大三上课件-病理生理学钾代谢障碍

周新文钾代谢障碍

DisorderofPotassiumMetabolism主要内容

明确机体内钾的分布，钾的平衡以及钾平衡的调节

了解低钾血症和高钾血症诊断和治疗原则

能够从钾的摄入，排出和钾在细胞内外的转移三个方面阐明低钾血症和高钾血症的病因

联系钾的正常功能理解高钾血症和低钾血症时机体的功能代谢变化PartI:钾的平衡和调节PartII:低钾血症PartIII:高钾血症钾功能细胞代谢--酶活性、合成代谢ICFKmmol/LK+-----静息膜电位RMP渗透压K+H+-------酸碱平衡ECFK+4.2+/-0.3mmol/LPotassiumBalanceandregulationⅠ正常钾在机体的含量和分布

Ⅲ钾稳态的调节与维持Ⅱ钾的摄入和排出途径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钾平衡的调节Plasmapotassiumislargelyregulatedthroughtwomechanisms:肾脏的调节(2)钾在细胞内外的转移EliminationofpotassiumfromthekidneyglomerulusproximaltubuleloopofHenlecollectingtubuledistaltubuleK+K+K从肾小球的滤过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在远曲小管和集合管被重吸收或分泌“fine-tune”theconcentrationofpotassiumintheECFlumen主细胞bloodK+Na+Na+K+Cl-Cl-K+CO2HCO3-Cl-Cl-H+K+CO2闰细胞

(whenKlevelsarelow)Na–KionexchangeK–Hionexchange影响钾从集合管和远曲小管排出的因素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钾平衡的调节Plasmapotassiumislargelyregulatedthroughtwomechanisms:肾脏的调节(2)钾在细胞内外的转移MovementofPotassiumacross

theCellMembrane

Na+/K+ATPasemembranepump的活性

Twodeterminantfactors:

细胞膜对钾离子的通透性1.激素

—insulin,glucagon,catecholamines,thyroidhormone2.细胞外液的pH和血浆渗透压3.Others—rateofcellbreakdown,hypoxia,exerciseInfluencingFactorsMaintenanceofPotassiumHomeostasis

肾脏的调节

钾在细胞内外的转移

钾从结肠的分泌PartⅡ低钾血症（Hypokalemia）:

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

ECF2%DietaryintakeSerum[K+]<3.5mmol/LG.Ilosses---呕吐，腹泻Renallosses---利尿剂，肾脏疾病

Lossesfromtheskin---过度排汗，烧伤ExcessivelossesICF[K+]mayormaynotbedecreasedTotalbodyKcontent—

decreased(Kdeficit)ShiftingfromECFtoICF—

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

Ⅱ.丢失增加1.胃肠道丢失Diarrhea→大量排出富含钾的碱性消化液→K

depletion,acidosis,ECFvolumecontraction→↑secretionofaldosterone

Vomiting→mainlyincreasedrenalexcretionofK+duetometabolicalkalosiscausedbylossofgastricacid,contractionofECFvolumeEtiologyandPathogenesis

Ⅰ.摄入不足Ⅱ.排出增加1.胃肠道丢失

2.经肾脏丢失(1)利尿剂→increasedflowrateanddeliveryofNa+,Cl-andwatertothedistaltubule→increasedNa+-K+exchange;volumecontraction→increasedaldosterone→renalKexcretion↑

EtiologyandPathogenesisⅠ.摄入不足Ⅱ.排出增加1.胃肠道丢失

2.经肾丢失(1)利尿剂

(2)SomediseasesofthekidneyRenaltubularacidosis(肾小管性酸中毒)ExcessiveRenalLosses(1)利尿剂(2)SomediseasesofthekidneyRenaltubularacidosisDiureticrecoveryphaseofacuterenalfailure

(3)Ald作用过强Aldosteronism,Cushing’ssyndrome(4)Magnesium(镁)deficiency

DiureticrecoveryphaseofacuterenalfailureWhyMagnesiumdeficiency

?glomerulusproximaltubuleloopofHenlecollectingtubuledistaltubuleK+K+K在髓袢升支粗段被重吸收（Na/K/2Cl共转运体）Sodium-potassiumATPasedependent!Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinMgdependent42岁女性患者急诊入院，主要症状：进食减少，恶心，频繁呕吐20天。既往史：3年前被确诊为糖尿病。诊断：糖尿病酮症酸中毒。用胰岛素治疗，酮症酸中毒得到缓解。同时发现存在尿路感染和严重的低钾血症(血[K+]：~2mmol/L).因此给予大剂量的庆大霉素治疗33天，同时口服和静脉大剂量补钾41天。然而，低钾血症持续存在(2.55mmol/L).CaseReport

使医生感到惊奇的是，病人突然出现四肢痉挛性僵直。直到此时，医生才检测了血镁，只有0.2mmol/L!(正常血[Mg2+]：1.5~2.5mmol/L).立刻静脉输注MgSO4。几天后，症状完全消失，虽然补钾的量减少，血钾在3天内就恢复了正常。血镁也恢复正常。(《中华内科杂志》1980年1月)Questions:

1.Whatarethecausesofhypokalemiaandhypomagnesemiainthispatient?2.Whydidthedoctorfailtodiagnosehypomagnesemiaearlier?ExcessiveRenalLosses(1)利尿剂(2)肾脏疾病RenaltubularacidosisDiureticrecoveryphaseofacuterenalfailure(3)Ald作用过强Aldosteronism,Cushing’ssyndrome(4)Magnesiumdeficiency(5)碱中毒EtiologyandPathogenesisⅠ.摄入不足Ⅱ.排出增加1.胃肠道丢失

2.经肾丢失3.经皮肤丢失Profusesweating,burnsorscaldsEtiologyandPathogenesisⅠ.摄入不足Ⅱ.丢失增加Ⅲ.K+

向细胞内转移1.Overdoseofinsulin2.-adrenergicagonistoverdose

Na+Na+/K+-ATPaseK+K+H+AlbuterolInsulinEtiologyandPathogenesisⅠ.摄入不足Ⅱ.丢失增加Ⅲ.K+向细胞内转移1.Overdoseofinsulin2.-adrenergicagonistoverdose3.Alkalosis4.Barium(钡),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)急性低钾血症[K+]i/[K+]e↑RMPmorenegativethannormal超极化阻滞,excitability↓肌肉软弱无力,弛缓性麻痹,腹胀，麻痹性肠梗阻

Ratioof[K+]ito

[K+]emaybenormal,RMPandexcitabilityunchanged缺钾慢性低钾血症代谢障碍肌坏死EffectsontheHeart

ABriefReviewoftheBioelectricPhenomenaoftheHeart

ExcitabilityAuthorhythmicityConductivityContractivityRMPandAPofaVentricularMuscleCelloftheHeartabCTheActionPotentialofSinoatrialNode,VentricularMuscleandPurkinje’sFiber窦房结心室肌Purkinje’sFiber自律性++_444441.Effectsonexcitability

RMP<-90mvEm-EtexcitabilityCa2+inflow平台期,有效不应期Phase3,超常期APprolongedEffectsoflowserum[K+]ontheactionpotentialofthemyocardialcellnormal

normal

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

Kchannelconductanceofthecellmembraneofthefastresponseautonomiccellsaccelerationofspontaneousdiastolicdepolarization,autorhythmicityTheMembranePotentialofPurkinje’sFiber340124max.diast.potentialnormalhypokalemia3.Effectsonconductivity

0期复极的速度和幅度

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,保钾利尿剂K向细胞外转移tissueinjury,acidosis,insulindeficiency,familialhyperkalemicperiodicparalysisK的摄入增加—rapidIVKadministration

EffectsontheBodyⅠ.对神经肌肉兴奋性的影响重度高钾血症（血清钾浓度为7~9mmol/L）肌无力→弛缓性麻痹轻度高钾血症（血清钾浓度为5.5~7.0mmol/L）肌肉轻度震颤、剌痛，手足感觉异常Ⅰ.对神经肌肉兴奋性的影响Ⅱ.对心脏的影响1.Effectsonexcitability

EffectsontheBody轻度高钾血症：[K+]i/[K+]e变小→静息膜电位与阈电位距离↓→心肌兴奋性↑重度高钾血症：心肌细胞静息膜电位过小，甚至等于或低于阀电位→心肌兴奋性↓或消失

EffectsontheBodyⅠ.对神经肌肉兴奋性的影响Ⅱ.对心脏的影响1.Effectsonexcitability

2.Effectsonautorhythmicity高钾血症→心肌细胞膜对K+通透性升高→达最大复极电位后，细胞内钾外流比正常快，而Na+内流相对减慢→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