The Reproductive Physiology of Preeclampsia
The Reproductive Physiology of Preeclampsia
Written By: Neha Suresh, Intern
Human pregnancy has been extensively studied to understand the physiology of a birthing person during this time. Preeclampsia is a pregnancy complication characterized by hypertension (high blood pressure), proteinuria (protein in the urine), and edema (swelling) - all of which are signs of damage to organ systems, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in birthing people whose blood pressure had been normal. The risk factors are so broad that doctors test every pregnant person for signs of preeclampsia by measuring blood pressure and checking the urine for protein, usually at every prenatal appointment beginning at 20 weeks.
If left undetected, preeclampsia can lead to serious complications, such as eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelet count) syndrome, and seizures for the birthing person. For the foetus, preeclampsia could lead to placental abruption (the removal of the placenta from the uterus prematurely), fetal growth restriction, and preterm birth.
Preeclampsia has remained one of the great medical mysteries of our time; very little is understood about the source of the disease. Our current understanding of the disease is based on investigation of the placental stage of development. This article is a deep dive into the different types of hypertension that occur during pregnancy, the specific physiology of preeclampsia, and related conditions.
Hypertensive disorders of pregnancy complicate 10% of pregnancies worldwide. Hypertension during pregnancy is classified based on the severity and time of occurrence. Mild forms of hypertension include chronic and gestational hypertension. Chronic hypertension is not caused by pregnancy, and is a result of a birthing person having high blood pressure for years preceding the pregnancy. Gestational hypertension is the physiological increase of blood pressure in the early stages of pregnancy. If developed after 20 weeks of pregnancy, this increase in blood pressure is considered gestational hypertension and usually resolves itself after 12 weeks of giving birth.
The more severe types of hypertension disorders during pregnancy are preeclampsia and eclampsia. Preeclampsia is classified with hypertension (systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg), proteinuria (protein in urine, ≥0.3 g protein in 24-h urine specimen), and end organ damage. Eclampsia occurs when a birthing person with preeclampsia develops seizures.
Recently, other aspects of childbirth, such as postpartum depression, have been studied with respect to preeclampsia, prodding further research and analysis into this condition. Most studies have concluded that birthing people with preeclampsia develop postpartum depression as a consequence of seeing their newborn child in the NICU.
Additionally, the long term effects of preeclampsia include elevated risk of hypertensive and cardiovascular disease for the birthing person. Intrauterine exposure to preeclampsia for the fetus results in predisposition to neurological disorders such as ADHD and metabolic abnormalities. (Lu et. al, 2019)
Understanding preeclampsia requires an understanding of the intricacies of a normal pregnancy. The uterus is a small, muscular organ with three layers- the outermost perimetrium, the middle, myometrium, and the innermost layer, the endometrium. The endometrial layer is shed every month during menstruation and, during pregnancy, the same endometrial layer is transformed into a protective mucous layer, called the decidua for the foetus.
Terminal branches of uterine arteries, called spiral arteries, infiltrate the myometrium and are transformed during pregnancy. During the pregnancy, spiral arteries remodel themselves from narrow, thick walled blood vessels to larger vascular channels that allow a larger amount of oxygen to flow through them.
Thirty hours after fertilization, the fertilized cells, on their way to become the embryo, begin to rapidly divide. On the sixth day, these dividing cells are called the blastocyst. Trophoblasts are cells that form the outer layer of this blastocyst, and they develop into a large part of the placenta, the nutrient source for the embryo. Trophoblast invasion into the decidua and then into the myometrium with spiral arteries is a critical process in establishing a successful pregnancy.
The fertilized cells are considered an embryo after 10-12 days of fertilization, and the embryo is considered a foetus at the 8 week mark of gestation. The key cause of preeclampsia most likely lies at the blastocyst stage, far before the development of an embryo.
Pathophysiology of Preeclampsia
Figure: (Redman et al, 2018)- Normal vs preeclamptic pregnancy
Preeclampsia results if either the trophoblasts do not invade the decidua properly or the spiral arteries do not remodel themselves enough to accommodate the pregnancy. If the placenta can’t gain access to the spiral arteries, this cuts off large supplies of blood and oxygen. As the pregnancy progresses, this problem intensifies.
A sharp decrease in the oxygen supply causes the placenta to release factors that alter the pregnant person’s circulatory system. In particular, these factors damage the endothelial cells that line blood vessels throughout the body. Blood vessels can no longer relax, causing preeclampsia’s characteristic hypertension.
Therefore, preeclampsia can prevent the placenta from getting enough blood. If the placenta doesn’t get enough blood, the foetus gets less oxygen and food. This can result in low birth weight and a restriction of growth for the foetus from the dysfunction of the blood vessels.
When damaged, endothelial cells of the birthing person release clotting factors, which lead to unnecessary clots throughout the body, making this a dangerous condition.
In addition, damaged endothelial cells allow protein to leak from the blood vessels. When this happens to blood vessels in kidneys, the protein leaks into the urine leading to preeclampsia’s second hallmark proteinuria, i.e. protein in urine. Since blood vessels all through the body are affected, this leads to a range of symptoms including headaches, increase in liver enzymes, and stomach pain.
When the kidney’s filtration system is damaged, a leakage of water is followed by a leakage of protein. Water and protein leaks into the tissue causing swelling, also called edema, throughout the body. This swelling is usually much worse than what is seen in a normal pregnancy.
If left untreated, preeclampsia develops into eclampsia once seizure activity occurs. Prolonged damage to a birthing person’s arteries restricts blood flow to the brain. When this abnormal blood flow interferes with the brain's ability to function, seizures occur.
For this period, a birthing person with preeclampsia is administered with magnesium sulfate, an anti-epileptic agent. While Magnesium sulfate is an effective anti-epileptic, the need for alternate therapeutics is imminent due to the lasting side effects and toxicity of magnesium sulfate. Therefore, early diagnosis of the condition and management of symptoms is vital for the health of the birth parent and child.
Postpartum preeclampsia, a rare condition that is most probably caused by the shift of fluids, affects the clotting of blood and breakdown of red blood cells after delivery leading to HELLP Syndrome, a life threatening condition. This is rare, but regular observation during and after the pregnancy is advised.
Currently, there is no sure way to prevent preeclampsia. Some contributing factors to high blood pressure can be controlled such as lowering salt consumption, increasing water consumption, regular exercise, and lying on your left side to reduce pressure on the blood vessels.
Studies have shown that calcium supplementation or low-dose aspirin may help some gestational individuals in specific circumstances, but not enough to recommend them to all pregnant individuals.
For both preeclampsia and eclampsia, what we do know is that an earlier diagnosis could help better manage the condition and save lives. Rigorous observation is necessary to make an early diagnosis of this little understood condition so that it can be managed and treated to prevent preterm birth and fatalities.
The greatest risk of eclampsia is just before delivery, during labor, and a day after delivery due to the maximized pressure on arteries at these times.
Most birthing people with preeclampsia still can deliver a healthy baby if the condition is detected early, and they receive regular prenatal care. Pregnancy is the human body’s most beautiful, complicated, and trying condition. Birthing people are advised to take this time to rest, monitor for signs, and listen to the needs of their body.
References
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