by caryn (10131 Posts), Sat May 20, 2006 09:32 pm
I'm only one of the resident science chicks, so this will probably get expanded further, but here's a little more expansion on Laura...
It is looking very much these days like the problem with the initial implantation of the placenta is caused by a response to the foreign proteins of the placenta, which the immune system either a) recognizes as an invader, and attempts to reject, or b) fails to reject strongly enough (!) . All sorts of things can predispose you to this problem: an autoimmune disease, a family history of hypertension, multiples, any of the various forms of insulin resistance like diabetes or PCOS or GD, and so forth. Perhaps the reason "first baby" is a risk factor is that the immune system has to practice recognizing and responding to fetal DNA in order to handle it properly; we really don't know.
At any rate, the placenta's spiral arteries just don't get in there deeply enough, and the placenta ends up shallowly implanted and sometimes abnormally small because its normal growth has been compromised by the immune system as well. Scientists are pretty sure about this part; almost every study I've seen lately starts off with a first sentence along the lines of "Preeclampsia is characterized by poorly implanted placentae that..."
The theory goes: right around mid-pregnancy, the fetus begins to pack on weight and demand more blood across the placenta, but the placenta can't ferry it. The fetus begins to be shortchanged with respect to oxygen and nutrients (so IUGR is often associated with PE.) Our best guess at this point is that when the placenta becomes hypoxic, a protein called sFlt-1 gets expressed in its cells. (SFlt-1 stands for soluble fms-like tyrosine kinase, which is a mouthful.)
Ordinarily our bodies produce a lot of something called VEGF, for vascular endothelial growth factor. VEGF's "job" is to rattle around the blood vessels looking for leaks, and plug them -- it shepherds repair molecules into the holes blood vessels develop as they age. SFlt-1 is a VEGF antagonist, which means it binds to VEGF and makes it unable to do its job.
This loss of VEGF means the vessels become leaky (so swelling, sometimes oliguria, and cerebral edema, which explains the headache, visual disturbances, and hyperreflexia) and the kidneys aren't repaired so they can't filter properly (so you start to spill protein) and the liver starts to become toxic (so all the bad bloodwork showing liver damage -- sFlt-1 is hepatotoxic.) Edema can increase pressure on the blood vessels from the surrounding tissue. As if this weren't enough, all sorts of vasoconstrictors start to be expressed as well, tightening down the blood vessel walls and further raising pressures. That constellation of responses is pretty much the clinical definition of "multiple organ failure."
Oddly enough, sFlt-1 is present in *all* pregnancies -- it's just present early, and in phenomenally large quantities, in hypertensive pregnancies. The hypothesis here is that ordinarily placentae are only significantly hypoxic during labor contractions, and that production of sFlt-1 would help to detach the placenta from the uterine wall. So this explains the high rates of placental abruption in the population of hypertensive pregnancies.
And some people have existing hypertension, kidney or liver damage, etc -- which means their bodies are just that much more sensitive to the beginning of this cascade. When things start to go wrong, they touch off a feedback loop, and things often get much worse very quickly as one cause drives an increase in the effect of another. The average time from diagnosis to delivery is right around two weeks, and we've had the whole gamut from mild PE posters who go for months on bedrest, to women who crash into HELLP syndrome between their 2 pm OB appointment and the start of SNL.
So it's *REALLY* important to monitor your own symptoms, push for further testing, and generally keep your eyes peeled for further problems if you've gotten a positive diagnosis and you aren't already in the delivery room. Better safe than sorry.
Hope this helps some, and I don't mean to scare you. Unfortunately it's a scary disease. :-/