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Hypertensive Disorders in Pregnancy (Williams 22 Edition)
Hypertensive Disorders in Pregnancy (Williams 22 Edition)
Index
Diagnosis
Etiology
Pathogenesis Pathophysiology Prediction and Prevention Management
INTRODUCTION
Gestational Hypertension - 3.7% in 150,000
(National Center for Health Statics, 2001)
Pregnancy-related hypertension:
Pregnancy-related deaths (16% of 3201 in US, 1991-1997)
Black women are 3.1 times to die as white women Hypertensive disorders remain among the most significant and intriguing unsolved problems in obstetrics
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Diagnosis
Gestational hypertension
Preeclamsia
Eclampsia
Gestational hypertension
BP 140/90mmHg for first time during pregnancy No proteinuria Blood Pressure returns to normal < 12 weeks postpartum Final diagnosis made only postpartum May have other signs or symptoms of preeclampsia, for example, epigastric discomfort or thrombocytopenia
Preeclampsia
Minimum Criteria
BP 140/90mmHg after 20weeks gestation Proteinuria 300mg/24hrs or 1+dipstick
Preeclampsia
Diastolic hypertension 95mmHg
Increase fetal death rate (38000 prenancy in 1976)
Worsening proteinuria
Increasing preterm delivery Neonatal survival was not significantly altered.
Thrombocytopenia
Severe vasospasm Microangiopathic hemolysis Platelet activation, aggregation
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Pathophysiology
Preeclampsia
Severity of Preeclampsia
Differentiation between mild & severe preeclampsia can be misleading because apparently mild disease may progress rapidly to severe disease Rapid increase in BP followed by convulsions is usually preceded by unrelenting severe headache or visual disturbances.
Eclampsia
Preeclampsia + convulsion Seizures that cannot be attributed to other causes in woman with preeclampsia
Seizures are generalized and may appear before, during, of after labor
Chronic hypertension
BP 140/90 mmHg before pregnancy or diagnosed before 20 weeks gestation (not attributable to gestational trophoblastic disease) or Hypertension first diagnosed after 20 weeks gestation and persistent after 12 weeks postpartum
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Endocrinedisorders
Diabetes mellitus Cushing syndrome Primary aldosteronism Pheochromocytoma Thyrotoxicosis
Chronic Hypertension
Chronic Hypertension can lead:
Ventricular hypertrophy, Cardiac decompensation, Cerebrovascular accidents, renal damage That complication are more likely during pregnancy if there is superimposed preeclampsia (which 25% of these women, 1998, Sibai).
Superimposed Preeclampsia
Placental abruption, growth restriction, preterm delivery, death. These complication of Superimposed Preeclamsia. Develops earlier than Pure preeclampsia, and it tends to be more severe and often accompanied by fetal growth restriction.
Nulliparous
Total:7.6% and severe: 3.3% (Hauth, 2000)
Risk factor
Chronic hypertension, multifetal gestation, maternal old age (>35 yrs), obesity, AfricanAmerican ethnicity
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
(Sibai, 2000)
Smoking during pregnancy reduced risk of hypertension during pregnancy (Bainbridge,2005 ; Zhang, 1999) Placenta previa also reduced the risk of hypertension
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
1983-1986
1/1150 deliveries
1999
1/1750 deliveries
1/2000
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Etiology
Basic concepts
Exposed to chorionic villi for the first time Exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole Have preexisting vascular disease Genetically predisposed to hypertension developing during pregnancy
Vascular endothelial damage with vasospasm, transudation of plasma, and ischemic and thrombotic sequelae. Currently plausible potential cause (2003, Sibai)
Abnormal trophoblastic invasion of Uterine vessels Immunological intolerance between maternal and fetoplacental tissues Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy Diatary deficiencies Genetic influences
Lipid-laden cells atherosis (Hertig, 1945) Obstruction of the spiral arteriolar lumen by atherosis may impair placental blood flow Placental perfusion diminished
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
OH- radikal
H 2 O2
Peroksida lipid
MEMBRANE
NUKLEUS
PROTEIN
Disfunctions of Endothel
Nutritional Factors
Dietary deficiencies and Excesses over the centuries have been blamed as the cause of eclampsia. Supplementation with various elements such as zinc, calcium, and magnesium to prevent preeclampsia (John, 2002) Obesity, is a potent risk factor for preeclampsia C-reactive protein, an inflammatory marker, was shown to be increase in obesity, which in turn was associated with preeclampsia (Wolf, 2001)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Genetic Factors
Hereditary hypertension is linked to preeclampsia
(Ness, 2003)
Preeclampsia- eclampsia is highly heritable in sisters, daughters, granddaughters, and daughtersin-law. (Chesley and Cooper, 1986) 60% concordance in monozygotic female twin pairs (Nilsson, 2004) HLA-DR reported an association preeclampsia and proteinuric hypertension (kilpatrick,1989)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Pathogenesis Vasospasm
Vascular constriction resistance and subsequent hypertension Maldistribution, ischemia of the surrounding tissues caused diminished blood flow necrosis, hemorrhage, and other end-organ disturbances.
Pathophysiology Vasospasm
Vasocontriction spiral arteries Failure of Cytotrophoblast invasion of the spiral arteries
Pathogenesis
Endothelial Cell Activation
Unknown factors (from placenta) are secreted into the maternal circulation
activation and dysfunction of the vascular endothelium.
Increased sensitivity to
infused angiotensin II
vasoconstriction
Platelets
The Texbooks Kidney Disease and Hypertension in Pregnancy, 2003
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Pathophysiology
Cardiovascular System Increased cardiac afterload caused by hypertension Cardiac preload in preeclampsia
Pathologically diminished hypervolemia of pregnancy Iatrogenically increased by iv crystalloid or oncotic solution
Cardiovascular System
Hemodynamic Changes Preeclampsia
Cardiac output elevated before hypertension developed than normal pregnancy.
(Hankin, 1984)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Cardiovascular System
Blood Volume
Blood volume in term
Normal pregnancy: 5000ml Not pregnancy: 3500ml Eclampsia: 3500ml
Hemoconcentration in preeclampsia
Vasoconstriction and Endothelial dysfunction with vascular permeability. Depending on severity, hemoconcentration is usually not as marked. Whereas, gestational hypertension have a normal blood volume (Silver, 1998)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Liver
Periportal hemorrhagic necrosis in the periphery of the liver lobule
Serum liver enzyme is elevated Hepatic rupture (more rare), subcapsular hematoma (more common). Treatment
Surgical intervention may be life saving Blood transfusion (recombinant VIIa) to help control heptic haemorrhage. Liver transplantation.
Spontaneous hepatic rupture in 121 cases and mortality rate was 30%
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Liver
HELLP syndrome
Hemolysis, Elevated Liver enzyme and Low Platelet 20% of severe preeclampsia and eclampsia Adverse outcome: 40% Other complication
Eclampsia (6%), Placental abruption (10%), ARF (5%), pulmonary edema (10%), subcapsular liver hematoma (1.6%)
Brain
Common Subjectif
Headache, visual disturbance - associated convulsion (eclampsia)
Anatomical pathology
Gross hemorrhage - severe hypertension
These complications in women with underlying chronic hypertension
Brain
Neuroimaging study
CT
All women with eclampsia have abnormal brain finding Hypodense cotical area petechial hemorrhage and infarction site (at autopsy)
MRI
Described remarkable changes in the posterior Cerebral artery area. 25% of women with eclampsia have areas of cerebral infarction
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Brain
Cerebral Blood Flow
Eclampsia loss of autoregulation of cerebral blood flow (Apollon, 2000)
Hyperperfusion similar in hypertensive encephalopathy.
Brain
Blindness It rare with preeclampsia alone It follow eclamptic convulsions in up 10% of women Develop up to a week or more following delivery
(Chambers and Cain, 2004)
Vasogenic edema of occipital lobe on MRI and CT Permanent visual defect, including blindness caused by Cerebral infarction (retinal artery ischemia)
(Moseman and Shelton,2002)
Brain
Cerebral Edema
Subjectif
Letharge, confusion, blurred vision to obtundation and, coma
Mental status change correlated with brain involvement seen with CT and MRI studies Sudden severe blood pressure elevatoins
Vasogenic edema Blood pressure control.
Electroencephalopgraphy
Reported that 75% of 65 women with eclampsia had abnormal finding within 48 hours of seizure.
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Uteroplacental perfusion
Vasospasm
Placental perfusion from vasospasm increases perinatal mortality and morbidity
Measurement
Spiral artery 500m (normal), 200 m (preeclampsia) Placental blood flow
Inaccesibility, complexity, and unsuitablity
http://hyper.ahajournals.org/cgi/content/full/38/3/718
Uteroplacental Perfusion
Doppler
Doppler measurement of blood velocity through uterine artery estimate uteroplacental blood flow
Vascular resistance is estimated by comparing arterial systolic and distolic velocity waveforms Abnormal waveforms fetal indication required sectio cesarean
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Prediction (Continued)
Roll over test
Hypertensive respone induce by having women at 28 to 32 weeks Lying laterally Recumbent position supine position
Hypertension abnormal Positive predictive value (true positive) : 33% (Dekker, 1990 ; Friedman and Lindhemier, 1999)
Prediction (Continued)
Fibronectin
Endothelial cell activation elevated serum cellular fibronectin level (Brubaker, 1992) Clinical study, Paarlberg (1998)
Low sensitivity: 69% Positive predictive value: 12%
Prediction (Continued)
Oxidative Stress
Lipid peroxides level increases descreases antioxidants activity preeclampsia prediction (Walsh, 1994) Marker
Lipid peroxides: malondialdehyde Pro-oxidants: iron, transferrin, ferritin, blood lipids, Trigliseride, free fatty acid, lipoproteins, Vit C & E
Hyperhomocysteinemia
Atherosclerosis risk factor (non pregnant) Around mildpregnancy with elevated serum homocysteine had risk of preeclampsia (DAnna, 2004;
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Hietala, 2001)
Prediction (Continued)
Cytokines
Released by vascular endothelium and leukocytes Over 50 cytokine are elevated in preeclampsia
Interleukin and TNF -
Cascade of markers (C-reactive protein) elevations in preeclampsia Not sufficiently predictive (Savvidou, 2002)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Prediction (Continued)
Placental Peptide
The inflamatory cascade placenta producing peptide markers for prediction of Preeclampsia Placental peptide:
Corticotropin-rh, Chorionic gonadotropin, activin A and inhibin A (Aquilina, 1999; Cuckle 1998)
Activin A and Inhibin A were increased markedly in preeclampsia (keelan and colleagues, 2002) Activin A and Inhibin A reported significant overlap in normotensive and preeclampsia (Grobman and Wang, 2002)
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Prediction (Continued)
Fetal DNA
Identification of Fetal DNA in marternal serum prediction of preeclampsia (Zhong, 2001) Endothelial activation and inflammation occur, fetal cells and cellular material maternal circulation.
Prediction (Continued)
Uterine Artery Doppler Velocimetry
Second trimester - uteroplacental vacular resistance (by doppler of uterine artery) Basic concepts
Impaired trophoblastic invasion of the spiral arteries uteroplacental blood flow descreases
Bower (1993)
Sensitivity: 78% Positive predictive value: 28%
Prevention
Dietary Manipulation
Salt restriction ineffective (Knuist, 1998) Prenatal Ca supplementation significant reduction in Blood Pressure and incidence of preeclampsia (Brucher, 1996) But, Levin, (1997) 4600 nulliparas calcium and placebo preeclampsia or gestational hypertension incidence was similar in each group.
Prevention (Continued)
Low dose aspirin
60 mg aspirin reduce the incidence of preeclampsia: selective TXA2, dominence of endothelial prostacyclin (Hauth, 1998, Wallenburg, 1986) Caritis, 1998; CLASP Collaborative Group, 1994; Hauth, 1993, 1998; Rotchell, 1998; Sibai, 1993a
Low-dose aspirin was ineffective in preventing preeclampsia
Williams Obstetric 22 edition, Chapter 34: Hypertensive Disorders in Pregnancy
Prevention (Continued)
Antioxidants
Davidge, 1992
Markedly reduced antioxidant activity in preeclampsia women.
Chappel, 1999
283 high risk women 18 - 22 weeks, Vit C and E versus placebo Significant reduction in preeclampsia (11%-17%)
Index
Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management
Management
Basic management objective for any pregnancy complicated by preeclamsia are:
1. Termination of pregnancy with the least possible trauma to mother and fetus. 2. Birth an infant who subsequently thrives 3. Complete restoration of health to the mother
Referensi
Williams Obstetric 22 Edition, Chapter 34: hypertension disorders in pregnancy The Texbooks Kidney Disease and Hypertension in Pregnancy, 2003 Dewhurst's Textbook of Obstetrics and Gynaecology 7th Edition Medical Physiology Lippincott Williams and Wilkins, 2nd edition 2004 http://hyper.ahajournals.org, 2002. Pathophysiology of Hypertension During Preeclampsia Linking Placental Ischemia With Endothelial Dysfunction. The Journal of Clinical Endocrinology & Metabolism, 2003. Endothelial Cells and Peripheral Blood Mononuclear Cells Are a Potential Source of Extraplacental Activin A in Preeclampsia.