Pathophysiology of the Clinical Manifestations of Preeclampsia

Five to 7% of all pregnancies are complicated by preeclampsia. Proteinuria and hypertension dominate the clinical picture, because the chief target organ is the kidney (glomerular endotheliosis). The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease (1). The first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other end-organ damage. This review focuses on the pathophysiology of stages 1 and 2 and then considers the potential that changes in soluble angiogenic factors may underlie much of the disease process. On the basis of the observation that the only definitive cure for preeclampsia is delivery of the placenta and that women who experience a molar pregnancy, in which a placenta develops without a fetus, frequently develop severe preeclampsia, it is reasonable to assume that the placenta plays a central role in the pathogenesis of the disease. Pathologic examination of placentas from preeclamptic pregnancies generally reveals placental infarcts and sclerotic narrowing of arteries and arterioles, with characteristic diminished endovascular invasion by cytotrophoblasts and inadequate remodeling of the uterine spiral arterioles (2). Although gross pathologic changes are not always seen in the placentas of women with preeclampsia, placental profiles including abnormal uterine artery Doppler and placental morphology have been used to identify a subset from a cohort of high-risk women who go on to develop the syndrome (3). Uterine artery Doppler studies that assess the pulsatility index (PI) reveal increased …