高血压英文ppt精品课件hypertensive disorders in pregnancy （2）

Hypertensive Disorders in Pregnancy Scope Terminology and classification Risk factors Etiology Pathophysiology Prediction and prevention Management Incidence 3.7 % of pregnancies 16% of pregnancy-related deaths Eclampsia 1 in 2000 deliveries Classification by the working group of the NHBPEP (2000) 1. Gestational hypertension 2. Preeclampsia 3. Eclampsia 4. Preeclampsia superimposed on chronic hypertension (superimposed preeclampsia) 5. Chronic hypertension Gestational hypertension BP = 140/90 mmHg for first time during pregnancy No proteinuria BP returns to normal = 140/90 mmHg after 20 wk gestation Proteinuria = 300 mg/24hr or =1+ dipstick Mild preeclampsia Severe preeclampsia Severe preeclampsia BP = 160/110 mmHg Proteinuria 5 g/24hr or = 2+ dipstick (persistent) Cr 1.2 mg/dl Platelets = 300mg/24 hr in hypertensive women but no proteinuria before 20 wk A sudden increase in proteinuria or BP or platelet count = 140/90 mmHg before pregnancy or diagnosed before 20 wk , not attributable to GTD or Hypertension first diagnosed after 20 wk and persistent after 12 wk postpartum Diagnosis Gestational HT Also called transient HT Final Dx : after delivery , by exclusion BP : resting BP , Korotkoff phase V is used to defined diastolic pressure GHT may later develop preeclampsia 10% of eclamptic seizures develop before overt proteinuria is identified BP rise , increase both mother and fetus risks Preeclampsia Described as “pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation” Proteinuria & glomerular pathology develop late in the course , pathophysiologic process begin as early as implantation Preeclampsia Diastolic hypertension = 95 , increase fetal death rate 3 fold Worsening proteinuria resulted in increasing preterm delivery Epigastric pain from hepatocellular necrosis , ischemia and edema that stretches Glisson capsule Thrombocytopenia from platelet activation & aggregation , microangiopathic hemolysis induced by severe vasospasm Preeclampsia Hemoglobinemia , Hburia , Hyperbilirubinemia : indicative of severe disease Cardiac dysfunction , pulm edema , obvious IUGR : indicative of severe disease Severity of preeclampsia assess by freq & intensity of abnormalities Superimposed preeclampsia 1. Hypertension (=140/90) is documented antecedent to pregnancy 2. Hypertension is detected before 20 wk , unless there is GTD 3. Hypertension persists long after delivery Additional previous Hx or family Hx of HT End organ damage : LVH , retinal change Risk abruption , IUGR , preterm & death Underlying causes of CHT Essential familial hypertension Obesity Arterial abnormalities Endocrine disorders Glomerulonephritis Renoprival hypertension Connective tissue disease PCKD ARF Risk factors for preeclampsia Nulliparous Advanced maternal age Race and ethnicity (genetic predisposition & envoronmental factor) Multifetal gestation Obesity BMI 35 kg/m2 Etiology Theory account for the observation : hypertensive disorder more likely to develop in : 1. exposed to chorionic villi for first time 2. exposed superabundance of chorionic villi (Twin ,mole) 3. Preexisting vascular disease 4. Genetic predisposition Etiology 1. Abnormal trophoblastic invasion of uterine vessels 2. Immunological intolerance between maternal and fetoplacental tissues 3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy 4. Dietary deficiencies 5. Genetic influences Abnormal trophoblastic invasion Normal implantation , uterine spiral arteries undergo extensive remodeling as they are invaded by endovascular trophoblasts Incomplete invasion (decidual vessels , not myometrial vessels) : preeclampsia Abnormal trophoblastic invasion Atherosis : pathology Endothelial damage Insudation of plasma constituents into vessel walls Proliferation of myointimal cells Medial necrosis Lipid accumulation in myointimal cells & macrophages Aneurysmal dilatation Obstruction of spiral arteriole Placental growth factors : implications for abnormal placentation Placental growth factors : regulate vascular endothelial cell and trophoblast function Highly expressed in trophoblasts during normal pregnancy Significantly decreased in preeclampsia Asso with placental bed hypoxia & ischemia (Abnormal placentation) J Soc Gyn Investig 2003 : 10 : 178-88 Placental protein 13 (PP-13) PP-3 levels slowly increase during pregnancy In 1st trimester , lower than normal were found in IUGR ,preeclampsia In 2nd & 3rd trimester , higher than normal concentrations were found in preeclampsia , IUGR , preterm delivery Used for assess risk to develop placental insuff Placenta 2004 : 25 : 608-622 Immunological factors Acute graft rejection Impaired formation of blocking antibodies to placental antigenic sites Lack of effective immunization in first pregnancies Lower proportion of Th1 , Th2 dominance Immunologic factors Increased risk for first conception , new partner , conception very shortly after beginning sexual relation (5% if 12mo) Any kind of previous pregnancy (completed , spontaneous miscarriage or elective abortion) protective against preeclampsia Tolerate semi-allogenic graft through fathers alloantigen J. of Reprod Immunology 2003 (59) : 93-100 Immunological factors IL10 regulate s arterial pressure in early primate pregnancy IL-10 & TNF : vasodilation of early pregnancy Anti-human IL-10 MAb caused significant increase in MAP TNF- alone or combine with IL-10 not alter MAP Cytokine 29 (2005) 176-185 Immunological factors Serum from preeclamptic pt contains IgG autoantibody Reacts with AT1 receptor AT1-AA induce signaling in vascular cells and trophoblasts Including AP-1 and NF-kB activation Results in tissue factor production , reactive oxygen species (ROS)generation Autoimmunity Reviews 4 (2005) : 61-65 Vasculopathy & inflammatory Placental factors released by ischemic changes Decidua activated , release noxious agents provoke endothelial cell injury Endothelial cell dysfunction Cytokines : TNF , IL Vasculopathy & inflammatory Oxidative stress (ROS , free radical) self- propagating lipid peroxides formation Generate highly toxic radicals injure endothelial cells Modify NO2 production Interfere PG balance Vasculopathy & inflammatory Oxidative stress : produce lipid-laden macrophage foam cells Activation of microvascular coagulation : Thrombocytopenia Increased capillary permeability : proteinuria and edema Angiogenic growth factors & HT HT : disease of inadequate or aberrant responses to angiogenic growth factors Preeclampsia is accompanied by high circulating levels of soluble VEGF receptor-1 (inactive complexes with VEGF + plGF) High AGF : contribute to peripheral & pulm edema , microalb , progression of atherosclerosis Angiogenesis 7 : 2004 : 193-201 L-Arginine attenuate HT Supplementation L-Arginine (precursor for nitric oxide) in pregnant rats Significant decrease arterial pressure In both pregnant rats with reduced uterine perfusion pressure & pregnant control Hypertension 2004 : 43 : 832-6 N-acetylcysteine prevent HT Reduced uterine perfusion pressure rats Were treated with N-acetylcysteine (100mg/kg) twice daily until delivery Significant increase in BP in reduced uterine perfusion pressure procedure Which alleviated by N-acetylcysteine Without adversely effect fetal weight Am j of Obs & Gyn 2005 : 193 : 952-6 Melatonin against oxidative damage Melatonin solution injected intraperitoneally before occlusion Protects against ischemia/reperfusion- induced oxidative damage to mitochondria in rat placenta Could be use in treat preeclampsia & states involvings free radical production (fetal hypoxia & IUGR) J.Pineal Res. 200 : 31 : 173-178 Prostaglandin Platelet activation : hallmark of SPE Platelet PGH synthase 1-derived (PGHS1- derived) & TxA2 Low dose aspirin treatment decreased platelet aggregation & prevented thrombosis Decrease progesterone during parturition : sustain parturition J of Clin Inv , April 2005 : 115 : 986-995 PS/PC induce preeclampsia Phosphatidylserine (PS) 80% / Phosphatidylcholine (PC) 20% Significant elevation in SBP Significant increase in TAT levels Significant decrease platelet counts Significant increase proteinuria Significant reduction in fetal & placental weight Semin Thromb Hemost. Jun2005 : 31 : 34-20 Endothelin-1 Increased ET-1 in amniotic fluid & plasma of infant and mother in preeclampsia Asso with abnormal placentation J Vet Intern Med. 2005 Jul-Aug : 19 : 594-8 Nutritional factors Dietary taboos : meat , protein , purines , fat , dairy products , salt Supplement of Zn , Ca , Mg prevent preeclampsia ? Fruits & vegetables : antioxidant Ascorbic acid intake 10% Develop upto 1 wk or more after delivery Called “Amaurosis” Extensive ocipital lobe vasogenic edema Resolve completely in all case Rare cerebral infarct or retinal a. ischemia Retinal detach : resolve within 1 wk Cerebral edema Widespread vasogenic edema S&S : Lethargy , confusion , blurred vision , coma Waxed & waned Rx : Manitol , Dexamethasone Uteroplacental perfusion Compromised uteroplacental perfusion from vasospasm Mean diameter of myometrial spiral arterioles decrease Doppler flow velocity of uterine artery Ring-like : higher in peripheral than in central vessels Preeclampsia was higher resistance Prediction Biological , biochemical & biophysical markers To identify markers of l faulty placentation l reduced placental perfusion , l endothelial cell activation & dysfunction , l activation of coagulation Roll-over test 28-32 wk Abnormally sensitive to infused angiotensin II Positive predictive value 33% Uric acid Decreased renal urate excretion in preeclampsia Serum uric acid exceeding 5.9 at 24 wk (PPV 33%) Not useful in differentiating GHT from preeclampsia Fibronectin Endothelial cell activation Low sensitivity 69% Positive predictive vaules 12% Higher levels by 12 wks (PPV 29% NPV 98%) Coagulation activation Thrombocytopenia and platelet dysfunction Increased destruction cause platelet volumes increase (younger platelet) Preeclampsia : PAI-1 increase increased relative to PAI-2 because of endothelial cell dysfunction Oxidative stress Increased levels of lipid peroxides Prooxidants : iron , transferin , ferritin , TG , FFA , lipoprotein Antioxidants : ascorbic acid , vitamin E Hyperhomocysteinemia in mid pregnancy risk for atherosclerosis , 3-4 fold risk preeclampsia , influenced by folic acid supplement Cytokines Released by vascular endothelium & leukocytes , and macrophages & lymphocytes at decidua Interleukin , TNF , CRP : inflammatory response Possibly predictive preeclampsia Placental peptides Corticotropin-releasing hormone , hCG , Activin A , inhibin A Variably elevated depend on duration & severity of preeclampsia Overlap with normal pregnancy VEGF and PIGF : regulate placental development , both antagonized by sFlt1 Excessive sFlt1 , PIGF in 1st trimester : high risk Fetal DNA Fetal DNA in maternal serum At the time endothelial activation , fetal cells released into maternal circulation Elevations after 28 wk indicate impending disease Uterine artery doppler Impaired trophoblastic invasion of spiral arteries , leading to reduction in uteroplacental blood flow 8-22 wk , sensitivity 78% , PPV 28% , unreliable in low risk pregnancies Combined inhibin A & activin A , sensitivity 86% Combined hCG & AFP , sensitivity 2-40% hCG hCG in second trimester , 2.0 MoM Sensitivity 23.7% Specificity 89.4% Relative risk 2.54 Positive predictive value 9.5% Negative predictive value 96.6% Endocrine Reviews , April2002 : 23 : 230-257 Inhibin A and Activin A Activin A : control trophoblast differentiation in first trimester : high in preeclampsia Inhibin A 15-19 wk , 2.0 MoM Sensitivity 48.6% Specificity 23.6% Activin A more sensitive than inhibin A at 21-25 wk Endocrine Reviews , April2002 : 23 : 230-257 Vasoactive Decrease active renin , AT I & I , aldosterone , activity of ACE in 3rd trim AT II infused test : positive at less than 10 ng/kg Ratio inactive urinary kallikrein /urine creatinine at 16-20 wk : lower 5 fold in who developed preeclampsia Endocrine Reviews , April2002 : 23 : 230-257 Prevention Salt restriction : ineffective Inappropriate diuretic therapy Low dietary calcium increased risk GHT Fish oil capsules : modify abnormal PG balance : ineffective Low dose aspirin (60mg) : ineffective Antioxidants : vitamin C & E : reduced endothelial cell activation , reduction in preeclampsia Low milk intake risk preeclmpsia Case control study Mean milk intake per day in preeclampsia 75 mg/d (RR 0.49 VS RR 0.86) 7% reduction in risk of preterm delivery (RR 0.84) 16% reduction in baby deaths (RR 0.84) 8% reduction in SGA babies (RR 0.92) The Cochrane Database of Systematic Reviews 2003 Antiplatelet prevent preeclampsia For high risk (previous SPE , DM , CHT , renal dis , autoimmune disease) : 27% reduction in risk of preeclampsia For mod risk (first preg , mild rise BP no proteinuria , abnormal uterine a doppler, positive roll over test , multiple preg , FH SPE , teenage) : 15% reduction Started before implantation & trophoblast invasion ,crucial time before 16 or 12 wk The Cochrane Database of Systematic Reviews 2003 Vitamin E supplement Either at high risk of preeclampsia or with established preeclampsia No difference in risk of stillbirth , neonatal death , perinatal death , preterm birth , IUGR & birthweight Decrease risk of developing clinical preeclampsia (RR 0.44) using fixed-effect models (no diff using random-effects models) The Cochrane Database of systematic Reviews 2005 Vitamin E supplement Dosage : above recommended dietary intake of 7 mg of alpha-TE (daily 400 iu or 800 iu) GA : no difference in risk of stillbirth , preterm birth ,IUGR & preeclampsia between before to 20 wk and both before & after 20 wk No difference side-effect (acne , transient weakness, skin rash) The Cochrane Database of systematic Reviews 2005 Vitamin C supplement No difference in risk of stillbirth , perinatal death, IUGR , birthweight Increase risk of preterm birth (RR 1.38) Heterogeneity : Decreased preeclampsia (RR 0.47) Dosage : above RDI of 60 mg (500 , 1000mg) GA : no difference before & after 20 wk The Cochrane Database of Systematic Reviews 2005 Antioxidant 39% reduction in risk of preeclampsia (RR 0.61) Reduced risk of SGA infant (RR 0.64) More preterm birth (RR 1.38) No difference in develop preeclampsia among low & high risk (RR 0.66 & 0.44) GA : no diff ( 2 lb/wk during 3rd trimester) OPD surveillance unless overt HT , proteinuria , visual disturbances or epigastric discomfort Antepartum management Admit if new onset HT , esp persistent or worsening HT or develop proteinuria Detail examine : headache , visual disturbances , epigastric pain , wt gain Wt , OD Proteinuria at least every 2 d BP q 4 hr , except midnight & morning Cr , Hct , plt , liver enz. Antepartum management Evaluate fetal size , AF Reduced physical activity Sedative not prescribed Ample , not excess, protein & calories diet Sodium & fluid intake not limit or forced Further Mg depend on : severity , GA , condition of Cx Termination of pregnancy Delivery is the cure for preeclampsia Headache , visual disturbances or epigastric pain : indicative convulsions Oliguria : ominous sign SPE : objectives to forestall convulsions , prevent intracranial hemorrhage , & serious vital organ damage Termination of pregnancy Preterm : conservative justified in mild case , F/U NST or BPP Mod or severe preeclampsia : prompt delivery : l IV oxytocin , l preinduction withprostaglandin or osmotic dilator , l c/s if indicated Induction of labor not harmful to infants , but unsuccessful 35% Antihypertensive drug To prolong pregnancy , or modify perinatal outcomes Labetolol : l lower mean BP, l no difference : mean pregnancy prolongation , birthweight , c/s rate l IUGR 2 fold Antihypertensive drug RCT : blocker (Labetolol) , calcium channel blockers (Nifedipine , Isradipine) no benefit Meta-analysis : treatment induced decrease maternal BP , may adversely affect fetal growth Prophylactic atenolol decrease incidence preeclampsia Antihypertensive drug ACEI should avoid in 2nd & 3rd trimester Complication : oligohydram , IUGR , bony malformations , limb contractures , persistent PDA , pulm hypoplasia , RDS , prolonged neonatal hypotension , neonatal death Early preg taken ACEI : discontinued as soon as possible Nicardipine Nicardipine start 3 mg/hr ,titrate , max 3-9 mg/hr Target DBP 10 mEq/L : respiratory depression 12 mEq/L : respiratory paralysis & arrest Cr 1.3 : half dose MgSO4 MgSO4 Acute cardiovascular effect Decrease MAP Increase CO 13% Decrease SVR Transient nausea & flushing Persist for only 15 min MgSO4 Uterine effects Depress myometrial contractility Inh calcium entry to myometrial cell Dose dependent : at least 8-10 mEq/L No uterine effect , when given for prophylaxis eclampsia (oxytocin stimulation of labor , admit to delivery intervals , route of delivery) MgSO4 Fetal effects Promptly cross placenta Neonatal depression occurs only if severe hypermagnesemia at delivery Decrease in beat-to-beat variability Possible protective effect against cerebral palsy in VLBW infants Substantial gross motor dysfunction reduced No serious harmful effects Compared with anticonvulsants MgSO4 reduce recurrent sz 50% compared to diazepam , reduce maternal & perinatal morbidity (not sig) Materna