Hypertensive Disorders in Pregnancy - 4 | Fruit of the Womb
Fruit of the Womb
Fruit of the Womb

Hypertensive Disorders in Pregnancy - 4

In our last post, we mentioned that preeclampsia is often the end-stage clinical manifestation of irreversible pathologic changes that take place early in pregnancy. Indeed, there is good evidence that abnormal early placental development plays a key role in setting the stage for a woman to eventually develop preeclampsia, especially in its most severe forms. We know that pregnancy is a prerequisite for preeclampsia, but the presence of a baby is not! Some of the most severe and earliest onset cases (sometimes before 20 weeks) of preeclampsia occur with ‘molar pregnancies’ characterized by abnormal placental tissue and no baby. However, molar pregnancies do not typify the more common placental abnormalities seen in preeclampsia. The example does make the point, however, that all you need is a placenta that isn’t ‘happy’ with its intrauterine environment and somehow this can lead to the clinical picture of preeclampsia. So, what are the placental abnormalities that culminate in preeclampsia.

Once upon a time, in a post long, long ago, we talked about early embryonic development. Shortly after the early embryo (the zygote) first enters the uterus, it begins to ‘differentiate’ into some cells that will eventually form the baby and others that will eventually form the placenta. At this point, the ‘baby’ is called a ‘blastocyst’ and it must attach to a favorable location on the inner lining of the uterus (the endometrium) within about 48 hours. Over the next week (and prior to the time of the next expected menstrual period), the blastocyst solidifies its attachments to the endometrium and, while continuing to differentiate into tissues that will eventually form the placenta or the baby, literally buries itself in the endometrial lining.

The early placental cells (trophoblasts) first anchor the blastocyst to the endometrium. Over the next 6 weeks (the embryonic period), as all the major internal and external structures of the baby are developing, some of the trophoblasts undertake an essential and, potentially, dangerous journey through the maternal endometrial tissues where they are exposed to both nonspecific and specific mediators of the mother’s immune response. Under optimal (normal) circumstances (if the mother’s immune responses help them out), at the end of this journey the trophoblasts will actually invade and replace (remodel) the lining and muscular walls of the mother’s ‘spiral arterioles’ in the endometrium (between 6-10 weeks) and upper third of the myometrium (between 14-22 weeks).

Ultimately, this ‘decidualization’ of the spiral arterioles transforms them from narrow, coiled, high resistance blood vessels into structures (‘uteroplacental vessels’) with low resistance and high capacitance, through which blood readily flows to fill the placental bed. During this process, these vessels also lose their ability to constrict in response to common factors/conditions that cause other blood vessels in the mother’s body to constrict, thereby assuring blood flow to the placenta, even under circumstances such as stress that might otherwise interrupt placental perfusion and cause damage to the baby.

We have known for several decades that abnormal invasion of the spiral arterioles is characteristic of preeclampsia, however, it has only been in recent years that another very important part of this process has been recognized. It appears that with normal placental development, in the first wave of invasion, the fetal trophoblasts not only replace the lining and muscular wall of the endometrial portion of the spiral arterioles, but also PLUG these vessels at their tops, thereby limiting blood flow into the growing placental bed during first trimester. This seems somewhat counter-intuitive. Don’t the developing baby and placenta need all the oxygen they can get from the maternal blood? Apparently not! Indeed, it appears that until a certain stage of development (10-12 weeks), oxygen might actually be toxic to the fetal tissues.

Furthermore, limiting the amount of oxygen also seems to promote the elaboration of certain growth and angiogenic (blood vessel growth promoting) factors that allow the placenta to grow (arborization of the placental villi that are bathed by maternal blood in the placental bed) to a size that will be necessary to transport sufficient oxygen and nutrients to the baby at later stages of the pregnancy. Anyway, even though we do not understand how, it appears that in pregnancies destined to develop preeclampsia, the normal ‘plugging’ of the spiral arterioles does not occur and this results not only in a smaller placenta, but a situation in which blood flow is impeded from both the maternal side (spiral arterioles) into the placental bed and the fetal side, through the vessels of the truncated placental villi.

Although these abnormalities in placental development do not result in preeclampsia until later in pregnancy, there are certain things we can look for during pregnancy that can suggest these abnormalities are present and the pregnancy is ‘at risk’. In the next post we will discuss them and some of the clinical features of preeclampsia that develop, probably, as the placental response to the ‘hostile’ environment that eventually results from these changes…
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