低鈉血癥鑒別診斷

1、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

2、假性低鈉血癥，見于明顯的高脂血癥和高蛋白血癥。病 因假性低鈉血癥（滲透壓正常）高脂血癥、高蛋白血癥（顯著升高）高滲透性性低鈉血癥（高血糖、甘露醇或甘油治療）低血容量性低鈉血癥胃腸道消化液丟失（如嘔吐、腹瀉、胰腺炎及胰腺造瘺和膽瘺等； 皮膚水鹽丟失（大量出汗、大面積三度燒傷、胰腺纖維性囊腫）體腔轉(zhuǎn)移丟失 （小腸梗阻、腹膜炎、急性靜脈阻塞、嚴(yán)重?zé)齻龋┠I性失鈉（慢性腎臟疾病、失鹽性腎病、鹽皮質(zhì)功能減退、SIADH、糖尿病酮癥酸中毒、利尿劑）腦性鹽耗損綜合征（下視丘腦或腦干損傷引起）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

3、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（一）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）病理生理 低鈉血癥從病因來說，不外是鈉的丟失和耗損，或者是總體水相對增多，總的效應(yīng)是血漿滲透壓

4、降低(血鈉濃度是血漿滲透壓維系的主要成分)。失鈉又常伴有失水，不管低鈉血癥的病因為何，有效血容量均縮減，從而引起非滲透壓性ADH釋放，以圖增加腎小管對水的重吸收，以免血容量進(jìn)一步縮減。然而這種保護(hù)機(jī)制更加重了血鈉和血漿滲透壓的降低，這種代償機(jī)制發(fā)生于有效血容量縮減的早期，當(dāng)血Na+下降到135mmol/L時，ADH釋放則被抑制。 正常時細(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，腎小球濾過率降低，可導(dǎo)致腎前性氮質(zhì)

5、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，極少引起癥狀；鈉在125130mmol/L之間時，也只有胃腸道癥狀。此時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。腦水腫臨床表現(xiàn)有抽搐、木僵、昏迷和顱內(nèi)壓升高癥狀，嚴(yán)重可出現(xiàn)腦幕疝。如果低鈉血癥在48h內(nèi)發(fā)生，則有很大危險，可導(dǎo)致永久性神經(jīng)系統(tǒng)受損的后果。慢性低鈉血癥者，則有發(fā)生滲透性脫髓鞘的危險，特別在糾正低鈉血癥過分或過快時易于發(fā)生。除腦細(xì)胞水腫和顱高壓臨床表現(xiàn)外，由于血容量縮減，可出現(xiàn)血壓低、脈細(xì)速和循環(huán)衰竭，同時有失水的體征?？傮w鈉正常的

6、低鈉血癥則無腦水腫臨床表現(xiàn)。實驗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 (275-290 mM) 尿滲透壓（UOSM） :正常: 400-500 mM最大稀釋 50-100 mM (USG 1.002-1.003)最大濃縮 900-1200 mM (USG 1.030-1.040)濃縮尿: 500 mM (至少!), USG UOSM POSM is not enough to R/O Diabetes Insip

7、idus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 295 mOsm/kg高血糖或甘露醇的使用（高滲性低鈉血癥）如果在280-295 mOsm/kg之間 :假性低鈉血癥：高脂血癥或高蛋白血癥如果280 mOsm/kg評價容量狀態(tài)血漿滲透壓 280 mOsm/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

8、血癥的診斷思路 低鈉血癥的治療應(yīng)根據(jù)病因、低鈉血癥的類型、低鈉血癥發(fā)生的急慢及伴隨疾病而采取不同處理方法，故強(qiáng)調(diào)低鈉血癥的治療應(yīng)個別化，但總的治療措施包括： 去除病因； 糾正低鈉血癥； 對癥處理； 治療合并癥。 治 療低鈉血癥的糾正速度24小時內(nèi)升高10-12mmol/L，48小時內(nèi)血鈉升高18 mmol/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小時內(nèi)升高10-12mmol/L，48小時內(nèi)血鈉升高18 mmol/LVerbalis, Joseph

9、 G., Stephen R. Goldsmith, Arthur Greenberg, Robert W. Schrier, and Richard H. Sterns. Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations. The American Journal of Medicine 120 (2007): S1-S21.治 療慢性低鈉血癥 = 腦適應(yīng)重要是控制低鈉血癥的糾正速度 腦適應(yīng)性、細(xì)胞內(nèi)溶質(zhì)外溢血鈉糾正過快，大腦容易受損傷由于腦細(xì)胞不能重新攝取溶質(zhì)，細(xì)胞萎縮“中樞腦橋髓鞘溶解” / “滲透性

10、脫髓鞘作用” 大腦局限在顱內(nèi)，構(gòu)音困難、吞咽困難、癲癇、神智改變、四肢輕癱、低血壓1-3天內(nèi)糾正低鈉血癥24小時內(nèi)升高10-12mmol/L，48小時內(nèi)血鈉升高/= 4mEq/L :Conivaptan 40mg/day: 24 hoursConivaptan 80mg/day: 10 hoursPBO: no increase within 4 day infusionChange in serum Na from baseline to end of treatmentConivaptan 40mg/day: 6.3 mEq/LConivaptan 80mg/day: 9.4 mEq/LP

11、BO: 0.8 mEq/LPatients with increase in Na /=6mEq/L or Na /=135 mEq/LConivaptan 40mg/day: 69% (6.3)Conivaptan 80mg/day: 88.5% (23)PBO: 20.7% (6)Change in serum Na from Baseline to 6-9days post treatment :Conivaptan 40mg/day: 8.1mEq/L (n=13)Conivaptan 80mg/day: 4.7 mEq/L (n=26)PBO: 5.2 mEq/L (n=17)Ass

12、essment of the Efficacy and Safety of Intravenous Conivaptan in Euvolemic and Hypervolemic HyponatremiaDiscontinuation was mainly due to Infusion site reactionsOther ADRs: hypotension, postural hypotension, pyrexia, hyperkalemia, infusion site thrombosisProspective, multi-center, randomized centrall

13、y, double-blind, placebo controlledConducted 2 trials to assess reproducibility (SALT-1 & SALT-2)Tolvaptan 15mg tab 1 tab PO Daily x 30 days OR PBOImportant Patient Population Criteria:InclusionEtiologies: CHF, cirrhosis or SIADHExclusion Criteria:Other etiologiesHypovolemic hyponatremiaOther cardia

14、c diseases (post-MI, SVT, SBP90)Serum Na 120 mmol/L w/ neurological impairmentPoor prognosis not tolerating fluid shifts: short-term survivalTolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for HyponatremiaNew England Journal of Medicine 355 (2006): 2099-112Similar Baseline Characteri

15、stics across study groups (except height in SALT-2), Mean baseline Na: 128 mEq/LCo-Administration/Co-intervention: Fluid restriction was not mandatory; treatment with other agents were not allowed (demeclocycline, lithium, urea)Dose adjustments were made at the discretion of the investigator at Day

16、4 Drug was administered until day 30, final assessments done at day 37Values were statistically significantIncreases in Na were greater in Tolvaptan group than PBO in both trials and in both stratifications at Day 4 and much more at Day 30Increases were more rapid (by day 4) and greater (marked hypo

17、natremia)New England Journal of Medicine 355 (2006): 2099-112.Tolvaptan patients reached normal Na levels on day 4 and 30 more than PBODay 4: SALT-1 (40% vs 13%) SALT-2 (55% vs11%) Day 30: SALT-1 (53% vs 25%) SALT-2 (58% vs25%) Less “marked” hyponatremia Day 4: SALT-1 (13% vs 49%) SALT-2 (10% vs 40%

18、) Day 30: SALT-1 (7% vs 35%) SALT-2 (15% vs 32%) not sigSF-12 scoresShowed difference in “mental component summary” in “marked hyponatremia” patients, but not overallVitality, social functioning, calmness, sadnessNo difference in physical component summaryOTHER:Day 37 analysis: Na concentrations sho

19、wed no difference between each armTolvaptan (Samsca) Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia. New England Journal of Medicine 355 (2006): 2099-112.ADRMost common: Thirst (14%;5%); Dry mouth (13%;4%)Incidence: Tolvaptan: 171 patients PBO: 176, not all ADRs were deemed to be related to study drugweakness, nausea, constipation, peripheral edema, ascites, diarrhea, fatigue, vomitingTolvaptan: 8 patients withdrew due to ADR Rash, dysguesia, nocturia, urinary