肾脏泌尿功能的调节

第三节肾脏泌尿功能的调节

Regulationofurineformationofthekidney尿生成的调节

regulationofurineformation肾血流量的调节 神经—体液调节

regulationofrenalbloodflownervousandhumonalcontrol(对滤过的调节) (对重汲取和分泌) 自身神经体液 调节调节调节ADH醛固酮甲状旁腺素Aldosteroneparathyroidhormone

一、抗利尿激素

antidiuretichormone,ADH

合成部位：视上核(supraopticnucleus)、室旁核(paraventricularnucleus)合成ADH运输：丘脑—垂体束贮存释放：神经垂体（贮存于膨大神经末梢中）前激素ADH九肽

蛋白水解酶靶器官：远曲小管集合管ThehypothalamuscontainstwotypesofneuronsthatsynthesizeADHinthesupraopticnucleusandparaventricularnucleus.onceADHissynthesized,itistransporteddowntheaxonsoftheneuronstotheirtips,terminatingintheposteriorpituitarygland.作用：1.提高远曲小管和集合管上皮细胞对水的通透性，促进水的重汲取尿液浓缩、尿量削减（抗利尿）[主要作用]。ThemostimportantrenalactionofADHistoincreasethewaterpermeabilityofthedistaltubule,collectingtubule.Thiseffecthelpsthebodytoconservewaterincircumstancessuchasdehydration.2.增加内髓部集合管对尿素的通透性并削减肾髓质的血流量。ADHincreasestheureapermeabilityofcollectingtubuleininnerzoneanddecreasesthebloodflowinmedulla.3.促进髓绊升支粗段对NaCl的重汲取，使直小血管收缩。ADHincreasesthereabsorptionofNaClinthicksegmentofascendinglimbandsoleadstoconstrictionofvasarecta.（一）、作用机理：ADH与远曲小管、集合管上皮细胞管周膜上受体结合激活膜内的腺苷酸环化酶上皮细胞中cAMP管腔膜中蛋白激酶激活膜蛋白磷酸化膜构型转变水通道开放管腔膜对水通透性。ADH，水通道小泡内移，对水通透性。

ADHcombineswiththereceptorinbasolateralmembraneandactivatedtheadenylatecyclase,itproducescyclicadenosinemonophosphate,whichleadstoactivationofproteinkinaseinbasolateralmembrane,thenthemembraneproteinisphosphorylated,sotheconfigurationofmembranechanges,thisprocessincreasesthepermeabilitytowaterbytheopenofwaterchannel.（二）ADH分泌的调节(theregulationofADHsecretion)

血浆晶体渗透压的转变

(thechangeofcrystalosmoticpressure)有效刺激因素effectivestimuli循环血量的转变

(thechangeofeffectivebloodvolume)1、血浆晶体渗透压的转变特点：敏感，晶体渗透压转变1～2%时即有反应。电解质(+)有效尿素无效感受器：位于视上核及其四周区域。大量出汗、腹泻、失水血浆晶体渗透压视上核及其周围区域渗透压感受器(+)神经垂体膨大神经末梢去极化释放ADH远曲小管、集合管对水通透性对水重汲取，尿液浓缩尿量削减。TheprecisewaythattheosmoticconcentrationoftheextracellularfluidscontrolsADHsecretionisnotclear.Yetsomewhereinornearthehypothalamusaremodifiedneuronreceptorscalledosmoreceptors.whentheextracellularfluidbecomestooconcentrated,fluidispulledbyosmosisoutoftheosmoreceptorcell,initiatingappropriatenervesignalsinthehypothalamustocauseadditionalADHsecretion.

水利尿waterdiuresis大量饮清水尿量饮1000ml清水，隔30分钟尿量，（1小时末达高峰，2—3小时恢复）饮1000mlNS，隔30分钟变化不大

2、循环血量的转变（容量感受器途径）

过度输液，血量过多(+)左心房内膜下容量感受器

迷走N，传入冲动中枢，间接抑制下丘脑—垂体后叶系统释放ADH远曲小管集合管对水通透性对水重汲取尿量。Whenbloodvolumeincreasesbecauseofexcesstransfuse,thevolumereceptorinendometriumofleftatriumsendsimpulsethroughVagusnervetocenterandinhibitthereleaseofADHbyHypothalami-Pituitaryposteriorlobesystem,sothewaterpermeabilityindistaltubuleandcollectingtubuledecreases,thereforethereaborptionofwaterdecreasesandtheurinevolumeincreases.3、其它因素①AP(+)颈动脉窦压力感受器窦NADH反射性释放尿量②痛刺激、情绪紧张ADH尿量③弱冷刺激ADH尿量④下丘脑病变累及视上核、室旁核ADH合成释放障碍尿崩症(diabetesinsipidus)。Whenarterialpressureincreases,pressoreceptoincarotidsinussendssignalstohypothalamicnucleithroughsinusnervethatdecreasesADHsecretion.ADHsecretioncanalsobecontrolledbyotherstimulisuchaspainandnervousmood.二、醛固酮的作用（Aldosterone）分泌部位：肾上腺皮质球状带靶器官：远曲小管集合管作用：促进对Na+的主动重汲取，同时促进 K+的排出——保Na+排K+作用。Aldosterone,secretedbythezonaglomerulosecellsoftheadrenalcortex,isanimportantregulatorofsodiumreabsorptionandpotassiumsecretionbytherenaltubules.Theprimarysiteofaldosteroneactionisontheprincipalcellsofthecorticalcollectingtubule.themechanismbywhichaldosteroneincreasesodiumreabsorptionwhileatthesametimeincreasingpotassiumsecretionisstimulatingthesodium-potassiumATPasepumponthebasolateralsideofthecorticalcollectingtubulemembrane.（一）作用机制：醛固酮进入远曲小管集合管的上皮细胞后与胞浆受体结合形成激素—胞浆受体复合物通过核膜与核中受体结合激素—核受体复合物促进mRNA的合成醛固酮 促进小管上皮细胞Na+

泵运转诱导蛋白 促进生化氧化供应ATP促进加强Na+

增加管腔膜对Na+

通透性的主动重汲取(保Na+)造成小管腔内负电位K+被分泌到小管液（排K+)Aldosteronediffusesreadilytotheinteriorofthetubulaarepithelialcellsandcombineswithahighlyspecificcytoplasmicreceptorprotein,thenthealdosterone-receptorcomplexdiffusesintothenucleuswhereitmayundergofurtheralterations,finallyinducingoneormorespecificportionsoftheDNAtoformoneormoretypesofmessengerRNArelatedtotheprocessofsodiumandpotassiumtransport.（心房利尿肽ANP）28个氨基酸残基集合管对Na+重吸收(-)，使出入球小动脉舒张心钠素（Cardionatrin）(-)aldosterone释放

ADH

肾素分泌作用：促进肾脏排钠排水Thefunctionofcardionatrinistopromotethesecretionofsodiumandwaterbykidney.thecardionatrincanreducethereleaseofaldosterone、ADHandrenin.（二）醛固酮分泌的调节：肾素—血管紧张素—醛固酮系统、血K+、血Na+浓度促肾上腺皮质激素（ACTH）对醛固酮分泌的日常调节不起重要作用

Potassiumionconcentrationandtherenin-angiotensinsystemarebyfarthemostpotentinregulatingaldosteronesecretion.1.肾素—血管紧张素—醛固酮系统（renin-angiotensin-aldosteronesystem,RAAS）RAA系统的活性取决于血浆中肾素浓度，故凡能影响肾素分泌的因素均可间接影响醛固酮的分泌。肝硬化继发性醛固酮增多症水肿、腹水组织液循环血量肾素醛固酮cirrhosisofliversecondaryaldosteronismEdema、Hydroperitoniatissuefluidbloodvolumereninaldosterone2.血K+和血Na+浓度①血K+Na+

直接刺激肾上腺皮质球状带醛固酮分泌保Na+排K+②血K+Na+

醛固酮分泌保Na+排K+功能减弱③醛固酮的分泌对K+浓度转变较敏感，K+仅增加0.5～1.0mmol/L醛固酮（敏感度K+>Na+）Increasedpotassiumionconcentrationintheextracellularfluidgreatlyincreasesaldosteronesecretion.asmallpercentageincreaseinpotassiumconcentrationcancauseaseveralfoldincreaseinaldosteronesecretion.三、甲状旁腺激素(parathyroidhormone,PTH)

的作用分泌部位：甲状旁腺作用：1.促进远球小管和集合管对Ca2+的重汲取，削减尿Ca2+排出量；2.抑制近球小管对磷酸盐的重汲取，增加尿中磷酸盐的排出量；3.抑制近球小管对Na+、K+、HCO3-和氨基酸的重汲取。PTHissecrectedbyparathyroidglands.PTHprovidesapowerfulmechanismforcontrollingextracellularcalciumandphosphateconcentrationsbyregulatingintestinalreabsorption,renalexcretion,andexchangebetweentheextracellularfluidandboneoftheseions.PTHdecreasescalciumexcretionandincreasesphosphateexcretionbythekidneys.moreover,itincreasestherateofreabsorptionofmagnesiumionsandhydrogenionswhileitdecreasesthereabsorptionofsodium,potassium,andaminoacidions.第四节血浆清除率plasmaclearance肾功能测量方法(useofclearancemethodstoquantifykidneyfunction)：1.尿浓缩和稀释试验(UrineconcentrationtestandUrinedilutiontest)——反映肾小管功能2.酚红排泄试验(excretiontestofphenolsulfonphthalein)——反映肾小管功能3.血浆清除率试验(plasmaclearancetest)—反映肾小球滤过率、肾血流量尿浓缩试验——主要测定肾小管对水重汲取功能 正常浓缩功能尿比重可达1.030Urineconcentrationtestmainlyquantifiesthereabsorptiontowaterofrenaltubule.尿稀释试验——测定多水情况下尿液变淡程度正常成人短时间内饮水1～1.5L，尿比重可<1.003Urinedilutiontestmainlyquantifiesthedilutiondegreeofurine.酚红排泄试验——反映肾小管的分泌排泄功能0.6%酚红1ml静脉注射15分钟排泄出注入量25%以上 2小时排泄出注入量60%以上 病理：15分钟<12% 2小时<40%

血浆清除率的概念和意义概念：血浆清除率（plasmaclearance.C）指肾脏在单位时间内（通常用每分钟）能将多少毫升血浆中所含的某物质完全清除出去，这个被完全清除了的某物质的血浆毫升数，这叫该物质的血浆清除率（ml/min），它反映肾脏对不同物质的清除能力。

U·V U：尿中某物质的浓度

C= V：每分钟尿量

P P：血浆中某物质的浓度

意义：用血浆清除率可衡量肾脏生理活动情况。

Theplasmaclearanceofasubstanceisthevolumeofplasmathatiscompletelyclearedofthesubstancebythekidneysperunittime.thisprovidesausefulwayofquantitatingtheeffectivenesswithwhichthekidneysexcretevarioussubstances.1.肾小球滤过率的测定：菊粉清除率、内生肌酐清除率菊粉inulin滤过后，既不被重汲取也不被分泌，故测定菊粉的血浆清除率可代表肾小球滤过率。

U·V1ml/min×125mg/100mlC菊粉===125ml/min

P1mg/100mlInulinclearancecanbuusedtoestimateGFR.inulinisfreelyfilteredandisnotreabsorbedorsecretedbytherenaltubules,therateatwhichthatinulinisexcretedintheurine(U*V)isequaltothefiltrationrateofthesubstancebythekidneys(GFR*p),theGFR,therefore,canbecalculatedastheclearanceoftheinulin.2.肾血流量的测定(estimationofrenalplasmaflow)碘锐特diodrast、对氨基马尿酸（PAH）静脉注射后，经肾循环一周后可完全清除掉（通过滤过和分泌）。即在肾动脉中该物质有肯定浓度，流到肾静脉中其浓度接近0，那么该物质每分钟的尿中排出量（U·V），应等于每分钟通过肾脏的血浆中所含的量，该物质血浆清除率为每分钟通过肾脏的血浆量。

Theorectically,ifasubstanceiscompletelyclearedfromthelasma,theclearancerateofthatsubstanceisequaltothetotalrenalplasmaflow,inotherwords,theamountofthesubstancedeliveredtothekidneysinthebloodwouldbeequaltotheamountexcretedintheurine.Thus,renalplasmaflowcouldbecalculatedasRPF=U*V/p.U·V=X·PX：每分钟通过肾脏的血流量U·VX==CP此时，可测定C来代表每分钟肾血浆流量，再估量出肾血流量。注意此时C=肾血浆流量≠肾血流量血浆量：肾血浆流量全血的55%，肾血流量=×100553.对肾小管功能的推测一种物质C>125ml/min提示肾小管必定有分泌排泄

Ifplasmaclearanceofasubstanceismorethan125ml/min,itmustbesecretedbytherenaltubule.第五节尿的排放(micturition)一、输尿管(ureter)的运动输尿管连接肾盂(pelvis)处平滑肌细胞有自律性(autorhythmicity)，兴奋下传产生蠕动波3次/min，其推动速度2­—3cm/s。肾盂中尿量越多，内压越大，自动节律性频率越高，蠕动增强，反之亦然。尿因输尿管蠕动，一阵阵被推入膀胱(bladder)。二、膀胱和尿道的神经支配

盆Npelvicnerves

传入传出副交感NS2—4三对N腹下NHypogastricnerves

传入传出交感NL1—5

阴部Npudendalnerve

传入传出躯体NS2—4受意识掌握

传入纤维传出纤维盆N膀胱充胀感觉膀胱逼尿肌收缩、膀胱内括约肌舒张促排尿腹下N传导膀胱痛觉膀胱逼尿肌松弛、膀胱内括约肌收缩阻止排尿阴部N传导尿道感觉尿道外括约肌收缩阻止排尿（受意识和反射掌握）

三、排尿反射(micturitionreflex)膀胱内压当尿量>400ml才明显提高当尿量达到700ml时，内压为35cmH2O，逼尿肌(detrusormuscles)产生节律收缩，排尿欲增高。内压达到70cmH2O时产生痛感，不得不排尿

Intravesicalpressureevidentlyincreaseswhentheurinevolumeismorethan