Pathophysiology Of Pregnancy Induced Hypertension And Pre-Eclampsia

The first posting of my final year of the medical school is Obstetric and Gynaecology (O&G) so for the next 7 weeks or so, I'm going to write once per week articles related to this. To be completely honest, I'm not fond of O&G but I need to study and grasp concepts related to this subject so I would be able to perform well in the professional exam that would be held in August 2019. I spent roughly 6-7 hours in the ward (the rest of it in the library) trying to familiarise myself with signs and symptoms related to conditions of this discipline. It's not an easy task, it's actually easy if you were interested in it, but I'm not, so it will be twice as hard for me.

In this article, I'm going to write as simple as possible regarding one of the most detrimental conditions of a pregnant mother called Pregnancy-induced Hypertension (PIH) as it is associated with a high morbidity and mortality rate if it is not diagnosed early or managed properly. I'm sure the majority of us understand and quite familiar with hypertension, even if you are not taking medicine as your major subject. According to a study conducted by Kintiraki E. in 2015, PIH was diagnosed among 6-10% of people who are pregnant. Apart from causing harm to the mother and to the developing foetus, PIH can be complicated by a condition called pre-eclampsia and eclampsia, which are a much higher concern than hypertension itself.

The pathophysiological processes will affect pretty much every single organ in the body, especially, the kidney and the liver. In pregnancy, it is important for the foetus to get as many nutrients it can get from the mother to ensure a proper overall growth. This is achieved by means of trophoblastic invasion to the wall of the uterus which contains spiral arteries. Spiral arteries, as the name implies, are spiral in shape and embedded throughout the structure of the uterus. As the trophoblast invades through the spiral artery, it will modify them into a low resistance conduit so that blood would flow much efficiently to the foetus.

Throughout the pregnancy, the flow of the maternal blood to the foetus increases as it nutritional demands increases. During the first trimester, the maternal blood flow at the rate of 50 ml/min while at terms, it flows between 500 to 750 ml/min. As the speed of the blood flow increases, it is important for the vessel which acts as a bridge from the maternal circulation to the foetal circulation to be able to adapt and withstand the pressure which came along with it. Hypertension during pregnancy is usually caused by the failure of second wave modification of spiral arteries by trophoblast at the second layer of the uterus (myometrial layer). The conduits were supposed to be a wide bore, low resistance and large capacitance vessel but as the trophoblast failed to proceed with the modification, it becomes the opposite of what we should have expected (narrow bore, high resistance and small capacitance vessel).

Obviously, as the resistance of the vessel increases, nutrients, gases etc. can't be delivered fast enough to the growing foetus which could potentially be harmed. The invasion process, however, would only be completed by the 20th week of gestation which is why pregnancy-induced hypertension is only diagnosed if the signs and symptoms ensued after the 20th week of pregnancy. In the most severe cases, some of the trophoblastic cells would enter the maternal circulation which would activate the maternal antibody to form antibody-antigen complexes which subsequently would be deposited in the kidney, causing kidney damage and proteinuria. It's important to note that, proteinuria can be caused by a variety of pathophysiological processes. In pre-eclampsia, the cause of proteinuria can be attributed to either the aforementioned antibody-antigen complex or deposition of thrombus at the kidney causing kidney damage.

As the trophoblast failed to modify spiral arteries in the second uterine layer, they retained their original characteristics which means, later on, we can expect some problems in fetoplacental perfusion as placenta can't keep up with the demand of the growing foetus. Later on, areas of ischaemic necrosis would form and there would be a condition called as the basal membrane haemorrhage as a consequence of the high blood pressure imposed on the spiral artery to compensate with the fetoplacental deficiency. So what would happen then? The body would try to fix it by using platelets and clotting factor which will reduce the number of platelets available causing thrombocytopenia. Some of the spiral arteries might be occluded by a thrombus, further reducing the blood flow to the placenta and eventually, there would be fetal growth restriction.

That's quite a story, isn't it? For laymen, you just need to know that pregnancy-induced hypertension, if goes untreated can cause harm to the mother and foetus, so take the advice of your physician seriously. Now, pre-eclampsia can be defined as:

Elevated blood pressure of more than 140 mmHg (systolic) and 90 mmHg (diastolic), measured on two separate occasions, 4 hours apart after 20 weeks of pregnancy in a previously normotensive woman, accompanied by significant proteinuria (300mg in 24 hours).

From the definition itself, it is important to know what kind of hypertension that a pregnant woman presented with. If it exists prior to 20th week, then the diagnosis of chronic hypertension is more appropriate although people with chronic hypertension would usually experience a much severe form of hypertension from 20th week onwards with significant proteinuria. In this case, it is a pre-eclampsia superimposed on chronic hypertension. People who experienced a rise in blood pressure after 20th week onwards without significant proteinuria can be diagnosed as non-proteinuric gestational hypertension. I know it sounds obvious but differentiating the diagnosis based on the patient's presentation is important for management later on.

Without proper treatments, the blood pressure can rise beyond 160mmHG (systolic) and 110 mmHg (diastolic) in which we can consider it as a hypertensive crisis. This can be attributed to some chemicals released by the placenta to compensate the pathophysiological processes. Thromboxane is one of the chemicals released to facilitate arterial constriction. There are a few types of prostaglandin-derived chemicals which are prostaglandin itself, prostacyclin and thromboxane. The first two exhibit a vasodilation effect while the latter is vasoconstrictive. An increase in Thromboxane could worsen hypertension which is why when a pregnant mother has a history of pre-eclampsia in her previous pregnancy, she will be given aspirin as prophylaxis. Aspirin would block the action of cyclooxygenase enzyme that would reduce the production of Thromboxane. Cool, huh? PIH and pre-eclampsia would affect other systems such as:

• Cardiovascular system: In a normal pregnancy, significant peripheral vasodilation are to be expected. When a pregnant woman is having PIH, there is mark peripheral vasoconstriction which would increase intravascular pressure and subsequently caused oedema. In pre-eclampsia, oncotic pressure further reduced as most of the protein in the vessel were excreted in the urine; people would be presented with generalised severe oedema, almost similar to people with nephrotic syndrome.

• Renal system: There is a specific lesion which is caused by pre-eclampsia; glomeruloendotheliosis. This would lead to a further loss of protein, reduced oncotic pressure and thus, generalised oedema.

• Haematological system: The most significant finding pertaining to the haematological system is thrombocytopenia in which I have explained in the post earlier. Basically more platelet would be used to repair endothelial/basal damage as a consequence of hypertension.

• Hepatic system: Damage to vessels were associated with a higher released of liver enzymes. Together with low platelet level, they form a specific syndrome called as the HELLP syndrome (Haemolysis, Elevated Liver Enzyme, and Low Platelet).

• Neurological system: Progression to a much severe condition called as eclampsia. This would be discussed in a different post.

Managing PIH and pre-eclampsia would require a considerable commitment from patients and physicians to ensure that the patient's blood pressure is within an acceptable level. We will discuss the treatment in my next article. For now, I think I'll be adjourned for the day. It's tiring but this is the life I chose to live in.

References: [1], [2], [3]

All images were taken from Pixabay

Images: [1], [2], [3], [4], [5]