藥理學(xué)教學(xué)課件：Normal Metabolism of Water and Electrolytes

DisordersofWaterand

ElectrolytesMetabolism一般不吃飯七天會死,不喝水三天就會死。I.NormalMetabolismofWaterandElectrolytes1.BodyfluidandOsmolality

2.NormalMetabolismofWaterandSodium

TokeephomeostasisHomeostasisindicatesastableinternalenvironmentwithinthebody,whichmeans:(a)bodyfluid:normalvolume,compositionandpH;(b)normaltemperature,bloodpressure,cardiacoutput;(c)normallevelofhormones,etal.

Normalbodyfluidisthemostimportantpartinthehomeostasis.

Bodyfluidisthefluidsinthebody.Bodyfluidisasolutionwithsolutes(electrolytes,glucose,aminoacids,fattysubstancesandotherconstituents)andsolvent(water).

1.BodyfluidandOsmolalityCopyright2009,JohnWiley&Sons,Inc.BodyFluidCompartmentsInfluentialfactorsonthevolumeofbodyfluid------------------------------------------------organ(tissue)watercontent-------------------------------------------------fat25%~30%muscle76%bone14%~46%liver70%skin72%--------------------------------------------------Question:Afattypersonandathinpersonwiththesamebodyweightlostthesamevolumeofbodyfluid,whoseconditionisworse?baby’scharacters需熱量相對較大出入水量約占1/2ECF—adult1/7ECF水的交換率比成人快3-4倍，不顯性失水>成人腎臟，中樞神經(jīng)系統(tǒng)發(fā)育不夠健全，腸道液體交換較快→→→易水電解質(zhì)紊亂Osmosisandosmoticpressure滲透壓

Osmosisisthenetdiffusionofwaterthroughaselectivelypermeablemembrane.Theosmoticpressure[determinedbythenumber

ofparticles(solute)]pullsthewatertothesidewithmorenumberofnon-diffusibleparticles.ClassificationofosmoticpressureThecrystalosmoticpressureismainlyformedmainlybyparticlesofelectrolytes.

在維持細(xì)胞內(nèi)外水的平衡中起決定性作用Thecolloidalosmoticpressureisformedbyparticlesofproteins.在維持血管內(nèi)外體液交換和血容量方面起重要作用osmoticpressure4/5oftotalosmolalityofECFisdeterminedbyNa+andCl-.50%ofintracellularosmolalityiscausedbyK+.Thetotalosmolalityis280～310mmol/L(average300mmol/L)inbodyfluid.Charactersofisotonicity

Theosmoticpressureinthecellsandoutthecellsusuallyarethesame.Thereisatendencytokeeptheisotonicitybetweenintracellularandextracellularspaces.

Whichtypeofmoleculemoveforkeepingisotonicity?

H2O2.NormalMetabolismofWaterandSodium

Functionsofwater

促進(jìn)物質(zhì)代謝調(diào)節(jié)體溫潤滑Copyright2009,JohnWiley&Sons,Inc.SourcesofBodyWaterGainandLossFluidbalancerelatedtoelectrolytebalanceIntakeofwaterandelectrolytesrarelyproportionalKidneysexcreteexcesswaterthroughdiluteurineorexcesselectrolytesthroughconcentratedurineBodycangainwaterbyIngestionofliquidsandmoistfoods(1900mL/day)Metabolicsynthesisofwaterduringcellularrespirationanddehydrationsynthesis(300mL/day)BodyloseswaterthroughKidney(1200mL/day)Evaporationfromskin(500mL/day)Exhalationfromlung(350mL/day)Feces(150mL/day)Copyright2009,JohnWiley&Sons,Inc.DailyWaterGainandLossFunctionofsodium維持體液的滲透壓和酸堿平衡參與細(xì)胞動作電位的形成Balanceofsodium1)ContentofsodiumThecontentofsodiumis40~50mmol/KgofBW.Thesodiumcanbedividedintotwoparts:

(A)Exchangeablepool

Exchangeablepoolincludessodiuminextracellularfluid(50%)andintracellularfluid(10%).60%ofsodiumisexchangeable.

(B)non-exchangeablepool40%ofNa+isboundwithinbonemasswhichisnon-exchangeable.BalanceofsodiumTheconcentrationofNa+inICF,([Na+]i)is10mmol/L.TheconcentrationofNa+inECF,([Na+]e)is130~150mmol/L.

ECF45%ICF10%Bone45%SerumNa+

concentration:135~145mmol/L2)Na+balanceofintakeandlossBodyneeds500mgeachday.–food

LossofsodiumMainlybykidneySkinFeces.<10%

Regulationofwaterandsodiummetabolism

Normalmetabolismofwaterandsodiummeans:1)normalvolume,2)normalcomposition3)normalosmoticpressureofbodyfluid.Itisregulatedbynervoussystemandhormones:

1)Thirst(neuro-regulation)2)Antidiuretichormone,ADH3)Aldosterone4)Atrialnatriureticpeptide(ANP).1)Thirst(neuro-regulation)

Thirstisakindofsense(feeling)comingfromthirstcenter,withwhichwewillaskfordrinkingwater.Causesofthirst:

(A)IncreasedECFosmolality(1~2%)stimulatesthethirstcenterviaosmoreceptorin

lateralhypothalamicarea

下丘腦外側(cè)區(qū).Thentherewillbethesenseofthirst.Afterthedrinkofwater,theincreasedECFosmolalitywilldecreasetonormal,thenthesenseofthirstwilldisappear.(B)Decreasedeffectivebloodvolume(hypovolemia)stimulatesthethirstcenterviavolumereceptorinvenaecavaeandatrium.(C)ElevatedlevelofangiotensinIIcanstimulatesthethirstcenter.(Hypovolemia→renalischemia→reninrelease→angitensinI→angiotensinII)(D)Drynessofmouthcanalsostimulatesthethirstcenter.Afterthedrinkingofwater,thebloodvolumewillincreasetonormal.

nothirstincreaseofECFosmolality(1~2%)hypovolemiaelevatedangiotensinIIdrynessofmouthosmoreceptor(anteriorhypothalamus)volumereceptorinvenaecavaeandatriumthirstcenter(anteriorhypothalamus)senseofthirstanddrinkofwaterdecreaseofECFosmolalityincreaseofECFvolumedecreaseofangiotensinconcentrationIIdisappearofdrynessIsitenough?

Thirstonlyisnotenoughtoregulatethebalanceofwaterandsodium.

Thedefectsof(neuro-regulation)thirstare:1)Therewillbenoobviousthirstinpatientswithhypovolemiaiftheosmolalityisnotincreased.2)Apatientwithcomawillnothavethesenseofthirst.

(tooyoungbaby,toooldman)2)Antidiuretichormone,ADH抗利尿激素

(argininevasopressin,AVP)

ADHissynthesizedbycellsinthesupraopticandparaventricularnucleiofhypothalamus下丘腦視上核和室旁核,andstoredinandreleasedfromposteriorpituitary神經(jīng)垂體.ThefollowingfactorswillincreasethesecretionofADH

(A)IncreasedosmolalityofECF(1%～2%)

increasesADHsecretionbystimulatingtheosmoreceptor(inhypothalamus).(B)DecreasedvolumeofECF（5%～10%）viavolumereceptor(invenaecavaeandatrium).(C)Reductionofbloodpressureviabaroreceptors(inarchofaortaandcarotis)(D)Stresssituations(patientsduringsurgery,severetraumaandpain)(E)IncreasedangiotensinⅡ(F)Somedrugs:anesthetics麻醉劑(+),alcohol(-)

3)Aldosterone醛固酮

Aldosteroneisthemajorregulatorofsodiumexcretionandreabsorption.Aldosteroneisasteroidhormoneproducedbytheadrenalcortex.保鈉排鉀Thefollowingfactorsareknowntostimulatethesecretionofaldosterone:(A)

AngiotensinII

major(B)Na+↓inECFmajor(C)K+↑inECFmajor腎交感神經(jīng)興奮，腎上腺素，去甲腎上腺素→renin↑Aldosterone低血容量、動脈血壓↓→腎入球小動脈管壁牽張感受器受刺激→球旁細(xì)胞分泌腎素↑流經(jīng)致密斑Na+↓→球旁細(xì)胞分泌腎素↑→血管緊張素IIIII↑→腎上腺皮質(zhì)球狀帶分泌醛固酮↑4）Thenatriureticpeptidefamily

心房鈉尿肽

(A)AtrialnatriureticpeptideANPisa28-aminoacidpeptidereleasedfromthe

atriuminresponsetoincreasedatrialstretchviamechanoreceptors.(B)Brainnatriureticpeptide(BNP)(C)C-typenatriureticpeptide(CNP)

ThemainlyeffectofANPistoincreasethekidney’sabilitytoexcretebothwaterandsodium.Summaryofregulatingwaterandsodiummetabolism

(1)Neuro-regulationThirst(2)HormoralregulationADHAldosteroneANPII.DisordersofWaterandSodiumMetabolismAccordingtotheclinicimportance:Dehydration1.Hypertonicdehydration2.Hypotonicdehydration3.IsotonicdehydrationOverhydration4.HypotonicoverhydrationWaterintoxication5.IsotonicoverhydrationEdema

Dehydration

Concept:Thevolumeofbodyfluiddecreasesbelowthenormalrangeafterthelossofbodyfluid.Indehydrationthe[Na+]emaybeinthreemanifestations:

---------------------------------------------------------------Dehydration[Na+]Osmoticpressure(mmol/L)(mOsm/L)---------------------------------------------------------------Hypertonic>150>310Hypotonic<130<280Isotonic130~150280~310----------------------------------------------------------------1.IsotonicDehydration(1)ConceptThereislossoffluid(dehydration),thewaterlossisequaltosaltloss.TheECFinthebodyisisotonic.The[Na+]is130~150mmol/L.Theosmolarityis280~310mOsm/L.(2)Causes

(a)Lossoffluidiscausedbyvomiting,hemorrhageandfromtheburnedarea.Shortterm(b)Theisotonicdehydrationcanbeinducedfromhypertonicandhypotonicdehydrationbytherenalregulation.

(3)Adaptiveresponses

ThemainchangeinisotonicdehydrationisthereducedvolumeofECF.(a)Itstimulatesthethirst,sothatthepatientwillasktodrinkwatertoreplacethevolumeofECF.(notasstrongashypertonicdehydration)(b)ADHreleaseisstimulated,sothatthewaterreabsorptionwillincreasetoreplacethevolumeofECF.(notasmuchashypertonicdehydration)(c)Secretionofaldosteroneisincreasedduetohypovolemia.(notasmuchashypotonicdehydration)NormalPlasmaInterstitialfluidIntracellularfluid(4)Effectonthebody

(a)UrinevolumeisdiminishedbecauseofthedecreasedGFR,increasedADHandaldosteronesecretion.尿鈉氯↓(b)Nowatershiftandrelatedsymptomsandsigns.(c)Poorskin

elasticity

and眼窩凹陷,becauseofthereductionofinterstitialfluid.(5)PrincipleoftreatmentHypotonicsalineisneededtoreplacethefluiddeficiency.CaseDiscussion

1.A36-year-oldmanwashospitalizedwitha3-dayhistoryoffeverandwaterydiarrhea.Hisbloodpressurewas90/60mmHg,thepulsewas112/min,temperatureis38.0℃.Theabdomenwasdistendedwithlowskinelasticity.Thelaboratoryresultswere:Arterialblood:pH=7.21,PaCO2=26mmHg,PaO2=108mmHg.[Na+]=135mmol/L[K+]=3.0mmol/L[HCO3-]=16mmol/LUrine:pH=5.0,Specificgravity=1.028Thepatient’sproblemswere:(1)isotonicdehydration(2)metabolicacidosis(3)hypokalemia.2.HypertonicDehydration(1)Concept

Bothwaterandsodiumarelost(hypovolemia),butthewaterlossisinexcessofsaltloss(hypernatremia).

(basicreason)

ThenthevolumeofECFisreduced.The[Na+]isover150mmol/L,Theplasmaosmoticpressureisover310mOsm/L.(2)Causes1)Decreasedwaterintake:

喝不上水，不知道喝水，不能喝水

①nowaterduringnavigationorindesert,②nosenseofthirstduetobraininjuryorcoma,③severevomiting,④difficultyinswallowingbecauseofesophagealdiseases.⑤underdoseofinfusionintreatmentofpatients

Atthesametime,purewaterlossfromlung(300ml/d)andskin(500ml/d)isnotavoidable,evenincreased.2)Increasedlossofwater①viaskin不感蒸發(fā)-純水，汗-水>鈉②viarespiration純水③viakidneyADH↓-純水滲透性利尿--水>鈉④gastrointestinaltract水>鈉ifwaterreplenishisnotenough.(3)Alterationsofmetabolismandfunction

1)Adaptive(compensatory)responsesofthebody2)Characteristiceffectsofhypertonicdehydrationonthebody1)Adaptive(compensatory)responsesofthebody①DrinkmorewaterbecauseofseverethirstHyperosmolarityandhypovolemiastimulatethesenseofthirst.Diminishedsalivaandthedrymucousmembranes唇干口燥leadtothesenseofthirst.

②IncreasedwaterreabsorptionbyincreasedADH.ADHreleaseisstimulatedbythehyperosmolarityoftheECFandthehypovolemia.NormalPlasmaInterstitialfluidIntracellularfluid2)Characteristiceffectsofhypertonicdehydrationonthebody①Thirstoccursattheearlystageofhypertonicdehydration.②Oliguria

occursattheearlystageofhypertonicdehydration.(<400~500ml/day).Urinespecificgravity↑（Metabolicwasteslikeureaand

uricacid

areretainedinthebodybecauseoftheoliguria.）

尿鈉早期or輕癥→血容量變化不大→ALD不增多有鈉排出，濃度因水重吸收↑→尿鈉↑晚期或重癥血容量↓→ALD↑→尿鈉↓

③FeverFevermaybepresentbecausewaterisnecessarytoregulatethebodytemperature.Feverismoresevereininfantsbecauseofthedysfunctionofthermoregulatorycenter,whichiscalledinfantiledehydrationfever.皮膚蒸發(fā)水分↓→散熱↓嬰幼兒體溫調(diào)節(jié)能力↓④Intracellulardehydration

WaterwillshiftfromICFtoECFbecausetheECFishypertonic.Allthecellswillshrink.

Inwhichorganisthecellshrinkagemostdangeroustothepatient?

Braincelldehydrationproducesbraindysfunctionlikelethargy(weakness,apathy,absenceofinterest),whichmayprogressestocoma(unconsiousness)whenthewaterdeficientissevere.Increasedirritability(musculartwitch,delirium)mayoccur,especiallyinchildren.Twitch:uncontrollablesudden,quickmovementofmuscleDelirium:violentmentaldisturbanceaccompaniedbywildtalk(wildexcitement)intracranialhemorrhage顱內(nèi)出血，subarachnoidhemorrhage蛛網(wǎng)膜下腔出血3.HypotonicDehydration(1)ConceptThereislossofbothwaterandsodium(hypovolemia),thesaltlossisinexcessofwaterloss(hyponatremia).

TheECFishypotonic([Na+]e<130mmol/L),theosmolarityislowerthan280mOsm/L.(2)Causes

丟失體液后補(bǔ)水>補(bǔ)鈉Inappropriatetreatment:Replaceofwateronlytothepatientswithdehydrationcausedbyvomiting,diarrhea,gastricsuctionandexcessivesweating,lost.①viaskin大汗后，燒傷②viagastrointestinaltract③viakidney排鈉性利尿劑+限鹽急性腎功能衰竭多尿期滲透性利尿+補(bǔ)鈉↓ALD↓or對ALD反應(yīng)性↓(3)Alterationsofmetabolismandfunction

1)Adaptiveresponses

Aldosteronesecretionisstimulatedbythelowsodiumconcentration,exceptinthecaseofadrenocorticalinsufficiency.NormalInterstitialfluidIntracellularfluidPlasma2)Characteristiceffectofhypotonicdehydrationonthebody①Urinevolume

Urinevolumeisvariable(low,normal,high)dependingontheADHsecretion.

Attheearlystageofhypotonicdehydration,decreasedosmolarityisthesuperiorchange,whichinhibitsADHsecretion,theurineisnotdecreased.

Atthelatestage,severehypovolemiaisthesuperiorchange,whichincreasetheADHrelease,theurinevolumeisdecreased.

腎外因素：早期或輕度--低滲透壓→ADH↓→尿量不少低鈉→ALD↑→尿鈉↓

晚期或重度--血容量↓↓→ADH↑→尿量↓低鈉→腎素血管緊張素系統(tǒng)醛固酮系統(tǒng)→鈉重吸收↑綜合→尿鈉有所回升腎臟原因：

尿鈉↑2)Characteristiceffectofhypotonicdehydrationonthebody②Hypotensionevenshock

Thebloodpressuremaydecrease.Posturalhypotensionandshockwilloccurbecausethedecreasedbloodvolume.(increasedurineandwatershiftsintothecells)

(comparewithhypertonicdehydration)③Severelyreducedinterstitialfluid

Decreasedfluidintheskintissueresultsinthereduceofskinelasticity.Whentheskinispinched,ittendstoremaininfold.Eyeballtensionisdecreased,theeyeballsaresoftandsunken.(lowproteinconcentrationandcolloidosmoticpressure)脫水征明顯④Intracellularoverhydration

WaterwillshiftfromECFtoICFbecausetheICFisrelativelyhypertonic.Thecellwillswell.

Inwhichorganisthecellswellingmostdangeroustothebody?Braincelloverhydrationproducesbraindysfunction.(Cranialcavityisfixed)(severeheadache,highbrainpressure,nausea,vomitting,confusionandcoma)⑤Thereisnoobviousthirstatearlystagebecauseofthelowcrystalosmoticpressure.summary血鈉（mM）血漿滲透壓（mOsm/L）Isotonic(等滲性缺水)水、鈉按比例丟失130~150280~310Hypertonic(高滲性缺水)waterloss>sodiumloss>150>310Hypotonic(低滲性缺水)waterloss<sodiumloss,<130<280（三）對機(jī)體的影響(effects)渴感：IsotonicHypertonicHypotonic無明顯渴感明顯渴感(除渴感障礙者)無渴感2.尿液改變Isotonic(等滲性脫水)Hypertonic(高滲性脫水)Hypotonic(低滲性脫水)3.體液變動與后果1）Isotonic：ECF↓，ICF±→ECF嚴(yán)重減少者，可發(fā)生休克。

2）Hypertonic：ICF中的水向高滲的ECF轉(zhuǎn)移，加以喝水、少尿血容量不足得以緩解→較少發(fā)生休克；嚴(yán)重患者ICF中的水向ECF轉(zhuǎn)移→腦細(xì)胞缺水→CNSdysfunction

脫水熱：體溫調(diào)節(jié)中樞脫水,調(diào)節(jié)功能紊亂；汗腺脫水,泌汗功能減退→體溫升高。

3）Hypotonic:低滲ECF中的水向ICF轉(zhuǎn)移→容易發(fā)生休克。

組織間液↓→脫水體征明顯（皮膚彈性減退、眼窩及嬰兒囟門凹陷等表現(xiàn)）（四）脫水的治療原則（treatmentpriciple)首先是恢復(fù)正常血容量，并處理可能并發(fā)的酸堿、電解質(zhì)紊亂。積極控制導(dǎo)致缺水的基本原因。

1.輕度缺水：增加鹽、水的攝入。2.明顯缺水：靜脈補(bǔ)液-依據(jù)病史、出入量、體重記錄估算體液丟失和需要補(bǔ)充的液體量。

1)Isotonic:.先給生理鹽水?dāng)U充血容量，血壓一旦恢復(fù)改用低滲鹽水，以提供較多的水，使之易于進(jìn)入細(xì)胞內(nèi)，有助于排除代謝廢物。

2)Hypertonic：先補(bǔ)糖，再補(bǔ)鹽