Pre-Eclampsia Flashcards
What is pre-eclampsia?
vascular disorder
pregnancy specific disorder
hypertensive disorder of pregnancy
Hypertensive disorders of pregnancy are the leading cause of maternal and fetal morbidity and mortality. What are the 4 different types
chronic hypertension
- women who enter pregnancy already having high blood pressure
Gestational hypertension
- women who develop high blood pressure throughout their pregnancy
Pre-eclampsia
- high blood pressure with organ failure
chronic hypertension + superimposed pre-eclampsia
- women who enter pregnancy already having high blood pressure that then go on to develop pre-eclampsia
What is the clinical classification of pre-eclampsia?
- development of high blood pressure in the second half of pregnancy
COMBINED WITH ONE OF THE FOLLOWING:
- proteinuria
- increased protein in the urine (a sign of kidney dysfunction) - other maternal organ dysfunction
- fetal growth restriction
- indicated dysfunction of the placenta
What are the symptoms of pre-eclampsia and why can these symptoms make it hard to determine if it is pre-eclampsia without getting checked ?
- generalised edema
(accumulation of body fluids) - severe head aches
- abdominal pain
These symptoms are all relatively common in pregnancy so it is hard to determine pre-eclampsia with just symptoms alone
When do symptoms of pre-eclampsia usually begin to arise and why is this an issue?
late in the course of disease (usually 3rd trimester)
symptoms occur to late in disease progression to help prevent and treat
pre-eclampsia can progress to eclampsia. What is eclampsia?
results in seizures and coma
- seen more often in developing countries
What are the two subtypes of pre-eclampsia?
early diagnosis/onset (before 34 weeks)
late diagnosis/onset ( after 34 weeks)
What are the risk factors involved in pre-eclampsia?
- family history
- relatives/mother-in law has had pre-eclampsia - maternal/paternal factors
- advaced maternal age
- african american descent
- previous pre-eclamptic pregnancy
- obesity
- poor nutrition (selenium deficient diets = increased risk)
- nulliparous (first pregnancy)
- multiple gestation - existing disease
- chronic hypertension
- chronic renal disease
- vascular disease
- diabetes
COVID 19 is a new determined risk factor for pre-eclampsia
women who develop covid 19 in pregnancy are 2x more likely to develop pre-eclampsia
How do vaccinations help with pre-eclampsia prevalence?
women who have been vaccinated for COVID 19 are not at risk for developing pre-eclampsia or many other complications in pregnancy
maternal and fetal outcome for those who get vaccinated have been positive
What are the current options for treatment for pre-eclampsia?
note there is no specific treatment or drug for pre-eclampsia but there are drugs that can help manage the symptoms
High blood pressure can be managed by anti-hypertensives (labetalol, nifedipine, methyldopa)
- to minimise vascular damge by high blood pressure
- usually need two or three of these depending on mothers actual blood pressure and their response to the drugs
However, usually there is just monitoring of fetus and mother
What are the complications with treating the high blood pressure in pregnancy?
lowering the blood pressure may reduce the blood flow to the maternal organs and also the fetus
last think that we want to happen is to reduce blood flow to a baby that may already be growth restricted from the pre-eclampsia
What medication could be taken to help prevent pre-eclampsia progression?
aspirin (low dose)
- needs to start early (16 weeks) until late pregnancy
at the moment there is now evidence that suggests aspirin has any negative consequences for fetus
only recommended for women with moderate (at least 2 risk factors) to high risk (based on risk factors)
What is the ‘cure’ for pre-eclampsia
remove the placenta (give birth)
- could be okay for those elate onset
- has many risks for women with early onset
pre-eclampsia resolves in 48 hours of birth
What is thought to be the cause of pre-eclampsia?
lack of spiral artery remodelling into the myometrium and not as effective remodelling occurs in the endometrium
Therefore there is low caliber/high resistance vessels
What occurs in normal pregnancy with vasculature remodelling?
trophoblasts invade the endometrium and first third of the myometrium to remove the smooth muscle cells and endothelial cells
This remodelling allows for the spiral arteries in the uterus to open up creating a high calibre/low resistance vessels capable of delivering and increased amount of blood to the placenta and in turn fetus
What are the differences seen between pre-eclamptic and normal spiral arteries in pregnancy?
- diameter is increased so more blood can flow easily through the vessel
- a lot less smooth muscle cells so ability of the vessel to constrict is significantly reduced
- there are receptors on endothelial cells which enable to vessel to respond to things that cause restriction
(with lowered amounts there are less receptors to respond creating a weaker response)
How does the limited remodelling of the spiral arteries impact the placenta?
- placenta develops in a low oxygen environment due to lack of blood flow (this is normal for the first trimester as babies grow in a hypoxic environment)
- The blood is stop start and not a continuous flow (there is enough then there isnt)
- this causes disruption of placental development
These two together cause ischeamia re-profusion injury which causes abnormal placental development leading to reduced placental perfusion ( less blood is coming into that placenta and then going to the baby)
The placenta responds to this by producing negative factors which enter the maternal blood stream
This is then why growth restricted babys are seen
How does the impacted placenta lead to the clinical symptoms seen pre-eclampsia?
dysfunctional placenta produces proteins which enter the maternal circulation and also has oxidative stress because of the ischemia re-profusion injury
- this leads to blood vessel dysfunction systematically in mother
- leading to vasoconstriction of blood vessels
This damage to vessels causes the high blood pressure, damage to maternal organs and comprise fetal growth
endothelial cells respond to what is going on in the blood how?
can be by:
- the shear tension and stress by blood movement
- factors flowing in blood (can influence and cause vasculature to create and release vasoactive substances which can diffuse into smooth muscle cells to influence blood vessel activity)
In a healthy pregnancy how do the vessels allow for decreased peripheral resistance and arterial pressure to allow increased blood flow for fetus?
endothelial cells produce an increased amount of nitric oxide (NO) and prostacyclin (PGI2) which diffuse into smooth muscle cells of vessel causing vasodilation
Why is there a drop in arterial blood pressure in the first trimester?
due to mass vasodilation occurring
the body is preparing for an increase in blood volume for the fetus
What changes occur in pre-eclampsia to change the overall vasculature activity?
Placental factors get produced in high amounts causing:
- reduction in the bioavailability of NO and PGI2
- increase kidney production of angiotension 2 (causes an increase in blood pressure)
- increases vasoconstrictors (angiotensin 2 and endothelin-1)
- increases the sensitivity of the smooth muscle to the vasoconstrictors
The production of placental factors in pre-eclampsia causes what overall shift to the maternal vasculature?
shifts from vasodilation to vasoconstriction state
therefore there is an increase to peripheral resistance and arterial pressure
Placental factors that are released into maternal circulation are anti-angiogenic factors. What does this mean?
they are not good for blood vessel formation and development and homeostasis
What are the ligands for specific endothelial bound membrane receptors which promote endothelial health and vasodilation?
TGF-beta 1 (transforming growth factor beta 1)
VEGF (vascular endothelial growth factor)
PIGF (placental growth factor)
What occurs in pre-eclampsia to these good guy ligands?
- placenta realises there is not enough blood flowing to it and ischemia profusion injury
- it releases its placental factors to increase the amount of membrane bund receptors for the good guys but it cannot do this so instead produces soluble versions of this
- soluble version bind to the good guys in the blood which prevents them from binding to the endothelial membrane bound receptors for the good guys
- this causes impaired vasodilation and endothelial dysfunction
How does oxidative stress cause vascular dysfunction in pre-eclampsia?
- placental ischemia causes an increase in amount of superoxide, hydrogen peroxide and peroxynitriate (ROS)
- due to too much ROS there is damage to cellular level (e.g. DNA damage and damage to proteins that are needed for maintaining endothelial health )
- this then further contributes to vascular dysfunction
in pre-eclampsia there is a decrease in the bioavailability of internal antioxidants
(cannot mop up all of the ROS)
What are the tools clinicians use at the moment to help pre-eclampsia
monitor mother
monitor development of baby
try to maintain clinical symptoms (e.g. aspirin and anti-hypertensive drugs)
if it gets to severe then baby and placenta is delivered
