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1、 Etiology&Pathogenesis Clinical features Physiopathology Classification Diagnosis ManagementRoberts,J.M.et al.Hypertension 2005;46:1243-1249Roberts,J.M.et al.Hypertension 2005;46:1243-1249Used with permissionTwo-stage model of the pathophysiology of preeclampsiaTwo-stage model of the pathophysiology
2、 of preeclampsiaStage 2 develops in some,but not all women with stage 1Normal:vessel remodeling(血管重铸血管重铸)of the decidua and myometriumtransforming into large-capacitance,low-resistance vesselsPreeclampsia:incomplete remodelinglimited to the superficial deciduamyometrial segments remain narrowIncompl
3、ete vessel remodeling Reduced placental perfusion placenta ischemia(缺血)(缺血)and hypoxemia(缺氧)(缺氧)Oxidative distress Endothelia dysfunction affected production of Nitric Oxide/Prostaglandins(前列腺素)Immune system dysfunction Genetic predisposition MalnutritionGenetic factorsimmunological factorsMaternal
4、vascular diseaseEnvironmental factorsReduced uteroplacental perfusionFaulty placentationEndothelial activationSystemic vascular dysfunctionCapillary leakvasospasmHypertensionCerebral edema(eclampsia)EdemaProteinuriaCoagulation abnormalities(HELLP)Fetal growth restriction(FGR)Basic change:System Vaso
5、spasm(全身小动脉痉挛)(全身小动脉痉挛)Hemorrhage,edema,hyperemia充血充血,thrombosis Visual disturbances:blurred vision,blindness,retinal detachment(视网膜脱落)(视网膜脱落)Reduced renal perfusion and glomerular filtration肾小球肾小球滤过率滤过率 Proteinuria;increased uric acid;oliguria Ischemia,edema elevated serum transaminases(ALT,AST,AKP
6、.);jaundice(黄疸)(黄疸)Subcapsular hematoma(肝包膜下出血肝包膜下出血)or hepatic rupture Peripheral vascular resistance,cardiac output(低低排高阻排高阻),blood pressure Cardiac failure(心力衰竭心力衰竭),pulmonary edema(肺水肿肺水肿)Blood volume,hematocrit (HCT,红细胞压积红细胞压积),blood concentrationHypercoagulability(高凝高凝),thrombocytopenia(血小血小板减
7、少板减少)Placental ischemia and hypoxia High-resistance circuit with decreased blood Fetal growth restriction,fetal distress(胎儿窘迫胎儿窘迫)HypertensionEdemaProteinuriaSevere cases Headache blurred vision nausea,vomit right upper quadrant pain seizure(抽搐)Usually occurs after 20 gestational weeksWHAT LINKS STA
8、GE 1&2?Theory exploration: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 2Roberts,J.M.,Gammill H.S.(2005)Diverse manifestations are possible:maternal
9、 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 predisposing factors,a profound reduction in placental perfusion may be required for preeclampsia to de
10、velop.Roberts,J.M.,Gammill H.S.(2005)Predisposing factorsReduced placental perfusionCould maternal genetics play a role in the link between stage 1&2?Stage 1Stage 2GeneticsWhat do we know?We know that abnormalities in lipid metabolism have a genetic basis.We have learned that preeclampsia is charact
11、erized by profound lipid abnormalities such as hypertriglyceridemiaGratacos,E.(2000)Could abnormal lipid metabolism be a genetic factor linking the stages of preeclampsia?Stage 1Stage 2Abnormal lipid metabolismPreeclampsia is characterized by metabolic abnormalities similar to those present in ather
12、osclerosis: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.Stage 1 Abnormal lipid metabolism Stage 2+Oxidative Stress+InflammationGrataco
13、s E.,2000 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 fetal tissuesAnt
14、ibodies to oxidatively modified LDLs present in maternal and fetal tissuesConcentrations of certain antioxidants reduced in preeclamptic women.Roberts,J.M.,Gammill H.S.(2005)In summary:Hypertriglyceridemia and predominance of small-dense LDLs prior to pregnancy could be one predisposing factor for d
15、eveloping preeclampsia.Oxidative stress and inflammation may trigger the maternal disease.Gratacos E.,(2000)Could endocrine dysfunction be a factor linking Stage 1 and Stage 2?Stage 1Stage 2Endocrine dysfunctionThere is growing evidence suggesting that preeclampsia may be an early manifestation of t
16、he“metabolic syndrome”:elevated triglyceride levelshyperinsulinemia insulin resistance relative glucose intolerance elevated blood pressure These factors have been linked to the development of preeclampsia.Innes,K.,Weitzel,L.,Laudenslager,M.(2005)Studies have repeatedly demonstrated that metabolic abnormalities precede the clinical signs of preeclampsia:Insulin resistance and associated hyperinsulinemiaGlucose intoleranceHypertriglyceridemiaThis suggests that insulin resistance and dyslipidemia