Hypertensive Disorders in Pregnancy

Preeclampsia and Eclampsia

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

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.

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. 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. 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 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. 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. Altered handling of fatty acids by the liver is key in the pathogenesis of preeclampsia.

Genetic factors

Endothelial Factors

Coagulation Factors

Calcium

Fatty Acid Metabolism

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

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- Glissons cpasule being stretched Hepatic rupture Impaired liver function Thrombocytopenia HELLP Syndrome Fetal compromise-IUGR, Oligohydramnios LV dysfunction

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 3040% below the expected. Higher SVR

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)

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.

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

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.

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.

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

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.