病理生理学课件：肾脏病理生理学

肾脏病理生理学RenalpathophysiologyDepartmentofpathophysiology肾功能泌尿功能内分泌功能通过泌尿排除代谢废物，并维持水、电解质和酸碱平衡，维持机体内环境的恒定。肾素PGsEPO1，25-OH2VD31.Excretoryfunction2.Regulatoryfunction3.Endocrineandmetabolicfunction肾功能不全发展过程

当各种原因引起肾功能障碍时：首先表现为泌尿功能障碍，继之引起体内代谢紊乱与内分泌功能障碍，严重时还可使各系统发生病理变化。

分急性和慢性，但都以尿毒症告终。ContentsBasicpathologicaltachesforrenalfailureAcuterenalfailure(ARF)Chronicrenalfailure(CRF)Uremia(尿毒症）尿生成过程血浆经肾脏生成尿，是由肾小球滤过、肾小管的重吸收和分泌三个相联系的环节实现的。PeritubularcapillaryRenaltubuleH2OH2OH2OUrine

肾小球滤过

Glomerularfiltration

肾小管重吸收

Tubularreabsorption

肾小管分泌

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)抑制水钠重吸收；刺激近球细胞释放肾素；脂氧合酶LTs（炎症介质）收缩血管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.

各种原因→短期内→泌尿功能↓↓→内环境严重紊乱Fatality20-70%PrerenalARF(肾前性ARF)EtiologyandclassificationofARFIntrarenalARF(肾性ARF)PostrenalARF(肾后性ARF)PrerenalARF(肾前性ARF)CauseTheeffectivecirculatingbloodvolume↓CharactersFunctionalARF＊尿量减少、尿钠<20mmol/L、＊尿肌酐/血肌酐>40；＊去除病因，肾功能迅速恢复。EtiologyandclassificationofARFMechanismsofPrerenalARFTheeffectivecirculatingbloodvolume↓renalbloodvolume↓GFR↓Renaltubularreabsorption↑oliguriaDisturbanceofhomeostasisCauseObstructionofurinarytracePrerenalARF(肾前性ARF)EtiologyandclassificationofARFPostrenalARF(肾后性ARF)CharactersFunctionalARFinearlystageIntrinsicrenaldiseases

(mainlyATN)OrganicARFPrerenalARF(肾前性ARF)EtiologyandclassificationofARFPostrenalARF(肾后性ARF)IntrarenalARF(肾性ARF)CharactersCause1.AcutetubularnecrosisAcuterenalischemiaAcuterenalpoisons

（heavymetals,organicsolvents,drugs,biologicalagents)CausesofintrarenalARF正常中毒正常肾与HgCL2中毒肾髓质之比较（200×）朱砂（硫化汞、循环泌尿系统）、甲基汞（神经系统、水俣病）硫辛酸调控Nrf-2/HO-1通路对急性百草枯中毒大鼠肾损伤的保护作用1.Acutetubularnecrosis2.IntrinsicrenaldiseasesacuteglomerulonephritisacuteinterstitialnephritisacutevascularnephritisCausesofintrarenalARF分型：

ARF肾前性（30~60%)肾性（20~40%)肾后性（1~10%)肾小球肾炎间质性肾炎血管疾病肾小管坏死中毒沉着物缺血010203040506070FernandoL,1967，ARF,MadridpresentstudyPre-RenalRenalPost-Renal急性肾功能衰竭

(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肾血流量和肾小球滤过率的自身调节RPF：肾血浆流量GFR：肾小球滤过率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肾小球因素肾小管因素Damagedcells

RenalTubularcellEndothelialcellMesangialcellMechanismofcellinjuryTubulorrhexiclesionNephrotoxiclesion肾小管细胞坏死性损伤凋亡性损伤小管破裂性损伤:累及各段肾小管,基底膜破坏内皮细胞系膜细胞肾毒性损伤:累及近球小管,基底膜完整缺血中毒中毒

内皮细胞肿胀内皮细胞受损→血小板聚集、微血栓形成→毛细管内凝血内皮细胞受损→舒血管因子↓缩血管因子↑→GFR↓AngⅡ、ADH、腺苷、庆大霉素、硝酸铀→系膜细胞收缩→GFR↓⒈受损细胞的种类及特征累及远端肾小管,微绒毛消失,核固缩,出现凋亡小体NormalCellApoptoticcellCellundergoingapoptosisMechanismofcellinjuryATPanddysfunctionofionpumpsOxygenfreeradical

ReducedGSH

ActivityofPLA2

Cytoskeletalstructuralchanges

IncreaseincellapoptosisNa+、K+-ATP↓Ca2+-ATP↓Na+andwaterretention,cytoplasmfreeCa2+↑Ca2+overloadATP↓Ischemia,poisonsCellswellingOFRpro.↑clearance↓perioxidizingGSH↓PLA2↑PGs、LTsCellinjuryMitochondriaCa2+↑ADP、poisonsMechanismofcellinjuryMechanismofcellinjury(1)肾脏氧供特点(2)髓袢升支粗段（mTAL）及降支粗段(S3段)对缺氧敏感，与其位于低氧环境和主动重吸收耗氧量大有关(3)内源性调节因子与mTAL损伤：(4)肾中毒和肾缺血互相增强对肾小管损伤①腺苷②花生四烯酸(及)代谢产物③NO④血红素氧化酶(HO)／一氧化碳(CO)/HO在肾小管表达不同与ARF功能损伤有关的因素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和肾小管损害程度较轻

病程较短症状较轻预后较好

非少尿型与少尿型可相互转化OligurictypeARFNonoliguricARF不少尿，尿比重低而固定，尿钠低，氮质血症。ChangesoffunctionandmetabolismAcuterenalfailure,ARFDefinitionCausesandclassificationPathogenesisAlterationsofmetabolismandfunctionPreventionandtreatment

Treatingthecausesandprecipitatingfactors

Treatingtheconsequencesoliguricstage

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

diureticstagePathophysiologicalbasisfortreatmentARF治疗新进展

半胱氨酸蛋白酶抑制剂、NOS合酶抑制剂、ROS清除剂减轻上皮细胞损伤；生长因子促进小管上皮细胞修复；抗ICAM-1、E-选择素、IL-18抗体和α-MSH阻断白细胞和上皮细胞相互作用；精氨酸-甘氨酸-天冬氨酸多肽防治肾小管阻塞；心房钠尿肽、钙通道阻断剂和ET拮抗剂增加肾血流。Chronicrenalfailure，CRFConceptionEtiologyPathogenesisAlterationsofmetabolismandfunctionWhatischronicrenalfailure?

CRFisasyndromeofimpairedhomeostasisowingtostructuraldamage(reducedfunctionalnephrons)ofthekidneys.

Thedisturbancesarecharacterizedbymetabolicacidosis,hypocalcemia,hyperphosphatemia,alterationinVitaminDmetabolismandthepresenceofcertaintoxicmaterialsInbodyfuid.DefinitionEtiologyRenaldiseases★chronicglomerulonephritisRenalvasculardiseasesChronicurinaryobstructionChronicrenalfailureRenaldisease：慢性肾小球肾炎最常见,占50-60%西方国家: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内生肌酐清除率占正常值的%临床表现肾功能不全肾功能衰竭尿毒症无症状期Chronicrenalfailure，CRFDefinitionEtiologyClinicalcoursesPathogenesisPathogenesisofCRFIntactnephronhypothesisTrade-offhypothesisGlomerularHyperfilitrationhypothesisBricker’shypothesizesPathogenesis-hypothesis

Intactnephronhypothesis(健存肾单位减少)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为什么CRF会进行性发展？血液动力学变化（肾小球高滤过）代谢变化（肾小管高代谢）尿毒症毒素(甲基胍,PTH,H+,等)细胞因子-生长因子-血管活性物质遗传因素：“肾衰基因”基因多态性（如ACE基因）其他Pathogenesis

ActivationofRASOxidationandstressAldosteroneAlbuminuriathefunctionofprimarydiseaseSecondaryprogressiveglomerularfibrosisActivationofRASActivationofRAS

肾小管萎缩

间质纤维化

肾单位

进行性损坏间质单个核细胞侵润

释放某些细胞因子和生长因子

刺激成纤维细胞细胞外基质增多小管内液Fe++的生成氧自由基增多

ATP合成增加补体旁路激活(C3途经)

膜攻击复合物形成(C5b-9)

肾小管氧耗增加慢性肾衰高血糖，高血压OxidationandstressOxidationandstressAldosteroneAldosteroneAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaAlbuminuriaMoleculesinvolvedinpotentialmechanismsinthedevelopmentofproteinuria-inducedrenaltubulointerstitialinjury.慢性肾功能衰竭

(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.水代谢失调进水↑→水中毒进水↓→脱水2.钠代谢失调—CRF的肾为“失盐性肾”

∵渗透性利尿、甲基胍抑制重吸收Na+摄入↑→钠潴留摄入↓→低钠血症

血磷↑主要是GFR↓所致。血钙↓主要是肠道吸收钙减少所致。

[Ca][P]=常数;1,25-(OH)2D3↓;

肠道吸收钙减少;

肠粘膜损伤。3.钾代谢失调—肾排K+固定，与摄入量无关早期:正常（∵醛固酮↑、肾小管上皮钠泵↑）晚期:高钾血症，低钾血症

4.钙磷代谢障碍

早期：肾小管功能泌H+保碱功能↓，AG正常晚期：GRF

，固定酸排泄障碍，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(肾性骨营养不良）

1.P

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

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

RenalOsteodystrophy囊性纤维性骨炎骨质软化症CKD-MBD概念以往用语：“肾性骨病”和“肾性骨营养不良”，未能很好地包含钙、磷代谢紊乱的内容。2005年在国际肾脏病一体化治疗协调委员会（K/DIGO）召开的矿物质代谢及其骨病的会议上提出统一用语为“慢性肾脏病的矿物质和骨代谢异常”（ChronicKidneyDisease-MineralandBoneDisorder，CKD-MBD）。CKD-MBD表现是全身性疾病，常具有下列一个或一个以上：1.钙、磷、甲状旁腺激素（PTH）或维生素D代谢异常；2.骨转化、矿化、骨容量、骨骼线性生长或骨强度的异常；3.血管或其他软组织钙化。CKD-MBD特点普遍性全身性致残性间接致死性-高磷与高死亡率相关

——知晓率低！我国目前对CKD-MBD的治疗现状：很少早期监测与治疗大多在严重SHPT（已经出现骨骼畸形）才开始使用活性VitD制剂治疗方法、药物剂量、疗程不统一缺乏严密的监测（尤其是PTH等）若PTH过度抑制，ABD随之发生血钙、磷及CaXP过高，转移性钙化发生PTX未得到普及SHPTPTHPTH加重Ca.P代谢异常皮肤搔痒贫血神经系统异常心、血管病变骨吸收增加，陷窝形成纤维组织增生新骨形成也增加骨痛，骨骼畸形全身多脏器损害转移性钙化继发性甲状旁腺功能亢进症SecondaryHyperparathiyroidism

(SHPT)异常骨改变-骨骼畸形骨软化及继发性甲旁亢均可致骨骼畸形。骨盆口呈“心形”，四肢关节干骺端增宽、骨性关节面呈毛刷状改变,胸廓畸形呈鸡胸状，颌面骨呈“狮面”样改变。SHPT实验室检查血清总钙及游离钙通常降低或正常血清磷水平升高甲状旁腺激素水平升高(正常值10-65pg/ml）骨特异性碱性磷酸酶水平升高骨钙素（Osteocalcin)水平升高SHPT治疗降低血磷纠正低血钙药物治疗－活性维生素D的应用介入治疗－甲状旁腺组织注射酒精或1,25(OH)2D3；甲状旁腺切除术(次全及全切术加自体移植)始终贯穿充分透析Alt