内分泌高血压幻灯中课件.ppt
激素与高血压,曾正陪北京协和医院内分泌科,内分泌高血压幻灯中,1,激素与高血压曾正陪内分泌高血压幻灯中1,激素/血管活性物质与高血压,容量和/或血压 肾素-血管紧张素-醛固酮系统（RAAS）儿茶酚胺(E,NE)盐皮质激素(Aldo,DOC,B,et al)糖皮质激素(F,et al)内皮素(ET)肾上腺紧张素（Adrenotensin）内皮收缩因子(EDCF),内分泌高血压幻灯中,2,激素/血管活性物质与高血压容量和/或血压内分泌高血压幻灯中2,激素/血管活性物质与高血压,容量和/或血压 胰岛素抵抗 生长激素(GH)催乳素(PRL)血管加压素(AVP)甲状旁腺高血压因子(PHF)神经肽 Y(NPY)内源性洋地黄素（Ouabain）口服避孕药 甘草,内分泌高血压幻灯中,3,激素/血管活性物质与高血压容量和/或血压内分泌高血压幻灯中3,内分泌高血压幻灯中,4,内分泌高血压幻灯中4,激素/血管活性物质与高血压,容量和/或血压 降钙素基因相关肽(CGRP)心钠素(ANP)脑钠素(BNP)C-型利钠肽(CNP)肾上腺髓质素(AM)缓激肽（Bradykinin）降钙素 P 物质(Substance P),内分泌高血压幻灯中,5,激素/血管活性物质与高血压容量和/或血压,激素/血管活性物质与高血压,容量和/或血压 前列环素(PGI2)一氧化氮(NO)一氧化碳(CO)内皮舒张因子(EDRF)内皮超极化因子(EDHF),内分泌高血压幻灯中,6,激素/血管活性物质与高血压容量和/或血压内分泌高血压幻灯中6,内分泌高血压幻灯中,7,内分泌高血压幻灯中7,激素/血管活性物质与高血压,Increased Renin Angiotensin Aldosterone Cortisol Catecholamine Endothelin EDCF GH PHF NPY Vasopressin,Decreased prostacyclin CGRP Adrenomedullin ANP,BNP,CNP EDRF Bradykinin NO CO PTH Substance P EDHF,BP,内分泌高血压幻灯中,8,激素/血管活性物质与高血压Increased R,心血管激素与高血压 ANP ET-1 BNP eNOS HO-2 CNP,AM,NP,ET,NO,CO,VASOCONSTRICTION,VASODILATATION,内分泌高血压幻灯中,9,心血管激素与高血压,心血管激素通过内分泌/旁分泌/自分泌机制 调节心血管的功能和结构,ANPBNP,Endothelin(ET)CNP/AdrenomedullinNitric oxide(NO)Carbon monoxide(CO),内分泌高血压幻灯中,10,心血管激素通过内分泌/旁分泌/自分泌机制ANPEn,心血管内分泌代谢学 Cardiovascular Endocrinology&Metabolism Heart-传统的循环器官&重要的内分泌腺 Endothelium-做为体内最大的内分泌腺体具有分泌功能 第一届国际心血管内分泌代谢学大会 The First International Conference of Cardiovascular Endocrinology and Metabolism(CVEM)已于1998年在日本举行.,内分泌高血压幻灯中,11,心血管内分泌代谢学内分泌高血压幻灯中11,Rethink Treatment,Hypertension is a Disease of Blood Vessels Vascular Biology is Altered(Structural and Functional)Target the VasculatureRisk Factors(Traditional)Risk Factors(Nontraditional-Vascular Biology)Target Organs-Optimal Treatment,内分泌高血压幻灯中,12,Rethink Treatment Hyperte,The Blood Vessel is an Organ,Largest Organ in the Body5 x Heart in Mass6 Tennis Courts in Area,内分泌高血压幻灯中,13,The Blood Vessel is an Organ内分,The Vascular System RegulatesVascular Health and Tone ThroughChronic Active Balance Between:,Vasoconstrictors VasodilatorsGrowth Promoters Growth Inhibitors_ Vascular Tone Vascular Health(Damage),内分泌高血压幻灯中,14,The Vascular System Regulates,A new type of secondary hypertension Endothelin-secreting malignant hemangioendothelioma(Yokokawa et al,1991)Case 1.80 yr.F,Headache,nodule on scalp,HT(180/90)Case 2.74 yr.F,ibid.HT(160/106),Plasma ir-ET 10 fold Plasma ir-ET and BP after surgery immunostaining of ET(+)ir-ET in tissue extract(+)ET-mRNA expression(+),内分泌高血压幻灯中,15,A new type of secondary hyp,内分泌性高血压-非肾上腺性高血压,肾素 肾血管性高血压 肾素分泌瘤内皮素 恶性血管内皮瘤生长激素、生长介素 肢端肥大症、巨人症 T3,T4 甲状腺功能亢进症PTH,PHF 甲状旁腺功能亢进症口服避孕药 女性高血压内皮功能受损 糖尿病血管损伤 甲状腺功能减退症,糖尿病,激素,疾病,内分泌高血压幻灯中,16,内分泌性高血压-非肾上腺性高血压肾素,内分泌性高血压-肾上腺性高血压,醛固酮 原发性醛固酮增多症皮质醇 库欣综合症皮质酮 皮质酮瘤去氧皮质酮 去氧皮质酮瘤 17-羟化酶缺乏症 11-羟化酶缺乏症 儿茶酚胺 嗜铬细胞瘤,激素,疾病,内分泌高血压幻灯中,17,内分泌性高血压-肾上腺性高血压,内分泌性高血压,激素 机制 疾病NE PR CO HR 嗜铬细胞瘤ALDO PV CO PR 原发性醛固酮增多症 F CO PR 库欣综合症AT II CO PR 肾素分泌瘤ET PR para/endo/autocrine 恶性血管内皮瘤,PR:peripheral resistance,PV:plasma volume,CO:cardiac output,内分泌高血压幻灯中,18,内分泌性高,原发性醛固酮增多症 醛固酮瘤 aldosterone-producing adenoma(APA)特发性醛固酮增多症 idiopathic hyperaldosteronism(IHA)糖皮质激素可抑制性醛固酮增多症 glucocorticoid-suppressible hyperaldosteronism(GSH)醛固酮癌 aldosterone-producing adrenal carcinoma 异位醛固酮瘤 ectopic aldosterone-producing adenoma 原发性肾上腺增生症 primary adrenal hyperplasia(PAH)肾素有反应性醛固酮腺瘤aldosterone-producing renin responsive adenoma(AP-RA),病因学,内分泌高血压幻灯中,19,原发性醛固酮增多症病因学内,原发性醛固酮增多症,1、高血压 缓慢发展的良性过程，少数为恶性高血压 一般降压药效果不好 眼底变化与高血压程度不平行 病程长者可出现心、脑、肾等并发症,临床表现,内分泌高血压幻灯中,20,原发性醛固酮增多症临床表现内分泌高血压幻灯中20,原发性醛固酮增多症,临床表现,2、高尿钾、低血钾 血钾25mmol/24h 20mmol/24h 低钾血症 软瘫、乏力、周期性麻痹 ECG-U波、心律失常 多尿、夜尿量日尿量 碱中毒、手足麻木、抽搐 肾功不全,内分泌高血压幻灯中,21,原发性醛固酮增多症临床表现2、高尿钾、低血钾内分泌高血压幻灯,原发性醛固酮增多症,临床表现,3、糖耐量减退或糖尿病4、儿童生长发育障碍5、散发性或家族性,内分泌高血压幻灯中,22,原发性醛固酮增多症临床表现3、糖耐量减退或糖尿病内分泌高血压,原发性醛固酮增多症,血清钾浓度 尿钾水平 醛固酮/肾素活性 比值 Captopril 试验,筛选试验,内分泌高血压幻灯中,23,原发性醛固酮增多症筛选试验内分泌高,原发性醛固酮增多症,Aldosterone Plasma Renin Activity Cortisol-normal 18-hydroxycorticosterone(18-OHB)APA,PAH 100ng/dl IHA,EH 100ng/dl,诊断,内分泌高血压幻灯中,24,原发性醛固酮增多症诊断内分泌高血压幻灯中24,原发性醛固酮增多症,CT scan-首选，薄层扫描（2-3mm)MRI-价格贵,不如 CT清楚 I 131-6-b-iodomethylnorcholesterol(NP-59)扫描 肾上腺静脉插管取血 18-OHB,18-OHF测定,定位诊断,内分泌高血压幻灯中,25,原发性醛固酮增多症 CT sc,原发性醛固酮增多症,钙通道阻滞剂（CCB）安体舒通（Spironolactone）氯化钾制剂 阿米诺利（Amiloride）手术-APA,PAH 地塞米松-GSH,治疗,内分泌高血压幻灯中,26,原发性醛固酮增多症,原发性醛固酮增多症,除有严重的心、脑、肾等血管病变外，大多数原醛腺瘤病人术后病情可缓解或治愈 术后低血钾的纠正较快而血压恢复较慢 IHA及GSH病人需终生服药,预后,内分泌高血压幻灯中,27,原发性醛固酮增多症,嗜铬细胞瘤（Pheochromocytoma）,诊断的临床思路病史:发作性症状 三联征:头痛、心悸、多汗 体位性低血压 难治性高血压 家族史：嗜铬细胞瘤 Von Hippel-Lindau Syndrome MEN,内分泌高血压幻灯中,28,嗜铬细胞瘤（Pheochromocytoma）内分泌高血,嗜铬细胞瘤（Pheochromocytoma）,诊断的临床思路 体格检查:不稳定性、难治性高血压 体位性低血压 VHLS-或 MEN-相关体征,内分泌高血压幻灯中,29,嗜铬细胞瘤（Pheochromocytoma）内分泌高,嗜铬细胞瘤（Pheochromocytoma）,激素测定 尿儿茶酚胺(NE,E,DA)代谢产物(VMA,MN,NMN)血浆儿茶酚胺(NE,E,DA)Clonidine 抑制试验(if plasma CA 1000-2000pg/ml)血浆嗜铬粒蛋白 A(chromogranin A),内分泌高血压幻灯中,30,嗜铬细胞瘤（Pheochromocytoma）激素测定内分泌,嗜铬细胞瘤（Pheochromocytoma）,解剖定位 形态学:(most sensitive,less specific)CT MRI 形态学与功能:(most specific,less sensitive)131I-metaiodobenzylguanidine(MIBG),内分泌高血压幻灯中,31,嗜铬细胞瘤（Pheochromocytoma）内分泌,嗜铬细胞瘤 Pheochromocytoma,药理学诊断试验 Clonidine 抑制试验 plasma catecholamine 1000-2000pg/ml clonidine 0.3mg Regitine 抑制试验 BP170/110 mmHg regitine 5mg Glucagon 激发试验 glucagon 1mg,内分泌高血压幻灯中,32,嗜铬细胞瘤 Pheochromocy,嗜铬细胞瘤（Pheochromocytoma）,药物治疗-adrenergic blockade phentolamine 1+2 phenoxybenzamine 1 2 prazosin 1 urapidil 1 2-adrenergic blockade propranolol 1+2 atenolol 1 2 esmolol 1 calcium channel blockades ACE inhibitors nitroprusside,内分泌高血压幻灯中,33,嗜铬细胞瘤（Pheochromocytom,嗜铬细胞瘤（Pheochromocytoma）治疗,131-I-MIBG-甲基酪氨酸（-methyl paratyrosine）血液动力学监测（Hemadynamic monitor）血容量补充手术,内分泌高血压幻灯中,34,嗜铬细胞瘤（Pheochromocytoma）内分泌高血压幻,嗜铬细胞瘤Pheochromocytoma rule of 10s 10%双侧 10%肾上腺外 10%腹腔外 10%恶性 10%家族性 10%儿童 10%血压正常,内分泌高血压幻灯中,35,嗜铬细胞瘤Pheochromocytoma内分泌高血压幻灯中,Characteristics of Endocrine Hypertension,Morbidity-1.1%,4.7-7.9%,more?Etiology-hormones secrete abnormal Pathogenesis-effects of hormones on PVR,CO,CI,HR,VSMC,et al.Curability-remove tumor,内分泌高血压幻灯中,36,Characteristics of End,Think it firstDiagnose it earlyTreat it correctlyCure it probably,Endocrine Hypertension,内分泌高血压幻灯中,37,Think it firstEndocrine Hypert,内分泌高血压幻灯中,38,内分泌高血压幻灯中38,
