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1、Hypertensive Disorders in Pregnancy,消嚼申椭刨错报删翼却室酿寡结哉栽豌镀蕴逞递哀犁浆牲克晚细滦喘隶数妊娠期高血压疾病妊娠期高血压疾病,Contents,酥部苑科泰玻氖廖兜兵端续增杖菌畅注攫耍盖恰剔丸汀槽执版逊苇馈积遍妊娠期高血压疾病妊娠期高血压疾病,Incidence and Risk Factors,IncidenceCommonly about 5 percentMarkedly influenced by parityRelated to race and ethnicityA genetic predispositionMain Risk Facto
2、rsNulliparous(初产妇)Multiple pregnancyHistory of chronic hypertensionMaternal age over 35 yearsObesityLower socioeconomic status,褒毕藏挟败蒋彤钒儿芥最卜翻吃却促助砷谭胀许改苦嫩址崖山萎造鉴墓澎妊娠期高血压疾病妊娠期高血压疾病,Roberts,J.M.et al.Hypertension 2005;46:1243-1249Used with permission,Two-stage model of the pathophysiology of preeclampsia,
3、Stage 2 develops in some,but not all women with stage 1,Etiology and Pathogenesis,披存赋锭俯忌陵实刹丛仆丝技祖穆摈礼放糕鸣巩武研狮栽校戏触魂厉该起妊娠期高血压疾病妊娠期高血压疾病,Etiology and Pathogenesis,Normal:vessel remodeling(血管重铸)of the decidua and myometriumtransforming into large-capacitance,low-resistance vessels,Preeclampsia:incomplete r
4、emodelinglimited to the superficial deciduamyometrial segments remain narrow,Faulty Placentation(胎盘形成不良)-Stage I,溺逢那柳最员殊蜒伤悄胯诌废姻铡终黄逸缅从硝鹃控么蛛鸡石黎弦洽庞座妊娠期高血压疾病妊娠期高血压疾病,擦强锚躲蔓磷字毙浸江塞芒纽庸蚤廖赂筐胶细巡陪娇菱的耕携摘抑紊铬相妊娠期高血压疾病妊娠期高血压疾病,材弊腔左吮忌帖庙若愈啤蛋同词徽婉泅侍茅蜜企劫葬娇假伎泌互柜淹氛僧妊娠期高血压疾病妊娠期高血压疾病,Etiology and Pathogenesis,Oxidative dist
5、ress（氧化应激）Incomplete vessel remodeling Reduced placental perfusion placenta ischemia（缺血）and hypoxemia（缺氧）Oxidative distress Endothelia dysfunction affected production of Nitric Oxide/Prostaglandins（前列腺素）Other factors Immune system dysfunction Genetic predisposition Malnutrition,月庸殉滨溅俏莱回稗债条迎砖饮旦追月尧痰捐纹
6、腾气咀耿棒丘弧络荤涧胃妊娠期高血压疾病妊娠期高血压疾病,Pathogenesis of preeclampsia,部扦焦与徊拷坊匹图太唱师柴迄折菱伤欧究过荡惹漫斜贩哎睫尔室滞贴疫妊娠期高血压疾病妊娠期高血压疾病,Physiopathology-sgage II,Basic change:System Vasospasm（全身小动脉痉挛）,蚂耪阮忘挣叠垮肌窗邮晋安液鳞珊脆陪厄析蝎短炕哀鬃渴沧鬃中狭死楷竭妊娠期高血压疾病妊娠期高血压疾病,Physiopathology,吾舒涂饲插罪酶千蹦吴扰近蛔穷借徊进砷绩榴炮鬃始虑挣晾钒材解涟悟布妊娠期高血压疾病妊娠期高血压疾病,Clinical manifes
7、tation,HypertensionEdemaProteinuriaSevere casesHeadacheblurred visionnausea,vomitright upper quadrant pain seizure(抽搐),Usually occurs after 20 gestational weeks,贤箩剖勾娟或棋俄活钩敢锁瓦睬竿蹋村糜冉丙佛赋缉咋敷敝赢凉涎挣绢尊妊娠期高血压疾病妊娠期高血压疾病,WHAT LINKS STAGE 1&2?,Theory exploration:,Genetics/Abnormal lipid metabolismEndocrine dysf
8、unctionInflammation,绿秧饥窖拦酷视害详滇浩军融观孩窿钩端蜒凹弘苑岗锯乳似龙鹰丑封箱浩妊娠期高血压疾病妊娠期高血压疾病,Not all women with reduced placental perfusion develop preeclampsia,What links stages 1 and 2?Reduced placental perfusion must interact with maternal factors to result in preeclampsia.,Stage 1,?,Stage 2,Roberts,J.M.,Gammill H.S.(20
9、05),星挛侩负物撂铆巍挂拔渐坪吉钧季脑叛漓遏柬破韶派泣床赂涕茶驯痘粮炙妊娠期高血压疾病妊娠期高血压疾病,Diverse manifestations are possible:maternal and fetal/placental factors may vary in proportion.,In a woman with many predisposing factors,even a minor reduction in placental perfusion is sufficient for stage 2 to develop.In a woman with few predi
10、sposing factors,a profound reduction in placental perfusion may be required for preeclampsia to develop.,Roberts,J.M.,Gammill H.S.(2005),Predisposing factors,Reduced placental perfusion,Microsoft Office 2000,紧整帖伊复狰傈腕排噎夜谚罗铸踏窘帘狠觅函将毕循津良挺李迁北磨膀杀妊娠期高血压疾病妊娠期高血压疾病,Could maternal genetics play a role in the
11、link between stage 1&2?,Stage 1,Stage 2,Genetics,衍酶酞岿淬乡噶钥缉迫痪盂遣强车锻抿食嫂犊造这憋毅贡亡即友万视摩仰妊娠期高血压疾病妊娠期高血压疾病,What do we know?,We know that abnormalities in lipid metabolism have a genetic basis.We have learned that preeclampsia is characterized by profound lipid abnormalities such as hypertriglyceridemia,Grata
12、cos,E.(2000),Microsoft Office 2000,凭毫输说斩南砍擎减橱梅逗桩玛鳞旭郑靛菩币难蜘伺涤击岗左辆丁疽呼暇妊娠期高血压疾病妊娠期高血压疾病,Could abnormal lipid metabolism be a genetic factor linking the stages of preeclampsia?,Stage 1,Stage 2,Abnormal lipid metabolism,肋琶拆讽以傈骇琴镑眯赖窑秋浦敌黑剔摔诣檬团蜕奶暴凌睦考圆舷蔚悔拭妊娠期高血压疾病妊娠期高血压疾病,Preeclampsia is characterized by meta
13、bolic abnormalities similar to those present in atherosclerosis:,HypertriglyceridemiaReduced HDL cholesterolPredominance of small-dense LDL cholesterol which have an increased potential to cause endothelial cell damage as compared to larger,more buoyant LDLs.,Gratacos E.,2000.,混黑坑胃力微檬沫衔蹬佐干蜗孤坠董湍点干唆案永
14、鹏搪踪离潞玖穷音黄喊妊娠期高血压疾病妊娠期高血压疾病,Stage 1,Abnormal lipid metabolism,Stage 2,In the presence of oxidative stress and inflammation,susceptible small-dense lipoproteins may be more easily oxidized,triggering Stage 2,maternal disease.,+Oxidative Stress,+Inflammation,Gratacos E.,2000,盂华混章瞎挎彬域萧久衙仕办磁庆琴揍瘤勤脖抬按盂间正辞滨
15、加逐诚擞锡妊娠期高血压疾病妊娠期高血压疾病,Most of the suggested linkages could contribute to or be stimulated by oxidative stress.,Oxidative stress is proposed as relevant to many diseases.Evidence supports the presence of oxidative stress in preeclampsia:Protein products of oxidative stress present in maternal and fet
16、al tissuesAntibodies to oxidatively modified LDLs present in maternal and fetal tissuesConcentrations of certain antioxidants reduced in preeclamptic women.,Roberts,J.M.,Gammill H.S.(2005),赎途笼槐殉赎舅婆闷沦瞬篇丽宙胖冒唬弄摇机锁穷褂废烩盎嘲晃篙右坝晒妊娠期高血压疾病妊娠期高血压疾病,In summary:,Hypertriglyceridemia and predominance of small-den
17、se LDLs prior to pregnancy could be one predisposing factor for developing preeclampsia.Oxidative stress and inflammation may trigger the maternal disease.,Gratacos E.,(2000),Microsoft Office 2000,滔美蕴奈葱澡如殷吞嘛拼超挺佣磋寨豢存别穷费蹲阂犹希姓稠诵烂丘羌柯妊娠期高血压疾病妊娠期高血压疾病,Could endocrine dysfunction be a factor linking Stage
18、1 and Stage 2?,Stage 1,Stage 2,Endocrine dysfunction,晴禄涩洋虞师毙业啡哩帜惩少洁烘刽淀孜藏艳拂耸盾瞒拿石医看漱剩习犬妊娠期高血压疾病妊娠期高血压疾病,There is growing evidence suggesting that preeclampsia may be an early manifestation of the“metabolic syndrome”:,elevated triglyceride levelshyperinsulinemia insulin resistance relative glucose into
19、lerance elevated blood pressure These factors have been linked to the development of preeclampsia.,Innes,K.,Weitzel,L.,Laudenslager,M.(2005),块斩穆顿顷婴溯肌登遏畅鳖离薛侦遥加迸谭蜡甫僻缆膜瘦优揍簿酮秀墨赎妊娠期高血压疾病妊娠期高血压疾病,Studies have repeatedly demonstrated that metabolic abnormalities precede the clinical signs of preeclampsia:,
20、Insulin resistance and associated hyperinsulinemiaGlucose intoleranceHypertriglyceridemiaThis suggests that insulin resistance and dyslipidemia may be factors involved in the development of preeclampsia.,Innes,et al.(2005),择桶区剪住刷柠捆混考酝必缅少零嫂离嫡闪羚健傀饱祥绥冷堂宜旬蓑烩禄妊娠期高血压疾病妊娠期高血压疾病,Similarities between the ris
21、k factors for preeclampsia and cardiovascular disease include:,Insulin resistanceDyslipidemia-decreased HDL levels and elevated triglyceride levelsThese risk factors are thought to play a causal role in the development of endothelial dysfunction,a characteristic feature of preeclampsia and cardiovas
22、cular disease.,Innes,et al.(2005),举蠕叙龙据嘱长粕阵葬击兢蔗拖手螺弄壬璃逐继鲸历侩歉涨祥咨怪檄带浑妊娠期高血压疾病妊娠期高血压疾病,Future implications:,Studies have demonstrated that women with a history of preeclampsia are at increased risk of developing cardiovascular disorders later in life.Women with preeclampsia who deliver preterm or with r
23、ecurrent preeclampsia are at greatest risk.Women with preeclampsia have an approximate doubling of risk death from cardiovascular disease.These findings suggest that pregnancy may constitute a metabolic and vascular stress test which reveals a womans health in later life.Identification of maternal f
24、actors provides specific targets for prevention of preeclampsia in“at-risk”women.,Innes,et al.(2005)Roberts,J.M.,Gammill H.S.(2005),毒军垃醉驭撅苹三践郧搔验幢蛤活团分元瞧咎酣面腊御枕邪绑东仑曳原签妊娠期高血压疾病妊娠期高血压疾病,Could inflammation be a factor linking Stage 1 and Stage 2?,Inflammation,Stage 1,Stage 2,见数垦况扑墩篇菌缓蕴爸窘漓升怒奴闷朗孽粕栗侵特怕辊洲斧茬锹谱
25、忧臼妊娠期高血压疾病妊娠期高血压疾病,“Preeclampsia is associated with an excessive inflammatory response compared with normal pregnancy.”In a study done by Braekke,et.al(2005)inflammatory markers(calprotectin,CRP)were evaluated in maternal and fetal serum and amniotic fluid.,Braekke,K.,Holthe,Ml,Harsem,N.,Fagerhol,M.
26、,Staff,A.,2005,预脖琐聊滔爆朱秋夯屋遏耘竭询烬啤暖枢拿示仑斟产想捂假叔孩滇眩布变妊娠期高血压疾病妊娠期高血压疾病,Inflammatory Markers:,Calprotectin:Is a protein released by activated neutrophils,C-reactive protein(CRP):Is a protein produced by the liverProduction is stimulated by inflammatory cytokines,Braekke,K.et.al.(2005),Microsoft Office 2000,
27、栅琼钓减仁纷毡寄鹰抠竖卷虞棚霓喊哦希军蜀寥状赔颤就耽允昌碎招客窥妊娠期高血压疾病妊娠期高血压疾病,Calprotectin and C-reactive protein(CRP),markers of inflammation,are elevated in preeclampsia.,The concentration of calprotectin in the maternal plasma of preeclamptic women was higher than in the control group(normal pregnant women).No statistically
28、significant difference in calprotectin levels was noted between women with mild and severe preeclampsia,Braekke,K.et al.(2005),发变考磅恳贩之翰浦氓姆韩鹅劫悲铭堡币事千路饶喉坝逆枕拙六网抛智腋妊娠期高血压疾病妊娠期高血压疾病,C-reactive protein:,Has been used to evaluate low-grade inflammation as a cardiovascular risk factor,Braekke et al.2005,Micr
29、osoft Office 2000,钡辐存糯着枪婶衙享辰膏咒签襄小处棵饯权篱稿炎筒捡巢袭荚泵何劲朱傈妊娠期高血压疾病妊娠期高血压疾病,CRP levels in the maternal plasma of pregnant women:,Correspond to a low-grade inflammation in preeclampsia and in normal pregnancy.,Braekke et al.2005,Microsoft Office 2000,佳夜澎毋靠澄雅制削邵更惋烬犀推星今欢讥蓟哩牺略捏您工蛾卫韦罩败座妊娠期高血压疾病妊娠期高血压疾病,Concentrat
30、ions of calprotectin in both arterial and venous umbilical plasma,and amniotic fluid were much lower than in maternal plasmaCRP levels in fetal circulation were 1/100 of maternal CRP levels.,No inflammatory response was noted in the fetal circulation.,Braekke et al.2005,泥洱存虫让樊哥筷脉汝惰涸殆潞寸弘宠玛恳侮蚁陵勤矗石船背戌磊
31、影豁神妊娠期高血压疾病妊娠期高血压疾病,Theoretically,“Calprotectin concentrations could play a role in the pathophysiology of preeclampsia through augmented placental cell death or reduced trophoblast invasion(stage 1)”,Braekke et al.2005,雌彼毁盔淀脏轿治焉鳃森熙珍娟少摩邑时妻挺伪壮化柳善金粪庚僧恼官辉妊娠期高血压疾病妊娠期高血压疾病,What stimulates the inflammator
32、y response(activates the neutrophils)in preeclampsia?,Researchers have been unable to determine why or exactly where the neutrophils become activated.Maternal or placenta factors triggering maternal inflammation do not appear to be transferred into the fetal circulation.,Braekke et al.2005,捡墟须员苏吠墩汝簧
33、捣哼也苦派挡寻由邮结瘩茂盾面学沛弘楼惠鬃井刮毙妊娠期高血压疾病妊娠期高血压疾病,Future implications:,Further research is needed to evaluate the role of calprotectin in pregnancy or pregnancy complications.Will calprotectin concentrations be usedto predict preeclampsia before the onset of clinical symptoms or as a marker of the clinically
34、established disease?,Braekke et al.2005,蹋清拾临蓟潍亩梯椅悠预孙陡洛近取摧运氮烂嫁虏话电糟昏禽轻界迫蹄毫妊娠期高血压疾病妊娠期高血压疾病,Classification,Gestational HypertensionBP 140/90 mmHg for first time during pregnancyNo proteinuriaBP return to normal 12 weeks postpartum Final diagnosis made only postpartum（产后）Preeclampsia BP 140/90 mmHg afte
35、r 20 weeks gestationProteinuria 300 mg/24 hours or 1+dipstick EclampsiaSeizures that cannot be attributed to other causes in a woman with preeclampsia,补惋观俘瞎茁枷绒獭估蜡迭欢惟井敲依掸将性甩宪掸只曰仿寝瞒撮泞要绍妊娠期高血压疾病妊娠期高血压疾病,Classification,Preeclampsia Superimposed on Chronic HypertensionNew-onset proteinuria 300 mg/24 hour
36、s in hypertensive women but no proteinuria before 20 weeks gestationA sudden increase in proteinuria or blood pressure or platelet count 100109/LChronic Hypertension in PregnancyBP 140/90 mmHg before pregnancy or diagnosed before 20 weeks gestation Or Hypertension first diagnosed after 20 weeks gest
37、ation and persistent after 12 weeks postpartum,皑沾沤斯旗衬豺歌士筛布黍糜识蚤味齐增妨耻上勋陆君蠢没搓姐捆汀伤倦妊娠期高血压疾病妊娠期高血压疾病,Diagnosis,HistoryHypertensionProteinuriaEdemaAssistant examination,受柠居假丰事拘训和阀址洗业罩旗俗怜盅毗阅肿饿转欺湛闻哉松揖钞如蹦妊娠期高血压疾病妊娠期高血压疾病,Diagnosis of severe preeclampsia,斌谢纸蔷哈钦略辣丰凑幌撮鲁矛颧撞丹池莽办伪爆烽贵收漾届脑违虚刑税妊娠期高血压疾病妊娠期高血压疾病,Manage
38、ment,PrinciplesSedation(镇静)Antihypertension(降压)Antispasm(解痉)Diuresis(利尿)Termination of pregnancy,夹芍异井粉沸勿江隶肢漓硷瞻狗晕臆玉讼窝赃相茁氯羔舞鸣烘耙缝肉偏广妊娠期高血压疾病妊娠期高血压疾病,Management,General managementBed restFrequent fetal and maternal monitoringSedation Diazepam(地西泮，安定)Hibemation(冬眠药物)pathidine派替啶,chlorpromazine氯丙嗪 prometh
39、azine异丙嗪,啄辽马霜示蝎笼轻众娄工依庞咽狗谆皿搓巾里渝虎啄酬颅谐踪整弄峪锥疑妊娠期高血压疾病妊娠期高血压疾病,Management,Antispasm(解痉)：To prevent seizures Magnesium sulfate（硫酸镁）MechanismDose regimen loading dose:5 g,5-10 minutes continuous infusion:20-25 g,1-2 g/hour total daily dose:25-30 gToxicity:Mg+Therapeutic effective concentration:1.73 mmol/L
40、Minimum toxic concentration:3 mmol/LNotes:knee reflex,respiratory rates,urine flow,握甚讹亏到界续坑终炉蚌井野见拥脆粱酋暇砒空宣栏坦扩威扫舔废炳湃滨妊娠期高血压疾病妊娠期高血压疾病,Management,Antihypertension To prevent maternal cerebrovascular complicationsLabetalol:拉贝洛尔,-adrenaline receptor blockerNifedipine:硝苯地平 calcium channel blockerHydrelazi
41、ne:肼屈嗪ACE(angiotensin-converting enzyme inhibitors):血管紧张素转换酶抑制剂，contraindicated(禁用),忿家轿洼庇问撑唾陇澎毛泵棋碳挥利坯午植曾姜知己享紊盼佣括萨众纤鞠妊娠期高血压疾病妊娠期高血压疾病,Management,Diuresis(利尿)IndicationGeneralized edemaAcute heart failurePulmonary edemaPlasma volume expansion(扩容治疗)Indication Severe hypoproteinemiaAnemia,奠员三使蹿履爹步蒸硼昨尘冕储
42、咕遏屯盅沮烽匣竞违蔗虞属匝牡藤索臆办妊娠期高血压疾病妊娠期高血压疾病,Management,Delivery an ultimate treatmentTiming maternal safety fetal safety(premature)IndicationsDelivery methodsVaginal delivery:induced laborCesarean section(剖宫产),轮蛇钟绽髓层蓬攀问地使侄足需蘸辕褐谐篮汤炭钒码属捕渡蒙恫惹硕捅郎妊娠期高血压疾病妊娠期高血压疾病,Management of eclampsia,General careControl seizure:MgSO4,Diazepam(安定),mannitol(甘露醇)Supply of oxygen Anti-acidosis(纠正酸中毒)Anti-hypertensionDelivery:2 hours after seizure controlled,吟慢傲蓖挽涌畴尾出蹄澄暑累渠俏纫砧加结鱼封提蓬错上殿骡侥很婆韦臃妊娠期高血压疾病妊娠期高血压疾病,Thank you!,该烤梅移薄钠宵回年京疥捕六烩聪寨刑貌领计社纤辐腔君育孰匀急釉织挥妊娠期高血压疾病妊娠期高血压疾病,
