高血壓英文ppt精品課件hypertensive disorders in pregnancy （2）

1、Hypertensive Disorders in Pregnancy,?????????????? ???????? ??????? ???????,Scope,Terminology and classificationRisk factorsEtiologyPathophysiologyPrediction and preventionManagement,Incidence,3.7 % of pregnancies1

2、6% of pregnancy-related deathsEclampsia 1 in 2000 deliveries,Classificationby the working group of the NHBPEP (2000),1. Gestational hypertension2. Preeclampsia3. Eclampsia4. Preeclampsia superimposed on chronic hype

3、rtension (superimposed preeclampsia)5. Chronic hypertension,Gestational hypertension,BP >= 140/90 mmHg for first time during pregnancyNo proteinuriaBP returns to normal < 12 wk postpartumFinal diagnosis mad

4、e only postpartumMay have other S&S of preeclampsia , eg. epigastric discomfort or thrombocytopenia,Preeclampsia,Minimum criteriaBP >= 140/90 mmHg after 20 wk gestationProteinuria >= 300 mg/24hr or >=1+ d

5、ipstickMild preeclampsiaSevere preeclampsia,Severe preeclampsia,BP >= 160/110 mmHgProteinuria 5 g/24hr or >= 2+ dipstick (persistent)Cr > 1.2 mg/dlPlatelets < 100,000 /mm3Microangiopathic hemolysis El

6、evated ALT or ASTPersistent headache , visual disturbance , epigastric pain,Eclampsia,Seizures that cannot be attributed to other causes in a woman with preeclampsiaSeizures are generalized May appear before , during

7、or after labor10% develop after 48 hr postpartum,Superimposed preeclampsia,New onset proteinuria >= 300mg/24 hr in hypertensive women but no proteinuria before 20 wkA sudden increase in proteinuria or BP or platelet

8、 count < 100,000 in women with hypertension and proteinuria before 20 wk,Chronic hypertension,BP >= 140/90 mmHg before pregnancy or diagnosed before 20 wk , not attributable to GTD orHypertension first diagnose

9、d after 20 wk and persistent after 12 wk postpartum,Diagnosis,,Gestational HT,Also called transient HTFinal Dx : after delivery , by exclusionBP : resting BP , Korotkoff phase V is used to defined diastolic pressureGH

10、T may later develop preeclampsia10% of eclamptic seizures develop before overt proteinuria is identifiedBP rise , increase both mother and fetus risks,Preeclampsia,Described as “pregnancy-specific syndrome of reduced o

11、rgan perfusion secondary to vasospasm and endothelial activation”Proteinuria & glomerular pathology develop late in the course , pathophysiologic process begin as early as implantation,Preeclampsia,Diastolic hyperte

12、nsion >= 95 , increase fetal death rate 3 foldWorsening proteinuria resulted in increasing preterm deliveryEpigastric pain from hepatocellular necrosis , ischemia and edema that stretches Glisson capsuleThrombocyto

13、penia from platelet activation & aggregation , microangiopathic hemolysis induced by severe vasospasm,Preeclampsia,Hemoglobinemia , Hburia , Hyperbilirubinemia : indicative of severe diseaseCardiac dysfunction , pul

14、m edema , obvious IUGR : indicative of severe diseaseSeverity of preeclampsia assess by freq & intensity of abnormalities,Superimposed preeclampsia,1. Hypertension (>=140/90) is documented antecedent to pregnancy

15、2. Hypertension is detected before 20 wk , unless there is GTD3. Hypertension persists long after deliveryAdditional previous Hx or family Hx of HTEnd organ damage : LVH , retinal changeRisk abruption , IUGR , prete

16、rm & death,Underlying causes of CHT,Essential familial hypertensionObesityArterial abnormalitiesEndocrine disordersGlomerulonephritisRenoprival hypertensionConnective tissue diseasePCKDARF,Risk factors for pr

17、eeclampsia,NulliparousAdvanced maternal ageRace and ethnicity (genetic predisposition & envoronmental factor)Multifetal gestationObesityBMI > 35 kg/m2,Etiology,Theory account for the observation : hypertensiv

18、e disorder more likely to develop in :1. exposed to chorionic villi for first time2. exposed superabundance of chorionic villi (Twin ,mole)3. Preexisting vascular disease4. Genetic predisposition,Etiology,1. Abnormal

19、 trophoblastic invasion of uterine vessels2. Immunological intolerance between maternal and fetoplacental tissues3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy4. Dietary defici

20、encies5. Genetic influences,Abnormal trophoblastic invasion,Normal implantation , uterine spiral arteries undergo extensive remodeling as they are invaded by endovascular trophoblastsIncomplete invasion (decidual vesse

21、ls , not myometrial vessels) : preeclampsia,Abnormal trophoblastic invasion,Atherosis : pathology,Endothelial damageInsudation of plasma constituents into vessel wallsProliferation of myointimal cellsMedial necrosisL

22、ipid accumulation in myointimal cells & macrophagesAneurysmal dilatationObstruction of spiral arteriole,Placental growth factors : implications for abnormal placentation,Placental growth factors : regulate vascular

23、 endothelial cell and trophoblast functionHighly expressed in trophoblasts during normal pregnancySignificantly decreased in preeclampsiaAsso with placental bed hypoxia & ischemia (Abnormal placentation)J Soc Gy

24、n Investig 2003 : 10 : 178-88,Placental protein 13 (PP-13),PP-3 levels slowly increase during pregnancyIn 1st trimester , lower than normal were found in IUGR ,preeclampsiaIn 2nd & 3rd trimester , higher than norma

25、l concentrations were found in preeclampsia , IUGR , preterm deliveryUsed for assess risk to develop placental insuffPlacenta 2004 : 25 : 608-622,Immunological factors,Acute graft rejectionImpaired formation of block

26、ing antibodies to placental antigenic sitesLack of effective immunization in first pregnanciesLower proportion of Th1 , Th2 dominance,Immunologic factors,Increased risk for first conception , new partner , conception v

27、ery shortly after beginning sexual relation (5% if > 12mo)Any kind of previous pregnancy (completed , spontaneous miscarriage or elective abortion) protective against preeclampsiaTolerate semi-allogenic graft throug

28、h father’s alloantigenJ. of Reprod Immunology 2003 (59) : 93-100,Immunological factors,IL10 regulate s arterial pressure in early primate pregnancyIL-10 & TNFα : vasodilation of early pregnancyAnti-human IL-10 MAb

29、 caused significant increase in MAPTNF-α alone or combine with IL-10 not alter MAPCytokine 29 (2005) 176-185,Immunological factors,Serum from preeclamptic pt contains IgG autoantibodyReacts with AT1 receptorAT1-AA i

30、nduce signaling in vascular cells and trophoblastsIncluding AP-1 and NF-kB activationResults in tissue factor production , reactive oxygen species (ROS)generationAutoimmunity Reviews 4 (2005) : 61-65,Vasculopathy &am

31、p; inflammatory,Placental factors released by ischemic changesDecidua activated , release noxious agents provoke endothelial cell injuryEndothelial cell dysfunctionCytokines : TNFα , IL,Vasculopathy & inflammator

32、y,Oxidative stress (ROS , free radical) self-propagating lipid peroxides formationGenerate highly toxic radicals injure endothelial cellsModify NO2 productionInterfere PG balance,Vasculopathy & inflammatory,Oxidat

33、ive stress : produce lipid-laden macrophage foam cellsActivation of microvascular coagulation : Thrombocytopenia Increased capillary permeability : proteinuria and edema,Angiogenic growth factors & HT,HT : disease

34、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 periphera

35、l & pulm edema , microalb , progression of atherosclerosisAngiogenesis 7 : 2004 : 193-201,L-Arginine attenuate HT,Supplementation L-Arginine (precursor for nitric oxide) in pregnant ratsSignificant decrease arteri

36、al pressure In both pregnant rats with reduced uterine perfusion pressure & pregnant controlHypertension 2004 : 43 : 832-6,N-acetylcysteine prevent HT,Reduced uterine perfusion pressure rats Were treated with N-

37、acetylcysteine (100mg/kg) twice daily until deliverySignificant increase in BP in reduced uterine perfusion pressure procedureWhich alleviated by N-acetylcysteineWithout adversely effect fetal weightAm j of Obs &

38、 Gyn 2005 : 193 : 952-6,Melatonin against oxidative damage,Melatonin solution injected intraperitoneally before occlusionProtects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placentaCou

39、ld 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 SPEPlatelet PGH synthase 1-deri

40、ved (PGHS1-derived) & TxA2Low dose aspirin treatment decreased platelet aggregation & prevented thrombosisDecrease progesterone during parturition : sustain parturitionJ of Clin Inv , April 2005 : 115 : 986-99

41、5,PS/PC induce preeclampsia,Phosphatidylserine (PS) 80% / Phosphatidylcholine (PC) 20%Significant elevation in SBPSignificant increase in TAT levelsSignificant decrease platelet countsSignificant increase proteinuria

42、Significant reduction in fetal & placental weightSemin Thromb Hemost. Jun2005 : 31 : 34-20,Endothelin-1,Increased ET-1 in amniotic fluid & plasma of infant and mother in preeclampsiaAsso with abnormal placenta

43、tion 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

44、: antioxidant Ascorbic acid intake < 85 mg/d , predispose preeclmapsia 2 foldObesity increase risk preeclampsia,Genetic factors,Hereditary hypertension, preeclampsia , eclampsiaPolygenic inheritanceAsso with HLA-D

45、R4Maternal Ab against fetal anti HLA-DR IgHeterozygous for angiotensinogen gene variant T235Polymorphisms of genes for TNF , IL 1β , Lymphotoxin α,Genetics of preeclampsia,Familial predispositionAGT(encode angiotensi

46、nogen) & NOS 3 (encode nitric oxide synthestase) genes mutationClin Genet 2003 : 64 : 96-103,Is preeclampsia an infectious disease?,Analyze IgG Ab against HSV-2 , CMV , EBV , Toxoplasma gondii at first ANCSerone

47、gative for HSV-2, CMV , EBV increased risk preeclampsia (OR 1.7 ,1.6, 3.5)Seronegative for Toxo not associated with increase risk preeclampsia (OR 1.0)Acta Obstet Gynecol Scand 2001 : 80 : 1036-8,Pathogenesis,Vasospas

48、mEndothelial cell activationIncreased pressor resonsesProstaglandinsNitric oxideEndothelinsAngiogenic factors (VEGF , PIGF),Pathogenesis,Increased vascular reactivity to vasopressorDecrease PG I2 production by end

49、otheliumIncrease TxA2 secretion by plateletIncreased NO2 synth by endotheliumDecrease NO2 synthease,Comparison of mean ATII infusion doses required to evoke a pressor response,Pathophysiology,Endothelial damageInters

50、titial leakagePlatelet & fibrinogen depositIncrease subendothelial a. resistanceDecreased blood flowIschemia necrosis , hemorrhageMultiorgan involvement,Cardiovascular system,Increase after loadPreload diminish

51、Endothelial activation with extravasationDecreased cardiac outputHemoconcentration from generalized vasoconstriction and endothelial dysfynctionDecreased blood volume,Blood and coagulation,Thrombocytopenia from plate

52、let activation , aggregation & consumptionIncreased plt activating factor & thrombopoietinClotting factors decreaseErythrocytes rapid hemolysis (increase LDH , schizocyte , MAHA),Volume homeostasis,Decrease pl

53、asma levels of renin , AT II , aldosteroneDOC increaseVasopressin normal despite decreased plasma osmolalityANP increasedExtracellular fluid : edema : endothelial injury , reduced oncotic pressure,Kidney,RPF & GF

54、R reducedUric acid elevatedCreatinine clearance reduced , oliguriaDiminished urinary Ca due to increased tubular reabsorptionUrine sodium elevatedUrine osmolality , U:P Cr , FE Na : prerenal mechanism,Kidney,Protein

55、uria : glomerulopathy : increased permeability : albumin , Hb , globulin , transferinsAnatomical changes : glomeruli enlarge , capillary loops dilated & contracted , endothelial cells swollen fibrils deposit (glomer

56、ular capillary endotheliosis),Kidney,Renal tubular lesions : degenerative change , accumulation with castsARF from ATNOliguria , azotemia induced by hypovolemiaPreeclampsia with ARF occur in HELLP syndrome ½ , pl

57、acental abruption 1/3 Rarely , irreversible renal cortical necrosis,Liver,Periportal hemorrhage in liver peripheryElevated transaminaseHELLP syndrome Bleeding cause hepatic rupture(mortality 30%) , subcapsular hemato

58、maConservative treatment Recombinant factor VIIa,HELLP syndrome,No strict definitionIncidence 20% of severe preeclampsia or eclampsiaFactors contributing to death : include stroke , coagulopathy , ARDS , ARF , sepsis

59、Insufficient evidence : adjunctive steroid,Brain,Headache & visual symptoms asso with eclampsiaTwo cerebral pathology related1. gross hemorrhage due to ruptured a. caused by severe HT2. more widespread , edema hy

60、peremia , ischemia , thrombosis & hemorrhage caused by preeclampsia,Neuroimaging,CT : hypodense area in cortex , correspond to petechial hemorrhage and infarctionsRemarkable changes in area of distribution of poster

61、ior cerebral a.MRI : hyperperfusion due to vasogenic edemaEclampsia : 25% were area of infarction,Cerebral blood flow,Transcranial doppler ultrasonographyPreeclampsia : increase perfusion pressure , counter by increas

62、e cerebrovascular resistance(net no change)Eclampsia : loss of autoregulation , hyperperfusion similar to hypertensive encephalopathyEclampsia caused by transient loss of cerebrovascular autoregulation,Blindness,Visual

63、 disturbance common in SPE It follows eclampsia in >10%Develop upto 1 wk or more after deliveryCalled “Amaurosis”Extensive ocipital lobe vasogenic edemaResolve completely in all case Rare cerebral infarct or ret

64、inal a. ischemiaRetinal detach : resolve within 1 wk,Cerebral edema,Widespread vasogenic edemaS&S : Lethargy , confusion , blurred vision , comaWaxed & wanedRx : Manitol , Dexamethasone,Uteroplacental perfusi

65、on,Compromised uteroplacental perfusion from vasospasmMean diameter of myometrial spiral arterioles decreaseDoppler flow velocity of uterine arteryRing-like : higher in peripheral than in central vesselsPreeclampsia

66、was higher resistance,Prediction,Biological , biochemical & biophysical markers To identify markers of faulty placentation reduced placental perfusion , endothelial cell activation & dysfunction , activation

67、 of coagulation,Roll-over test,28-32 wkAbnormally sensitive to infused angiotensin IIPositive predictive value 33%,Uric acid,Decreased renal urate excretion in preeclampsiaSerum uric acid exceeding 5.9 at 24 wk (PPV 3

68、3%)Not useful in differentiating GHT from preeclampsia,Fibronectin,Endothelial cell activationLow sensitivity 69%Positive predictive vaules 12%Higher levels by 12 wks (PPV 29% NPV 98%),Coagulation activation,Thromboc

69、ytopenia and platelet dysfunctionIncreased destruction cause platelet volumes increase (younger platelet)Preeclampsia : PAI-1 increase increased relative to PAI-2 because of endothelial cell dysfunction,Oxidative stre

70、ss,Increased levels of lipid peroxidesProoxidants : iron , transferin , ferritin , TG , FFA , lipoproteinAntioxidants : ascorbic acid , vitamin EHyperhomocysteinemia in mid pregnancy risk for atherosclerosis , 3-4 fol