【高血壓英文課件】Hypertension-and-the-Kidney

HypertensionandtheKidneyChongMyungKang,M.D.DepartmentofInternalMedicineHanyangUniversityHospitalHypertensionandtheKidney1HypertensionandtheKidneyA.TheRoleoftheKidneyinHypertensionB.HypertensionasaCauseofRenalDiseaseC.HypertensionasaRiskFactorfortheProgressionofRenalDiseaseD.HypertensionasaConsequenceofRenalDiseaseHypertensionandtheKidneyA.2RoleofKidneyinHypertension1.Pressure-VolumeRegulation2.CongenitalOligonephropathy3.RenalTransplantationStudies4.SaltandHypertensionRoleofKidneyinHypertension3【高血壓英文課件】Hypertension-and-the-Kidney4【高血壓英文課件】Hypertension-and-the-Kidney5Fig.2.PredictedLong-termeffectsofaperipheralvasoconstrictorthathasarelativelyweekeffectonpressurenatriuresis.Thenormalcurve(Solidline)iscomparedwiththevasoconstrictorcurve(dashline).Initially,thevasoconstrictorwouldcausenatriuresis,becauseincreasedperipheralvascularresistanceelevatesarterialpressure(frompointAtopointB)abovetheset-pointforbalancebetweenintakeandoutputofsodiumduetoincreased.However,increasedarterialpressurewouldcauseatransientnatriuresisandareductioninextracellularfluidvolumeuntilarterialpressureeventuallystabilizedatalevel(pointC)atwitchsodiumintakeandoutputarebalanced.Fig.2.PredictedLong-termef6Fig.3.ProposedmechanismofpressurenatriuresisFig.3.Proposedmechanismof7Pressure-natriuresis(2)

(MedullaryBloodFlow)Medullarybloodflow(MBF)compriseonly1%ofRBF,butimportanteffectonpressure-natriuresisEndocrine¶crinefactors(renalnerve,AngIIprostaglandin,ANP,NO,kinin,vasopressinmodulateRPP&urineexcretionbyregulationofmedullarybloodflowReduceMBF;sympatheticNstimulation,COinhibition,kininantagonist,NOsynthaseinhibition,AngII,AVP--->raiseBPIncreaseMBF;ANP,prostaglandin,bradykinin,acetylcholine,CEI,Cablocker--->loweringBPPressure-natriuresis(2)

(Medul8Pressure-natriuresis(3)Abnormalpressure-natriuresisinessentialhypertension1.Increasedpreglomerularresistancewidespreadvasoconstrictionofpreglomerularvessels(arteriosclerosis,vasoconstrictors)-->relievedwithCablockers2.Increasedtubularreabsorptionexcessivemineralocorticoid,AngII(Salt-sensitive;dependonsaltintake)Pressure-natriuresis(3)Abnorma9Pressure-natriuresis(4)3.Decreasedglomerularcapillaryfiltrationcoefficient(Kf)

EssentialHPwithsubtledysfunctioninglomerularcapillarymembrane,glomerulonephritis4.Reducednumberoffunctioningnephrons

Hyperfiltratioh-->glomerulosclerosisPressure-natriuresis(4)3.Decr10Fig.4.Steady-staterelationshipsbetweenarterialpressureandurinarysodiumecreationandsodiumintakefornormalkidneyandfourtypesofrenaldysfunctionthatcausehypertension:decreasedkidneymass,increasedreabsorptionindistalandcollectingtubules,reductioninglomerularcapillaryfiltrationcoefficient(Kf),andincreasedpreglomerularresistance.Fig.4.Steady-staterelations11CongenitalOligonephropathyLowbirthweightbaby--->higherincidenceofhypertensioninmaturityFewernephrons,smallerkidneytobodysize(Japanese,African-American;adaptedtolesssalt&waterintropicalarea-->HPinsaltrepletestate)Nephronnumber;genetic,conditionsinutero(300,000--1,000,0000;lowsocioeconomicstate,ratexperiment,SHR)Lowbirthweight,shortstature;higherincidenceofNIDDM,nephropathyinIDDMCongenitalOligonephropathyLow12RenalTransplantationStudiesHypertensioncantravelwithkidneyF1hybrids(F1H)fromWKY&SHR;Afterbilateralnephrectomy,CEItreatedSHR&WKYkidneytransplantedtoF1HRecipientofSHR-->HP,recipientofWKY--normalNodifferencebetween2groupinBUN,RBF,GFRGeneticpredispositionforHPindonorsisrequiredtoelicitpost-transplantationHPSHR;decreasedcapacitytoexcretedietaryNaThus,intrinsicrenalmechanismplayamajorroleinmanifestationofprimaryhypertensionRenalTransplantationStudiesH13Fig.5.Effectsofrenalcross-transplantationsonsystolicbloodpressureinfivedifferentanimalmedelsofgenetichypertension.A.Normotensiverecipientsreceivedakidneyfromhypertensivedonors.B.Hypertensiverecipientsreceivedakidneyfromnormotensivedonors.Symbolsare:()Dahlsalt-senstivehypertensiverats;()MilanhypetensiveratsandMilannormotensiverats;()PraguehypertensiveratsandPraguenormotensiverats;NormotensiveWistarKyotorats(donors),spontaneouslyhypertensiveratsandF1hybrids(recipients)bredfromthefirsttwostrains;()normotensiveWistar-Kyotorats(donors),stroke-pronespontaneouslyhypertensiverats(donors)andF1hybrids(recipients)bredfromthefirsttwostrain.Fig.5.Effectsofrenalcross14Fig.6.Bloodpressureinhumanrenalgraftrecipientsatoneyearaftertransplantation.Basedonindirectevidence,donorswereassumedtohavebeennormotensive()orhypertensive().Thedifferencesinbloodpressurebetweenrecipientsofakidneyfromnormotensiveandhypertensivedonoroccurreddespitemorevigorousantihypertensivetreatmentinthelatter.Fig.6.Bloodpressureinhuma15SaltandHypertension(1)Aberrantresponseoftubuloglomerularfeedback(TGF)tosaltloadisresponsibleforessentialHPAfferentarteriolecontractorrelaxinresponsetoinc.ordec.inmaculadensaCl-delivery(autoregulationofRBF)FinetuningofSNGFRthroughTGF

Lowsaltintake-->dec.afferentarteriolarresistance&TGF-->maintainGPF&AngIIinc.RE-->maintainPGC-->SNGFRInabilityofkidneytoexcretesaltloadisresponsiblefordevelopmentofhypertensionSaltandHypertension(1)Aberra16Fig.7.Autoregulationofrenalplasmaflowandglomerularfiltrationrate.Noteafferentarteriolarresistance(RA)isregulatedbyboyhmyogenicresponseandtubuloglomerularfeedbackandangiotensinII(AngII)canselectivelyactonefferentresistance(RE)allowingthemaintenanceofSNGFRinthefaceofreducedrenalperfusionpressure.Fig.7.Autoregulationofrena17【高血壓英文課件】Hypertension-and-the-Kidney18SaltandHypertension(2)HP;aberrantTGFtosaltload-->verylowsaltintake;;noHP(Yanomamo,Xingu,PapuaNewGuinea,Kenya-->Nohypertension)Humanbodysystem;adaptedtosaltdepletionofterrestrialenvironment;;excessivesaltintakeincivilization-->essentialhypertensionSlowgeneticchangevsrapidenvironmentalchangeSaltandHypertension(2)HP;a19HypertensionasaCause

ofRenalDisease(1)MechanismofHPinducedrenaldamage1.Glomerularischemia&hypoperfusion2.GlomerularcapillaryHP&hyperperfusion-->inc.SNGFR-->transglomerularpassageofprotein-->inc.influxofprotein¯omoleculeintomesangium-->proliferation&inc.matrix--->GlomerulosclerosisHypertensionasaCause

ofRe20HypertensionasaCause

ofRenalDisease(2)Increasedproteintrafficintourinaryspace-->increasedproteinreabsorptionbyproximaltubule-->tubulointerstitialdamage(NH3production-->C3activate-->triggerinflammatoryresponseininterstitium,stimulatecellgrowth,hypertrophy,reactiveO2speciesProgressionofrenaldiseasecorrelatebestwithinterstitialdamageLeakageofplasmacomponentacrossGBM--->activateMAC-->GECdamage--->disruptnormalGBMturnover-->GBMdamageHypertensionasaCause

ofRe21Fig.9.MechanismwherebyimmunedamagetotheGBMresultsintheleakageofcomplementcomponentstotheepithelialsideofthemembrane.ThismayfacilitatetheassemblyofthemembraneattackcomplexontheepithelialcellanddisruptthenormalGBMturnover.Fig.9.Mechanismwherebyimmu22HypertensionasaCause

ofRenalDisease(3)“Hypertensivenephrosclerosis”Myointimalhyperplasia,hyalinearteriosclerosisinsmallarteries&arterioles--->progressiontoESRD(30%ofESRDinU.S.A.)HistoryofHPatleast5years,initiallynormalrenalfunction&urinalysis,proteinuria<1g/dayPrimaryrenalparenchymaldisease;abnormalurinalysispriortoonsetofhypertensionNohypertensivenephrosclerosisinpatientswithBPcontrolled<140/90mmHg

HypertensionasaCause

ofRe23HypertensionasaRiskFactorfor

ProgressionofRenalDisease(1)HPaccelerateprogressionofrenaldiseaseAntihypertensiveTxslowdowntheprogressionACEinhibitor;dilateefferentarteriole-->reduceintraglomerular