周新文鉀代謝障礙

DisorderofPotassiumMetabolism主要內容

明確機體內鉀的分布，鉀的平衡以及鉀平衡的調節

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，排出和鉀在細胞內外的轉移三個方面闡明低鉀血癥和高鉀血癥的病因

聯系鉀的正常功能理解高鉀血癥和低鉀血癥時機體的功能代謝變化PartI:鉀的平衡和調節PartII:低鉀血癥PartIII:高鉀血癥鉀功能細胞代謝--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正常鉀在機體的含量和分布

Ⅲ鉀穩態的調節與維持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鉀平衡的調節Plasmapotassiumislargelyregulatedthroughtwomechanisms:腎臟的調節(2)鉀在細胞內外的轉移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在遠曲小管和集合管被重吸收或分泌“fine-tune”theconcentrationofpotassiumintheECFlumen主細胞bloodK+Na+Na+K+Cl-Cl-K+CO2HCO3-Cl-Cl-H+K+CO2閏細胞

(whenKlevelsarelow)Na–KionexchangeK–Hionexchange影響鉀從集合管和遠曲小管排出的因素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鉀平衡的調節Plasmapotassiumislargelyregulatedthroughtwomechanisms:腎臟的調節(2)鉀在細胞內外的轉移MovementofPotassiumacross

theCellMembrane

Na+/K+ATPasemembranepump的活性

Twodeterminantfactors:

細胞膜對鉀離子的通透性1.激素

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

腎臟的調節

鉀在細胞內外的轉移

鉀從結腸的分泌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共轉運體）Sodium-potassiumATPasedependent!Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinMgdependent42歲女性患者急診入院，主要癥狀：進食減少，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。同時發現存在尿路感染和嚴重的低鉀血癥(血[K+]：~2mmol/L).因此給予大劑量的慶大霉素治療33天，同時口服和靜脈大劑量補鉀41天。然而，低鉀血癥持續存在(2.55mmol/L).CaseReport

使醫生感到驚奇的是，病人突然出現四肢痙攣性僵直。直到此時，醫生才檢測了血鎂，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，雖然補鉀的量減少，血鉀在3天內就恢復了正常。血鎂也恢復正常。(《中華內科雜志》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.經腎丟失3.經皮膚丟失Profusesweating,burnsorscaldsEtiologyandPathogenesisⅠ.攝入不足Ⅱ.丟失增加Ⅲ.K+

向細胞內轉移1.Overdoseofinsulin2.-adrenergicagonistoverdose

Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinEtiologyandPathogenesisⅠ.攝入不足Ⅱ.丟失增加Ⅲ.K+向細胞內轉移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竇房結心室肌Purkinje’sFiber自律性++_444441.Effectsonexcitability

RMP<-90mvEm-EtexcitabilityCa2+inflow平臺期,有效不應期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向細胞外轉移tissueinjury,acidosis,insulindeficiency,familialhyperkalemicperiodicparalysisK的攝入增加—rapidIVKadministration

EffectsontheBodyⅠ.對神經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→心肌細胞膜對K+通透性升高→達最大復極電位后，細胞內鉀外流比正常快，而Na+內流相對減慢→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