Pathophysiology of Preeclampsia
Gustaaf A. Dekker and Baha M. Sibai
Preeclampsia, occurring in 3-5% of pregnancies, is a major cause of maternal mortality, (iathrogenic) preterm birth, intra-uterine growth restriction (IUGR), and perinatal mortality. Long-term follow-up studies have demonstrated that babies who suffered IUGR are more likely to develop the so-called insulin resistance syndrome in adult life. Shallow, endovascular cytotrophoblast invasion in the spiral arteries, inappropriate endothelial cell activation and an exaggerated inflammatory response are key features in the pathogenesis of preeclampsia. In normal pregnancy, the cytotrophoblast invasion in the spiral arteries results in the around 100-120 spiral arteries being transformed from narrow arterioles into dilated, inelastic tubes without maternal vasomotor control. In preeclampsia, these physiologic changes in the spiral arteries are confined to the decidual portion of the arteries. The myometrial segments remain anatomically intact and do not dilate, and the adrenergic nerve supply to the spiral arteries remains intact.
The maternal syndrome preeclampsia is caused by a complex generalized dysfunction or inappropriate activation of the maternal endothelium, already detectable in the late first trimester of pregnancy. The endothelial activation is part of an exaggerated generalized (intravascular) inflammatory reaction involving leucocytes as well as the clotting and complement systems. Based on currently available data, the authors would like to propose an etiologic/pathogenetic model of couple specific immune maladaptation -driven superficial placentation with subsequently decreased free circulating levels of angiogenic growth factors and increased placental debris in the maternal circulation resulting in a (mostly hypertensive) maternal inflammatory response syndrome.
In recent years, exciting research data have shown that the maternal clinical syndrome of preeclampsia is an anti-angiogenic state resulting from an excess of anti-endothelial factors liberated by the diseased placenta. The final phenotype, the severity and specifics of the maternal preeclamptic syndrome being modulated by pre-existing maternal cardiovascular/metabolic ‘fitness’ including acquired and genetic thrombophilic disorders, auto-immune disorders, chronic hypertension, obesity, and a large series of maternal susceptibility genes.
Main Topics: Preeclampsia : Pathophysiology
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