病理生理學課件：腎臟病理生理學

腎臟病理生理學RenalpathophysiologyDepartmentofpathophysiology腎功能泌尿功能內分泌功能通過泌尿排除代謝廢物，并維持水、電解質和酸堿平衡，維持機體內環(huán)境的恒定。腎素PGsEPO1，25-OH2VD31.Excretoryfunction2.Regulatoryfunction3.Endocrineandmetabolicfunction腎功能不全發(fā)展過程

當各種原因引起腎功能障礙時：首先表現(xiàn)為泌尿功能障礙，繼之引起體內代謝紊亂與內分泌功能障礙，嚴重時還可使各系統(tǒng)發(fā)生病理變化。

分急性和慢性，但都以尿毒癥告終。ContentsBasicpathologicaltachesforrenalfailureAcuterenalfailure(ARF)Chronicrenalfailure(CRF)Uremia(尿毒癥）尿生成過程血漿經腎臟生成尿，是由腎小球濾過、腎小管的重吸收和分泌三個相聯(lián)系的環(huán)節(jié)實現(xiàn)的。PeritubularcapillaryRenaltubuleH2OH2OH2OUrine

腎小球濾過

Glomerularfiltration

腎小管重吸收

Tubularreabsorption

腎小管分泌

TubularsecretionFlowoffiltrateRenalcorpuscle

尿液排泄

UrinaryexcretionBasicpathologicaltachesforRFGlomerulardysfunctionTubulardysfunctionEndocrinedysfunctionGlomerulardysfunctionDecreaseofGFR(Bloodflow,Glomerulareffectivefiltrationpressure,Kf)Decreaseofglomerularcapillarysurfacearea

Alterationsofpermeabilityofglomerularfiltrationmembrane(nephrin，CD2AP,etc)ACTN4:α-actinin-4;CD2AP:CD2-associatedprotein;GEC:glomerularendothelialcell;ILK:integrin-linkedkinase;ZO-1:tightjunctionproteinZO-1;CD151:tetraspaninCD151;TRPC6:transientreceptorpotentialcationchannel6;NCK:proteinadaptorNCK.RenaltubulardysfunctionDysfunctionoftheproximalconvolutedtubules(reabsorption)DysfunctionofHenle’sloopDysfunctionofthedistalconvolutedtubules

Thefundamentalunitforrenalfiltrationandreabsorption

HCO3-H+/NH4+edema,polyuria,hyposthenuria,glycosuria,aminoaciduria,metabolicacidosis,isothenuriaRenalendocrinedysfunctionRenin-angiotensin-aldosteronesystem(RAAS)↑Erythropoietein(EPO)↓1,25-dihydroxyvitaminD3↓Kallikrein-kinin-prostaglandin-system(KKPGS）↓Parathyroidhormone(PTH)andgastrin↑Arachidonicacid(AA)metabolismdisorder

Erythropoietein(EPO)Arachidonicacid(AA)抑制水鈉重吸收；刺激近球細胞釋放腎素；脂氧合酶LTs（炎癥介質）收縮血管ClinicalExampleMale，68yearsold，puffiness,anuria.RepeatedtakingGentamicinandSMZforupperrespiratoryinfection.

R:eyelidpuffiness，legswithpittingedema

Chemicalexamination：

urineprotein（++），urinespecificgravity:1.015，

UNa:64mmol/L，serumcreatinine:809μmmol/L，

UN:16.2mmol/L.Questions2.Whatisthemechanismofoliguria?Whatisthereasonofoliguria?3.Whataretheeffectsofoliguriaforbody？Acuterenalfailure?Conception???

Etiologyandpathogenesis???AlterationsoffunctionandmetabolismConceptionofacuterenalfailure(ARF)Aheterogenousgroupofdisorders,whichischaracterizedbyasudden(withinhourstodays)deteriorationofrenalfunctionandusuallyassociatedwitholiguriaorannuriaresultinginaccumulationinthebloodofnitrogenouswasteproductsthatwouldnormallybeexcrectedintheurine.Thepatientspresentoftenwithazotemia,waterintoxication,hyperkalemiaandmetabolicacidosis.

各種原因→短期內→泌尿功能↓↓→內環(huán)境嚴重紊亂Fatality20-70%PrerenalARF(腎前性ARF)EtiologyandclassificationofARFIntrarenalARF(腎性ARF)PostrenalARF(腎后性ARF)PrerenalARF(腎前性ARF)CauseTheeffectivecirculatingbloodvolume↓CharactersFunctionalARF＊尿量減少、尿鈉<20mmol/L、＊尿肌酐/血肌酐>40；＊去除病因，腎功能迅速恢復。EtiologyandclassificationofARFMechanismsofPrerenalARFTheeffectivecirculatingbloodvolume↓renalbloodvolume↓GFR↓Renaltubularreabsorption↑oliguriaDisturbanceofhomeostasisCauseObstructionofurinarytracePrerenalARF(腎前性ARF)EtiologyandclassificationofARFPostrenalARF(腎后性ARF)CharactersFunctionalARFinearlystageIntrinsicrenaldiseases

(mainlyATN)OrganicARFPrerenalARF(腎前性ARF)EtiologyandclassificationofARFPostrenalARF(腎后性ARF)IntrarenalARF(腎性ARF)CharactersCause1.AcutetubularnecrosisAcuterenalischemiaAcuterenalpoisons

（heavymetals,organicsolvents,drugs,biologicalagents)CausesofintrarenalARF正常中毒正常腎與HgCL2中毒腎髓質之比較（200×）朱砂（硫化汞、循環(huán)泌尿系統(tǒng)）、甲基汞（神經系統(tǒng)、水俁?。┝蛐了嵴{控Nrf-2/HO-1通路對急性百草枯中毒大鼠腎損傷的保護作用1.Acutetubularnecrosis2.IntrinsicrenaldiseasesacuteglomerulonephritisacuteinterstitialnephritisacutevascularnephritisCausesofintrarenalARF分型：

ARF腎前性（30~60%)腎性（20~40%)腎后性（1~10%)腎小球腎炎間質性腎炎血管疾病腎小管壞死中毒沉著物缺血010203040506070FernandoL,1967，ARF,MadridpresentstudyPre-RenalRenalPost-Renal急性腎功能衰竭

(acuterenalfailure,ARF)Definitionetiologyandclassificationpathogenesis（oliguria?）

renalfunction

↓↓(oliguriaoranuria)causes？GFR↓↓GFR↓

Renalbloodflow

GlomerularfiltrationmembraneGlomerularFiltrationRate(GFR)

GlomerulareffectivefiltrationpressureDysfunctionofglomerularfiltrationDecreaseofrenalbloodflowDecreaseofglomerulareffectivefiltrationpressureDecreaseofglomerularcapillarysurfaceareaAlterationsofpermeabilityofglomerularfiltrationmembraneNetFiltrationPressureBloodhydrostaticpressure(BHP)60mmHgoutColloidosmoticpressure(COP)-32mmHginCapsularpressure(CP)-18mmHginNetfiltrationpressure(NFP)10mmHgoutNFPBHP60outCOP32inCP10out18inRenalischemiaGlomerulopathyRenaltubularocclusionOriginalurinerefluxRenalcellinjury

PathogenesisofARFGlomerularfactorTubularfactorRenalischemia→GFR↓

RenalarteryperfusionPre.↓

PathogenesisofARFBp80-160mmHgRBF～Bp<80mmHgRBF↓,GFR↓,1/2-2/3Bp<40mmHgRBF=0腎血流量和腎小球濾過率的自身調節(jié)RPF：腎血漿流量GFR：腎小球濾過率80180405.3Contraction↑

(CA,RAA,ET↑）

Relaxing↓(PGE2↓,

kinin

↓）Renalischemia→GFR↓

RenalarteryperfusionPre.↓

Renalbloodvesselcontraction

PathogenesisofARFEndothelialcellBloodflowNormalCellswellingDecreaseofbloodflowAcuterenalfailureCellinjurandaccumulationofplate

Swellingofendothelialcells

PathogenesisofARF

IntrarenalDICRenalischemia→GFR↓

RenalarteryperfusionPre.↓

RenalbloodvesselcontractionGFR↓RBF↓Perfusionpre.↓BloodvesselconstrictionBP↓CA,ET,RAS↑,PGE2,kinin

↓RenalischemiaEndothelialswellingDICAcutegromerularitsNormalAcutegromerularitsDecreaseofglomerularcapillarysurfacearea

→GFR↓RenalischemiaGlomerulopathyRenaltubularocclusionOriginalurinerefluxRenalcellinjury

PathogenesisofARFGlomerularfactorTubularfactorUrineflowDenudedtubularmembraneInjuredtubularcellsObstructionfromdebrisandnecroticcellsRenaltubularobstructionRenalischemiaRenalintoxicationGromerularTubularTransfusionreactionCrushingsyndrome1)TubularobstructionIschemianephrotoxinTubularobstruction→intra-pressure↑EPCfalloffGEFP↓TubularnecrosisGFR↓Oliguria→ARFCastDifferenttypebloodtransfusionExtrusionsyndromeStreptocide（SMZ）HbMb2.RenaltubulefactorProteinCastsGranularCastRBCCastsEpithelialCastsinUrineRenalischemiaGlomerulopathyRenaltubularocclusionOriginalurinerefluxRenalcellinjury

PathogenesisofARFGlomerularfactorTubularfactorurineTubularcellinjuryBasemembraneinjuryNecroticobstructionTubularcellsBasemembraneRenaltoxinUrineNecroticcellanddebrisInterstitialedemaTubuleandcapillarycompressedGFR↓OriginalrefluxtubuleobstructionOliguriaRenalischemiaGlomerulopathyRenaltubularocclusionOriginalurinerefluxRenalcellinjury

PathogenesisofARFGlomerularfactorTubularfactor腎小球因素腎小管因素Damagedcells

RenalTubularcellEndothelialcellMesangialcellMechanismofcellinjuryTubulorrhexiclesionNephrotoxiclesion腎小管細胞壞死性損傷凋亡性損傷小管破裂性損傷:累及各段腎小管,基底膜破壞內皮細胞系膜細胞腎毒性損傷:累及近球小管,基底膜完整缺血中毒中毒

內皮細胞腫脹內皮細胞受損→血小板聚集、微血栓形成→毛細管內凝血內皮細胞受損→舒血管因子↓縮血管因子↑→GFR↓AngⅡ、ADH、腺苷、慶大霉素、硝酸鈾→系膜細胞收縮→GFR↓⒈受損細胞的種類及特征累及遠端腎小管,微絨毛消失,核固縮,出現(xiàn)凋亡小體NormalCellApoptoticcellCellundergoingapoptosisMechanismofcellinjuryATPanddysfunctionofionpumpsOxygenfreeradical

ReducedGSH

ActivityofPLA2

Cytoskeletalstructuralchanges

IncreaseincellapoptosisNa+、K+-ATP↓Ca2+-ATP↓Na+andwaterretention,cytoplasmfreeCa2+↑Ca2+overloadATP↓Ischemia,poisonsCellswellingOFRpro.↑clearance↓perioxidizingGSH↓PLA2↑PGs、LTsCellinjuryMitochondriaCa2+↑ADP、poisonsMechanismofcellinjuryMechanismofcellinjury(1)腎臟氧供特點(2)髓袢升支粗段（mTAL）及降支粗段(S3段)對缺氧敏感，與其位于低氧環(huán)境和主動重吸收耗氧量大有關(3)內源性調節(jié)因子與mTAL損傷：(4)腎中毒和腎缺血互相增強對腎小管損傷①腺苷②花生四烯酸(及)代謝產物③NO④血紅素氧化酶(HO)／一氧化碳(CO)/HO在腎小管表達不同與ARF功能損傷有關的因素MechanismofcellrepairThegeneticregulationbyhypoxiaandischemiaTheproductionandactiveofHSPFunctionofcytokinesReconstructionofcellularskeletonandrenaltubuleThegeneticregulationbyhypoxiaandischemiaFIGURE1.Kidneytissueinjury(a–d)andrepair(e–h)overtimefollowing20minofbilateralrenalischemia/reperfusioninjury.MaleWistarratsweresubjectedtoshamorbilateralischemiabyclampingtherenalpediclesfor20minandthenremovingtheclampsandconfirmingreperfusion.Ratswereeuthanizedatvarioustimesandkidneytissueswerecollected.RepresentativephotomicrographsofH&E-stainedparaffin-embeddedkidneysections(at200×magnification)andimmunohistochemistryforKi67(at400×magnification)arepresentedfromthefollowingtimepoints:(a,e)Shamsurgery;(b,f)24h;(c,g)72h;and(d,h)120h.Allfieldswerechosenfromthecortexandoutermedulla.Arrowsinpanelsbandcindicatesloughingofcells,tubulardilationandnecrosis.Arrowsinpanelse–hshowKi67positivenucleiasanindicatoroftubularepithelialcellproliferation.Apoptosisinthekidneytissueovertimefollowing20minofbilateralrenalischemia/reperfusioninjury.MaleWistarratsweresubjectedtoshamorbilateralischemiabyclampingtherenalpediclesfor20minandthenremovingtheclampsandconfirmingreperfusion.Ratswereeuthanizedatvarioustimes,kidneytissueswerecollectedandtransferasedUTPnickendlabeling(TUNEL)immunostainingwasperformedtolabelapoptoticcells.Representativephotomicrographsat400×magnificationarepresented.ArrowsinpanelsshowTUNELpositivenucleiasanindicatoroftubularepithelialcellapoptosis.ThegeneticregulationbyhypoxiaandischemiaThegeneticregulationbyhypoxiaandischemiaTheproductionandactiveofHSPFunctionofcytokinesFunctionofcytokinesFunctionofcytokinesThemainpathwaysoftheeffectsofEPO.ApoptoticpathwaysinfluencedbyEPORenalischemia,renalpoisonsRenalarterialvasoconstriction(RAS↑,ET↑,NO↓,PGI2↓)OFR↑,Na+-K+ATPasedysfunctionIntrarenalDICInjuryofrenaltubularcellsSwellingofendothelialcellsRenalbloodflow↓TubularobstructionPassivebackflowGEFP↓Intrapressure↑,tubularurine↓GFR↓OliguriaThemechanismofacuterenalfailurecausedbyacuterenalischemiaClinicalExampleMale，68yearsold，puffiness,anuria.RepeatedtakingGentamicinandSMZforupperrespiratoryinfection.

R:eyelidpuffiness，legswithpittingedema

Chemicalexamination：

urineprotein（++），urinespecificgravity:1.015，

UNa:64mmol/L，serumcreatinine:809ummol/L，

UN:16.2mmol/L.2.Whatisthemechanismofoliguria?Whatisthereasonofoliguria?3.Whataretheeffectsofoliguriaforbody？Acuterenalfailure,ARFDefinitionCausesandclassificationPathogenesisAlterationsofmetabolismandfunctionOligurictypeARFNonoliguricARFAlterationsofmetabolismandfunctionOligurictypeARFTheoliguricstageThediureticstageTherecoverystageChangesoffunctionandmetabolismOligurictypeARFTheoliguricstageUrinousalterationsOliguriaAnuriaoliguria：400ml/d>urineoutput>100ml/danuria：urineoutput<100ml/dChangesoffunctionandmetabolismOligurictypeARFTheoliguricstageUrinousalterations(1)oliguria,anuria

(2)AlterationofurinouscotentsHyposthenuria，urinoussodium↑，hematuria，albuminuria，cylindruriaChangesoffunctionandmetabolism

IndexFunctionalARIOrganicARIUrinegravity>1.020（↑）<1.015（↓）osmoticpressure>500（↑）<400（↓）Urinenatrium<20（↓）>40（↑）Urinecreatine/bloodcreatine>40：1（↑）<20：1（↓）Urineroutine(-)(+)

DifferencesbetweenfunctionalARFandorganicARF2.Azotemia

urea

↑↑

creatinine

↑↑

uricacid

↑NPN↑OligurictypeARFTheoliguricstage1.UrinousalterationsChangesoffunctionandmetabolismThemarkedincreaseofnonproteinnitrogen(NPN)content,suchurea，creatinine,uricacid,etc

(>28.6mmol/L)AzotemiaOligurictypeARFTheoliguricstage1.Urinousalterations2.Azotemia3.WaterintoxicationChangesoffunctionandmetabolismOligurictypeARFTheoliguricstage1.Urinousalterations2.Azotemia3.Waterintoxication4.HyperkalemiaChangesoffunctionandmetabolismChangesoffunctionandmetabolismOligurictypeARFTheoliguricstage1.Urinousalterations2.Azotemia3.WaterintoxicationHyperkalemiaMetabolicacidosis

OligurictypeARFTheoliguricstageThediureticstage1.TherecoveryofGFR2.Theremoveoftubularobstruction3.Theweakfunctionofnewborntubule4.OsmoticdiuresisUrineoutput>400ml/dRenalfunctionisnotrecovery!!!ChangesoffunctionandmetabolismOligurictypeARFTheoliguricstageThediureticstageTherecoverystageChangesoffunctionandmetabolismGFR和腎小管損害程度較輕

病程較短癥狀較輕預后較好

非少尿型與少尿型可相互轉化OligurictypeARFNonoliguricARF不少尿，尿比重低而固定，尿鈉低，氮質血癥。ChangesoffunctionandmetabolismAcuterenalfailure,ARFDefinitionCausesandclassificationPathogenesisAlterationsofmetabolismandfunctionPreventionandtreatment

Treatingthecausesandprecipitatingfactors

Treatingtheconsequencesoliguricstage

1.RestrictFluidandsodium2.Treathyperkalemiaproperlyandemergetically3.Correctmetabolicacidosis4.Acutedialysiswhennecessary1.Maintainthebalanceofwaterandelectrolyte2.SupportivecareandtherapyContinuousdialysiswhennecessaryNewtherapies

diureticstagePathophysiologicalbasisfortreatmentARF治療新進展

半胱氨酸蛋白酶抑制劑、NOS合酶抑制劑、ROS清除劑減輕上皮細胞損傷；生長因子促進小管上皮細胞修復；抗ICAM-1、E-選擇素、IL-18抗體和α-MSH阻斷白細胞和上皮細胞相互作用；精氨酸-甘氨酸-天冬氨酸多肽防治腎小管阻塞；心房鈉尿肽、鈣通道阻斷劑和ET拮抗劑增加腎血流。Chronicrenalfailure，CRFConceptionEtiologyPathogenesisAlterationsofmetabolismandfunctionWhatischronicrenalfailure?

CRFisasyndromeofimpairedhomeostasisowingtostructuraldamage(reducedfunctionalnephrons)ofthekidneys.

Thedisturbancesarecharacterizedbymetabolicacidosis,hypocalcemia,hyperphosphatemia,alterationinVitaminDmetabolismandthepresenceofcertaintoxicmaterialsInbodyfuid.DefinitionEtiologyRenaldiseases★chronicglomerulonephritisRenalvasculardiseasesChronicurinaryobstructionChronicrenalfailureRenaldisease：慢性腎小球腎炎最常見,占50-60%西方國家:糖尿病ChronicglomerulonephritisNormal病因PolycystickidneydiseaseThecommoncausesofCRF1970’syears：

1.Chronicglomerulonephritis

2.chronicinterstitialnephritis

3.Diabetesnephropathy

Since1990：

1.Diabetesnephropathy(USA40%)

2.hypertention(USA33%)

3.Chronicglomerulonephritis(USA10%) UrolithiasisUrolithiasisHydronephrosis

Chronicrenalfailure，CRFDefinitionEtiologyClinalcourseClinicalcouseGFRAzotemiaStageofdecreasedrenalreserve

50-70%without↓Stageofrenalinsufficiency

<50%

mild↓Stageofrenalfailure10-25%marked↓Stageofuremia<10%severe255075100內生肌酐清除率占正常值的%臨床表現(xiàn)腎功能不全腎功能衰竭尿毒癥無癥狀期Chronicrenalfailure，CRFDefinitionEtiologyClinicalcoursesPathogenesisPathogenesisofCRFIntactnephronhypothesisTrade-offhypothesisGlomerularHyperfilitrationhypothesisBricker’shypothesizesPathogenesis-hypothesis

Intactnephronhypothesis(健存腎單位減少)causesProgressivelossofnephronsRemainingnephrons↓RenalfunctionfailtocompensateChronicrenalfailurePathogenesis

Intactnephronhypothesis

Trade-offhypothesisothermetabolicdisorderscausesProgressivelossofnephronsbloodconcentrationofsomesolutes

↑Relatedregulatoryfactors(suchashormones)↑Pathogenesis

Intactnephronhypothesis

Trade-offhypothesisGFR↓P↑normalPTH↑Newlesion(acidosis,osteomalacia)(excret↑)AprocessthatorganismdevelopsanewlesionbycorrectingandolddamagePathogenesis

Intactnephronhypothesis

Trade-offhypothesisGlomerularhyperfilitrationhypothesiscausesProgressivelossofnephronsglomerularfiltrationpressureinfewerintactnephron↑IntactnephronsfibrosisandscarringRenalfunctionfailtocompensatePathogenesisofCRFIntactnephronhypothesisTrade-offhypothesisGlomerularHyperfilitrationhypothesis

InterstitialandtubularcellinjuryhypothesisBricker’shypothesizes為什么CRF會進行性發(fā)展？血液動力學變化（腎小球高濾過）代謝變化（腎小管高代謝）尿毒癥毒素(甲基胍,PTH,H+,等)細胞因子-生長因子-血管活性物質遺傳因素：“腎衰基因”基因多態(tài)性（如ACE基因）其他Pathogenesis

ActivationofRASOxidationandstressAldosteroneAlbuminuriathefunctionofprimarydiseaseSecondaryprogressiveglomerularfibrosisActivationofRASActivationofRAS

腎小管萎縮

間質纖維化

腎單位

進行性損壞間質單個核細胞侵潤

釋放某些細胞因子和生長因子

刺激成纖維細胞細胞外基質增多小管內液Fe++的生成氧自由基增多

ATP合成增加補體旁路激活(C3途經)

膜攻擊復合物形成(C5b-9)

腎小管氧耗增加慢性腎衰高血糖，高血壓OxidationandstressOxidationandstressAldosteroneAldosteroneAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaMoleculesinvolvedinpotentialmechanismsinthedevelopmentofproteinuria-inducedrenaltubulointerstitialinjury.慢性腎功能衰竭

(chronicrenalfailure)DefinitionEtiologyClinicalcoursesPathogenesisAlterationsoffunctionandmetobolismChronicrenalfailureDefinitionEtiologyClinicalcourses

PathogenesisAlterationsoffunctionandmetobolismAlterationsoffunctionandmetobolismAlterationofurineUrineoutputnocturia

AsymptomcharacterizedbyurinatingatnightmorethanondayAlterationsoffunctionandmetobolismAlterationofurineUrineoutputnocturiapolyuria>2500ml/24h1.Intactnephronhyperfiltration2.Osmoticdiuresis3.Renalconcentrativefunction↓PolyuriabutNPNincrease!intactnephronandGFR

AlterationsoffunctionandmetobolismAlterationofurineUrineoutputnocturiapolyuria

oliguriaAlterationsoffunctionandmetobolismAlterationofurineUrineoutputUrineosmoticpressureEarlystage：hyposthenuria,specificgravity≦1.020

（concentration

，dilutionnormal）Laterstage：isosthenuria,specificgra.1.008~1.012

（concentration

，dilution）hematuria，albuminuria，cylindruriaAlterationsoffunctionandmetobolismAlterationofurineUrineoutput

UrineosmoticpressureAlterationofurinouscotentsAlterationsoffunctionandmetobolismAlterationofurineAzotemia(NPN↑)urea

，creatinine

，uricacid

↑↑

Clearancerateofendogenouscrestinine↓AlterationsoffunctionandmetobolismAlterationofurine

Azotemia(NPN↑)

Water,electrolytesimbalance

1.水代謝失調進水↑→水中毒進水↓→脫水2.鈉代謝失調—CRF的腎為“失鹽性腎”

∵滲透性利尿、甲基胍抑制重吸收Na+攝入↑→鈉潴留攝入↓→低鈉血癥

血磷↑主要是GFR↓所致。血鈣↓主要是腸道吸收鈣減少所致。

[Ca][P]=常數(shù);1,25-(OH)2D3↓;

腸道吸收鈣減少;

腸粘膜損傷。3.鉀代謝失調—腎排K+固定，與攝入量無關早期:正常（∵醛固酮↑、腎小管上皮鈉泵↑）晚期:高鉀血癥，低鉀血癥

4.鈣磷代謝障礙

早期：腎小管功能泌H+保堿功能↓，AG正常晚期：GRF

，固定酸排泄障礙，AGAlterationsoffunctionandmetobolismAlterationofurine

Azotemia(NPN↑)Water,electrolytesimbalance

MetabolicacidosisAlterationsoffunctionandmetobolismAlterationofurine

Azotemia(NPN↑)Water,electrolytesandacid-baseimbalance

Renalhypertension

1.Sodiumandwaterretention–sodium-dependenthypertension

2.Renin↑--renin-dependenthypertension

3.BP-decreasingsubstancefromkidney↓--PGA2

↓PGE2

↓?

RenalhypertensionAhypertensioncausedbyintrinsicRenaldiseasesAlterationsoffunctionandmetobolismAlterationofurine

Azotemia(NPN↑)Water,electrolytesandacid-baseimbalanceRenalhypertension

Renalosteodystrophy(腎性骨營養(yǎng)不良）

1.P

,Ca2+↓,PTH↑2.1,25(OH)2D3↓3.Chronicmetabolicacidosis?

RenalOsteodystrophyAseriouscomplicationofCRF(especially,ofuremia),whichincludesrenalrickets(forchildren),adultosteomalacia,osteitisfibrosa,osteoporosis,osteosclerosis,etc.?

RenalOsteodystrophy囊性纖維性骨炎骨質軟化癥CKD-MBD概念以往用語：“腎性骨病”和“腎性骨營養(yǎng)不良”，未能很好地包含鈣、磷代謝紊亂的內容。2005年在國際腎臟病一體化治療協(xié)調委員會（K/DIGO）召開的礦物質代謝及其骨病的會議上提出統(tǒng)一用語為“慢性腎臟病的礦物質和骨代謝異?！保–hronicKidneyDisease-MineralandBoneDisorder，CKD-MBD）。CKD-MBD表現(xiàn)是全身性疾病，常具有下列一個或一個以上：1.鈣、磷、甲狀旁腺激素（PTH）或維生素D代謝異常；2.骨轉化、礦化、骨容量、骨骼線性生長或骨強度的異常；3.血管或其他軟組織鈣化。CKD-MBD特點普遍性全身性致殘性間接致死性-高磷與高死亡率相關

——知曉率低！我國目前對CKD-MBD的治療現(xiàn)狀：很少早期監(jiān)測與治療大多在嚴重SHPT（已經出現(xiàn)骨骼畸形）才開始使用活性VitD制劑治療方法、藥物劑量、療程不統(tǒng)一缺乏嚴密的監(jiān)測（尤其是PTH等）若PTH過度抑制，ABD隨之發(fā)生血鈣、磷及CaXP過高，轉移性鈣化發(fā)生PTX未得到普及SHPTPTHPTH加重Ca.P代謝異常皮膚搔癢貧血神經系統(tǒng)異常心、血管病變骨吸收增加，陷窩形成纖維組織增生新骨形成也增加骨痛，骨骼畸形全身多臟器損害轉移性鈣化繼發(fā)性甲狀旁腺功能亢進癥SecondaryHyperparathiyroidism

(SHPT)異常骨改變-骨骼畸形骨軟化及繼發(fā)性甲旁亢均可致骨骼畸形。骨盆口呈“心形”，四肢關節(jié)干骺端增寬、骨性關節(jié)面呈毛刷狀改變,胸廓畸形呈雞胸狀，頜面骨呈“獅面”樣改變。SHPT實驗室檢查血清總鈣及游離鈣通常降低或正常血清磷水平升高甲狀旁腺激素水平升高(正常值10-65pg/ml）骨特異性堿性磷酸酶水平升高骨鈣素（Osteocalcin)水平升高SHPT治療降低血磷糾正低血鈣藥物治療－活性維生素D的應用介入治療－甲狀旁腺組織注射酒精或1,25(OH)2D3；甲狀旁腺切除術(次全及全切術加自體移植)始終貫穿充分透析Alt