Scientists find cause of preeclampsia?

[joelle]

I just wanted to say thanks to you all for helping me understand this research (especially Caryn!). This has featured fairly prominently in the British press and it was only through this forum that I've really understood it, so thank you.

[catherine]

Caryn's NHS link is excellent. Not only does it summarize the research, but it also evaluates the strength of some of the newspaper-derived claims regarding the significance of the findings. If only there was more material like that available!

[blythe]

Thanks for the extra nudge to read the NHS link. Wow. I have found a new site to add to my favorites!

[celticepona]

Ok just to summarize, and correct me if I am wrong (I am a very concrete thinker and layperson ;) ) ..they are basically saying if an ACE inhibitor could hypothetically be used to treat high blood pressue in preeclampsia? Of course it could if it werent for the dangers to the baby! I take an ACE inhibitor when I am not pregnant, Altace, and as soon as I deliver I am switched from Aldomet back to Altace to get my bps back under control as it is obviously a more powerful bp med...but as you all have mentioned it cannot be used during pregnancy...hence those of us on Aldomet and other bp drugs that seem to be 'weaker' towards the end of the pregnancy often are not effective in controlling the bp...and yes Altace is excellent at keeping bps under control postpartum...but PRE-E is indeed much more than high blood pressure and encompasses so many more symptoms...but lets hope that this research points us closer to finding a "cure."

[caryn]

Yes, it says that in PE women, the ratio of the kinds of angiotensinogen is off a bit. The kind that is easy to cleave into angiotensin is more common in our bloodwork. This might explain why chronic hypertensives respond to ACE inhibitors (if they don't develop that horrid cough that an awful lot of people experience as a side effect) and might be a reason to use ACE inhibitors on PE patients outside of pregnancy, and might tell something interesting about which pathways to target -- but it would be hard to design a trial that could use ACE inhibitors in pregnant women ethically.

You could probably do it -- but it would be difficult. And honestly, I'm not convinced it would help all that much, since *all the other problems* would still be there, like the shallowly implanted placenta.

Theoretically, let's say that you can keep the mother's bp from rising with a drug that's safe for pregnancy that exploits this pathway. Isn't that possibly bad, because the placenta is raising the mother's blood pressure *on purpose* to pump more blood across the interface to the fetus? Isn't the blood pressure increase *adaptive* in a lot of normal pregnancies? I mean, the objections to lowering bp via meds are still in play if this pathway becomes targetable -- the ones that point out how IUGR and compromised blood flow and bp meds don't play together well! This wouldn't solve the problem of a shallowly implanted placenta, so while I can imagine it being helpful for a subset of chronics... I can also imagine it being unhelpful for many other PE patients.

As is often the case, this is highly preliminary stuff. Very interesting highly preliminary stuff. :)

[amandamm]

quote:

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Originally posted by Caryn
Theoretically, let's say that you can keep the mother's bp from rising with a drug that's safe for pregnancy that exploits this pathway. Isn't that possibly bad, because the placenta is raising the mother's blood pressure *on purpose* to pump more blood across the interface to the fetus? Isn't the blood pressure increase *adaptive* in a lot of normal pregnancies? I mean, the objections to lowering bp via meds are still in play if this pathway becomes targetable -- the ones that point out how IUGR and compromised blood flow and bp meds don't play together well! This wouldn't solve the problem of a shallowly implanted placenta, so while I can imagine it being helpful for a subset of chronics... I can also imagine it being unhelpful for many other PE patients.

As is often the case, this is highly preliminary stuff. Very interesting highly preliminary stuff. :)

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I will start off saying that you know WAY more about all this than me... but when your blood pressure rises it isn't because you are pumping MORE blood... blood pressure is how much pressure your blood is putting on the vessels, no? That is how my husband explained it to me...

[caryn]

True enough! That's what comes of typing quickly on my phone keyboard. :)

The placenta is "trying" to improve the oxygen and nutrient exchange rates at the placental interface with the maternal bloodstream. In a normal pregnancy, it does this in at least two ways. One is to embed very deeply into the maternal arteries so that blood is almost falling downhill into the placenta -- because there is so little resistance to flow. It replaces the maternal cells lining the arteries with its own cells which are not responsive to maternal vasoconstrictive signalling. So the arteries stay flared open all the time and oxygen and nutrients bathe the placental interface and the fetus can take whatever it needs and grow as rapidly as it would like. The other is to upregulate maternal blood volume so that the mother actually has more blood in her system than a nonpregnant woman.

In a PE pregnancy, the spiral arteries don't get remodelled to the same extent. In some cases this is a genetic issue where the cells doing the remodelling cannot affect the maternal immune response in the normal way. In some cases it might be preexisting maternal inflammation that affects their ability to signal each other. (It's like noisy crosstalk instead of a clean radio signal.) It has some connection to the fact that the mother's body *wants* to restrict the degree to which the fetus can grow, so that it will still fit out of the pelvis at birth, so when it detects an environment that will cause the fetus to grow too rapidly, it compromises implantation to restrict growth somewhat.

This affects both strategies. Not as much blood can flow through the arteries, and also the ability of the placenta to turn up maternal plasma volume is compromised.

So since the placenta can't use those strategies, instead it turns up the frequency with which the blood is pumped past the interface by turning up the pressure. So it's trying to get the same amount of nutrients and oxygen from the smaller amount of available blood by increasing the frequency with which it circulates. IIRC this can also cause more tachycardia (faster maternal pulse) and more shortness of breath and more hunger for maternal symptoms.

Does that make more sense? I have a shorthand explanation of this stuff in my head that doesn't always do justice to the complexity of the physiology!

[amandamm]

I think I am totally lost! haha!

[caryn]

It is an *insanely complicated disease*.

How about this? Turning up the pressure makes the same blood go past your lungs and digestion and then past the placenta more often, by pumping it around the cycle more rapidly. So the fetus can strip lots of oxygen and nutrients out of the bloodstream even if the placenta isn't bathed in as much blood as a normal pregnancy.

What happens here is another differential, for math people -- or, for not-math people, what happens here is like a waterfall. The oxygen and nutrients flow across the placental interface because, chemically speaking, across the interface is downhill. That difference in heights is like the difference in oxygen content on either side of the placenta -- the oxygen etc. wants to flow downhill, across, to the fetus.

In addition to this difference in chemical composition between the maternal and fetal sides, usually the blood wants to fall into the placenta as well, because of what they call a pressure gradient. It's like the placenta is way downhill from the rest of the body, so blood preferentially goes there. (Brains are also like this.) But because of the way the placenta sets up, the waterfall isn't as big in a PE pregnancy as it is in a normal pregnancy. Normal pregnancies have a 20-foot waterfall where we have a slight downhill slope and/or maybe a couple of feet of drop.

Honestly, I kept emailing people and going to conferences until this made sense to me, and I could still have it wrong. :) It's weird and not terribly well-understood and I'm not a physiologist, either.

[caryn]

Our Medical Board has weighed in here.