生理學(xué)-腎臟生理(八年制)

腎臟生理

RenalPhysiology

----腎臟的排泄功能

ExcretoryFunctionoftheKidney1機(jī)體通過(皮膚-呼吸-肝臟-消化道)

腎臟排出代謝終產(chǎn)物及異物保持內(nèi)環(huán)境的穩(wěn)定Overview:RenalFunction2Thekidneyperformsthefollowingfunctionbyformationandexcretionofurine

腎臟通過尿的生成和排泄，執(zhí)行以下主要功能

1.調(diào)節(jié)水電解質(zhì)平衡Na+,K+,Cl-,H+,HCO3-.Regulationofwaterandinorganic-ionbalance2.排泄機(jī)體代謝終產(chǎn)物及藥物和毒物.Removalofwasteandforeignchemicalsfromblood3.SecretionofHormones:Renin,activeVitD3,促紅細(xì)胞生成素Erythropoietin(EPO),postglandins. 腎衰，腎透析,貧血,補(bǔ)EPO;補(bǔ)鈣與VitD33本章重點(diǎn)內(nèi)容1.GlomerularFiltration腎小球過濾2.Re-absorptionandSecretionintheRenalTubuleandCollectingDuct腎小管和集合管的重吸收及分泌3.UrineConcentration尿的濃縮

也是本章難點(diǎn)內(nèi)容4概 述Introduction一、腎的功能解剖和腎血流量（一）

腎單位和集合管（二）

皮質(zhì)腎單位和近髓腎單位（三）

近球小體二、腎血液循環(huán)特征（一）

自身調(diào)節(jié)80-180mmHg機(jī)理不清（二）

神經(jīng)和體液調(diào)節(jié)5腎的功能解剖6一.腎的功能解剖和腎血流量(一)腎單位和集合管(NephronandCollectingDuct)腎臟的基本功能單位是腎單位(Nephron),包括腎小體(renalcorpuscle)和腎小管(renaltubule)每側(cè)腎有~100萬個(gè)腎單位,~40萬個(gè)腎單位即可維持正常泌尿功能.不能再生.40歲后,數(shù)量隨年齡增加而遞減,每10年約減少10%.80歲余40%腎單位,功能代償增加.思考:為什么老年人易腎功能受損?易見藥物腎毒性?7腎單位和集合管腎小囊Bowmancapsule腎小體(renalcorpuscle):腎小球glomerulus腎單位

(nephron)腎小管(renaltubule):近球小管proximaltubule髓袢細(xì)段(thinsegmentofLoopofHenle)遠(yuǎn)球小管distaltubule集合管collectingduct:與多個(gè)腎單位的遠(yuǎn)曲小管相連,尿濃縮和稀釋功能Summary:NephronandCollectingDuct8腎單位(腎小球,腎小管)和集合管示意圖9髓袢的組成（StructureofLoopofHenle)ThickDescendinglimb髓袢(LoopofHenle)10腎小體結(jié)構(gòu)(Structureofrenalcorpuscle):

腎小囊Bowmancapsule+腎小球glomerulus11Majorstructuralcomponentsoftheglomerulus,thefilteringunitofthekidneyPozzi&Zent.JCI201212Glomerulus,magnified~1440times13腎小球掃描電鏡圖14(二)皮質(zhì)腎單位和近髓腎單位執(zhí)行不同的功能皮質(zhì)腎單位corticalnephron：占85-90%,入球小動(dòng)脈與出球小動(dòng)脈口徑之比約為2:1.髓袢短.主要功能:尿的初始過濾Question1:入球小動(dòng)脈口徑粗于出球小動(dòng)脈之意義？Question2:但其入球和出球動(dòng)脈壓卻相差無幾？

近髓腎單位juxtamedullarynephron： 占10-15%,髓袢長,

可深入到內(nèi)髓.有U型直小血管.主要功能:尿的濃縮與稀釋Question２：皮質(zhì)腎單位形成的尿液如何被濃縮？15近髓腎單位負(fù)責(zé)尿濃縮與稀釋皮質(zhì)腎單位負(fù)責(zé)尿液初始濾過Henle’sloopHenle’sloop16CorticalandJuxtamedullaryNephrons髓質(zhì)的U型小血管vasarecta17Juxtaglomerularcells(球旁細(xì)胞,入球小動(dòng)脈上皮樣細(xì)胞)—secretethehormonereninMaculadensa(致密斑,遠(yuǎn)曲小管起始部分)—specializedsensorcells(sodiumand/orchloride,etc.)近球小體18二、腎血液循環(huán)特征1.腹主動(dòng)脈→腎動(dòng)脈，1200ml/min

占心輸出22%.94%在皮質(zhì)(Why?!),

5-6%在外髓<1%在內(nèi)髓2.髓質(zhì)的U型小血管vasarecta(Function?)

Figure3.腎血流量在動(dòng)脈血壓80-180mmHg范圍內(nèi)自身調(diào)節(jié)(生理意義?)，機(jī)理不清--肌源學(xué)說。

Figure 移植的腎臟,無神經(jīng)支配,血流量的自動(dòng)調(diào)節(jié) 其它:骨骼肌,心肌，腦血流量的自動(dòng)調(diào)節(jié)神經(jīng)和體液調(diào)節(jié) 腎交感神經(jīng)—血管收縮、血流減少,去甲腎上腺素、血管緊張素II,副交感功能不詳Question:失血性休克shock，腎血管代償性收縮之意義？腎血管代償性收縮過度之后果？19CorticalandJuxtamedullaryNephrons髓質(zhì)的U型小血管vasarecta20GFRRBF03250408012016020024028060504030201006005004003002001000RENALARTERIALPRESSURE(mmHg)mlper100gkidneyperminGFRRBF(dog)Autoregulationoftherenalbloodflow,

whichaffectsglomerularfiltrationrateReturn21尿的生成UrinaryFormationPartI:腎小球?yàn)V過GlomerularFiltration221.GlomerularFiltration:腎小球過濾血漿中的大部分物質(zhì)超濾液,原尿2.Re-absorptionintherenaltubuleandcollectingduct：腎小管和集合管重吸收原尿中的營養(yǎng)物質(zhì)，水，電解質(zhì)血漿3.Secretionintherenaltubuleandcollectingduct：腎小管和集合管分泌血漿中的物質(zhì)尿液Overview:UrineFormation尿的生成23腎小球?yàn)V過是尿生成的第一步

GlomerularFiltrationIstheFirstStepinUrineFormation24GlomerulusFiltration:AHistoricalReviewHenle,J.ZurAnatomiederNiere.Abh.Ges.Wiss.Gttingen,Math.Physik.K1.10:223,1862.WilliamBowman.OnthestructureanduseoftheMalpighianbodiesofthekidneywithobservationsofthecirculationthroughthatgland.Phil.Trans.R.Soc.Lond.(Part1):57,1842.Concludedfiltrationmusttakeplaceinglomerulus.25ThreelayersofGlomerularFilterGlomerularcapillaryendotheliumBasementmembranePodocytes,withfiltrationslitsGlomerularFilter腎小球?yàn)V過膜26腎小球?yàn)V過膜GlomerularFilter腎小球27Glomerularcapillaryandfilter,magnified~36,000timesGlomerularFilter28Figure1.ThisschematicshowstwoadjacentpodocyteFPwiththeinterposedslitdiaphragm(SD)complex.ThelocalizationofNEPH-1attheSDanditsheterophilicinteractionwithnephrinremaintobeestablished.Theactincytoskeletonisthecommondownstreampathwayandreceivesinputformthreepodocytedomains:theapicaldomains,thelateralSD-containingdomain,andthebasaldomainoftheFPsoleplate,whichlinksthepodocytetotheGBM.InterferencewithanyofthethreedomainswillultimatelycauseFPeffacementandproteinuria/nephriticsyndrome.-act4,-actinin-4;31,31integrin;-DG,-dystroglycan;-DG,-dystroglycan;Na(+)/H(+)ERF2,Na(+)/H(+)exchangerregulatoryfactor2;P,paxillin;P-cad,P-cadherin;Synpo,synaptopodin;T,talin;V,vinculin.Molecularanatomyofthepodocytefootprocess(FP)actincytoskeleton.JAmSocNephrol.2002Dec;13(12):3005-15.29CD151-deficientpodocytesadherelesstightlytotheGBMthandowild-typepodocytesPozzi&Zent.JCI201230Nephringene-promoterdrivenLacZstainingwasspecifictopodocyteswithintransgenickidneys.JASN2004;15:2851-285631FiltrationthroughGlomerularFilterFiltrationisbasedonSIZEFiltrationisalsobasedonCHARGE,becausethebasementmembraneandthefiltrationslitsarerichinnegativelychargedproteinsForsamesize,anionicsubstancesareretainedbytheglomerulusfilter32Filtrate/FiltrandRatio33腎小球?yàn)V過膜的通透性----與溶質(zhì)分子大小及電荷有關(guān)----大分子帶負(fù)電者不易通過內(nèi)層:腎小球毛細(xì)血管的內(nèi)皮細(xì)胞 窗孔結(jié)構(gòu)50-100nm,血細(xì)胞不能透過; 負(fù)電,蛋白質(zhì)難以通過中層:基底膜,決定何種溶質(zhì)可以通過 網(wǎng)狀纖維結(jié)構(gòu),4-8nm,負(fù)電,蛋白質(zhì)不能通過外層:腎小囊臟(內(nèi))層上皮細(xì)胞層,又稱腎小球外層上皮

4-14nm,負(fù)電,蛋白質(zhì)不能通過思考：基底膜腎小球腎炎:濾過膜電性受損，蛋白尿34GlomerularFiltrationWhatforcesfavororopposefiltration?351.Forcesfavororopposefiltration2.腎小球?yàn)V過率(Glomerularfiltrationrate,GFR):GFRisthevolumeoffluidfilteredfromtheglomeruliintoBowman’sspaceperunittime5815358Why?平均毛細(xì)血管壓~35mmHg,腎小球毛細(xì)血管壓~60mmHg36

腎小球?yàn)V過率影響因素濾過膜:通透性增加GFR增加,面積小GFR低,