醫(yī)學(xué)教學(xué)課件：Pathophysiology of Hypertension

PathophysiologyofHypertensionBloodPressureDefinition:theforceexertedbythebloodagainstthewallsofthebleedvesselsAdequatetomaintaintissueperfusionduringactivityandrestArterialbloodpressure:primaryfunctionofcardiacoutputandsystemicvascularresistanceBloodPressureArterialBP=CardiacOutput(CO)xSystemicvascularresistance(SVR)CardiacOutput=strokevolumexbeatsperminSystemicvascularresistance=forceopposingthemovementofbloodwithinthebloodvesselsWhatistheeffectonBPifSVRincreasedandCOremainsconstant?MechanismsthatRegulateBPSympatheticNervousSystemVascularEndotheliumRenalSystemEndocrineSystemHypertension

MechanismsthatRegulateBPSympatheticNervousSystem(SNS)

–norepinephrinereleasedfromsympatheticnerveendings-toreceptorsalpha1,alpha2,beta1&beta2ReactswithinsecondsIncreasesHeartRate-chronotropicIncreasedcardiaccontractility-inotropicProduceswidespreadvasoconstrictioninperipheralarteriolesPromotesreleaseofreninfromthekidney

Hypertension

SNSReceptorsInfluencingB/PHypertension

MechanismsthatRegulateBPSympatheticNervousSystem(SNS)–SympatheticVasomotorCenter–locatedinthemedulla–interactswithmanyareasofthebraintomaintainBPwithinnormalrangeundervariousconditionsExercise–changestomeetoxygendemandPosturalChanges–peripheralvasoconstrictionHypertension

MechanismsthatRegulateBPSympatheticNervousSystem(SNS)

–Baroreceptors:specializednervecellsthecarotidarteriesandtheaorticarchSensitivetoBPchanges:Increase:InhibitsSNS

–peripheralvesseldilation.Decreasedheartrate,anddecreasedcontractilityoftheheart+increasedparasympatheticactivity(vagusnerve)decreasedheartrateDecrease:ActivatesSNS

–peripheralvesselconstriction,increasedheartrate,andincreasedcontractilityoftheheart

Hypertension

MechanismsthatRegulateBPVascularEndotheliumSinglecelllayerthatlinesthebloodvesselsProducevasoactivesubstances:EDRFEndothelium-deriverelaxingfactor

–

HelpsmaintainlowarterialtoneatrestInhibitsgrowthofthesmoothmusclelayerInhibitsplateletaggregationVasodilation–prostacyclinEndothelin(ET)potentvasoconstrictorEndothelialdysfunctionmaycontributetoatherosclerosis&primaryhypertensionHypertension

MechanismsthatRegulateBPRenalSystemControlNa+excretion&extracellularfluidvolumeRenal-Renin-angiotensin-aldosterone

ReninconvertsangiotensinogentoangiotensinIAngiotensin-convertingenzyme(ACE)convertsIintoangiotsensinIIImmediate:Vasoconstrictor–increasedsystemicvascularresistanceProlonged:StimulatestheadrenalcortextosecretAldosterone–Na+andWaterretentionRenalMedulla-Prostaglandins-vasodilatoreffectHypertension

Renin-Angiotensin

Hypertension

Renin-AngiotensinSystemHypertension

MechanismsthatRegulateBPEndocrineSystemStimulatestheSNSwithEpinephrine–increasesHRandcontractilityActivatesB2-adrenergicreceptorsinperipheralarteriolesofskeletalmuscle=vasodilationActivatesA1-adrenergicreceptorsinperipheralarteriolesofskinandkidneys=vasoconstictionAdrenalCortex–Aldosterone–stimulateskidneystoretainNa+IncreasedNa+stimulatesposteriorpituitary–ADH–reabsorbsECF/waterHypertension

AldosteroneMechanismIncreasedAldosterone=Increasessodiumreabsorption=Increaseswaterreabsorption=Increasesbloodvolume=IncreasescardiacoutputHypertension

MechanismsthatRegulateBPRegulatorymechanismsinthehealthpersonfunctioninresponsetothedemandsonthebodyWhenHypertensiondevelops,oneormoreofthesemechanismsaredefectiveSympatheticNervousSystemVascularEndotheliumRenalSystemEndocrineSystemSecondaryHypertension

PathophysiologySpecificcauseofhypertensioncanbeidentified5+%ofadulthypertensionCauses:CoarctationorcongenitalnarrowingoftheaortaRenaldisease–renalarterydisease/parenchymalEndocrinedisorders:Pheochromocytoma,CushingSyndrome,HyperaldosteronismNeurologydisorders–braintumors/headinjurySleepapneaMedications–sympatheticstimulantsPregnancy-inducedhypertensionHypertension

PathophysiologyPrimary(Essential)Hypertension:ElevatedBPwithoutanidentifiedcauseAccountsfor95%ofallcasesofhypertensionCause–unknownContributingFactors:

IncreasedSNSactivity,overproductionofNa+retaininghormones&vasoconstrictors,increasedNa+intakeRiskFactors:ModifiablePrimaryHypertension

PathophysiologyHeredity–interactionofgenetic,environmental,anddemographicfactorsWater&SodiumRetention

–20%ofptswithhighNa+dietdevelopHTNAlteredRenin-AngiotensinMechanism

–foundin20%ofpatients

Stress&IncreasedSNSActivity

InsulinResistance&Hyperinsulinemia

EndothelialCellDysfunction

Hypertension

ClinicalManifestation

DxismadeaftermultiplereadingsoverseveralweeksNIH/JointCommitteeDefinition:Category Systolic DiastolicOptimal <110 and <80Normal <120 and <85HighNormal 130-139 or 85-89Stage1

140-159 or 90-99Stage2 160-179 or 100-109Stage3 =>180 or =>110 PrimaryHypertension

RiskFactors

AgeAlcoholCigaretteSmokingDiabetesMellitusElevatedserumlipidsExcessNa+indietGenderFamilyHistoryObesityEthnicitySedentaryLifestyleSocioeconomicStressPrimaryHypertension

ClinicalManifestationsTargetOrganComplications:Myocardium

–angina/leftventricularhypertrophyBrain

–TIA/CVAPeripheralvascular

–PeripheralpulsechangeKidney

–renalfailureCreatinine/ProteinuriaEyes

–HemorrhageswithorwithoutpapilledemaPrimaryHypertension

ClinicalManifestations“SilentKiller”

–asymptomaticandinsidiousSevereHTN

–fatigue,reducedactivitytolerance,dyspnea,dizziness,palpitations,anginaHypertension

MedicalDiagnosisHistoryandPhysicalExaminationRenalFunctionSerumCreatinine&UrineCreatinineClearanceElectrolytes–especiallyK+BloodGlucoseSerumLipids/EKGAmbulatoryBPMonitoringPrimaryHypertension

MedicalManagementRiskStratificationLevelofBPPresenceofTargetOrganDiseaseOtherRiskFactors

Hypertension

MedicalManagement

RiskStratificationPrimaryHypertension

MedicalManagementLifestylemodificationNutritionaltherapyAlcoholconsumptionPhysicalactivityTobaccoavoidanceStressmanagementDrugTherapyHypertension

NutritionHypertension

RiskFactorModificationPrimaryHypertension

MedicalManagement

SteppedApproach

LifestylemodificationNotatGoalBP DrugTherapyNotatGoalBP Substitutemed/adda2ndmed/increasedoseNotatGoalBP Continueadding/changingmedsuntilcontrolPrimaryHypertension

MedicalManagement–DrugTherapyDiureticsThiazideLoopK+SparingAdrenergicBlockers/InhibitorsB-AdrenergicBlockersCentralActingAdrenergicAntagonistsPeripheralActingAdrenergicAntagonistsA-AdrenergicBlockersVasodilatorsAngiotensinInhibitorsCalciumChannelBlockersHypertension

Medication-DiureticsHypertension

Medication–Beta-blockingAgents

Hypertension

Medication

CalciumChannelBlockers

Hypertension

Medication

AlphaAgonists&Vasodilators

Hypertension

AntihypertensiveDrugTherapy

PrimaryHypertension

LackofResponsivenesstoTherapyNonadherencetoTherapyDrug-RelatedCausesAssociatedconditionsSecondaryHypertensionVolumeoverloadPrimaryHypertension

HypertensiveC