低鉀血癥診斷策略成都軍區(qū)總醫(yī)院內(nèi)分泌科游志清1主要內(nèi)容鉀平衡低血鉀常見原因低鉀血癥的診斷流程2主要內(nèi)容鉀平衡低血鉀常見原因低鉀血癥的診斷流程3人體鉀的數(shù)據(jù)正常血鉀濃度體內(nèi)鉀總量。男性50—55mmol/Kg，女性40—50mmol/Kg鉀的分布:細(xì)胞內(nèi)98%，細(xì)胞外2%鉀的生理需要量:0.4mmol/Kg,3—4g（75—100mmol）鉀的排泄:腎85%，糞10%，汗5%無鉀攝入，腎排鉀40—50mmol/日4鉀平衡在細(xì)胞內(nèi)液（ICF）中K+中的濃度比細(xì)胞外液（ECF）中的高30--50倍，每日攝入K+量大約與ECFK+相當(dāng)。維護正常的血清K+濃度需要在ECF和ICF之間精細(xì)調(diào)節(jié)K+的分布（內(nèi)部K+平衡）和腎排泄K+

（外部K+平衡）。無論是在內(nèi)部（ECF和ICF）之間平衡紊亂（例如

K+的轉(zhuǎn)移）或外部平衡（如K+的消耗），均可導(dǎo)致

低鉀血癥。5轉(zhuǎn)運K+的主要途徑—維持細(xì)胞內(nèi)高鉀ElectrolyteBloodPress8:38-50,2010（Na+/H+exchanger）MetabolicalkalosisΘ6CorticalcollectingductROMK（RenaloutermedullaryK+Channel）阿米洛利：作用于腎臟遠(yuǎn)端小管，阻斷Na+-K+交換機制，促使鈉、氯排泄而減少鉀和氫離子分泌氫氯噻嗪主要抑制遠(yuǎn)端小管前段和近端小管(作用較輕)對氯化鈉的重吸收，從而增加遠(yuǎn)端小管和集合管的Na+-K+交換，K+分泌增多。氨苯喋啶：直接抑制腎臟遠(yuǎn)端小管和集合管的Na+-K+交換，從而使Na+、C1-、水排泄增多，而K+排泄減少呋噻米本類藥物主要通過抑制腎小管髓袢厚壁段對氯化鈉的主動重吸收（抑制基底膜外側(cè)存在與Na+-K+-ATP酶有關(guān)的Na+、Cl-配對轉(zhuǎn)運系統(tǒng)），遠(yuǎn)端小管Na+濃度升高，促進(jìn)Na+-K+和Na+-H+交換增加，K+和H+排出增多。通過抑制亨氏袢對Ca2+、Mg2+的重吸收而增加Ca2+、Mg2+排泄。尚可能抑制近端小管和遠(yuǎn)端小管對Na+、Cl-的重吸收，促進(jìn)遠(yuǎn)端小管分泌K+。7呋噻米：本類藥物主要通過抑制腎小管髓袢厚壁段對氯化鈉的主動重吸收，結(jié)果管腔液Na+、C1-濃度升高，而髓質(zhì)間液Na+、Cl-濃度降低，使?jié)B透壓梯度差降低，腎小管濃縮功能下降，從而導(dǎo)致水、Na+、Cl-排泄增多。由于Na+重吸收減少，遠(yuǎn)端小管Na+濃度升高，促進(jìn)Na+-K+和Na+-H+交換增加，K+和H+排出增多。至于呋塞米抑制腎小管髓袢升支厚壁段重吸收Cl-的機制，過去曾認(rèn)為該部位存在氯泵，目前研究表明該部位基底膜外側(cè)存在與Na+-K+-ATP酶有關(guān)的Na+、Cl-配對轉(zhuǎn)運系統(tǒng)，呋塞米通過抑制該系統(tǒng)功能而減少Na+、C1-的重吸收。另外，呋塞米可能尚能抑制近端小管和遠(yuǎn)端小管對Na+、Cl-的重吸收，促進(jìn)遠(yuǎn)端小管分泌K+。呋塞米通過抑制亨氏袢對Ca2+、Mg2+的重吸收而增加Ca2+、Mg2+排泄

8腎對的K+調(diào)控經(jīng)腎小球濾過的K+大部分被近曲小管和亨利氏袢重吸收終尿中的K+最終主要是由遠(yuǎn)曲小管（DCT）遠(yuǎn)端，連接小管和皮層集合管（CCD）控制。有兩個因素影響K+的排泄：

CCD終端流速=尿滲透壓×容積/血漿滲透壓

或尿滲透壓/肌酐

CCD主細(xì)胞凈分泌K+([K+]CCD)=（尿/血漿[K+])/(尿/血漿滲透壓）9腎對的K+調(diào)控QJMed2005;98:305–316ENaC,epithelialNa+channels10腎對的K+調(diào)控QJMed2005;98:305–31611腎對的K+調(diào)控ElectrolyteBloodPress8:38-50,2010CCD,corticalcollectingductENaC,epithelialNa+channels.Aldosterone+HCO3ˉplasma[K+]<3.5mmol/L,TTKG≥3indicatesfastNa+orslowClˉdisordersK+：ROMK+-12ENaC,epithelialNa+channels13主要內(nèi)容鉀平衡低血鉀常見原因低鉀血癥的診斷流程14低血鉀原因缺鉀性攝入不足，＜3克/日，2周排出過多腎，胃腸，其他轉(zhuǎn)移性：代堿，大量糖（+胰島素），周癱，應(yīng)急，棉子油，氯化鋇，葉酸，維生素B12稀釋性：水過多，水中毒15主要內(nèi)容鉀平衡低血鉀常見原因低鉀血癥的診斷流程病史腎排鉀評估血壓血氣分析血、尿電解質(zhì)，RASS，皮質(zhì)醇及ACTH16病史起病急緩伴隨癥狀過去史藥物史家族史17評判腎排鉀的指標(biāo)，尤其是低鉀麻痹時常用的4個指標(biāo)，均為隨意尿fractionalexcretionofK+,K+

排泄分?jǐn)?shù)TTKG,transtubularK+gradient，跨小管K+

梯度urineK+/creatinineratio，尿K+/肌酐比值urineosmolality/creatinine，尿滲透壓/肌酐比值主要目的：是否為腎排鉀增多18ArchInternMed.2004;164:1561-1566AspoturinesampleHypokalemicperiodicparalysis(n=30)Non–hypokalemicperiodicparalysis(n=13)

aplasmaK+≤3mmol/L

TTKG,transtubularK+gradient,=[(urine/plasma[K+])/(urine/plasmaosmolality)].19RVH,renalvascularhypertensionCAH,congenitaladrenalHyperplasiaRTA,renaltubularacidosisCOA,coarctationoftheaortaDKA,diabeticketoacidosisRST,renin-secretingtumorsAME,apparentmineralocorticoidexcess.P,potassiumC,creatinineGI,gastrointestinalPP,periodicparalysis

PRA,plasmareninactivityPAC,plasmaaldosteroneconcentrationIJKD2008;2:115-22

Andersen-Tawilsyndrome：CLDCLD：Congenitalchloride-losingdiarrheaPatientswithapotassiumexcretionrateof10mmol/dto15mmol/dandacreatinineexcretionrateof10mmol/dto15mmol/dwillhaveaurineK/Cratiolessthan1.5.

---JClinInvest1959;38:1149–65Cysticfibrosis

20Andersen-TawilsyndromeItisanautosmal-dominantchannelopathyresultinginepisodicattacksofmuscleweakness(mainlyacutehypokalemia,butcanbenormo-orhyperkalemia),cardiacarrhythmia(ventriculararrhythmiasandQTprolongation)anddistinctivephysicalfeatures.Thesefeaturesoftenincludeaverysmalllowerjaw(小頜畸形),dentalabnormalities,low-setears,widelyspacedeyes,andunusualcurvingofthefingersortoes(clinodactyly).Someaffectedpeoplealsohaveshortstatureandanabnormalcurvatureofthespine(脊柱側(cè)彎).21Andersen-TawilsyndromeTwotypesofAndersen-Tawilsyndromearedistinguishedbytheirgeneticcauses.Type1,whichaccountsforabout60percentofallcasesofthedisorder,iscausedbymutationsintheKCNJ2gene.Theremaining40percentofcasesaredesignatedastype2;thecauseofthesecasesisunknownMutationsinthegeneKCNJ2encodingapore-formingsubunitoftheinwardrectifierKchannelprotein,Kir2.1,whichisexpressedinskeletalmusclesandheart,leadtothissyndrome22Congenitalchloride-losingdiarrhea(CLD)Congenitalchloride-losingdiarrhea(CLD)isarareautosomalrecessivedisordercharacterizedbywaterydiarrhea,hypokalemiaandhypochloremicmetabolicalkalosiswithhighfecalcontentofClˉ(>90mEq/L)23CysticfibrosisCysticfibrosis(CF)isanexocrinediseaseaffectingmultipleorgansystems.Thedefectinthecysticfibrosistransmembraneregulator(CFTR),actingprimarilyasaClˉchannel,isassociatedwithCF,.HypokalemiaisnotuncommoninpatientswithCF,especiallyintropicalorsubtropicalareas.DefectivechloridereabsorptionbythedysfunctionalCFTRinthesweatductsofCFpatientsisresponsibleforexcessiveClˉandNa+lossinsweat.ECFvolumedepletionwithsecondaryhyperaldosteronismnotonlycausesNa+reabsorptionandK+secretionintheCCD,butmayalsoaugmentK+secretioninsweatductsandtherebycontributetothehypokalemia.2425ElectrolyteBloodPress8:38-50,2010ECF,extracellularfluidBP,bloodpressure26ECF,BPRVH:rightventricularhypertrophyAME:ApparentmineralocorticoidexcessDOC:11-deoxycorticosteroneElectrolyteBloodPress8:38-50,2010ECF,extracellularfluidBP,bloodpressure27Liddle’ssyndrome其原因是.ENaC的β或γ單位突變，導(dǎo)致其胞漿內(nèi)C末端丟失或結(jié)構(gòu)變化。突變后的ENaC保持被激活形式。notinternalized(clathrin-coatedpitspathway)ordegraded(Nedd4pathway)突變后的ENaC對阿米洛利和氨苯喋啶敏感28Apparentmineralocorticoidexcess(AME)AME,causedbymutationsinthegene(HSD11B2)encodingrenal-specific11β-hydroxysteroiddehydrogenasetype2(11β-HSD2).isararebutpotentiallyfatalautosomalrecessiveformofhypertensionandhypokalemicmetabolicalkalosisassociatedwithhyporeninemiaandhypoaldosteronemiaandanabnormalratioofurinarymetabolitesofcortisolwithahightetrahydrocortisol:tetrahydrocortisone(THF:THE)ratio11β-HSD2CortisolcortisoneMR+TheprincipalcellsofdistaltubuleslycyrrhetinicacidΘ29ElectrolyteBloodPress8:38-50,2010ECF,BPRTA,renaltubularacidosisGS,Gitelman’ssyndromeBS,Bartter’ssyndrome30Bartter’ssyndrome(BS)andGitelman’ssyndrome(GS)BSresultsfromdefectivereabsorptionofNaClintheLOHwhereasGSissecondarytodefectivereabsorptionofNaClintheDCT.HighurineCa2+andMg2+excretionisuniversallypresentinlesionsoftheloopofHenle(LOH)whereaslowurineCa2+andhighMg2+excretionisinvariablyfoundinlesionsofthedistalconvolutedtubule(DCT)CTAL,corticalthickascendinglimb31Bartter’ssyndrome(BS)andGitelman’ssyndrome(GS)ThefivesubtypesofBSarisefrominactivation

mutationsingenesencodingtheNa+/K+/2Clˉcotransporter(NKCC2),K+channel(ROMK),kidney-specificClˉchannel(CLCNKB),barttin(BSND)andcalcium-sensingreceptors(CaSR)32Fig.Transportproteinsinthethickascendinglimb(TAL)ofloopofHenle(LOH)(leftpanel)anddistalconvolutedtubule(DCT)(rightpanel)affectedbygenemutations.ElectrolyteBloodPress8:38-50,201033Bartter’ssyndrome(BS)andGitelman’ssyndrome(GS)Atthemolecularlevel,GSismostlyduetoinactivatingmutationsintheSLC12A3gene,whichencodesthethiazide-sensitiveNa+/Clˉcotransporter(NCC)ontheapicalmembraneoftheDCT34Fig.MechanismsforpersistenthypokalemiainGitelman'ssyndrome(GS)ROMK,renaloutermedullaryK+channelCNT,corticalconnectingtubulesNCC,thiazide-sensitiveNa+/ClˉcotransporterElectrolyteBloodPress8:38-50,201035Bartter’ssyndrome(BS)andGitelman’ssyndrome(GS)Amaternalhistoryofpolyhydramnios,ageofonset,neurologicsymptoms,deafness,presenceofnephrocalcinosisorrenalstones,andserumdivalentconcentrationwiththeirurineexcretionrateshelpdistinguishamongthesubtypesofBSandGS.BecauseCl-channelsareexpressedinboththebasolateralmembraneofLOHandDCT,somepatientswithclassicalBSmayhaveclinicalprofilessimilartothatofGS.36Bartter’ssyndrome(BS)andGitelman’ssyndrome(GS)UnlikeBS,non-steroidanti-inflammatorydrugs(NSAIDs)areusuallynoteffectiveinpatientswithGSduetotherelativelynormalurinaryprostaglandinE2excretion.37CharacteristicofBartter’ssyndrome(BS)andGitelman’ssyndrome(GS)38AR,autosomalrecessiveSeSAME,seizures,sensorineuraldeafness,ataxia,mentalretardation,andelectrolyteimbalance39PHYSIOLOGICALREVIEWSVol.80,No.1,January200040OrphanetJournalofRareDiseases2008,3:22

41DCT-1(top)andDCT-2(bottom)cells