腎臟泌尿功能(gōngnéng)的調(diào)節(jié)第一頁，共34頁。尿生成(shēnɡchénɡ)的調(diào)節(jié)regulationofurineformation腎血流量的調(diào)節(jié) 神經(jīng)—體液調(diào)節(jié)regulationofrenalbloodflownervousandhumonalcontrol(對(duì)濾過的調(diào)節(jié)) (對(duì)重吸收和分泌(fēnmì)) 自身神經(jīng)體液 調(diào)節(jié)調(diào)節(jié)調(diào)節(jié)ADH醛固酮甲狀旁腺素Aldosteroneparathyroidhormone

第二頁，共34頁。第三頁，共34頁。一、抗利尿(lìniào)激素

antidiuretichormone,ADH合成部位：視上核(supraopticnucleus)、室旁核(paraventricularnucleus)合成ADH運(yùn)輸：丘腦—垂體束貯存釋放：神經(jīng)垂體（貯存于膨大神經(jīng)末梢中）前激素(jīsù)ADH九肽蛋白水解酶靶器官：遠(yuǎn)曲小管集合管ThehypothalamuscontainstwotypesofneuronsthatsynthesizeADHinthesupraopticnucleusandparaventricularnucleus.onceADHissynthesized,itistransporteddowntheaxonsoftheneuronstotheirtips,terminatingintheposteriorpituitarygland.第四頁，共34頁。作用：1.提高遠(yuǎn)曲小管和集合(jíhé)管上皮細(xì)胞對(duì)水的通透性，促進(jìn)水的重吸收尿液濃縮、尿量減少（抗利尿）[主要作用]。ThemostimportantrenalactionofADHistoincreasethewaterpermeabilityofthedistaltubule,collectingtubule.Thiseffecthelpsthebodytoconservewaterincircumstancessuchasdehydration.2.增加內(nèi)髓部集合(jíhé)管對(duì)尿素的通透性并減少腎髓質(zhì)的血流量。ADHincreasestheureapermeabilityofcollectingtubuleininnerzoneanddecreasesthebloodflowinmedulla.3.促進(jìn)髓絆升支粗段對(duì)NaCl的重吸收，使直小血管收縮。ADHincreasesthereabsorptionofNaClinthicksegmentofascendinglimbandsoleadstoconstrictionofvasarecta.第五頁，共34頁。（一）、作用機(jī)理(jīlǐ)：ADH與遠(yuǎn)曲小管、集合管上皮細(xì)胞管周膜上受體結(jié)合激活膜內(nèi)的腺苷酸環(huán)化酶上皮細(xì)胞中cAMP管腔膜中蛋白激酶激活膜蛋白磷酸化膜構(gòu)型改變水通道開放管腔膜對(duì)水通透性。ADH，水通道小泡內(nèi)移，對(duì)水通透性。第六頁，共34頁。

ADHcombineswiththereceptorinbasolateralmembraneandactivatedtheadenylatecyclase,itproducescyclicadenosinemonophosphate,whichleadstoactivationofproteinkinaseinbasolateralmembrane,thenthemembraneproteinisphosphorylated,sotheconfigurationofmembranechanges,thisprocessincreasesthepermeabilitytowaterbytheopenofwaterchannel.第七頁，共34頁。（二）ADH分泌的調(diào)節(jié)(theregulationofADHsecretion)

血漿晶體滲透壓的改變

(thechangeofcrystalosmoticpressure)有效刺激(cìjī)因素effectivestimuli循環(huán)血量的改變(thechangeofeffectivebloodvolume)第八頁，共34頁。1、血漿晶體滲透壓的改變特點(diǎn)：敏感，晶體滲透壓改變1～2%時(shí)即有反應(yīng)。電解質(zhì)(+)有效尿素(niàosù)無效感受器：位于視上核及其附近區(qū)域。大量出汗、腹瀉、失水血漿晶體滲透壓視上核及其周圍區(qū)域滲透壓感受器(+)神經(jīng)垂體膨大神經(jīng)末梢去極化釋放ADH遠(yuǎn)曲小管、集合管對(duì)水通透性對(duì)水重吸收，尿液濃縮尿量減少。TheprecisewaythattheosmoticconcentrationoftheextracellularfluidscontrolsADHsecretionisnotclear.Yetsomewhereinornearthehypothalamusaremodifiedneuronreceptorscalledosmoreceptors.whentheextracellularfluidbecomestooconcentrated,fluidispulledbyosmosisoutoftheosmoreceptorcell,initiatingappropriatenervesignalsinthehypothalamustocauseadditionalADHsecretion.

第九頁，共34頁。水利尿waterdiuresis大量飲清水尿量飲1000ml清水，隔30分鐘尿量，（1小時(shí)末達(dá)高峰(gāofēng)，2—3小時(shí)恢復(fù)）飲1000mlNS，隔30分鐘變化不大第十頁，共34頁。inulinisfreelyfiltered電解質(zhì)(+)有效尿素(niàosù)無效腎小球?yàn)V過(lǜɡuò)率的測(cè)定：菊粉清除率、內(nèi)生肌酐清除率腎功能測(cè)量方法(useofclearancemethodstoquantifykidneyfunction)：asmallpercentageincreaseinpotassium（一）、作用機(jī)理(jīlǐ)：55contractsandtheintersphincterrelaxes.中蛋白激酶激活膜蛋白磷酸化膜構(gòu)型改變水通volumeismorethanconcentrationsbyregulatingintestinalreabsorption,renalclearancerateofthatsubstanceisequaltothetotalrenalplasmaTheprecisewaythattheosmoticconcentrationoftheextracellularfluids促進(jìn)遠(yuǎn)球小管和集合管對(duì)Ca2+的重吸收，減少尿Ca2+排出量；一種物質(zhì)C>125ml/min提示腎小管必定(bìdìng)有分泌排泄2、循環(huán)血量的改變（容量感受器途徑）過度輸液，血量過多(+)左心房內(nèi)膜下容量感受器

迷走N，傳入沖動(dòng)中樞，間接抑制下丘腦—垂體后葉系統(tǒng)釋放(shìfàng)ADH遠(yuǎn)曲小管集合管對(duì)水通透性對(duì)水重吸收尿量。Whenbloodvolumeincreasesbecauseofexcesstransfuse,thevolumereceptorinendometriumofleftatriumsendsimpulsethroughVagusnervetocenterandinhibitthereleaseofADHbyHypothalami-Pituitaryposteriorlobesystem,sothewaterpermeabilityindistaltubuleandcollectingtubuledecreases,thereforethereaborptionofwaterdecreasesandtheurinevolumeincreases.第十一頁，共34頁。3、其它因素①AP(+)頸動(dòng)脈竇壓力感受器竇NADH反射性釋放尿量②痛刺激、情緒(qíngxù)緊張ADH尿量③弱冷刺激ADH尿量④下丘腦病變累及視上核、室旁核ADH合成釋放障礙尿崩癥(diabetesinsipidus)。Whenarterialpressureincreases,pressoreceptoincarotidsinussendssignalstohypothalamicnucleithroughsinusnervethatdecreasesADHsecretion.ADHsecretioncanalsobecontrolledbyotherstimulisuchaspainandnervousmood.第十二頁，共34頁。二、醛固酮的作用(zuòyòng)（Aldosterone）分泌部位：腎上腺皮質(zhì)球狀帶靶器官：遠(yuǎn)曲小管集合管作用：促進(jìn)(cùjìn)對(duì)Na+的主動(dòng)重吸收，同時(shí)促進(jìn)(cùjìn) K+的排出——保Na+排K+作用。Aldosterone,secretedbythezonaglomerulosecellsoftheadrenalcortex,isanimportantregulatorofsodiumreabsorptionandpotassiumsecretionbytherenaltubules.Theprimarysiteofaldosteroneactionisontheprincipalcellsofthecorticalcollectingtubule.themechanismbywhichaldosteroneincreasesodiumreabsorptionwhileatthesametimeincreasingpotassiumsecretionisstimulatingthesodium-potassiumATPasepumponthebasolateralsideofthecorticalcollectingtubulemembrane.第十三頁，共34頁。（一）作用機(jī)制：醛固酮進(jìn)入遠(yuǎn)曲小管集合管的上皮細(xì)胞后與胞漿受體結(jié)合形成激素—胞漿受體復(fù)合物通過核膜與核中受體結(jié)合激素—核受體復(fù)合物促進(jìn)(cùjìn)mRNA的合成醛固酮 促進(jìn)(cùjìn)小管上皮細(xì)胞Na+泵運(yùn)轉(zhuǎn)誘導(dǎo)蛋白 促進(jìn)(cùjìn)生化氧化提供ATP促進(jìn)(cùjìn)加強(qiáng)Na+ 增加管腔膜對(duì)Na+通透性的主動(dòng)重吸收(保Na+)造成小管腔內(nèi)負(fù)電位K+被分泌到小管液（排K+)Aldosteronediffusesreadilytotheinteriorofthetubulaarepithelialcellsandcombineswithahighlyspecificcytoplasmicreceptorprotein,thenthealdosterone-receptorcomplexdiffusesintothenucleuswhereitmayundergofurtheralterations,finallyinducingoneormorespecificportionsoftheDNAtoformoneormoretypesofmessengerRNArelatedtotheprocessofsodiumandpotassiumtransport.第十四頁，共34頁。（心房利尿(lìniào)肽ANP）28個(gè)氨基酸殘基集合管對(duì)Na+重吸收(-)，使出入球小動(dòng)脈舒張心鈉素（Cardionatrin）(-)aldosterone釋放 ADH 腎素分泌作用：促進(jìn)腎臟排鈉排水Thefunctionofcardionatrinistopromotethesecretionofsodiumandwaterbykidney.thecardionatrincanreducethereleaseofaldosterone、ADHandrenin.第十五頁，共34頁。第十六頁，共34頁。（二）醛固酮分泌的調(diào)節(jié)：腎素—血管緊張素—醛固酮系統(tǒng)、血K+、血Na+濃度(nóngdù)促腎上腺皮質(zhì)激素（ACTH）對(duì)醛固酮分泌的日常調(diào)節(jié)不起重要作用Potassiumionconcentrationandtherenin-angiotensinsystemarebyfarthemostpotentinregulatingaldosteronesecretion.第十七頁，共34頁。1.腎素—血管緊張素—醛固酮系統(tǒng)(xìtǒng)（renin-angiotensin-aldosteronesystem,RAAS）RAA系統(tǒng)(xìtǒng)的活性取決于血漿中腎素濃度，故凡能影響腎素分泌的因素均可間接影響醛固酮的分泌。第十八頁，共34頁。肝硬化繼發(fā)性醛固酮增多癥水腫、腹水(fùshuǐ)組織液循環(huán)血量腎素醛固酮cirrhosisofliversecondaryaldosteronismEdema、Hydroperitoniatissuefluidbloodvolumereninaldosterone第十九頁，共34頁。2.血K+和血Na+濃度①血K+Na+直接刺激(cìjī)腎上腺皮質(zhì)球狀帶醛固酮分泌保Na+排K+②血K+Na+醛固酮分泌保Na+排K+功能減弱③醛固酮的分泌對(duì)K+濃度改變較敏感，K+僅增加～1.0mmol/L醛固酮（敏感度K+>Na+）Increasedpotassiumionconcentrationintheextracellularfluidgreatlyincreasesaldosteronesecretion.asmallpercentageincreaseinpotassiumconcentrationcancauseaseveralfoldincreaseinaldosteronesecretion.第二十頁，共34頁。三、甲狀旁腺激素(jīsù)(parathyroidhormone,PTH)

的作用分泌部位：甲狀旁腺作用：1.促進(jìn)遠(yuǎn)球小管和集合管對(duì)Ca2+的重吸收，減少尿Ca2+排出量；2.抑制(yìzhì)近球小管對(duì)磷酸鹽的重吸收，增加尿中磷酸鹽的排出量；3.抑制(yìzhì)近球小管對(duì)Na+、K+、HCO3-和氨基酸的重吸收。PTHissecrectedbyparathyroidglands.PTHprovidesapowerfulmechanismforcontrollingextracellularcalciumandphosphateconcentrationsbyregulatingintestinalreabsorption,renalexcretion,andexchangebetweentheextracellularfluidandboneoftheseions.PTHdecreasescalciumexcretionandincreasesphosphateexcretionbythekidneys.moreover,itincreasestherateofreabsorptionofmagnesiumionsandhydrogenionswhileitdecreasesthereabsorptionofsodium,potassium,andaminoacidions.第二十一頁，共34頁。第四節(jié)血漿(xuèjiāng)清除率plasmaclearance腎功能測(cè)量方法(useofclearancemethodstoquantifykidneyfunction)：1.尿濃縮和稀釋試驗(yàn)(UrineconcentrationtestandUrinedilutiontest)——反映(fǎnyìng)腎小管功能2.酚紅排泄試驗(yàn)(excretiontestofphenolsulfonphthalein)——反映(fǎnyìng)腎小管功能3.血漿清除率試驗(yàn)(plasmaclearancetest)—反映(fǎnyìng)腎小球?yàn)V過率、腎血流量第二十二頁，共34頁。尿濃縮試驗(yàn)——主要(zhǔyào)測(cè)定腎小管對(duì)水重吸收功能 正常濃縮功能尿比重可達(dá)Urineconcentrationtestmainlyquantifiesthereabsorptionto

waterofrenaltubule.尿稀釋試驗(yàn)——測(cè)定多水情況下尿液變淡程度正常成人短時(shí)間內(nèi)飲水1～，尿比重可Urinedilutiontestmainlyquantifiesthedilutiondegreeofurine.酚紅排泄試驗(yàn)——反映腎小管的分泌排泄功能0.6%酚紅1ml靜脈注射15分鐘排泄出注入量25%以上 2小時(shí)排泄出注入量60%以上 病理：15分鐘<12% 2小時(shí)<40%第二十三頁，共34頁。血漿清除率的概念和意義概念：血漿清除率（plasmaclearance.C）指腎臟在單位時(shí)間內(nèi)（通常用每分鐘）能將多少毫升血漿中所含的某物質(zhì)完全清除出去，這個(gè)被完全清除了的某物質(zhì)的血漿毫升數(shù)，這叫該物質(zhì)的血漿清除率（ml/min），它反映腎臟對(duì)不同物質(zhì)的清除能力。U·V U：尿中某物質(zhì)的濃度(nóngdù) C= V：每分鐘尿量 P P：血漿中某物質(zhì)的濃度(nóngdù)

意義：用血漿清除率可衡量腎臟生理活動(dòng)情況。Theplasmaclearanceofasubstanceisthevolumeofplasmathatiscompletelyclearedofthesubstancebythekidneysperunittime.thisprovidesausefulwayofquantitatingtheeffectivenesswithwhichthekidneysexcretevarioussubstances.第二十四頁，共34頁。1.腎小球?yàn)V過(lǜɡuò)率的測(cè)定：菊粉清除率、內(nèi)生肌酐清除率菊粉inulin濾過(lǜɡuò)后，既不被重吸收也不被分泌，故測(cè)定菊粉的血漿清除率可代表腎小球?yàn)V過(lǜɡuò)率。U·V1ml/min×125mg/100mlC菊粉===125ml/minP1mg/100mlInulinclearancecanbuusedtoestimateGFR.inulinisfreelyfilteredandisnotreabsorbedorsecretedbytherenaltubules,therateatwhichthatinulinisexcretedintheurine(U*V)isequaltothefiltrationrateofthesubstancebythekidneys(GFR*p),theGFR,therefore,canbecalculatedastheclearanceoftheinulin.第二十五頁，共34頁。2.腎血流量的測(cè)定(estimationofrenalplasmaflow)碘銳特diodrast、對(duì)氨基馬尿酸（PAH）靜脈注射后，經(jīng)腎循環(huán)一周后可完全清除(qīngchú)掉（通過濾過和分泌）。即在腎動(dòng)脈中該物質(zhì)有一定濃度，流到腎靜脈中其濃度接近0，那么該物質(zhì)每分鐘的尿中排出量（U·V），應(yīng)等于每分鐘通過腎臟的血漿中所含的量，該物質(zhì)血漿清除(qīngchú)率為每分鐘通過腎臟的血漿量。Theorectically,ifasubstanceiscompletelyclearedfromthelasma,theclearancerateofthatsubstanceisequaltothetotalrenalplasmaflow,inotherwords,theamountofthesubstancedeliveredtothekidneysinthebloodwouldbeequaltotheamountexcretedintheurine.Thus,renalplasmaflowcouldbecalculatedasRPF=U*V/p.第二十六頁，共34頁。U·V=X·PX：每分鐘通過腎臟的血流量U·VX==CP此時(shí)，可測(cè)定(cèdìng)C來代表每分鐘腎血漿流量，再估計(jì)出腎血流量。注意此時(shí)C=腎血漿流量≠腎血流量血漿量：腎血漿流量全血的55%，腎血流量=×10055第二十七頁，共34頁。3.對(duì)腎小管功能的推測(cè)一種物質(zhì)C>125ml/min提示腎小管必定(bìdìng)有分泌排泄Ifplasmaclearanceofasubstanceismorethan125ml/min,itmustbesecretedbytherenaltubule.第二十八頁，共34頁。第五節(jié)尿的排放(páifànɡ)(micturition)一、輸尿管(ureter)的運(yùn)動(dòng)輸尿管連接腎盂(shènyú)(pelvis)處平滑肌細(xì)胞有自律性(autorhythmicity)，興奮下傳產(chǎn)生蠕動(dòng)波3次/min，其推進(jìn)速度2-—3cm/s。腎盂(shènyú)中尿量越多，內(nèi)壓越大，自動(dòng)節(jié)律性頻率越高，蠕動(dòng)增強(qiáng)，反之亦然。尿因輸尿管蠕動(dòng)，一陣陣被推入膀胱(bladder)。第二十九頁，共34頁。二、膀胱和尿道的神經(jīng)(shénjīng)支配盆Npelvicnerves傳入傳出副交感NS2—4三對(duì)N腹下NHypogastricnerves傳入傳出交感NL1—5陰部(yīnbù)Npudendalnerve傳入傳出軀體NS2—4受意識(shí)控制

傳入纖維傳出纖維盆N膀胱充脹感覺膀胱逼尿肌收縮、膀胱內(nèi)括約肌舒張促排尿腹下N傳導(dǎo)膀胱痛覺膀胱逼尿肌松弛、膀胱內(nèi)括約肌收縮阻止排尿陰部N傳導(dǎo)尿道感覺尿道外括約肌收縮阻止排尿（受意識(shí)和反射控制）

第三十頁，共34頁。第三十一頁，共34頁。三、排尿(páiniào)反射(micturitionreflex)膀胱內(nèi)壓當(dāng)尿量>400ml才明顯提高當(dāng)尿量達(dá)到700ml時(shí)，內(nèi)壓為35cmH2O，逼尿肌(detrusormuscles)產(chǎn)生節(jié)律收縮(shōusuō)，排尿欲增高。內(nèi)壓達(dá)到70cmH2O時(shí)產(chǎn)生痛感，不得不排尿Intravesicalpre