病理生理學水鈉代謝障礙

水、電解質代謝紊亂Dept.ofPathophysiologyTongjiMedicalCollege,HUST周新文WaterandelectrolytesinhumanbodyIntracellularwateranditssolutescontributetothebasicstructureofcells,andcomposetheliquidenvironmentinwhichorganellesstayandfunctionExtracellularwateranditssolutescomposetheliquidenvironmentinwhichcellsliveandmaintainnormalfunctionsPartI:正常體液的容量、分布和平衡PartII:水鈉代謝障礙Inthischapter:PartIII:鉀代謝障礙PartI:正常體液的容量、分布和平衡VolumeanddistributionofbodyfluidMajorelectrolytesanditsdistributionWaterandsodiumbalanceandregulationBodyfluid:theliquidpartsofthebodyItcontainswaterandalotofsolutes.Totalbodyfluidvarieswithgender/age/bodyadiposecontent.

Men:60%ofthebodyweightWomen:50%ofthebodyweightNewborninfant>Adult>Oldperson

ICF40%ECF20%Thetotalbodyfluidiscomprisedofseveraldifferentcompartments.

Interstitial15%Plasma5%Transcellularfluid1%

theECFcompartment（1%）whichisseparatedbyalayerofepithelium.cerebrospinalfluid（腦脊液）；theperitoneal,pleural,andpericardialcavities(腹、胸、心包腔液);thejointspaces（關節(jié)腔）;thegastrointestinaltract（腸腔）ItisreferredtoasathirdspacebecausethisfluidisnotreadilyavailableforexchangewiththerestoftheECFTranscellularfluid電解質:

陽離子（cation）Na+,K+,Ca2+,Mg2+

陰離子（anion）Cl-,HCO3-

,HPO42-

,Pro-

Differentcompositionandvolumeofbodyfluidindifferentcompartmentsofthebody----Isthereamovementorexchangeofthecomponents?Twoconcepts:Diffusion(擴散)isthemovementofchargedorunchargedparticlesalongaconcentrationgradient.Osmosis（滲透作用）isthemovementofwateracrossasemipermeablemembrane(i.e.,onethatispermeabletowaterbutimpermeabletomostsolutes)OsmosisandOsmoticPressureWhenasemi-permeablemembrane(amembranethatallowswatertoflowthroughbutnotthesoluteparticles)separatestwosolutionsofdifferentconcentrations,therewillbeamovementofwaterfromthesolutionwhereitsconcentrationislowertothesolutionwhereitsconcentrationishigher.ThisphenomenoniscalledOsmosisanddrivingpressureiscalledasOsmoticpressure(determinedbythenumberofdissolvedparticles).滲透壓（Osmoticpressure）晶體滲透壓（Crystalosmoticpressure）膠體滲透壓（Colloidosmoticpressure）K+,HPO42-Na+,Cl-ProWhythecolloidpressureininterstitialspaceisverylow?Whatistheeffectofcolloidosmoticpressure?WhatisthefunctionofECFOsmolarity?Osmoticpressure:280-310mOsm/L水的功能:機體代謝調節(jié)體溫潤滑作用結合水發(fā)揮多種生理功能電解質的功能:維持滲透性和酸堿平衡維持細胞膜電位（神經(jīng)、心肌、肌肉等）參與新陳代謝和生理功能Waterbalance40%BW15%BW5%BWInterstitialPlasmaICF吸收水分Kidney(urine)1500ml

Intestine(stool)200mlLung(watervapor)400ml

Skin(sweatandevaporation)400ml排出水分Intake

OutputDigestivetractsNutrientsmetabolismRegulationoffluidvolumeandosmoticpressureDisturbanceVolumeOsmoticpressureADHRAASANPThirstThirstADHRAASRegulationpathwaysTheregulationofthirstyreactionStimulus:increaseinextracellularosmolality

Decreaseinbloodvolume

IncreaseofAngII渴覺中樞（下丘腦視旁核、視上核）osmoreceptorsTheregulationofthirstyreaction渴覺中樞（下丘腦視旁核、視上核）Stimulus:increaseinextracellularosmolality

Decreaseinbloodvolume

IncreaseofAngIIBodyreaction:TheregulationofADHADHreleasedBP/Bloodvolume-Stretchreceptor+Plasmaosmoticpressure+OsmoreceptorADHenhancesreabsorptionoffreewaterinrenaltubules.300mosm300mosmNoADHNowaterreabsorptionDiuresisADHenhanceswaterreabsorptionH2OintobloodAnti-diuresisHighquantityLowosmoticpressureFunctionofADHLowquantityHighosmoticpressureADHismoresensitivetothechangeofosmoticpressure.1-2%changeofosmoticpressurewillchangetheproductionofADH.Whenbloodvolumeisdecreased>10%,ADHwillbeincreasedAtthistime,thedecreasedofbloodvolumemaybelife-threatening.ADHreleasedBP/Bloodvolume_Stretchreceptor+Plasmaosmoticpressure+Osmoreceptor+Plasmaosmoticpressure-Osmoreceptor-?TheregulationofRAAS1.Inhibitionofsodiumreabsorptioninthecollectingduct2.Decreaseinreninsecretionfromthemaculadensaandaldosteronesecretion.3.VasodilationStimulus：Bloodvolume/pressureSerumNa+AngII

TheregulationofANP（心房利鈉肽）Functions：AcuteseverehemorrhageDecreaseinbloodvolumeandarterialpressureThirstcenter+ADHRAAS+ANPDrinkwaterReabsorptionofwaterandsodiuminkidneyvasoconstrictionIncreaseinbloodvolumeandarterialpressureWaterChannels

2003ChemistryNobelPrize

Inmid-1980’shestudiedvariousproteinsfoundinthemembraneofredbloodcellsandalsofoundoneinthekidneysandwasabletodeterminethepeptidesequenceandthecorrespondingDNAsequence.(CHIP2828kDa)

PeterAgre’sWorkWaterpermeabilityinhumanerythrocytes:Identificationofmembraneproteinsinvolvedinwatertransport.EurJCellBiol,1986,41(2):252-262.

Aquaporin,AQPItisafamilyofproteininthecellmembrane.Itlocatedintheanimal,plantandmicroorganism.Thereareatleast11aquaporinsnow.AQP2isalsocalledaswaterchannelofthecollectingduct.Thisistheonlywaterchannelwhichisfoundbeingregulatedbyhormonetillnow.ADHcanincreasethenumberofAQP2andwaterpermeability.Thehumanaquaporingenefamily.CurrentGenomics,2000,1(1):91-102.Modulationofvasopression-elicitedwatertransportbytraffickingofaquaporin2-containingvesicles.AnnuRevPhysiol,1999,61(1):683-697.WaterChannels(aquaporin)

2003ChemistryNobelPrizePartII:水鈉代謝障礙水鈉代謝障礙的分類高滲性脫水低滲性脫水等滲性脫水Classificationofdisordersofwaterandsodiumbalance

VolumeHypervolemiaNormovolemiaHypovolemia<130Na+

mEq/L135-145>150NormalEdemaHyponatremiaHypernatremiaDehydration:anexcessivelossofbodyfluid.HypovolemichyponatremiaHypervolemichyponatremiaNormovolemichyponatremiaHypovolemichypernatremiaHypervolemichypernatremia

NormovolemichypernatremiaIsotonicdehydration

Isotonic:

referstothatsolutionshavethesameosmolalityastheICFHypotonicdehydrationHypertonicdehydrationWaterintoxicationSalt

intoxication(低容量性高鈉血癥)高滲性脫水脫水（dehydration）：水容量明顯減少高滲性脫水（hypertonicdehydration）:失水多于失鈉Concept:Characteristics:失水多于失鈉血清Na+濃度>150mmol/L血漿滲透壓>310mOsm/L病因和發(fā)病機制:1.水的攝入不足2.水的丟失增加(purewaterorhypotonicfluid)水源斷絕不能飲水渴感障礙theskin(burns,excessiveperspiration)

thelungs(hyperventilationofanycause)theIntestine(hemorrhages,diarrhea,vomiting)thekidneysThroughCausesofpolyuria（多尿）andincreaseddiuresis（利尿）

Centralcauses:Primary(Psychogenic)

polydipsia(煩渴)CentralDiabetesInsipidus(中樞性尿崩癥)

Kidneyandadrenalcauses:ARF(acuterenalfailure)inpolyuricstagePostobstructivediuresis（梗阻后利尿）滲透性利尿

(mannitol,uncontrolledDiabetesMellitus)NephrogenicDiabetesInsipidus(腎性尿崩癥)

利尿劑(themostcommoncause)Secondaryanddrug-inducedhypoaldosteronism(醛固酮減少癥)

.尿崩癥Centraldiabetesinsipidusischaracterizedbydecreasedsecretionofantidiuretichormone(ADH)thatresultsinpolyuriaandpolydipsiabydiminishingthepatient'sabilitytoconcentrateurine.NephrogenicdiabetesinsipidusischaracterizedbyadecreaseintheabilitytoconcentrateurineduetoaresistancetoADHactioninthekidney.NoADHNowaterreabsorptionDiuresisADHenhanceswaterreabsorptionH2OintobloodAnti-diuresisHighquantityLowosmoticpressureLowquantityHighosmoticpressureDiabetesInsipidus:IncreasedwaterlossfromthekidneyHypertonicdehydrationHypertonicdehydrationCausesofhypertonicdehydration:Prolongedhypertonicdehydration:Quitealot!Themajorityoforiginaldehydrationduetoexcesswaterlossishypertonicdehydration,why?Quiterare!Why??機體代謝改變ThirstyADHreleaseDrinkwaterBloodvolumeSerumNa+

WaterreabsorbedfromrenaltubuleOsmoticpressureofECFVolumeofECF尿少。ICFInterstitialPlasmaECFisdecreasedICFispulledoutofthecellBloodisdilutedCelldehydration細胞內(nèi)液向細胞外液轉移。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。DegreeVolumeofwaterlossClinicalmanifestation(%ofbodyweight)Mild2-5Thirst,OliguriaModerate5-10Severethirst,drynessofmucosa,feverSever10-15Delirium,stupor,comaClinicalManifestationofHypertonicDehydration中樞神經(jīng)脫水:嗜睡、肌肉抽搐、昏迷，甚至死亡治療原則:TreatingtheprimarydiseaseFluidreplacement:Orallyorintravenouslysupplyof5%-10%glucose-electrolytesolutions:properamountsofNaCl,KClaccordingtothebodyneedsHypotonicdehydration(低容量性低鈉血癥)失鈉多于失水Characteristics:LossofsaltmorethanwaterSerumNa+<130mmol/LPlasmaosmoticpressure<280mOsm/LConcept:原因和機制（1）經(jīng)腎丟失：如長期使用利尿劑，腎實質疾病，醛固酮分泌不足等尿鈉排出過多（2）腎外丟失：如經(jīng)消化道（嘔吐，腹瀉），皮膚（大汗、大面積燒傷)

丟失；胸水、腹水形成常見的是丟失液體后處理措施不當引起

渴不明顯ADHreleaseisinhibitedduetothedecreasedosmolarityofECFMilddehydrationModerate-severedehydrationADHisreleasedduetothedecreasedvolumeofECFAldisreleasedduetothedecreasedvolumeofECF尿量減少機體代謝改變OsmoticpressureofECFVolumeofECF尿量一般不減少。。。。。。。。。。

。。。。。。。。。ICFInterstitialPlasmaECFisdecreased.ECFistransportedintothecellBloodiscondensed.Shockiseasiertooccurring,why?CelledemaTransmembranewatermovementfromECFtoICF。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。DegreeVolumeofwaterlossClinicalmanifestation(perkgofbodyweight)Mild0.5g/KgFatigue,dizziness,paleModerate0.5-0.7g/KgLossofskinturgor,cramps,apathy,hypotensionSever0.75-1.25g/KgOliguria,shock,stuporClinicalManifestationofHypotonicDehydrationTheinterstitialfluidvolumeissharplydecreased:

shock—circulatoryfailurewillbedevelopedifnopropertreatments

治療原則:TreatingtheprimarydiseaseAdministrationof0.9%sodiumchloridesolutionor5%glucosenorm