This review integrates the currently available information on the molecular, cellular, and systemic mechanisms involved in the pathophysiology of preeclampsia. It highlights that the growth, protection, and promotion of the conceptus requires the modulation of an intact maternal immune system, communication between the mother and fetus, and adaptation of the maternal organic functions. A malfunction in any of these factors, on either side, will result in a failure of the cascade of events required for the normal course of pregnancy. Maladaptive processes, initially aiming to protect the conceptus, fail to anticipate the gradually increasing cardiovascular volume load during the course of pregnancy. As a result, multiple organ dysfunctions install progressively and eventually reach a state where mother and/or fetus are at risk of severe morbidity or even mortality, and where the termination of pregnancy becomes the least harmful solution. The helicopter view on pathophysiologic processes associated with preeclampsia, as presented in this paper, illustrates that the etiology of preeclampsia cannot be reduced to one single mechanism, but is to be considered a cascade of consecutive events, fundamentally not unique to pregnancy.
Keywords: extracellular vesicles; gestational physiology; immune tolerance; inflammation; intra-abdominal pressure; maternal hemodynamics; pathophysiology; preeclampsia; venous congestion; venous hemodynamics.