Once again, let's start with my disclaimer.
Yesterday, we explored the Maternal-Fetal Conflict, the idea that pregnancy complications result from mother and child having different needs for their survival. Dr. David Haig theorized that the fetus must be sending some signal to the mother that led to the cascade of symptoms in preelcampsia. This work was built on by Dr. Ananth Karumanchi, who discovered two proteins that can explain almost every symptom that comes up in PE.
In a normal pregnancy, the placenta digs into the uterus, building new blood vessels and redirecting nutrients and oxygen to the growing baby. Early on, the baby doesn't need much, but the placenta is taking quite a bit to store up for later. As the baby gets bigger and bigger, it requires more and more nutrients.
During labor, the flow of blood to and through the placenta is significantly lessened during contractions. This isn't a problem, though, because the placenta has such a good store saved up. It dips into its supplies and keeps the baby well nourished and oxygenated during this process. As the saved oxygen is transferred to the baby, the placenta starts to release a protein called sFlt1. This protein binds to another protein found in the body, VEGF, which is the "repairman" of the circulatory system. Once sFlt1 has bound to VEGF, it can no longer repair the blood vessels.
When this process happens in a normal labor, the sFlt1 is limited to the placenta and only affects the repair of the blood vessels connecting the placenta to the uterus. This serves an important function in allowing the placenta to detach after delivery.
In PE, the placenta does not attach as well or as deeply to the uterus as it should. It simply cannot ferry the nutrients and oxygen in the amounts needed. Early on, this isn't a problem, but as the baby gets bigger and demands more, it can't keep up. It starts dipping into its savings long before labor has begun. This means sFlt1 is released earlier and in larger quantities and has a chance to move out of the placenta into the mother's blood stream. As it spreads throughout her body binding to her VEGF, the normal wear and tear on her blood vessels isn't repaired.
Fluid starts leaking out of the blood vessels into the surrounding tissue, leading to swelling. Mom's body reacts to this leaking by tightening down the blood vessels, which in turn raises the blood pressure. As the blood vessels in the kidney become leaky, protein in the blood slips through into the urine. And that right there is preeclampsia.
The higher blood pressure forces more blood to and through the placenta, leading to a temporary improvement in nutrient transfer to the baby, but it also causes damage to the blood vessels which weren't all that great to begin with. This leads to worse nutrient transfer, more dipping into reserves, more sFlt1, and a continuing cycle of more and more damage. The only way to stop it is to remove the placenta, aka deliver the baby.
Dr. Karumanchi found the levels of sFlt1 were elevated in women with PE, and that levels started to increase on average 5 weeks before symptoms appeared. However, the higher levels weren't much different between those women with mild PE and severe PE/HELLP. He reasoned there must be another chemical at play. It turned out to be endoglin, which is toxic to the liver and affects red blood cells and platelets.
These two proteins, sFlt1 and endoglin, can explain almost everything in PE. There may be other proteins involved as well. Research, as always, is ongoing.
The most exciting prospect from this research is the possiblity of a screening test. If women can know five weeks in advance that trouble is coming, they can be monitored more closely and their symptoms managed to give both mother and baby the best chance of survival.