What happens biologically during Pre-E

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Re : What happens biologically during Pre-E

Postby caryn » 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. :-/

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Re : What happens biologically during Pre-E

Postby laura » Sat May 20, 2006 08:45 pm

Also this explains why there's no 'cure' for preeclampsia. BP meds don't work- because the high blood pressure is just the reaction to the problem.

So, the 20 million dollar question is: How would you fix it, after it has already started? How do you increase the blood flow to the baby without damaging something else?

So preeclampsia is essentially the reaction to something that happened probably before you even knew you were pregnant!

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Re : What happens biologically during Pre-E

Postby laura » Sat May 20, 2006 08:41 pm

And I can expound a little more, until we get our science chicks in here.

As Ileana describes, there's a problem with the placenta. Recent research has established that the blood vessels attaching the placenta to the uterus in preeclamptic women aren't as deep or strong as they should be.

This set up works fine for the first part of pregnancy, but often there's a point where the baby grows large enough that these puny little vessels don't supply as much blood as the baby needs. The body responds by racheting up the blood pressure. Well, hyperperfusion might work for getting more blood to the baby- but it is a bad long term strategy, as the increased blood pressure can cause organ damage (most commonly to the kidneys) but also to the placenta itself.

In an attempt to keep the organs from getting blasted by this pressure- the body then starts the vasospasm part- the blood vessels start shutting intermittently on their own-- which can cause a whole host of other problems, including further damage to the vessels and destruction of red blood cells and platelets.

Meanwhile, the vessels begin to show the strain by leaking from the pressure and vasospasm. The watery part of the blood seeps out of the veins and acumulates in the extremities, like hands and feet. The swelling can get extreme, and the extra fluid the body has to process further stresses the kidneys, that are already groaning under the increased blood pressure. If it gets extreme, the fluid doesn't get pushed out, the kidneys don't work as well, and the swelling becomes pathologic-- it can end up as pulmonary edema in the lungs, or around the heart, or the swelling can enter the cranium and compress the brain and cause strokes or hemmorages.


Hope this helps!

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Re : What happens biologically during Pre-E

Postby ileana » Sat May 20, 2006 07:12 pm

I'm sure that there are others that understand and can explain the process better than I do, but they might not be able to get in here during the weekend. I read these things about 3 years ago, and I'm too lazy to go get quotes from books, but here's what I remember.

Preeclampsia is a disease of the placenta. I think that there are multiple mechanisms that can cause the placenta to get diseased, and there's a whole theory on what actually goes wrong. Anyway, in the end, the diseased placenta starts influencing the other organs.

There is no specific diagnostic test for preeclampsia/diseased placenta, but the most common systems that fail when preeclampsia strikes are the endothelium (which causes the hypertension and swelling) and the kidneys (causing them to start not filtering all the protein). Other systems that may fail are: liver - elevated liver enzymes causing right upper quadrant pain and epigastric pain, blood: low plateles and/or hemolisys, central nervous system: reflexes, visual disturbances, etc. Swelling can be that bad that it affects eyes and cause THE headache.

So basically when two or more systems start failing after 20w (when the placenta is fully functional), they diagnose preeclampsia.

Thanks for the great question! I hope this answers at least part of your question!

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Re : What happens biologically during Pre-E

Postby princess purr » Sat May 20, 2006 06:16 pm

I'm not a pro or a doc, but I think with the protien your kidneys are not working properly and not breaking down protein so it passes through your urine
With blood pressure I think you vessels are restricking and not relaxing making the pressure go with.
I'm not sure what causes hypereflexia but I had that majorly. Your reflexs are in over drive. The doc would just touch my knee and my leg would move.
Hopefully someone has better answers them me!

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What happens biologically during Pre-E

Postby abbie » Sat May 20, 2006 05:30 pm

Okay ladies, I'm sure a lot of you have researched a ton about this disorder and may help to provide me some insight into what it really means to have Pre-E. I have a minor in bio/ and took lots of chem in college... but I have no clue how this works.

What exactly is happening that makes your BP rise and your protein to enter your urine? What do these symptoms do to your body chemically/biologically? Also, what's up with the hypereflexia - how does that enter the picture?

Any little tidbit of info would be great.

Thank you all in advance.


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