生理学-复件尿生成-自编newest

Formationand

ExcretionofUrine

HANXiaohua

Room423,BoyaBuildingOverallfunctionofthekidneys

Excretion：waste/foreignproductsRegulation：

-volumeandosmoticpressureoftheextracellularfluid.-acid-basebalanceofthebody.Secretion：

-renin,EPO,1,25-(OH)2vitaminD3

尿毒症

-面色泛黄食欲不佳困倦乏力浮肿高血压史铁生第一届：2006-3-9，慢性肾病的早期检测和预防第二届：2007.3.8，了解您的肾脏第三届：2008.3.13，神奇的肾脏第四届：2009.3.12，稳定血压，保持肾脏健康第五届：2010.3.11,保护您的肾脏，控制糖尿病第六届：2011.3.10，保护肾脏，挽救心脏第七届：2012.3.8，捐献肾脏，延续生命世界肾脏日（WorldKidneyDay）:

每年3月份第2个星期四ContentsFunctionalanatomyandbloodflowofkidneyGlomerularfiltrationSolutetransportintherenaltubuleandcollectingductUrinaryconcentrationanddilutionRegulationofurinaryformationClearanceSection1

FunctionalAnatomyandBloodFlowoftheKidneys80-120万/kidney肾小体肾小管肾小球(毛细血管球)肾小囊(内层、囊腔、外层)近端小管髓袢细段远端小管近曲小管髓袢降支粗段髓袢降支细段髓袢升支细段髓袢升支粗段远曲小管肾单位（一）NephronNephron（肾单位）

Corticalnephronandjuxtamedullarynephron

功能参与尿的生成参与尿液的浓缩和稀释

(二）Juxtaglomerularapparatus(JGA,球旁器）

髓袢升支粗段靠近毛细血管网的部分致密斑球外系膜细胞球旁细胞（1）球旁细胞

(juxtaglomerularcell)

-入球小动脉特殊分化的平滑肌细胞

-分泌renin（2）致密斑（maculadensa)

-远曲小管起始部一小块柱状上皮细胞，呈斑状隆起

-感受小管液中NaCl含量变化（3）球外系膜细胞

(extraglomerularmesangialcell)-吞噬和收缩功能肾A叶间A弓形A小叶间A入球小A毛细血管球

肾V叶间V弓形V小叶间V管周毛细血管网出球小A

(直小血管）

二RenalbloodflowCharacteristicofrenalbloodflow（1）Kidneysreceive20%ofcardiacoutput-94%inthecortex-5%intheoutermedulla-1%intheinnermedulla（2）Regulationofrenalbloodflow

ekidneysreceive1/4ofthecardiacoutput(1)Autoregulationofrenalbloodflow80180Myogenictheory(肌源学说）

arterialpressure

VesselwalltensionStretch-activatedcationchannelsVascularsmoothmusclecontractionopenVoltage-dependentcalciumchannelsleadingtoinfluxofCa2+-RBF,GFRNaClinmaculadensaafferentarteriolarresistanceTubulo-glomerularfeedbackmechanismAdenosineorATP?(2)Nervousandhumoral

regulationofrenalbloodflowSympatheticnerve

Humoralfactors

(-)RBF

(+)RBFEpinerphrinePGE2NorepinephrinePGI2angiotensinII心房钠尿肽

ADHdopamineTXA2NOendothelinkinins(激肽）

Section2

FunctionofGlomerularFiltration

componentbloodplasmaInitialurinewater

protein

glucose

urea

uricacid

creatinine

chloride

sodium

potassium

90～93

7～9

0.1

0.03

0.002

0.001

0.37

0.32

0.02

93

(trace)

0.1

0.03

0.002

0.001

0.37

0.32

0.02

Initialurineisanultrafiltrate.Glomerularfiltrationrate(GFR,肾小球滤过率)

thevolumeofultrafiltrate

formedbybothkidneysperminute.GFR=125ml/min

RatioofGFRtorenalplasmaflow(%)FF:125ml/min660ml/min

Filtrationfraction(FF,滤过分数)19%ofRPFisfilteredintobowman’sspace.=19%*100%

Glomerularfiltrationmembrane

anditspermeability

-肾小球毛细血管内皮细胞-基膜（basementmembrane)-肾小囊上皮细胞(podocytes)

窗孔网孔外层板致密板内层板

网孔（4-8nm）（基膜胶原及糖蛋构成微纤维网）

Fenestration

(窗孔，50-100nm）裂隙膜nephrin分子间孔道

滤过屏障:

Mechanicalbarrier

r<2.0nm,permeabler=2.0-4.2nm,thelargerthelessr>4.2nm,notpermeable

Electricalbarrier

positivecharged,easilypermeablenegativecharged,hardlypermeableGFR=KfXPUFFiltrationcoefficientEffectivefiltrationpressure（EFP）FactorsaffectingGFREFP=(肾小球毛细血管血压+囊内胶体渗透压）

-（血浆胶体渗透压+肾小囊内压）囊内胶渗压

入球端有效滤过压=55–(30+15)=10mmHg

滤过平衡有效滤过压=0

有效滤过压=毛细血管压-(血浆胶体渗透压+肾小囊内压)1.Glomerulareffectivefiltrationpressure(1)Glomerularcapillarypressure-80-180mmHg:GFRnochange-40-50mmHg：GFRdecreasetozero(2)Capsularpressure（3）PlasmacolloidosmoticpressureFactorsaffectingGFR

2.Glomerularfiltrationmembrane-Permeability/Area3.Renalplasmaflow：

影响滤过平衡位置急性肾小球肾炎临床：

-血尿、蛋白尿、少尿、水肿、高血压Section3

SoluteTransportintherenaltubuleandcollectingductReabsorptionsubstancesaretransferredfromthetubularfluidtotheblood.

Secretionsubstancespassacrossthetubuleepitheliumtothetubularfluid.

一、SolutetransportReabsorption

-Water:99%-NaCl:most-Glucose:all-HCO3-:most-Urea:partial-Creatinine:noSecretion-H+-K+-NH3-Creatinine

Passivetransport-simplediffusion-facilitateddiffusion-solventdrag(溶剂拖曳)

Activetransport

-primaryactivetransport-secondaryactivetransport

EndocytosisMechanismforsolutetransportParacellularrouteBasolateralmembraneTightjunctionIntercellularspaceApicalcellmembraneTranscellularrouteSolutetransportindifferenttubules

ReabsorptionofNaClandwaterReabsorptionofglucose/aminoacidsHCO3-reabsorptionandH+secretionCa2+reabsorptionUreareabsorptionandsecretionSecretionofNH370%Na+K+Cl-H2OCa2+reabsorbed85%HCO3-reabsorbed100%Glucose,aminoacid:reabsorbedH+secreted（一）ReabsorptionofNaCl

andwater

Proximaltubule

(近端小管）

-70%ofNaClandwater2/3:近端小管前半段吸收

1/3:近端小管后半段吸收

H2OH2OEarlyproximaltubulesH2O重吸收大于Cl的重吸收，小管内Cl浓度增高AnionHAnionHAnionlateproximaltubule:跨细胞和旁细胞途径（一）ReabsorptionofNaCl

andwater

Proximaltubule

（近端小管）

-70%ofNaClandwater

Loopofhenle(髓袢）

-20%NaCl-15%H2O

速尿髓袢升支粗段：顶端膜对K通透性高，基底侧膜对Cl通透性高，

K通过顶端膜K通道返回小管腔，造成小管内电位比组织间隙高+6mVReabsorptionofNaClandwater

Proximaltubule

（近端小管）

-60-70%ofNaClandwaterLoopofhenle(髓袢）

-20%NaCl+15%H2ODistalconvolutedtubuleandcollectingduct

-12%NaCl-water:regulatedbyADH-Na+/K+:regulatedbyaldosterone(醛固酮)

远曲小管前段重吸收NaCl机制Thiadiazide噻嗪类

远曲小管后段重吸收NaCl机制Solutetransportindifferenttubules

ReabsorptionofNaClandwaterReabsorptionofglucoseHCO3-reabsorptionandH+secretionCa2+reabsorptionUreareabsorptionandsecretionSecretionofNH370%Na+K+Cl-H2OCa2+reabsorbed85%HCO3-reabsorbed100%Glucose,aminoacid:reabsorbedH+secretedGSGSGlucoseisonlyabsorbedbyproximaltubule.Glucosereabsorptioniscoupledtosodiumbysecondaryactivetransport.

(二）Reabsorptionofglucose

GLUT2Renalplasmaglucosethreshold(肾糖阈）

Theplasmaglucoseconcentration(180mg/dl)atwhichglucosebeginstoappearintheurine(尿中刚刚出现葡萄糖时的血糖浓度)

filteredreabsorbedexcretedPlasmaconcentrationGlucose300mg/dl

180mg/dl375mg/minTmTm(葡萄糖极限吸收量）

（三）HCO3-absorptionand

H+secretion{—{{Na+H++HCO3-Na+HCO3-H+H2CO3CO2+H2OH2CO3

H2O+CO2Na+HCO3-CarbonicanhydraseCarbonicanhydraseluminacellIntercellularspace（1）近端小管及髓袢：{—{Na+H++HCO3-Na+H2CO3CO2+H2OCarbonicanhydrasecellglutamineNH3H2PO4-HPO42-H+H+NH3NH4+NaCl+NH4Cl（2）远端小管及集合管

（四）K+reabsorption/secretion

K+absorption

-65-70%近端小管重吸收（溶剂拖曳）

-25%-30%髓袢重吸收K+secretion

-远端小管及集合管（尿K+主要来源）

-受到醛固酮调节

glutamineNH3H2PO4-HPO42-H+H+NH3NH4+NaCl+NH4ClNa+

吸收促进K+分泌{—{Na+H++HCO3-Na+H2CO3CO2+H2OCarbonicanhydrasecellglutamineNH3H+NH3NH4+NaCl+NH4Cl（五）NH3Secretion（六）SecretionoforganicionsPAH:对氨基马尿酸；αKG：α

酮戊二酸（谷氨酸代谢）（七）ReabsorptionofothersUrea

Reabsorption：近端小管、髓质集合管（溶剂拖曳）Secretion：髓袢细端（易化扩散）

Ca2+:solventdrag（PTH调节）

Aminoacid:sameasglucose

Protein:endocytosisatproximaltubulesSection4

UrinarydilutionUrinaryconcentration

尿渗透压：50-1200mOsm/L

Plasma:300mOsm/L渗透压计Urinarydilution/concentrationRole:maintainthebalanceofbodyfluidPolyuria:>2.5L/day

oliguria:<400ml/day

anuria:<100ml/day

比重计一、Urinarydilution

Location

distaltubuleandcollectingduct

Mechanism

髓袢升支粗段吸收

NaCl但对水不通透，

-水过剩抑制ADH分泌中枢性尿崩症：ADH完全缺乏

Osmoticgradientinrenalmedulla

（必要条件）

ADH(+)二、UrinaryconcentrationOsmoticGradientintheRenalMedullaNa+H2OM1:对水不通透，对溶质通透M2:对水通透，对溶质不通透低渗溶液高渗溶液逆流倍增（countercurrentmultiplication）Establishmentofosmolalitygradientinthemedulla

Outermedulla(外髓部）

髓袢升支粗段主动重吸收NaCl，对水不通透。Innermedulla（内髓部）

-内髓部集合管扩散出来的urea-髓袢升支细段扩散出来的NaClH2O

ReabsorptionofNaClatthickascendinglimbofHenle’sloop

arethedrivingforceforestablishmentofosmolalitygradientinrenalmedulla

Urea

playsaspecialroleintheconcentratingmechanism

Roleofvasarecta(直小血管）inkeepinghighermedullaryosmoticpressure:

-带走髓质中多余水分和溶质，维持肾髓质的渗透梯度。

OsmoticgradientinrenalmedullaUrinaryconcentration&dilution

ADHPermeabilityofH2OIndistaltubuleandcollectingductThickascendinglimbUreaNaClVasarecta

Section5

RegulationofUrinaryFormationGlomerularfiltrationTubulereabsorptionTubulesecretionIntrarenalautoregulationNervousandhumoralregulationSoluteconcentrationintherenaltubuleGlomerulotubularbanlanceRenalsympatheticnerveADHRenin-angiotensin-

aldosteronesystemANP

1.Soluteconcentrationintherenaltubule

肾小管溶质浓度小管液渗透压水重吸收NaCl重吸收尿量/NaCl

Osmoticdiuresis（渗透性利尿）

-mannitol-diabetesmellitus（一）Intrarenalautoregulation

Changesoftheperitubularcapillarypressureandplasmacolloidosmoticpressure2.Glomerulotubularbalance-近端小管对水和Na+的重吸收率始终占GFR的65-70%tubule

QuantityofthefilteredglucoseandaminoacidWhenGFRincreases,theglucoseandaminoacidfilteredincreaseproportionally.Sodiumreabsorptioniscoupledwiththereabsorptionofglucoseandaminoacid.

Therefore,whenGFRincreases,thereabsorptionofsodiumandwaterincrease.（二）Renalsympatheticnerveα-Receptorβ-Receptorafferent&efferentarteriolescontractionDecreaseofGFRIncreaseofNaClandwaterreabsorptioninproximaltubuleandloopofHenle.GranularcellsreninagiotensinⅡaldosterone保Na+排K+UrineDirectaction（三）HumoralRegulation

Argininevasopressin(AVP)or

Antidiuretichormone(ADH)Renin-angiotensin-aldosteronesystemAtrianatriureticpeptide(ANP)Synthesis/SecretionSynthesizedinSupraopticnucleus(SON)andparaventicularnucleus

(PVN)inhypothalamus.Transportedbyhypothalamic-hypophysialtracttotheposteriorpituitary(neurohypophysis),whereitisreleasedintothebloodstream.

（1）ADH

IncreaseNaClreabsorptioninthickascendinglimbofHenle’sloopandpermeabilityofureaincollectingductofinnermedulla.Increasepermeabilityofwaterindistaltubuleandcollectingduct(main)ADHFunctionBindingofADHtoV2receptoractivatesGs-AC-cAMP-PKAsystem,thenvesiclescontainingwaterchannelprotein(AQP2)fusewithmembrane.-ADHenhancethetranscriptionofAQP2gene.-WhenADHisabsent,endocytosis(internalization)ofAQP2occurs.TheNobelPrizeinChemistry2003NobelLaureatesPeterAgre(1949.1.30--)ProfessorofbiologicalchemistryJohnsHopkinsUniversitySchoolofMedicine,Baltimore,USA“forthediscoveryofwaterchannels”Thehuntforthewaterchannels

Xenopusoocytes(非洲爪蟾卵母细胞)microinjectedwithCHIP28

mRNAswelledrapidlywhenplacedinahypo-osmoticmedium.CHIP28:channel-likeintegralmembraneprotein,28kDaCHIP28

=

AQP1-Theconstrictionregion(0.28nm)inhibitsthepassageofmoleculeslargerthanwater.-Becauseofthepositivechargeatthecenterofthechannel,positivelychargedionsaredeflected.Choroidplexus/脉络丛；Cornea/角膜Lacrimalglands/泪腺;Testis/睾丸-AQP1(blue)：proximaltubuleanddescendingthinlimb.

AQP2(green)：apicalpartofcollectingductprincipalcells

AQP3(red)

AQP4(purple)basolateralofcollectingductprincipalcells.-AQP7(orange):apicalpartofstraightproximaltubules.PlasmaosmoticpressureosmoreceptorcellslocatedintheanteriorhypothalamusshrinkADH(1)PlasmaosmoticpressureFactorsaffectingADHrelease

crystalosmoticpressureplasmaADH

<=275-290mOsm/Lzero289-307mOsm/LADH+thirst

ForstimulatingADHrelease-IncreasedcrystalosmoticpressureformedbyNaClismosteffective-ureaareineffectiveWaterdiuresis(水利尿）b(2)Bloodvolume/BloodpressureBloodvolumeStretchreceptors（左心房、心包内肺V)VagusnerveADHBloodpressureBaroreceptor(主动脉弓，颈动脉窦）ReninAngiotensinⅡFactorsaffectingADHrelease+ADHrelease:pain,nausea,nicotine,morphine

-ADHrelease:alcohol,ANP(3)OtherfactorsforADHreleaseFactorsaffectingADHreleaseReninSecretedbygranularcellsofjuxtaglomerularapparatusangiotensinogenangiotensinⅠangiotensinⅡaldosteronereninACESecretionFunctionACE:angiotensin-convertingenzymeBloodpressureofafferentarteriolesActivationofsympatheticnerve-

+ß2-receptoringranularcellGFRNaClamountinthemaculadensaRegulationofreninreleaseAngiotensinⅡFacilitatesynthesisandsecretionofaldosterone(肾上腺皮质球状带）StimulatereabsorptionofNaClintheproximaltubuleIncreasereleaseofADHInducethirst.ApotentvasoconstrictorUrine球状带：醛固酮束状带：糖皮质激素网状带：雄激素球状带束状带网状带Aldosterone（醛固酮）SecretionZonaglomerulosaoftheadrenalcortexFunctionStimulatethereabsorptionofNa+andthesecretionofK+inthedistaltubuleandcollectingductIncreasesNa+channelinluminalmembraneInduceenzymesforATP

synthesisinmitochondriaStimulatesNa+pumpinbasolateralmembraneIncreasesK+secretion

(胞内高K+

和小管腔内负电位）

IncreaseCl-reabsorptionAldosteroneinducedproteinsECFLumenRegulationofaldosterone

AgⅡ

[K+](0.5-1.0mmol/L)

高血压诊断：-收缩压》140mmHg；-收缩压》90mmHg

高血压分类-原发性高血压-继发性高血压

-肾性高血压

-内分泌疾病

-主动脉狭窄

肾实质病变或肾动脉狭窄Cushing’sSyndrome治疗高血压常用药物1）利尿剂：双氢克尿塞2）β受体阻滞剂：双氢克尿塞3）钙通道阻滞剂

(Calciumchannelblocker）

-氨氯地平（络活喜）；硝苯地平缓释片

4）血管紧张素转换酶抵制剂(ACEI)-卡托普利（开搏通）；苯那普利（洛汀新）5）血管紧张素Ⅱ受体阻滞剂(ARB）

-氯沙坦（科素亚）和缬沙坦6）α受体阻滞剂：哌唑嗪

InhibitreabsorptionofNaClincollectingductInhibitreninsecretionInhibitaldosteronesecretionInhibitADHsecretionAtrialnatriureticpeptide(ANP，心房钠尿肽)Release：心房受牵拉（血容量增加）HyperaldosteronismorConn’ssyndorme

(原发性醛固酮增多症)，病因：肾上腺皮质（球状带）肿瘤或增生症状：

-高血压

-低血钾及低钾症候群（肌肉无力，肾浓缩功能下降，ECG缺钾及心率失常）

-代谢性碱中毒Simonisa54-year-oldprofessorwhomaintainsahealthylifestyle.Recently,heexperiencedgeneralizedmuscleweaknessandheadaches.Heattributedtheheadachetothestressofpreparinghisgrant.Simonwenttothehospitalanddidseveralexaminations.Hisbloodpressurewassignificantlyelevatedat180/110mmHg.HisLaboratorytestswerelistedintable1.Arterialblood

pH:7.5/PCO248mmHg（normal：40）VenousbloodNa+142mEq/L(normal:140)K+2.0mEq/L(normal:4.5)HCO3-36mEq/L(normal:24)Cl-98mEq/L(normal:105)creatinine1.1mg/dl(normal:1.2)UrineNa+excretion200mEq/24h(normal)K+excretion1350mEq24h(elevated)24hcatecholaminenormalThephysiciansuspectedSimon’shypertensionwascausedbyanabnormalityintherenin-angiotension–aldosteronesystem.Heorderedadditionaltests:

plasmareninactivity:dereasedserumaldosterone:increasedserumcortisol:normalAcomputedtomographicscanconfirmedthepresenceofasingleadenoma(腺瘤）ontheleftadrenalgland.ThetestconfirmedthediagnosisthatProfSimonhadhyperaldosteronismWhatfactorsmayelevateSimon’sbloodpressure?

Whatspecificetiologyisruledoutbythenormalvaluefor24-hoururinarycatecholamineexcretion?Pa=cardiacoutput*TPR搏出量(心肌收缩力,

前/后负荷）+心率交感N缩血管物质Pheochromocytoma(肾上腺嗜铬细胞瘤瘤）wasruledoutBynormal24-hoururinarycatecholamineexcretion2.ThephysiciansuspectedSimonhadprimary

hyperaldosteronism.Howdoesanincreased

aldosteronelevelcauseincreasedbloodpressure?IncreasedaldosteroneincreasedNa+reabsorptionandK+secretioninthelatedistaltubuleandcollectingducts.SincetheamountofNa+intheECFdeterminestheECFvolume,increasedbloodvolumeproducesanincreaseinvenousreturn,thenthroughtheFrank-Starlingmechanism,increasecardiacoutput.3.ExplainwhySimon’surinaryNa+

excretionwasnormal.

Thisiscalledescapefromaldosterone(醛固酮逃逸）1）ECFvolumeexpansioninhibitsrenalsympatheticnerveactivity,whichinhibitsNa+reabsorptionintheproximaltubule.2)ECFvolumeexpansioncausesdilutionoftheperitubularcapillaryproteinconcentration,leadingtothedecreaseinNa+reabsorptioninproximaltubules3)ECFvolumeexpansionstimulatethesecretionofartrialnatriureticpeptide(ANP)4.Whatexplanationcanyougivefor

ProfessorSimons’hypokalemia?AldosteronestimulatesK+secretionbytheprinciplecellsoflatedistaltubulesandcollectingducts.5.ExplainProfessor’smuscleweaknessbased

onhisseverehypokalemia

WhentheextracellularK+concentrationislowerthannormal,therestingmembranepotentialoftheskeletalmusclecellsemorenegative.DecreasedplasmaCa2+-细胞外液量或BP升高抑制近端小管对Na+及水的重新收，从而减少Ca2+吸收（80%Ca2+溶剂拖曳方式吸收）-代谢性碱中毒减少Ca2+重吸收。6.Whatacid-baseabnormalitydidprofessorSimonhave?

Whatistheappropriatecompensationforthisdisorder?TheincreasedarterialpH7.5andHCO3-areconsistentwithmetabolicalkalisis.InadditiontoincreaseNa+reabsorptionandK+secretion,aldosteronestimulateH+secretionbytheintercalatedcellsofthelatedistaltubuleandcollectingduct.ThisH+secretionislinkedtoreabsorptiontoHCO3-,producingthemetabolicalkalosis.

Section６

Clearance(清除率）

两肾在单位时间（每分钟）内能将多少毫升血浆中的某一物质完全清除出去。这个完全清除了该物质的血浆毫升数称为该物质的清除率(ml/min)

Thevolumeofplasmaclearedofaspecificsubstanceperminute一、Definitionofclearance

肾脏清除某物质的量，相当于多少毫升血浆所含该物质的量

PC=UV(mg/min)

C=UV/P(ml/min)C=renalclearance(ml/min)P=plasmaconcentration(mg/dl)ofthesubstanceU=urineconcentration(mg/dl)ofthesubstanceV=flowrateofurineformation(ml/min)二、Calculationofclearance

某甲每分钟尿量(V)1ml/min尿中某物质的浓度（U）100mg/100ml血浆中该物质的浓度（P）1mg/100ml

该物质的血浆清除率

C=U×V／P＝100ml/min葡萄糖清除率：0ml/min尿素清除率：70ml/min

(三）Significanceofdetectingclearance

MeasuringGFRMeasuringrenalbloodflowDeducingthefunctionoftherenaltubule

Inulinisfiltered,butnotreabsorbedorsecretedbyrenaltubules

U×V=GFR×P C=GFR=U×V/P

=C=125ml/min125mg/100ml×1ml/min1mg/100ml1.MeasuringGFR

-ClearanceofInulin(菊粉清除率）

-Clearanceofendogenouscreatinine

（内生肌酐清除率）U×V=C×PC=660ml/min（C：肾血浆流量）

RPF=C/55%=1200ml/min（血浆占全血55%）2.Detectingrenalbloodflow(RBF)

血浆中某一物质在肾循环一周后完全被清除

Diodrast(碘锐特）orPAH（对氨基马尿酸）

3.Deducingthefunctionofrenaltubule

C>GFR:secretion(肌酐C=175ml/min)

C<GFR:reabsorption

(ureaC=70ml/min)Section7

Micturition(尿的排放）Micturitionistheprocessbywhichtheurinarybladderemptieswhenitesfilledandisaspinalreflexcontrolledbythehighercenters150-250mL:尿意350-400mL：>700mL:痛觉及失控volumePressureInternalsphincterExternalsphincter

Detrusor（逼尿肌）

PelvicN（盆N，副交感）

HypogastricN

（腹下N，交感）PudendalN（阴部N)Micturitionreflex

膀胱内尿量（400-500ml）

膀胱牵张感受器（+）盆神经脑干、大脑皮层排尿反射高级中枢骶髓排尿反射初级中枢盆神经膀胱逼尿肌＋尿道内括约肌－尿道感受器（＋）阴部神经尿道外括约肌开放

排尿阴部神经Centraldiabetesinsipidus

(中枢性尿崩症）Lisaisapostgraduatestudentwhoworkedpart-timeinapediatrician’soffice.RecentlyLisa’slifeseemedtorevolvearoundbeingclosetoabathroomandadrinkingfountain.Shewasurinatingeveryhour(polyuria)anddrinkingmorethan5Lofwaterdaily(polydipsia).Lisa’semployerwasconcernedandwonderedifshehadapsychiatricdisorderinvolvingcompulsivewaterdrinking(primarypolydipsia)ordiabetesinsipidusLisamadeanappointmentwithherphysician.Herphysicianfoundthephysicalexaminationwerenormal.Herbloodpressurewas105/70mmHg,herheartratewas85beats/min.

Lisa’sLaboratorytestvalues:

plasmaUrine

Na+:147mEqu/L(normal:140)Osmolarity:301mOsm/L(normal:290)70mOsm/LGlucose90mg/dl(70-100mg/dl)negativeLisa’sphysicianperformeda2-hourwaterdeprivation

test.Attheendofthetest,Lisa’surineosmolarityremainedat70mOsm/L.LisawastheninjectedsubcultaneoulywithdDAVP(ananalogueofargininevasopression).Afterinjection,Lisa’surineosmolarityincreasedto500mOsm/L.Becauseshehadnohistoryofheadinjuryandsubsequentmagneticresonanceimagingscansruledoutabraintumor,Lisa’sphysicianconcludedthatLisahaddevelopedaformofcentraldiabetesinsipidusLisastartedtreatmentwithdDAVPnasalspray.Shedescribedthesprayasamazing.AslongasLisausedthenasalspray,herurineoutputisnormal,andsheisnolongerconstantlythirsty.Whatisthenormalvalueforurineosmolarity?Describethemechanism

thatregulatetheurineosmolarityUrineosmolarity:50-1200mOsm/L>300mOsm/L:hyperosmoticurine<300mOsm/L:hyposmoticurineOsmoticgradientinrenalmedullaUrinaryconcentration&dilution

ADHPermeabilityofH2OIndistaltubuleandcollectingductThickaccendinglimbUreaNaClVasarectaTheinitialtestonLisa’bloodandurine

suggestedthatthecauseofthepolyuriawas

not