低鈉血癥鑒別診斷-朱大龍課件

低鈉血癥（Hyponatremia）朱大龍南京大學(xué)醫(yī)學(xué)院附屬鼓樓醫(yī)院水、鈉代謝的調(diào)節(jié)定義血清鈉＜135mmol/L為低鈉血癥；僅反映鈉在血漿中濃度的降低，并不一定表示體內(nèi)總鈉量的丟失，總體鈉可以正常甚或稍有增加。臨床上極為常見，特別在老年人中。主要癥狀為軟弱乏力、惡心嘔吐、頭痛思睡、肌肉痛性痙攣、神經(jīng)精神癥狀和可逆性共濟(jì)失調(diào)等。分類根據(jù)滲透壓低滲性低鈉血癥等滲型低鈉血癥高滲性低鈉血癥根據(jù)低鈉血癥發(fā)生時(shí)的血容量變化低血容量性低鈉血癥失鈉多于失水。血容量正常性低鈉血癥總體水增加而總鈉不變。高血容量的低鈉血癥總體水增高大于血鈉升高根據(jù)血鈉降低的程度可分為重度低鈉血癥＜120mmol/L中度低鈉血癥＜130mmol/L輕度低鈉血癥＜135mmol/L此外還有假性低鈉血癥，見于明顯的高脂血癥和高蛋白血癥。血容量正常性低鈉血癥SIADH糖皮質(zhì)激素缺乏腎病綜合癥不適當(dāng)利尿精神性多飲甲狀腺功能減退癥嚴(yán)重慢性肺部疾病、惡液質(zhì)、營養(yǎng)不良高血容量性低鈉血癥充血性心力衰竭肝功能衰竭慢性腎功能衰竭腎病綜合征SIADH惡性腫瘤（肺燕麥細(xì)胞癌、前列腺癌、胸腺癌、淋巴瘤等）肺部縱膈疾病-肺炎、曲霉病、膿腫、TB,PPV中樞神經(jīng)系統(tǒng)疾病–膿腫、創(chuàng)傷、腦膜炎、中風(fēng)、SAH內(nèi)分泌疾病–Addison病、甲減手術(shù)后急性間歇性卟啉癥藥物性SSRI、苯丙胺相關(guān)藥、長春新堿、環(huán)磷酰胺，卡馬西平，溴隱亭NSAIDS：通過降低腎臟的前列腺素低血容量性低鈉血癥（二）正常容量或高容量性低鈉血癥（一）正常容量或高容量性低鈉血癥（二）正常時(shí)細(xì)胞內(nèi)滲透壓保持穩(wěn)態(tài)平衡。當(dāng)血漿鈉濃度降低，細(xì)胞外液滲透壓下降，細(xì)胞外水流血細(xì)胞內(nèi)，使細(xì)胞腫脹，以致細(xì)胞功能受損甚至破壞，其中以腦細(xì)胞腫脹，可導(dǎo)致低鈉血癥最嚴(yán)重的臨床表現(xiàn)。血容量縮減如果得不到糾正，則可使血壓下降，腎血流量減少，腎小球?yàn)V過率降低，可導(dǎo)致腎前性氮質(zhì)血癥。臨床表現(xiàn)低鈉血癥的臨床表現(xiàn)嚴(yán)重程度取決于血鈉水平和血鈉下降的速率。血鈉在125mmol/L以上時(shí)，極少引起癥狀；鈉在125～130mmol/L之間時(shí)，也只有胃腸道癥狀。此時(shí)主要癥狀為軟弱乏力、惡心嘔吐、頭痛思睡、肌肉痛性痙攣、神經(jīng)精神癥狀和可逆性共濟(jì)失調(diào)等。實(shí)驗(yàn)室檢查血生化及電解質(zhì)測定血漿滲透壓測定尿滲透壓測定血BNP測定點(diǎn)尿鈉濃度測定血尿酸水平滲透壓血漿滲透壓（Posm) Posm=2(Na+K)+血糖+血尿素氮 正常=2(140)+5+5=290(275-290mM)尿滲透壓（UOSM）:正常:400-500mM最大稀釋50-100mM(USG1.002-1.003)最大濃縮900-1200mM(USG1.030-1.040)濃縮尿:>500mM(至少!),USG>1.017UOSM>POSMisnotenoughtoR/ODiabetesInsipidus診斷確定是否為真正的低鈉血癥血漿滲透壓（Posm）正常范圍280-295mOsm/kg如果>295mOsm/kg高血糖或甘露醇的使用（高滲性低鈉血癥）如果在280-295mOsm/kg之間:假性低鈉血癥：高脂血癥或高蛋白血癥如果<280mOsm/kg評價(jià)容量狀態(tài)血漿滲透壓<280mOsm/kg高容量性:充血性心力衰竭、肝硬化、腎病綜合癥、急慢性腎功能衰竭正常容量性：SIADH、甲減、精神性多飲、腎病綜合癥不適當(dāng)利尿、嗜啤酒狂、手術(shù)后、鈉攝入不足、極低蛋白飲食等低容量性胃腸消化液丟失、皮膚出汗、利尿劑使用、腦鹽耗綜合癥、體腔轉(zhuǎn)移丟失、鹽皮質(zhì)激素不足（Addison?。┑外c血癥的診斷思路低鈉血癥的糾正速度24小時(shí)內(nèi)升高<10-12mmol/L，48小時(shí)內(nèi)血鈉升高<18mmol/L治療急性低鈉血癥

=腦水腫、腦疝方法:去除病因癥狀輕到中度:無需進(jìn)一步干預(yù)治療；嚴(yán)重癥狀:高滲鹽水輸注(3%)3%NaCl檢測輸液速度-避免中樞腦橋脫髓鞘病變檢測血鈉水平q2h24小時(shí)內(nèi)升高<10-12mmol/L，48小時(shí)內(nèi)血鈉升高<18mmol/LVerbalis,JosephG.,StephenR.Goldsmith,ArthurGreenberg,RobertW.Schrier,andRichardH.Sterns."HyponatremiaTreatmentGuidelines2007:ExpertPanelRecommendations."TheAmericanJournalofMedicine120(2007):S1-S21.治療慢性低鈉血癥（續(xù)）低血容量性:生理鹽水-恢復(fù)組織灌注正常容量性和高容量性限制液體攝入袢利尿劑/鹽片口服血管加壓素受體拮抗劑--考尼伐坦、托伐普坦其他地美環(huán)素引起腎性尿崩癥2-5天發(fā)生嚴(yán)重的多尿高鈉血癥腎毒性、光敏感、皮疹尿素長期治療有效(5年)動(dòng)物模型顯示有益鋰劑下調(diào)血管加壓素刺激的水通道蛋白2的表達(dá)有效性不確定引起腎性尿崩癥hyponatremiaTreatmentGuidelines2007:ExpertPanelRecommendations."TheAmericanJournalofMedicine120(2007):S1-S21.慢性低鈉血癥（等容量或高容量性）無癥狀:首選病因治療限制水的攝入袢利尿劑/鹽片攝入抑制ADH釋放：地美環(huán)素V2受體拮抗劑考尼伐坦、托伐普坦有癥狀:（低鈉性腦病、嚴(yán)重腦水腫）3%高滲鹽水DesiredchangeinNa×TBWTBW:0.6×weight(kg)inmen&0.5×weight(kg)inwomen緩慢糾正，避免并發(fā)癥抗利尿激素受體（AVPR）拮抗劑一種新的治療低鈉血癥的藥物，阻斷V2R與抗利尿激素受體結(jié)合，進(jìn)而抑制腺苷酸環(huán)化酶信號(hào)途徑從而排除自由水但是對尿鈉、尿鉀無作用。Conviptan已被美國FDA批準(zhǔn)用于等容量和高容量性低鈉血癥患者的應(yīng)用，而在2009年，歐洲EMEA和美國FDA均批準(zhǔn)Tolvaptan用于SIADH患者低鈉血癥的治療。另外目前用于臨床試驗(yàn)研究階段的藥物還包括Lixivaptan和Satavaptan。

Multi-center,double-blind,placebocontrolled,randomlyassigned(4days)Conivaptan30minLD(20mgdilutedto100mlD5W)infusion96hrCIVdays1-4(dilutedto250ml)40mg/day80mg/day

Placebo100mlD5WasLD250mlD5WImportantExclusionCriteria:HypovolemichyponatremiaCardiacproblems:HyponatremiarequiringimmediatetreatmentMedicationsinteractingwithCYP4503A4OthermedicationsAssessmentoftheEfficacyandSafetyofIntravenousConivaptaninEuvolemicandHypervolemicHyponatremiaAmericanJournalofNephrology27(2007):447-57Timetoincrease>/=4mEq/L:Conivaptan40mg/day:24hoursConivaptan80mg/day:10hoursPBO:noincreasewithin4dayinfusionChangeinserumNafrombaselinetoendoftreatmentConivaptan40mg/day:6.3mEq/LConivaptan80mg/day:9.4mEq/LPBO:0.8mEq/LPatientswithincreaseinNa>/=6mEq/LorNa>/=135mEq/LConivaptan40mg/day:69%(6.3)Conivaptan80mg/day:88.5%(23)PBO:20.7%(6)ChangeinserumNafromBaselineto6-9daysposttreatment:Conivaptan40mg/day:8.1mEq/L(n=13)Conivaptan80mg/day:4.7mEq/L(n=26)PBO:5.2mEq/L(n=17)AssessmentoftheEfficacyandSafetyofIntravenousConivaptaninEuvolemicandHypervolemicHyponatremiaDiscontinuationwasmainlyduetoInfusionsitereactionsOtherADRs:hypotension,posturalhypotension,pyrexia,hyperkalemia,infusionsitethrombosisProspective,multi-center,randomizedcentrally,double-blind,placebocontrolledConducted2trialstoassessreproducibility(SALT-1&SALT-2)Tolvaptan15mgtab1tabPODailyx30daysORPBOImportantPatientPopulationCriteria:InclusionEtiologies:CHF,cirrhosisorSIADHExclusionCriteria:OtheretiologiesHypovolemichyponatremiaOthercardiacdiseases(post-MI,SVT,SBP<90)SerumNa<120mmol/Lw/neurologicalimpairmentPoorprognosisnottoleratingfluidshifts:short-termsurvivalTolvaptan,aSelectiveOralVasopressinV2-ReceptorAntagonist,forHyponatremiaNewEnglandJournalofMedicine355(2006):2099-112SimilarBaselineCharacteristicsacrossstudygroups(exceptheightinSALT-2),MeanbaselineNa:~128mEq/LCo-Administration/Co-intervention:Fluidrestrictionwasnotmandatory;treatmentwithotheragentswerenotallowed(demeclocycline,lithium,urea)DoseadjustmentsweremadeatthediscretionoftheinvestigatoratDay4Drugwasadministereduntilday30,finalassessmentsdoneatday37ValueswerestatisticallysignificantIncreasesinNaweregreaterinTolvaptangroupthanPBOinbothtrialsandinbothstratificationsatDay4andmuchmoreatDay30Increasesweremorerapid(byday4)andgreater(markedhyponatremia)NewEnglandJournalofMedicine355(2006):2099-112.TolvaptanpatientsreachednormalNalevelsonday4and30morethanPBODay4:SALT-1(40%vs13%)SALT-2(55%vs11%)Day30:SALT-1(53%vs25%)SALT-2(58%vs25%)Less“marked”hyponatremiaDay4:SALT-1(13%vs49%)SALT-2(10%vs40%)Day30:SALT-1(7%vs35%)SALT-2(15%vs32%)notsigSF-12scoresShoweddifferencein“mentalcomponentsummary”in“markedhyponatremia”patients,butnotoverallVitality,socialfunctioning,calmness,sadnessNodifferenceinphysicalcomponentsummaryOTHER:Day37analysis:NaconcentrationsshowednodifferencebetweeneacharmTolvaptan(Samsca)

"Tolvaptan,aSelectiveOralVasopressinV2-ReceptorAntagonist,forHyponatremia."

NewEnglandJournalofMedicine355(2006):2099-112.ADRMostcommon:Thirst(14%;5%);Drymouth(13%;4%)Incidence:Tolvaptan:171patientsPBO:176,notallADRsweredeemedtoberelatedtostudydrugweakness,nausea,constipation,peripheraledema,ascites,diarrhea,fatigue,vomitingTolvaptan:8patientswithdrewduetoADR Rash,dys