html5-img
1 / 143

Hypertensive Disorders in Pregnancy

Hypertensive Disorders in Pregnancy. รองศาสตราจารย์ นายแพทย์ อติวุทธ กมุทมาศ. 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.

cody
Télécharger la présentation

Hypertensive Disorders in Pregnancy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Hypertensive Disorders in Pregnancy รองศาสตราจารย์ นายแพทย์ อติวุทธ กมุทมาศ

  2. Scope • Terminology and classification • Risk factors • Etiology • Pathophysiology • Prediction and prevention • Management

  3. Incidence • 3.7 % of pregnancies • 16% of pregnancy-related deaths • Eclampsia 1 in 2000 deliveries

  4. Classificationby 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

  5. Gestationalhypertension • BP >= 140/90 mmHg for first time during pregnancy • No proteinuria • BP returns to normal < 12 wk postpartum • Final diagnosis made only postpartum • May have other S&S of preeclampsia , eg. epigastric discomfort or thrombocytopenia

  6. Preeclampsia • Minimum criteria • BP >= 140/90 mmHg after 20 wk gestation • Proteinuria >= 300 mg/24hr or >=1+ dipstick • Mild preeclampsia • Severe preeclampsia

  7. Severe preeclampsia • BP >= 160/110 mmHg • Proteinuria 5 g/24hr or >= 2+ dipstick (persistent) • Cr > 1.2 mg/dl • Platelets < 100,000 /mm3 • Microangiopathic hemolysis • Elevated ALT or AST • Persistent headache , visual disturbance , epigastric pain

  8. Eclampsia • Seizures that cannot be attributed to other causes in a woman with preeclampsia • Seizures are generalized • May appear before , during or after labor • 10% develop after 48 hr postpartum

  9. Superimposed preeclampsia • New onset proteinuria >= 300mg/24 hr in hypertensive women but no proteinuria before 20 wk • A sudden increase in proteinuria or BP or platelet count < 100,000 in women with hypertension and proteinuria before 20 wk

  10. Chronichypertension • BP >= 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

  11. Diagnosis

  12. GestationalHT • 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Underlying causes of CHT • Essential familial hypertension • Obesity • Arterial abnormalities • Endocrine disorders • Glomerulonephritis • Renoprival hypertension • Connective tissue disease • PCKD • ARF

  18. Risk factorsfor preeclampsia • Nulliparous • Advanced maternal age • Race and ethnicity (genetic predisposition & envoronmental factor) • Multifetal gestation • Obesity • BMI > 35 kg/m2

  19. 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

  20. 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

  21. 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

  22. Abnormal trophoblastic invasion

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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 father’s alloantigen • J. of Reprod Immunology 2003 (59) : 93-100

  28. Immunological factors • IL10 regulate s arterial pressure in early primate pregnancy • IL-10 & TNFα : vasodilation of early pregnancy • Anti-human IL-10 MAb caused significant increase in MAP • TNF-α alone or combine with IL-10 not alter MAP • Cytokine 29 (2005) 176-185

  29. 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

  30. Vasculopathy & inflammatory • Placental factors released by ischemic changes • Decidua activated , release noxious agents provoke endothelial cell injury • Endothelial cell dysfunction • Cytokines : TNFα , IL

  31. 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

  32. Vasculopathy & inflammatory • Oxidative stress : produce lipid-laden macrophage foam cells • Activation of microvascular coagulation : Thrombocytopenia • Increased capillary permeability : proteinuria and edema

  33. 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

  34. 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

  35. 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

  36. 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

  37. Nutritional factors • Dietary taboos : meat , protein , purines , fat , dairy products , salt • Supplement of Zn , Ca , Mg prevent preeclampsia ? • Fruits & vegetables : antioxidant • Ascorbic acid intake < 85 mg/d , predispose preeclmapsia 2 fold • Obesity increase risk preeclampsia

  38. Genetic factors • Hereditary hypertension, preeclampsia , eclampsia • Polygenic inheritance • Asso with HLA-DR4 • Maternal Ab against fetal anti HLA-DR Ig • Heterozygous for angiotensinogen gene variant T235 • Polymorphisms of genes for TNF , IL 1β , Lymphotoxin α

  39. Genetics of preeclampsia • Familial predisposition • AGT(encode angiotensinogen) & NOS 3 (encode nitric oxide synthestase) genes mutation • Clin Genet 2003 : 64 : 96-103

  40. Is preeclampsia an infectious disease? • Analyze IgG Ab against HSV-2 , CMV , EBV , Toxoplasma gondii at first ANC • Seronegative 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

  41. Pathogenesis • Vasospasm • Endothelial cell activation • Increased pressor resonses • Prostaglandins • Nitric oxide • Endothelins • Angiogenic factors (VEGF , PIGF)

  42. Pathogenesis • Increased vascular reactivity to vasopressor • Decrease PG I2 production by endothelium • Increase TxA2 secretion by platelet • Increased NO2 synth by endothelium • Decrease NO2 synthease

  43. Comparison of mean ATII infusion doses required to evoke a pressor response

  44. Pathophysiology • Endothelial damage • Interstitial leakage • Platelet & fibrinogen deposit • Increase subendothelial a. resistance • Decreased blood flow • Ischemia necrosis , hemorrhage • Multiorgan involvement

  45. Cardiovascular system • Increase after load • Preload diminish • Endothelial activation with extravasation • Decreased cardiac output • Hemoconcentration from generalized vasoconstriction and endothelial dysfynction • Decreased blood volume

  46. Blood and coagulation • Thrombocytopenia from platelet activation , aggregation & consumption • Increased plt activating factor & thrombopoietin • Clotting factors decrease • Erythrocytes rapid hemolysis (increase LDH , schizocyte , MAHA)

  47. Volume homeostasis • Decrease plasma levels of renin , AT II , aldosterone • DOC increase • Vasopressin normal despite decreased plasma osmolality • ANP increased • Extracellular fluid : edema : endothelial injury , reduced oncotic pressure

  48. Kidney • RPF & GFR reduced • Uric acid elevated • Creatinine clearance reduced , oliguria • Diminished urinary Ca due to increased tubular reabsorption • Urine sodium elevated • Urine osmolality , U:P Cr , FE Na : prerenal mechanism

  49. Kidney • Proteinuria : glomerulopathy : increased permeability : albumin , Hb , globulin , transferins • Anatomical changes : glomeruli enlarge , capillary loops dilated & contracted , endothelial cells swollen fibrils deposit (glomerular capillary endotheliosis)

More Related