Pre-eclampsia Pathogenesis

The exact pathology behind pre-eclampsia is unknown but is thought to involve abnormal development of the placenta due to problems with the blood vessels that supply it. Studies have shown that inadequate blood supply to the placenta may also lead to the release of certain hormones and chemicals that damage the endothelium, the layer of cells that line blood and lymph vessels, leading to changes in inflammation, metabolism and possibly other reactions.

Some of the factors that are associated with pre-eclampsia pathology include:

• A placenta-derived TGF-beta coreceptor, soluble endoglin (sEng) is raised in cases of pre-eclampsia and falls after delivery of the baby. Levels of sEng also correlate with disease severity. sEng prevents the binding of TG-beta to its receptors and interrupts the cell signalling that leads to vasodilation.
• Natural killer (NK) cells are important regulators of placental formation. They are recruited in large numbers to the implantation site where they play an important role in the remodelling of the endometrium in preparation for pregnancy, a process called decidualization. NK cells enhance maternal immune tolerance of the placenta and suppress the inflammation caused by pathogenic T-helper cells. Disruption of the balance between anti- and pro-inflammatory immune cell populations may interfere with normal placentation and contribute to the pathology seen in pre-eclampsia.
• Studies also suggest that abnormal immune responses to the fetus or to inflammatory triggers may cause pre-eclampsia. Women with pre-eclampsia have been shown to have increased levels of circulating fetal erythroblasts and cell-free fetal DNA. This points to a pathogenesis that involves placental lesions leaking fetal material into the mother’s circulation and triggering immune reactions that cause endothelial damage and the symptoms of pre-eclampsia.
• Severe pre-eclampsia progresses to fulminant pre-eclampsia that may cause severe headaches, vision problems and abdominal pain in addition to the HELLP syndrome and eclampsia. HELLP is a serious complication of pre-eclampsia, with the letters denoting hemolyisis, elevated liver enzymes, and low platelet count.