Hypertensive Disorders in Pregnancy 1

8/6/2019 Hypertensive Disorders in Pregnancy 1

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Hypertensive Disorders in

Pregnancy

Preeclampsia and Eclampsia


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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


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Epidemiology

Preeclampsia is a disorder of unknown

etiology affecting 6-8% of all

pregnancies.Between 1979 and 1986incidence of severe preeclampsia

increased from 2.4 per 1000 deliveries to

5.2.


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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 tothromboxane.

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 topreeclampsia.

Glutamine substitution for arginine in position 506 in Factor V molecule. This renders the protein resistant to proteolytic inactivationby 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 lipidperoxides. The latter activate cyclooxygenase and impair PGI2.synthetase.

In the absence of PGI 2 and nitric oxide surface mediated platelet activation occurs causing adhesion a nd damage to spiralarteriesnreleasing 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 VIIIcoagulant activity.Endothelial cell damagereleases vWF factor and thrombin inactivates factor VIII C activity hence increasing ratioof 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.


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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


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Features of Severe Preeclampsia

BP >160 systolic or 110 diastolic on two occasions atleast 6 hrsapart.

Proteinuria > 5gms in 24 hr urine

Oliguria: UO < 400 ml in 24 hrs

Cerebral or visual disturbances like HA, blurred vision or alteredconsciousness.

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


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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


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Hematologic Changes

Colloid oncotic pressures are lower than in

normal pregnancy

Hypercoagulability(accentuation of thenormal hypercoagulablr state of

pregnancy.

Activation of the fibrinolytic system

Platelet activation (severe cases it causes

thrombocytopenia)


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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 inhibitsactive forms of Factors IX, X, XI, XII.


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Renal Function

Decreased GFR 25% below normal

122ml/hr in non-pregnant pts and 170ml/hr in pregnantpts

Glomerulopathy causes proteinuria

Serum creatinine rarely increase but if it does, it signifiessubstantial involvement

Urate clearance decreases and uric acid increases.

Mild preeclampsia often is associated with uric acidlevels 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


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Endocrine

RAAS Renin, angiotensin I, II, aldosteroneincrease markedly in normal pregnancy as alsoprostaglandin (PGI2) synthesis and Nitric oxide.

Breakdown of this normal balance betweenvasodilators or normalization of vascularresponse to angiotensin II.

Deficient production of PGI2

Lower ionized calcium levels RAAS suppression and lower levels of plasma

renin conc. and activity.


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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 hyperexcitabilityand hyperreflexia.

Hypertensive encephalopathy and loss of cerebralautoregulation when MAP exceeds a critival value.

Other proposed etiologies for seizures are vasospasm,microinfarctions, punctate hemorrhages, thrombosis andcerebral edema.


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Uteroplacental Perfusion

Decreased uteroplacental perfusion with

increased downstream resistance,

diastolic velocity decreases and

systolic/diastolic ratio increases.

IUGR and Oligohydramnios


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Treatment

Lab tests CBC, Coagulation assay, Electrolytes, BUN andcreatinine, uric acid, LFTs, Urine 24 hr protein

Magnesium Sulfate. 4-6 gms bolus over 20 mins followed by 1 to 2gms /hr. Pts should be monitored by reflexes respiratory rate, urineoutput 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 calciumchloride 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.

Hypertensive Disorders in Pregnancy 1

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