Hypertensive Disorders in Pregnancy

1. Hypertensive Disorders in Pregnancy Preeclampsia and Eclampsia

2. Definition • Preeclampsia • It is defined as the development of hypertension and proteinuria after the 20th wk of gestation. • Eclampsia • This is defined once the CNS is also involved. • HELLP

3. Epidemiology • Preeclampsia is a disorder of unknown etiology affecting 6-8% of all pregnancies.Between 1979 and 1986 incidence of severe preeclampsia increased from 2.4 per 1000 deliveries to 5.2.

4. Pathogenesis • Immunologic factors • 50% of the genes is paternal which interacts with maternal tissue as the fetal trophoblast migrates into the maternal decidua. • There is a second wave of trophoblastic invasion around 14-16 wks which results in disruption of muscular integrity of the spiral arteries, leading to their adrenergic denervation and converts them from high resistance to low resistance vessels. • Biochemical adaptations occur in the maternal vasculature with dominance of prostacyclin and nitric oxide in comparison to thromboxane. • Genetic factors • A familial tendency exists in some population and it may result from a recessive genetic inheritance. • Angiotensinogen gene T235 has been noted in association with preeclampsia. • Increased resistance to activated protein C, caused by a mutation of Factor V (Factor V Leiden mutation) predisposes to preeclampsia. • Glutamine substitution for arginine in position 506 in Factor V molecule. This renders the protein resistant to proteolytic inactivation by activated protein C and predisposes to thrombosis. • Endothelial Factors • Vascular endothelial damage and dysfunction is the common pathological factor. Metabolic end-products of normal vascular endothelium are PGI2 and EDRF(nitric oxide) Failure of trophoblastic invasion increases production of free radicals and lipid peroxides. The latter activate cyclooxygenase and impair PGI2.synthetase. • In the absence of PGI2 and nitric oxide surface mediated platelet activation occurs causing adhesion a nd damage to spiral arteriesnreleasing contents of dense granules, like TXA2 and serotonin • Lack of the normal stimulation of RAAS and hence increased response to angiotensin II • Coagulation Factors • Women with preeclampsia have thromboembolic tendencies which maybe in part due to alteration between vWF and Factor VIII coagulant activity.Endothelial cell damagereleases vWF factor and thrombin inactivates factor VIII C activity hence increasing ratio of vWF: VIII C. • Calcium • Intracellular free Ca is important for the vascular tone and contractility. In normal pregnancy it increases slowly but in preeclampsia this increase is significantly higher in the 3rd trimester. • Fatty Acid Metabolism • Altered handling of fatty acids by the liver is key in the pathogenesis of preeclampsia.

5. Criteria and Classification for Diagnosis • Hypertension • Sustained BP of 140 systolic or 90 mm Hg diastolic • Proteinuria • >300 mg protein in 24 hr urine collection • Preeclampsia • Mild • Severe • Eclampsia • HELLP

6. Features of Severe Preeclampsia • BP >160 systolic or 110 diastolic on two occasions atleast 6 hrs apart. • Proteinuria > 5gms in 24 hr urine • Oliguria: UO < 400 ml in 24 hrs • Cerebral or visual disturbances like HA, blurred vision or altered consciousness. • Pulmonary edema or Cyanosis • Epigastric or RUQ pain- Glisson’s cpasule being stretched • Hepatic rupture • Impaired liver function • Thrombocytopenia • HELLP Syndrome • Fetal compromise-IUGR, Oligohydramnios • LV dysfunction

7. Cardiovascular changes • ANP is higher • LV dysfunction • CVP can be misleading • No correlation between CVP and PCWP • Blood volume can be lower from 9% to 30-40% below the expected. • Higher SVR

8. Hematologic Changes • Colloid oncotic pressures are lower than in normal pregnancy • Hypercoagulability(accentuation of the normal hypercoagulablr state of pregnancy. • Activation of the fibrinolytic system • Platelet activation (severe cases it causes thrombocytopenia)

9. Changes that imply Hypercoagulability • Increased common pathway activity • Decreased Fibrinogen • Increased FDP • D-dimer positive • Decreased Antithrombin III ( AT III ) • Increased AT III antithrombin complex • Decreased platelets • Increased platelet aggregability • Decreased sensitivity to prostacyclin • Increased Beta-thromboglobulin • AT III levels are low. It is a protease inhibitor that inhibits active forms of Factors IX, X, XI, XII.

10. Renal Function • Decreased GFR 25% below normal • 122ml/hr in non-pregnant pts and 170ml/hr in pregnant pts • Glomerulopathy causes proteinuria • Serum creatinine rarely increase but if it does, it signifies substantial involvement • Urate clearance decreases and uric acid increases. • Mild preeclampsia often is associated with uric acid levels between 5.4-6.1mg/dl and severe is associated between 6.7-8.2 mg/dl. • Sodium excretion also diminishes. • Oliguria parallels the severity of preeclampsia

11. Endocrine • RAAS Renin, angiotensin I, II, aldosterone increase markedly in normal pregnancy as also prostaglandin (PGI2) synthesis and Nitric oxide. • Breakdown of this normal balance between vasodilators or normalization of vascular response to angiotensin II. • Deficient production of PGI2 • Lower ionized calcium levels • RAAS suppression and lower levels of plasma renin conc. and activity.

12. Respiratory, Hepatic, Neurologic Function • Pharyngolaryngeal edema • Pulmonary edema in 3% • Increased LFTs • Distention of liver capsule • Hepatic hemorrhage or rarely rupture • Headache, visual disturbances, CNS hyperexcitability and hyperreflexia. • Hypertensive encephalopathy and loss of cerebral autoregulation when MAP exceeds a critival value. • Other proposed etiologies for seizures are vasospasm, microinfarctions, punctate hemorrhages, thrombosis and cerebral edema.

13. Uteroplacental Perfusion • Decreased uteroplacental perfusion with increased downstream resistance, diastolic velocity decreases and systolic/diastolic ratio increases. • IUGR and Oligohydramnios

14. Treatment • Lab tests CBC, Coagulation assay, Electrolytes, BUN and creatinine, uric acid, LFTs, Urine 24 hr protein • Magnesium Sulfate. 4-6 gms bolus over 20 mins followed by 1 to 2 gms /hr. Pts should be monitored by reflexes respiratory rate, urine output and serum levels. • Therapeutic levels for Magnesium is 5-7 mg/dl • Loss of patellar reflexes at 10-12mg/dl, respiratory arrest at 15mg/dl and asystole at >20mg/dl. • Cardiac arrest is treated with Calcium gluconate 1gm or calcium chloride 300mg • Magnesium acts on cerebral NMDA receptors and peripheral neuromuscular junctions. • Decreased uterine activity, prolonged labor, excessive bleeding and neonatal depression. • Other drugs that can be used are Hydralazine, Labetalol, Nitroglycerine, Sodium nitroprusside and Nifedipine.