周新文鉀代謝障礙

DisorderofPotassiumMetabolism主要內(nèi)容

明確機(jī)體內(nèi)鉀的分布，鉀的平衡以及鉀平衡的調(diào)節(jié)

了解低鉀血癥和高鉀血癥診斷和治療原則

能夠從鉀的攝入，排出和鉀在細(xì)胞內(nèi)外的轉(zhuǎn)移三個方面闡明低鉀血癥和高鉀血癥的病因

聯(lián)系鉀的正常功能理解高鉀血癥和低鉀血癥時(shí)機(jī)體的功能代謝變化PartI:鉀的平衡和調(diào)節(jié)PartII:低鉀血癥PartIII:高鉀血癥鉀功能細(xì)胞代謝--酶活性、合成代謝ICFKmmol/LK+-----靜息膜電位RMP滲透壓K+H+-------酸堿平衡ECFK+4.2+/-0.3mmol/LPotassiumBalanceandregulationⅠ正常鉀在機(jī)體的含量和分布

Ⅲ鉀穩(wěn)態(tài)的調(diào)節(jié)與維持Ⅱ鉀的攝入和排出途徑DietaryKintake50~200mmol/dayECF2%Serum[K+]round4.5mmol/LK+SkintrivialnormallyColon10%Kidneys>80%Moreingested,moreexcretedLessingested,lessexcretedNotingested,excretiongoeson

Content,distribution,intakeandexcretionofKExcretionICF[K+]140-160mmol/L98%ofthetotalbodypotassiumTotalbodyKcontent50~55mmol/Kgbodyweight

Ⅲ鉀平衡的調(diào)節(jié)Plasmapotassiumislargelyregulatedthroughtwomechanisms:腎臟的調(diào)節(jié)(2)鉀在細(xì)胞內(nèi)外的轉(zhuǎn)移EliminationofpotassiumfromthekidneyglomerulusproximaltubuleloopofHenlecollectingtubuledistaltubuleK+K+K從腎小球的濾過K在近曲小管和Na,水被重吸收K在髓袢升支粗段被重吸收K在遠(yuǎn)曲小管和集合管被重吸收或分泌“fine-tune”theconcentrationofpotassiumintheECFlumen主細(xì)胞bloodK+Na+Na+K+Cl-Cl-K+CO2HCO3-Cl-Cl-H+K+CO2閏細(xì)胞

(whenKlevelsarelow)Na–KionexchangeK–Hionexchange影響鉀從集合管和遠(yuǎn)曲小管排出的因素Aldosterone—activatesNa+/K+ATPase,increasemembranepermeabilitytoK[K+]intheECFFlowrateoftubularfluidinthedistaltubulepHofECF—↓pHinhibitsNa+/K+ATPase+lumenbloodPrincipalCellK+Na+Na+K+Cl-Cl-K+[K+]↑②③CO2HCO3-Cl-Cl-H+K+CO2IntercalatedCell[H+]↑①FactorsInfluencingExcretionofK+bythe

DistalandCollectingTubules+Ald+++++--flowrate+Na–KionexchangeK–Hionexchange

Ⅲ鉀平衡的調(diào)節(jié)Plasmapotassiumislargelyregulatedthroughtwomechanisms:腎臟的調(diào)節(jié)(2)鉀在細(xì)胞內(nèi)外的轉(zhuǎn)移MovementofPotassiumacross

theCellMembrane

Na+/K+ATPasemembranepump的活性

Twodeterminantfactors:

細(xì)胞膜對鉀離子的通透性1.激素

—insulin,glucagon,catecholamines,thyroidhormone2.細(xì)胞外液的pH和血漿滲透壓3.Others—rateofcellbreakdown,hypoxia,exerciseInfluencingFactorsMaintenanceofPotassiumHomeostasis

腎臟的調(diào)節(jié)

鉀在細(xì)胞內(nèi)外的轉(zhuǎn)移

鉀從結(jié)腸的分泌PartⅡ低鉀血癥（Hypokalemia）:

Serum[K+]<3.5mmol/L,mayormaynotbeassociatedwithKdeficit.

ECF2%DietaryintakeSerum[K+]<3.5mmol/LG.Ilosses---嘔吐，腹瀉Renallosses---利尿劑，腎臟疾病

Lossesfromtheskin---過度排汗，燒傷ExcessivelossesICF[K+]mayormaynotbedecreasedTotalbodyKcontent—

decreased(Kdeficit)ShiftingfromECFtoICF—

normalorEtiologyandPathogenesisEtiologyandPathogenesisⅠ.攝入不足Fasting,anorexia,inabilitytoeat,prolongedIValimentationwithoutKsupplementation

Ⅱ.丟失增加1.胃腸道丟失Diarrhea→大量排出富含鉀的堿性消化液→K

depletion,acidosis,ECFvolumecontraction→↑secretionofaldosterone

Vomiting→mainlyincreasedrenalexcretionofK+duetometabolicalkalosiscausedbylossofgastricacid,contractionofECFvolumeEtiologyandPathogenesis

Ⅰ.攝入不足Ⅱ.排出增加1.胃腸道丟失

2.經(jīng)腎臟丟失(1)利尿劑→increasedflowrateanddeliveryofNa+,Cl-andwatertothedistaltubule→increasedNa+-K+exchange;volumecontraction→increasedaldosterone→renalKexcretion↑

EtiologyandPathogenesisⅠ.攝入不足Ⅱ.排出增加1.胃腸道丟失

2.經(jīng)腎丟失(1)利尿劑

(2)SomediseasesofthekidneyRenaltubularacidosis(腎小管性酸中毒)ExcessiveRenalLosses(1)利尿劑(2)SomediseasesofthekidneyRenaltubularacidosisDiureticrecoveryphaseofacuterenalfailure

(3)Ald作用過強(qiáng)Aldosteronism,Cushing’ssyndrome(4)Magnesium(鎂)deficiency

DiureticrecoveryphaseofacuterenalfailureWhyMagnesiumdeficiency

?glomerulusproximaltubuleloopofHenlecollectingtubuledistaltubuleK+K+K在髓袢升支粗段被重吸收（Na/K/2Cl共轉(zhuǎn)運(yùn)體）Sodium-potassiumATPasedependent!Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinMgdependent42歲女性患者急診入院，主要癥狀：進(jìn)食減少，惡心，頻繁嘔吐20天。既往史：3年前被確診為糖尿病。診斷：糖尿病酮癥酸中毒。用胰島素治療，酮癥酸中毒得到緩解。同時(shí)發(fā)現(xiàn)存在尿路感染和嚴(yán)重的低鉀血癥(血[K+]：~2mmol/L).因此給予大劑量的慶大霉素治療33天，同時(shí)口服和靜脈大劑量補(bǔ)鉀41天。然而，低鉀血癥持續(xù)存在(2.55mmol/L).CaseReport

使醫(yī)生感到驚奇的是，病人突然出現(xiàn)四肢痙攣性僵直。直到此時(shí)，醫(yī)生才檢測了血鎂，只有0.2mmol/L!(正常血[Mg2+]：1.5~2.5mmol/L).立刻靜脈輸注MgSO4。幾天后，癥狀完全消失，雖然補(bǔ)鉀的量減少，血鉀在3天內(nèi)就恢復(fù)了正常。血鎂也恢復(fù)正常。(《中華內(nèi)科雜志》1980年1月)Questions:

1.Whatarethecausesofhypokalemiaandhypomagnesemiainthispatient?2.Whydidthedoctorfailtodiagnosehypomagnesemiaearlier?ExcessiveRenalLosses(1)利尿劑(2)腎臟疾病RenaltubularacidosisDiureticrecoveryphaseofacuterenalfailure(3)Ald作用過強(qiáng)Aldosteronism,Cushing’ssyndrome(4)Magnesiumdeficiency(5)堿中毒EtiologyandPathogenesisⅠ.攝入不足Ⅱ.排出增加1.胃腸道丟失

2.經(jīng)腎丟失3.經(jīng)皮膚丟失Profusesweating,burnsorscaldsEtiologyandPathogenesisⅠ.攝入不足Ⅱ.丟失增加Ⅲ.K+

向細(xì)胞內(nèi)轉(zhuǎn)移1.Overdoseofinsulin2.-adrenergicagonistoverdose

Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinEtiologyandPathogenesisⅠ.攝入不足Ⅱ.丟失增加Ⅲ.K+向細(xì)胞內(nèi)轉(zhuǎn)移1.Overdoseofinsulin2.-adrenergicagonistoverdose3.Alkalosis4.Barium(鋇),crudecottonseedoilpoisoning5.Familialhypokalemicperiodicparalysis

Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinEffectsofhypokalemia

ontheBody—factorsinfluencingtheeffects:theunderlyingdiseases,thedegreeofhypokalemiaandrapidityofitsdevelopment,theratioof[K+]i/[K+]eEffectsonNeuromuscularExcitability

TheRestingMembranePotential(RMP)andActionPotential(AP)ofaskeletalmusclecellinthenormalstate

+350-60-90Millivolts

MillisecondsThreshold

NernstequationEm=-60lg[K+]icf/[K+]ecf(mv)急性低鉀血癥[K+]i/[K+]e↑RMPmorenegativethannormal超極化阻滯,excitability↓肌肉軟弱無力,弛緩性麻痹,腹脹，麻痹性腸梗阻

Ratioof[K+]ito

[K+]emaybenormal,RMPandexcitabilityunchanged缺鉀慢性低鉀血癥代謝障礙肌壞死EffectsontheHeart

ABriefReviewoftheBioelectricPhenomenaoftheHeart

ExcitabilityAuthorhythmicityConductivityContractivityRMPandAPofaVentricularMuscleCelloftheHeartabCTheActionPotentialofSinoatrialNode,VentricularMuscleandPurkinje’sFiber竇房結(jié)心室肌Purkinje’sFiber自律性++_444441.Effectsonexcitability

RMP<-90mvEm-EtexcitabilityCa2+inflow平臺期,有效不應(yīng)期Phase3,超常期APprolongedEffectsoflowserum[K+]ontheactionpotentialofthemyocardialcellnormal

normal

low[K+]eThresholdpotentialrepolarizationprolongeda.mus.v.mus.2.Effectsonautorhythmicity

Kchannelconductanceofthecellmembraneofthefastresponseautonomiccellsaccelerationofspontaneousdiastolicdepolarization,autorhythmicityTheMembranePotentialofPurkinje’sFiber340124max.diast.potentialnormalhypokalemia3.Effectsonconductivity

0期復(fù)極的速度和幅度

conductivity

Plasmapotassiumlevelsbelow3.0mEq/L:typicalECGchangesofhypokalemia4.Effectsoncontractility

Increasedinacutehypokalemia,

decreasedinchronichypokalemiaEffectsontheKidneyfunctionalandmorphologicalchanges

Effectsonacid-basebalanceH-KexchangeacrosscellmembranerenalhydrogenionexcretionhypokalemiaAlkalosisHowaboutthepHoftheurineinsuchconditions?Acidicorbasic?反常性酸性尿DiagnosisofhypokalemiaSerumconcentrationofpotassiumECG:lowTwave,prominentUwave,cardiacdysrhythmias.Complaintsofweakness,fatigue,andmusclecramps,MuscleparalysisPrinciplesofPreventionandTreatmentⅠ.TreatingtheprimarydiseaseⅡ.Replacementtherapywithpotassium1.Oralreplacement:40~120mmolofK/day2.IVinstillation:KCl≤40mmol/L,≤10mmolofK/h

Neverinject!Monitorserum[K+]andECG

BeverycarefultopatientwhohasanimpairedrenalfunctionPartIIIHyperkalemia:

Serum[K+]>5.5mmol/L,amedicalemergency.

EtiologyandPathogenesisK的排出不足Renalfailure,hypoaldosteronism,保鉀利尿劑K向細(xì)胞外轉(zhuǎn)移tissueinjury,acidosis,insulindeficiency,familialhyperkalemicperiodicparalysisK的攝入增加—rapidIVKadministration

EffectsontheBodyⅠ.對神經(jīng)肌肉興奮性的影響重度高鉀血癥（血清鉀濃度為7~9mmol/L）肌無力→弛緩性麻痹輕度高鉀血癥（血清鉀濃度為5.5~7.0mmol/L）肌肉輕度震顫、剌痛，手足感覺異常Ⅰ.對神經(jīng)肌肉興奮性的影響Ⅱ.對心臟的影響1.Effectsonexcitability

EffectsontheBody輕度高鉀血癥：[K+]i/[K+]e變小→靜息膜電位與閾電位距離↓→心肌興奮性↑重度高鉀血癥：心肌細(xì)胞靜息膜電位過小，甚至等于或低于閥電位→心肌興奮性↓或消失

EffectsontheBodyⅠ.對神經(jīng)肌肉興奮性的影響Ⅱ.對心臟的影響1.Effectsonexcitability

2.Effectsonautorhythmicity高鉀血癥→心肌細(xì)胞膜對K+通透性升高→達(dá)最大復(fù)極電位后，細(xì)胞內(nèi)鉀外流比正常快，而Na+內(nèi)流相對減慢→自律性↓Ⅰ.EffectsonneuromuscularexcitabilityⅡ.Effectsontheheart1.Effectsonexcitability2.Effectsonautorhythmicity3.Effectsonconductivityasmallerandslowerphase0upstrokeconductivity

EffectsontheBodyⅠ.EffectsonneuromuscularexcitabilityⅡ.Effectsontheheart1.Effectsonexcitability2.Effectsonautorhythmicity3.Effectsonconductivity4.Effectsoncontractilityhighserum[K+]inflowof[Ca2+]contractility

EffectsontheBodyⅠ.EffectsonneuromuscularexcitabilityⅡ.EffectsontheheartⅢ.Effectsonacid-basebalance

ECF[K+]secretionofinsulinandaldosteroneECF[K+]shiftedintocellswhile[H+]moveoutECF[K+]Na+-K+exchangeinr