低钠血症临床诊治进展

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1、1Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHPUMCH Clinical Endocrinology an

2、d Metabolism ForumEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症临床诊治进展低钠血症临床诊治进展顾顾 锋锋 岑晶岑晶 陈适陈适 中国医学科学院中国医学科学院&北京协和医学院北京协和医学院卫生部重点实验室卫生部重点实验室北京协和医院内分泌科北京协和医院内分泌科2Endocrinology Department & Ministry Endocrine

3、Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinolo

4、gy Department & Ministry Endocrine Key Laboratory, PUMCH内容提要内容提要低钠血症临床重要性低钠血症临床重要性低钠血症发病机制低钠血症发病机制低钠血症临床诊疗常规低钠血症临床诊疗常规低钠血症治疗及进展低钠血症治疗及进展3Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Mi

5、nistry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症临床重要性低钠血症临床重要性低钠血症临床重要性低钠血症临床重要性低钠血症发病机制低钠血症发病机制低钠血症临床诊疗常

6、规低钠血症临床诊疗常规低钠血症治疗及进展低钠血症治疗及进展4Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEn

7、docrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHp 基础疾病复杂，认识不足基础疾病复杂，认识不足p 急、慢性低钠血症临床表现、诊疗原则及预后不同急、慢性低钠血症临床表现、诊疗原则及预后不同p 慢性低钠血症非特异临床表现、容易误诊慢性低钠血症非特异临床表现、容易误诊p 抗利尿激素受体拮抗剂的治疗方案及应用前景抗利尿激素受体拮抗剂的治疗方案及应用前景低钠血症临床重要性低钠血症临床重要性

8、临床指南及关注问题临床指南及关注问题Joseph G. et al. Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations. The American Journal of Medicine, 2007. Vol 120 (11A), S1S215Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH

9、Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症临床最常见的水电解质紊乱严重急性低钠血症，致死率高慢性轻

10、度低钠血症，合并多种基础疾病，治疗不当或延误治疗时死亡率增加低钠血症过度治疗，导致严重的神经系统异常相关死亡率增加合并低钠血症的患者（包括轻度低钠血症），死亡率是正常人群的3 3 6060倍评价指标评价指标/ /人群人群发病率发病率血钠浓度血钠浓度 135mmol/l 135mmol/l151530%30%血钠浓度血钠浓度 125125？120-124120-12423% 23% 115-119115-11930% 30% 114 0.05 肌肉系统肌肉系统/11例例 12112mmol/l 1258mmol/l 0.05 腹部症状腹部症状(恶心、呕吐恶心、呕吐)/例例 12112mmol/l

11、 1258mmol/l 0.05 急诊急诊20(59%)重症监护重症监护3(9%)平诊平诊11(32%) 会诊时表现为低钠血症会诊时表现为低钠血症(共共34例例) 年龄年龄 51 20岁，岁， 女性女性21例，男性例，男性13例例 会诊时血钠值为会诊时血钠值为123.89.7mmol/l 明确原发或继发性肾上腺皮质功能减退史患者明确原发或继发性肾上腺皮质功能减退史患者 急诊急诊 15/20 平诊平诊/重症监护重症监护 4/14低钠血症临床重要性低钠血症临床重要性 PUMCH资料资料410Endocrinology Department & Ministry Endocrine Key Labo

12、ratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Depar

13、tment & Ministry Endocrine Key Laboratory, PUMCH低钠血症发病机制低钠血症发病机制低钠血症临床重要性低钠血症临床重要性低钠血症发病机制低钠血症发病机制低钠血症临床诊疗常规低钠血症临床诊疗常规低钠血症治疗及进展低钠血症治疗及进展11Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & M

14、inistry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH肾上腺皮质激素肾上腺皮质激素 甲状腺激素甲状腺激素 心钠素心钠素 脑钠素脑钠素 饮食饮食 渗透压中枢渗透压中枢 心、肝、心、肝、肾脏肾脏 抗利尿激素抗利尿激素 低钠血症发病机制低钠血症发病机制水钠平衡及其影响因素水钠平衡及其影响因素钠钠钠钠水水水水低低钠钠血血症症水钠平衡影响因素水钠平衡影响因素饮食12Endocrinology Department & Ministry Endocr

15、ine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocri

16、nology Department & Ministry Endocrine Key Laboratory, PUMCH 生理状态下血浆渗透压生理状态下血浆渗透压 280 295 mOsm/kg H2O 测定方法测定方法 freezing-point depression vapor pressure of pleasure Ion-selective electrodes（ISE）低钠血症发病机制低钠血症发病机制血浆渗透压血浆渗透压/ 有效渗透压有效渗透压2Na+(mmol/l)Glu(mg/dl)/18BUN (mg/dl)/2.8血浆总血浆总渗透压渗透压 血浆渗透压血浆渗透压 有效血浆渗

17、透压有效血浆渗透压13Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Departm

18、ent & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低血钠低血钠低血浆渗低血浆渗透压透压p 假性低钠血症假性低钠血症 (Pseudohyponatremia) 火焰光度测定法火焰光度测定法(Flame photometry) 测量测量NaNa+ += Na= Na 血浆容量血浆容量( (水水93% +93% +蛋白质蛋白质+ +脂肪脂肪 7%7%） 不影响渗透浓度不影响渗透浓度Ion-selective electrode

19、s（ISE）测量可避免测量可避免低钠血症低钠血症低渗性低渗性高渗性高渗性等渗性等渗性p 高渗性低钠血症高渗性低钠血症住院患者住院患者10-20% 葡萄糖或甘油等渗透性溶质葡萄糖或甘油等渗透性溶质将细胞内液体转移至细胞外将细胞内液体转移至细胞外稀释细胞外溶质，即血钠水平降低稀释细胞外溶质，即血钠水平降低直接测定血浆渗透压或校正直接测定血浆渗透压或校正Na+：NaNa+ (mmol/l) GluGlu (mg/dl)参考参考范围范围 (mg/dl)1.6 1.6 1001001001004002.42.4100100400400Reddy P and Mooradian A D. Diagnosi

20、s and management of hyponatraemia in hospitalised patients. Int J Clin Pract, 2009, 63 (10): 1494-1508 低钠血症发病机制低钠血症发病机制低钠血症与血浆渗透压注意问题低钠血症与血浆渗透压注意问题 14Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology De

21、partment & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低低钠钠血血 症症 低低 渗渗 等等/ /高渗高渗 高脂、糖、高脂、糖、高渗物质高渗物质 低血容低血容 非低血容非低血容 低钠血症发病机制低钠血症发病机制低钠血症分类低钠血症分类 原因：体内有其他增高渗透压的溶质原因：体内有其他增高渗透压的溶质诊断：直接测定血渗透压（诊断：直接测定血渗透压（280-295mOsm/H2O）治疗：血钠并不真低，不处理低钠治疗：血钠

22、并不真低，不处理低钠胃肠道、汗液、第三间隙丢失胃肠道、汗液、第三间隙丢失 肾脏丢失肾脏丢失 肾上腺皮质功能低减肾上腺皮质功能低减 脑耗盐综合症脑耗盐综合症失盐性肾病失盐性肾病利尿剂治疗：利尿剂治疗： 73% 73% 噻嗪，噻嗪，20%20%联用保钾利尿，联用保钾利尿，8%8%速尿速尿水摄入过多水摄入过多 心、肝脏功能障碍心、肝脏功能障碍肾水排泄不能肾水排泄不能 SIADH 糖皮质激素缺乏糖皮质激素缺乏 甲状腺功能减退甲状腺功能减退尿溶质排泄减少尿溶质排泄减少 15Endocrinology Department & Ministry Endocrine Key Laboratory, PUMC

23、HEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH等容量或高容量性等容量或高容量性非低容量性非低容量性低钠血症低钠血症 心、肝脏功能障碍心、肝脏功能障碍 肾水排泄异常肾水排泄异常 SIADH 甲状腺功能减退甲状腺功能减退 糖皮质激素缺乏糖皮质激素

24、缺乏 尿溶质排泄减少尿溶质排泄减少 水摄入过多水摄入过多 ADH过量造成肾远端小管重吸收水增多过量造成肾远端小管重吸收水增多水中毒水中毒稀释性低钠血症稀释性低钠血症容量不低容量不低细胞外液扩张细胞外液扩张低钠血症低钠血症(130mmol/l) 低血渗低血渗(20mmol/l)高尿渗高尿渗(100mmol/l) 心钠素分泌增加，促进排钠心钠素分泌增加，促进排钠肾素肾素-血管紧张素血管紧张素-醛固酮系统受抑制醛固酮系统受抑制醛固酮保钠作用下降醛固酮保钠作用下降 低钠血症发病机制低钠血症发病机制SIADH16Endocrinology Department & Ministry Endocrine

25、Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinolo

26、gy Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症发病机制低钠血症发病机制SIADH病因病因1CNS CNS 疾病疾病恶性肿瘤恶性肿瘤肺部疾病肺部疾病其其 它它药药 物物中枢神经系统中枢神经系统(CNS)(CNS)疾病疾病感染感染脑膜炎，脑炎，脓肿，脑膜炎，脑炎，脓肿，AIDSAIDS血管血管性和颅性和颅内占位内占位血栓，蛛网膜下腔或硬脑膜下血肿血栓，蛛网膜下腔或硬脑膜下血肿颅脑肿瘤、头颅外伤、脑积水颅脑肿瘤、头颅外伤、脑积水其他其他格林格林- -巴利综合征，巴利综合征，急性间歇性卟啉病急性间歇性卟啉病，自主性，自主性神经病

27、变神经病变垂体垂体术后术后，多发性硬化，精神病，多发性硬化，精神病恶性肿瘤恶性肿瘤癌癌肺肺小细胞肺癌小细胞肺癌( (燕麦细胞癌燕麦细胞癌) )（11-33%11-33%）、支气管类癌支气管类癌、间皮瘤间皮瘤口咽部口咽部胃肠道胃肠道胃、十二指肠、胰腺胃、十二指肠、胰腺生殖泌尿系统生殖泌尿系统尿道、膀胱、前列腺、子宫内膜尿道、膀胱、前列腺、子宫内膜内分泌胸腺内分泌胸腺肉瘤肉瘤Ewings 肉瘤肉瘤其它其它淋巴瘤、白血病淋巴瘤、白血病SIADH17Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinol

28、ogy Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocr

29、ine Key Laboratory, PUMCHCNSCNS疾病疾病恶性肿瘤恶性肿瘤肺部疾病肺部疾病其其 它它药药 物物药物药物化疗药物：环磷酰胺、长春新碱、长春碱化疗药物：环磷酰胺、长春新碱、长春碱抗精神病药：甲哌硫丙硫蒽、甲硫达嗪、氟哌啶醇抗精神病药：甲哌硫丙硫蒽、甲硫达嗪、氟哌啶醇抗抑郁药：单胺氧化酶抑制剂、三环类抗抑郁药：单胺氧化酶抑制剂、三环类抗、抗、选择性选择性5-5-HTHT摄取摄取抑制剂抑制剂 ADH增效剂：氯磺丙脲、甲苯磺丁脲、卡马西平、环磷酰胺增效剂：氯磺丙脲、甲苯磺丁脲、卡马西平、环磷酰胺外源给予外源给予ADHADH类似物（去氨加压素、血管紧张素、催产素）类似物（去氨加

30、压素、血管紧张素、催产素）其他：溴隐亭、其他：溴隐亭、3-MDMA、非甾体类抗炎药、非甾体类抗炎药肺部疾病肺部疾病肺部感染、肺结核、囊性纤维化、急性呼吸衰竭、正压通气、肺部感染、肺结核、囊性纤维化、急性呼吸衰竭、正压通气、哮喘哮喘 肺不张肺不张其它其它遗传性遗传性 NSIAD特发性特发性暂时性暂时性 强体力运动、麻醉、严重恶性、术后疼痛、应激等强体力运动、麻醉、严重恶性、术后疼痛、应激等.SIADH低钠血症发病机制低钠血症发病机制SIADH病因病因218Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndo

31、crinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry

32、Endocrine Key Laboratory, PUMCH北京协和医院北京协和医院2008-20092008-2009年入院诊治肺癌患者年入院诊治肺癌患者610610例例来诊时血钠下降者来诊时血钠下降者2727例（例（4.4%4.4%）小细胞肺癌小细胞肺癌41.7%鳞癌鳞癌37.1%腺癌腺癌22.2%肺癌病理类型肺癌病理类型陈适，顾锋陈适，顾锋 等等. .初诊时表现为低钠血症的肺癌初诊时表现为低钠血症的肺癌2727例临床特点分析例临床特点分析. .中国实用内科杂志。中国实用内科杂志。 20102010，9 9（3030）：）：803-804.803-804.低钠血症发病机制低钠血症发病机制

33、SIADH病因病因(肺癌肺癌)PUMCH 资料资料12727例患者基本情况例患者基本情况年龄年龄 (岁岁) 616113 病程病程 (月月) 1 1（6-12） 男男/女女 21/6 21/6 血钠血钠 (mmol/L) 129.1129.14.8 化疗效果（化疗效果（15例）例） 血钠正常血钠正常/未正常未正常 1-10 1-10 疗程疗程 8/7 8/7 19Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key

34、Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH相对低钠组相对低钠组 (130

35、 mmol/l) 例数例数 14例例 13例例 来诊年龄来诊年龄(岁岁) 5915 6410 病程病程(月月) 1 (1,2.5) 1 (1,2) 男男/女女(例例) 11/3 10/3 吸烟史吸烟史(例例)* 13 8 肺癌家族史肺癌家族史(例例) 1 2 小细胞肺癌小细胞肺癌(例例)* 9 2 肺门部占位肺门部占位(例例) 12 9 肿瘤直径肿瘤直径(cm) 6.02.1 6.22.1 脑转移脑转移(例例) 4/10 1/11 骨转移骨转移(例例) 4 5 陈适，顾锋陈适，顾锋 ，等，等. .初诊时表现为低钠血症的肺癌初诊时表现为低钠血症的肺癌2727例临床特点分析例临床特点分析. .中国

36、实用内科杂志。中国实用内科杂志。 20102010，9 9（3030）：）：803-804.803-804. 低钠血症是肺癌的临床表现之一低钠血症是肺癌的临床表现之一, , 在小细胞肺癌中比例更高在小细胞肺癌中比例更高 肺癌脑转移的患者低钠血症也有较严重的趋势肺癌脑转移的患者低钠血症也有较严重的趋势, , 常规化疗对纠正患者血钠疗效不佳常规化疗对纠正患者血钠疗效不佳* P0,05* P10=10倍倍 下丘脑无血脑屏障保护下丘脑无血脑屏障保护 ALA ALA与卟胆原具有神经毒性与卟胆原具有神经毒性 作用于下丘脑视上核与室旁作用于下丘脑视上核与室旁核核 ADH ADH不适当分泌不适当分泌低钠血症发

37、病机制低钠血症发病机制SIADH(急性间歇性卟啉病急性间歇性卟啉病)22Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, P

38、UMCH 急性间歇性卟啉病急性间歇性卟啉病 抗利尿激素不适当分泌综合征抗利尿激素不适当分泌综合征 低钠血症低钠血症青年女性，隐匿起病，慢性病程，急性加重青年女性，隐匿起病，慢性病程，急性加重间断腹痛间断腹痛5 5年，加重一周，反复抽搐年，加重一周，反复抽搐3 3天天 本次腹痛重，伴恶心、呕吐、便秘，尿色变深本次腹痛重，伴恶心、呕吐、便秘，尿色变深反复抽搐，血钠最低反复抽搐，血钠最低101mmol/l101mmol/l，血压最高，血压最高170/110mmHg 170/110mmHg ，HR120bpmHR120bpm，伴大量出汗伴大量出汗无铅接触史，父亲亦有腹部剧痛史无铅接触史，父亲亦有腹部剧

39、痛史血钠低时尿钠血钠低时尿钠40mmol/l40mmol/l，甲功正常，血，甲功正常，血F F不低不低日光晒尿（日光晒尿（+ +），尿卟胆原（），尿卟胆原（+ +），尿卟啉（），尿卟啉（- -）血红血红细胞锌卟啉原基本正常细胞锌卟啉原基本正常低钠血症发病机制低钠血症发病机制PUMCH case23Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Dep

40、artment & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症发病机制低钠血症发病机制CSW vs.SIADH脑损伤脑损伤 心血管系统心血管系统 肾脏肾脏 肾脏失盐肾脏失盐 脑钠素脑钠素 心钠素心钠素肾上腺素能肾上腺素能活性增强活性增强肾灌注增加肾灌注增加 肾上腺皮质激素？肾上腺皮质激素？ 不由肾上腺皮质激素介导不由肾上腺皮质激素介导的肾上腺皮质功能亢进的肾上腺皮质功能亢进?CSW (cerebral salt wa

41、sting)n 常见于头颅外伤或手术后常见于头颅外伤或手术后n 尿排钠和排氯首先增加，尿排钠和排氯首先增加，ADHADH继发性升高继发性升高n 治疗目的治疗目的 纠正低钠血症纠正低钠血症 改善低血容量改善低血容量n 明确诊断明确诊断CSWCSW或或SIADHSIADH非常重要非常重要 不同的发病机制及治疗原则不同的发病机制及治疗原则SIADH CSW 细胞外液细胞外液 正常或增多正常或增多 减低减低 尿钠水平尿钠水平 30mmol/l 30mmol/l 血尿酸血尿酸 降低，但血钠纠正后可正常降低，但血钠纠正后可正常 降低，血钠纠正后仍不正常降低，血钠纠正后仍不正常 尿渗透压尿渗透压 增高增高

42、增高增高 血渗透压血渗透压 降低降低 降低降低 血血BUN/CR 正常或降低正常或降低 增高增高 血钾血钾 正常正常 正常或增高正常或增高 中心静脉压中心静脉压 正常或增高正常或增高 降低降低6mmHg 肺动脉楔压肺动脉楔压 正常或增高正常或增高 降低降低120 mmol/LNa120 mmol/LNaNa 115 115-120-120mmol/Lmmol/L血血NaNa 110 4L)(4L)或减少或减少 既往存在的内分泌疾病既往存在的内分泌疾病 原发或继发性肾上腺皮质功原发或继发性肾上腺皮质功 能能/ /甲状腺功能减退甲状腺功能减退 既往颅脑损伤、放疗既往颅脑损伤、放疗 既往垂体既往垂体

43、/ /甲状腺手术甲状腺手术血容量的判断（综合判断） 1.1. 临床征象：体位性低血压，心率，皮肤干燥临床征象：体位性低血压，心率，皮肤干燥2.2. 血液动力学指标：中心静脉压，肺血液动力学指标：中心静脉压，肺A A楔压楔压3.3. BUN/CRBUN/CR值，值，HCTHCT值，值，BNPBNP值值4.4. RAASRAAS系统系统5.5. 低血钠时，随机尿钠浓度低血钠时，随机尿钠浓度30mmol/l30mmol/l6.6. 补液试验（补液试验（500ml500ml1000ml NS 1000ml NS ）低钠血症临床诊疗常规低钠血症临床诊疗常规诊治要点诊治要点29Endocrinology

44、Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine

45、Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症治疗及进展低钠血症治疗及进展低钠血症概况低钠血症概况低钠血症发病机制低钠血症发病机制低钠血症临床诊疗常规低钠血症临床诊疗常规低钠血症治疗及进展低钠血症治疗及进展30Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laborator

46、y, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH个体化治疗方案！个体化治疗方案！低钠血症相关并发

47、症低钠血症相关并发症快速纠正低血钠快速纠正低血钠 神经系统脱髓鞘神经系统脱髓鞘疾病疾病低钠血症严重程度低钠血症严重程度低钠血症病程低钠血症病程神经系统症状神经系统症状低钠血症治疗及进展低钠血症治疗及进展31Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, P

48、UMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症及其治疗相关并发症低钠血症及其治疗相关并发症未治疗未治疗 低钠血症性脑病、脑疝低钠血症性脑病、脑疝低钠血低钠血症相关症相关并发症并发症快速纠正低血钠快速纠正低血钠 神经系神经系统脱髓

49、鞘疾病统脱髓鞘疾病低钠血症治疗及进展低钠血症治疗及进展低钠血症相关并发症低钠血症相关并发症 急性低钠血症（急性低钠血症（484848小时）小时） 脑细胞排出有机溶质脑细胞排出有机溶质 死亡死亡 重新建立平衡重新建立平衡 32Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Labo

50、ratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低钠血症及其治疗相关并发症低钠血症及其治疗相关并发症过快纠正低钠血症过快纠正低钠血症 渗透性神经系统脱髓鞘疾病渗透性神经系统脱髓鞘疾病慢性低钠血症患者，快速补钠后，逆转细胞

51、内外渗透梯度慢性低钠血症患者，快速补钠后，逆转细胞内外渗透梯度 引起脑细胞脱水及萎缩，从而引起中央脑桥脱髓鞘症引起脑细胞脱水及萎缩，从而引起中央脑桥脱髓鞘症临床表现临床表现 神志改变、惊厥、肺换气不足、低血压神志改变、惊厥、肺换气不足、低血压 最终出现假性延髓麻痹、四肢瘫痪、吞咽困难最终出现假性延髓麻痹、四肢瘫痪、吞咽困难低钠血症相关低钠血症相关并发症并发症快速纠正快速纠正低血钠低血钠 神经系神经系统脱髓鞘统脱髓鞘疾病疾病低钠血症治疗及进展低钠血症治疗及进展过快纠正低血钠过快纠正低血钠(相关并发症相关并发症)33Endocrinology Department & Ministry Endoc

52、rine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHT2高信号高信号 髓磷脂髓磷脂 常见于脑桥中央，同时也可影响其他白质区，致基底节区/胼胝体/大脑白质脱髓鞘 2007年低钠血症指南要求 24小时内

53、增加小于10-12mmol/L 48小时内增加小于18mmol/L低钠血症治疗及进展低钠血症治疗及进展过快纠正低血钠过快纠正低血钠(渗透性脱髓鞘渗透性脱髓鞘)34Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Depa

54、rtment & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH低血容量性低血容量性 SIADH甲状腺甲状腺功能减退功能减退肾上腺肾上腺皮质皮质功能减功能减退退CSW针对不同发病机制针对不同发病机制个体化治疗方案个体化治疗方案低钠血症低钠血症低钠血症治疗及进展低钠血症治疗及进展传统个体化治疗方案传

55、统个体化治疗方案35Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH补容量补容量等渗盐水等渗盐水低容量性低容量性

56、 低钠血症低钠血症胃肠道，失汗胃肠道，失汗利尿剂（停药）利尿剂（停药） 脑性耗盐综合征脑性耗盐综合征 盐皮质激素缺乏盐皮质激素缺乏 补液公式：补液公式： 补钠量：补钠量： 男男 （142-Na142-Na） 体重体重0.6 0.6 mmolmmol 女女 （142-Na142-Na） 体重体重0.5 0.5 mmolmmol NS NSmmolmmol58.5/958.5/9mlml，先先1/31/3，后视情况而定，后视情况而定 血血NaNa：120mmol/L 4500mlNS 46g120mmol/L 4500mlNS 46g 血血NaNa：130mmol/l 3000mlNS 30g13

57、0mmol/l 3000mlNS 30g低钠血症治疗及进展低钠血症治疗及进展低血容量性低血容量性 (补充容量）补充容量）36Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry E

58、ndocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH限水限水如果低钠血症严重持续存在，或患者不配合限水，联合药物治疗如果低钠血症严重持续存在，或患者不配合限水，联合药物治疗传统治疗药物传统治疗药物抗利尿激素受体拮抗剂使用（有适应症时）抗利尿激素受体拮抗剂使用（有适应症时）药物药物剂量剂量副作用副作用地美环素地美环素300-

59、600mg Bid可逆性氮质血症、可逆性氮质血症、肾毒性肾毒性；需要监测测肾功能需要监测测肾功能尿素尿素15-60g Qd大剂量时氮质血症，服药不方便大剂量时氮质血症，服药不方便The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options. 2011低钠血症治疗及进展低钠血症治疗及进展SIADH3%3%高渗盐高渗盐 计算：计算：kgkg预想升高的预想升高的NaNa浓度浓度/mmol/hr /mmol/hr （70kg70kg，预想升高，预想

60、升高1mmol/l1mmol/l，则，则70mmol/hr70mmol/hr） 符合以下条件时，符合以下条件时，终止快速治疗终止快速治疗 症状消失症状消失 Na Na升至升至120mmol/l120mmol/l 纠正至纠正至10-12mmol/l10-12mmol/l的日限的日限 治疗过程中每治疗过程中每2 2小时测血小时测血NaNa一次；一次； 注意心衰注意心衰，若预计会心衰，可用，若预计会心衰，可用20-40mg20-40mg速尿速尿急急症症非非急急症症37Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCH

61、Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCH 补容量糖（盐）皮质激素的使用糖（盐）皮质激素的使用 小应激小应激 发热发热3838摄氏度，小手术、外伤摄氏度，小手术、外伤 增加一倍增加一倍 中应激中应激 发热发热3939摄氏度，中手术、外伤摄氏

62、度，中手术、外伤 氢可氢可50-100mg/d 50-100mg/d 大应激大应激 发热发热4040摄氏度，大手术、外伤摄氏度，大手术、外伤 氢可氢可100-200mg/d100-200mg/d氢化可的松氢化可的松 20-30mg/day20-30mg/day（强的松（强的松5-7.5mg/5-7.5mg/日）早日）早8AM, 8AM, 下午下午5 56 6点点 分服分服个体化原则个体化原则 临床表现：恶心、呕吐、纳差、高热、脱水、低血压临床表现：恶心、呕吐、纳差、高热、脱水、低血压 低血钠、低血糖、神志萎靡低血钠、低血糖、神志萎靡 处处 理：琥氢可理：琥氢可 100mg iv 100mg i

63、v stst，初始，初始2424小时小时200-400mg200-400mg 控制后，次日减半，控制后，次日减半，4-54-5日至维持量日至维持量 低钠血症治疗及进展低钠血症治疗及进展肾上腺皮质肾上腺皮质/甲状腺功能减退甲状腺功能减退无危象无危象危危 象象甲状腺功能减退甲状腺功能减退 甲状腺激素中度限液甲状腺激素中度限液肾上腺皮质功能减退肾上腺皮质功能减退38Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key La

64、boratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHVaptans(Vasopress

65、in antagonist)-抗利尿激素受体拮抗剂抗利尿激素受体拮抗剂Vaptans+V2R 阻断腺苷酸环化酶信号途径阻断腺苷酸环化酶信号途径排自由水排自由水 对尿钠、尿钾无作用对尿钠、尿钾无作用低钠血症治疗及进展低钠血症治疗及进展Vaptans作用机制作用机制管腔侧管腔侧基底侧基底侧V2RVaptansVeeraveedu P T, Palaniyandi S S, Yamaguchi K i et al. Arginine vasopressin receptor antagonists (vaptans): pharmacological tools and potential ther

66、apeutic agents. Drug Discovery Today, 2010, 15 (19-20): 826-841.39Endocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHEndocrinology Department & Ministry Endocrine Key Laboratory, PUMCHVeeraveedu PT, Palaniyandi SS, Y