Gjeldende hypoteser om patofysiologien ved preeklampsi : en gjennomgang og diskusjon av litteraturen

Preeclampsia is a maternal syndrome characterized by new onset hypertension and proteinuria in pregnancy. The pathogenesis in preeclampsia is still not fully understood. The leading hypotheses suggest that one or several vasoactive factors produced in the placenta enter the maternal circulation and may cause widespread endothelial dysfunction. This in turn gives rise to the clinical features of preeclampsia. The reason for an increased (or altered) release of vasoactive substances in preeclampsia is not well understood. Currently the most accepted explanation is that placenta in preeclamptic women is more ischemic due failure of the trophoblast to mediate a sufficient transformation of the maternal uterine spiral arteries that supply oxygenated maternal blood to placenta. Current research has provided many possible mediators of the endothelial dysfunction. This student thesis first gives an overview of the most frequently mentioned factors. These include soluble fms-like thyrosinkinase-1 (sFlt-1), soluble Endoglin (sEng), Vascular endothelial growth factor (VEGF), Placental growth factor (PlGF) and Nitrogen monoxide (NO). While NO is an important vasodilator, the other factors are primarily involved in angiogenesis. Oxidative stress with an increased production of reactive oxygen species and lipid peroxides is also a possible contributor of cell damage and endothelial dysfunction in the mother. The pathogenesis of preeclampsia is complex and multifactorial. An increase of maternal levels of vasoactive mediators can as a general model explain the development of the clinical symptoms, but is insufficient to explain the endothelial dysfunction in all women with preeclampsia. Studies have shown that women who develop preeclampsia don’t necessarily have elevated levels of mediators associated with preeclampsia, and, vice versa, women without preeclampsia may have “preeclamptic” levels. Similarly, women with preeclampsia may have normal trophoblast invasion and faulty trophoblast invasion may be seen in normal pregnancies. Thus, it may be hypothesised that preeclampsia is a syndrome consisting of distinct subgroups that differ in terms of pathogenesis. As discussed in the last part of my thesis these “paradoxes” are not always considered in the review literature of preeclampsia. Still, sufficient hypotheses of the patophysiology of preeclampsia should be able to explain all cases of the disease. I fact, in may be questioned whether it is reasonable to consider “preeclampsia” as an entity that has a common pathogenetic pathway, i.e. a disease or a syndrome. Future research should be based on such hypotheses