimeànarrowingbloodvesselàdecreaseinbloodflowSitesofsevereatherosclerosis:
CoronaryDisease
Coronaryarterydisease–mostcommoncauseisatherosclerosis
Transientischemia–cellstemporarilydeprivedofoxygen,manifestaspain–associatedwithstress/exercise
Myocardialischemia–cellstemporarilydeprivedofbloodandoxygen,manifestaspain,cardiacarrhythmiasthatmaybefatalàstroke.Embolimayform.
Myocardialinfarction–irreversiblemyocardialdamageandcelldeath(necrosis)duetoprolongedoxygenstarvation.Impairmentofheartandbrainfunction
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Plaque§ Acombinationofcholesterol,otherfattymaterials,calciumandbloodcomponentsthat
sticktothearterywalllining§ Ahardshellorscarcoverstheplaque
Twotypesofplaque§ Unstable-thinfibrouscaps
o Maycompletelyblockthearteryo Canruptureorformcloto Clotmaybreakfreeandbecomeanembolus(anydetached,travellingintravascular
masscarriedbycirculation,capableofcloggingarterialvesselsatasitedistantfromitspointoforigin)
§ Stable-thickfibrouscapso Partiallyblockvesselso Donottendtoformclotsoremboli
Initialtrigger
§ Hypertension:stressonbloodvesselwalls§ Diabetes:disruptionofendotheliumliningofbloodvesselsthatkeepsbloodflowing
smoothlybyproducingnitricoxide(NO)whichrelaxesthesmoothmusclesofthewallstopreventcellsfromstickingtowallsàincreasedformationofplaquesindiabetes
§ Turbulentbloodflow:duetoobstruction§ Smoking-nicotineàdecreaseinnitricoxidelevels§ Infection:e.g.chlamydiapneumoniaemaymanagewallandcausecholesterolaccumulation§ HighcholesterolandLDLlevels:increasefoamcells
Unmodifiableriskfactors
§ Ageandgender
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o Increasedincidenceinmalesandpost-menopausalwomeno Familyhistory-genetic
Modifiableriskfactors
§ Smoking§ Highalcoholintake§ Sedentarylifestyle§ Obesity§ Stress§ TypeIIdiabetes§ Hypertension§ Increasedcholesterol
Clinicalmanifestation-Angina
§ Stableanginao Predictablepatternofintermittentanginaduringexerciseorexcitementrelievedby
resto Usuallystableatheroscleroticplaque
§ Variantorprinzmetalanginao Unpredictablecourse,frequencyanddurationofpainatresto Atherosclerosisusuallypresentbutmaybeabsentand/orvasospasm-cause
unknownbuttheoriesincludehyperactivityofsympatheticsystem,increaseincalciumfluxinarterialsmoothmuscle,impairedproductionorreleaseofvasoconstrictor,disturbancesinproductionofNO
o Painrelievedbynitro-glycerineo Chestpainandshortnessofbreathoftennotpresentwhenwalking/exercising
§ Silentischemiao Nopainassociatedwithischemicevento Highincidenceinassociationwithmentalstresso Autonomicneuropathywithsensorydenervationo Detectedwithstressradionuclideimaging(Thallium201)andECG
§ Unstableanginao Myocardialischemiarangingbetweenstableanginatomyocardialinfarctiono Occursatrestandcanevenwakepeoplefromarestfulsleepo Suddenchestpaino Unpredictablecourse,frequencyanddurationofpaino Usuallyindicatorofatheroscleroticplaquewhichbecomesunstableàinfarctiono Symptomsoftenpersistformorethanafewminuteso Nitro-glycerinefailstorelievethepaino Causedbytheactualruptureofaplaqueinacoronaryartery
Diagnostictechniques
§ Electrocardiogramo STsegmentelevationordepressionandTwaveinversionindicationofMIdueto
tissuedamageleadingtoearlyrepolarisation§ Exercisestresstest
o GradedexercisewheresymptomsobservedplusHR,BPandECGrecorded
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