Lecture 15 Flashcards
What happens in the foetal placenta unit?
Interactions between the uterus that determines the pregnancy outcomes
What happens to the polar tropboblast?
It will proliferate and become the placenta
In the development of the placenta what to cell types does the trophoblasts form?
Syncytiotrophoblasts and cytotrophoblast
Describe syncytiotrophoblasts
Multinucleated, unicellular epithelial membrane. Secretes hormones and growth factors and regulates exchange of nutrients and waste products between the mother and placenta
Describe cytotrophoblast
Millions of individual epithelial like cells that lie under the syncytotrophoblasts cell. The lining itself is a villus centre
What are extravillous trophoblasts?
EVT - the are cytotrophoblast that exit the syncytium and invade the uterine wall
Why is pregnancy a demanding exercise challenge?
Because the mother will have to undergo enormous physiological changes both within the uterine and maternal foetal placenta
What happens to the cardiovascular system in pregnancy? - what is the aim
To support the appropriate growth for gestational age of the placenta and foetus
What are the overall demands systemically for cardiovascular adaptations that are enquired during pregnancy?
Increase in blood volume, increase in left ventricle volume and increasing contraction and beating
What does everything during pregnancy need to be regulated at?
A micro environment and also an macro multi organism environment
How much is blood volume increase in pregnancy?
35-50% over the course of 9 months
What is the increase in blood volume due to?
A massive change in preload that the heart needs to respond to
What mechanisms contributes to the increase in blood volume during pregnancy?
Increase in cardiac output by the frank starling and brain bridge mechanism
What else is increased during pregnancy?
Cardiac output, stroke volume and heart rate
What does the body require to accommodate for an increase in HR, SV, and CO?
Functional and structural remodelling
What are some examples of cardiac remodelling in pregnancy?
Left ventricular end diastolic volume increase, left ventricle stroke volume increased, mechanical work increased (efficiency) and left ventricular mass increased
What is eccentric hypertrophy?
A preload stimulus dilation of the ventricle
What is usually reversible 3-6 months post partum?
Cardiac remodelling
What is another accommodation during pregnancy?
A reduction in total peripheral vascular resistance to aid the distribution of blood to different organs
What happens in reversible vascular remodelling in pregnancy?
A substantial increase in uterine blood flow, a 5-fold increase
What is an increase in uterine blood flow driven by?
An increase in delivery of blood to the expanding due to the uterine organ
Why does the uterus need to have an increase in 5-fold of blood volume?
Because it is increasing in size and it needs to maintain delivery of oxygen and nutrients to the tissues.
What is the REAL purpose for an increase in uterine blood uterine?
To deliver maternal blood towards the placenta
What is the haemochorial placenta?
Blood and membrane of the placenta
Where does maternal blood sit on the haemochorial placenta?
On the surface of the placenta, there is no direct communication between the maternal circulators system with the foetal placental circulatory system
Where is the 5-fold blood volume needed?
The uterine blood flow needs to be delivered to the intervillus space. Which is the space between the villus structures of the placenta - in between the different attachment points on the endometrium
What happens when blood is delivered to the intervillus pace of the uterus?
There is an exchange of oxygen from the maternal circulation to the placental capillaries - accomplished by transport mechanisms across the epithelial membrane
What are the two main types of uterine vascular remodelling?
Upstream myogenic arteries and terminal spiral arterioles
What needs to happen due to the increase in demand for blood delivery in the uterus?
Has to be a change in vasoreactivity for the upstream small arteries
Where are the uterine arteries found?
North to south of the uterine cavity
What do the spiral arteries do?
Allow the blood to exist the uterine cavity and enter the placenta
What can altered vascular function be mediated by?
Signals from endothelial cells lining the lumen of the blood vessels
How can vasoreactivity be regulated?
By endothelial cells and relaxant factors from endothelial cells influencing contract ability of the smooth muscle cells that encircle the wall of the small arterioles
What are some mechanisms that are altered during pregnancy in resistance uterine arteries?
Nitric oxide and endothelial derived hyperpolarising factor
What is increased during pregnancy - in regards to altered vascular function and resistance?
Increase reserve of endothelial dependent relaxation
What law is used for changes in upstream uterine arteries during pregnancy?
Posiellules law - it can have a dramatic effect on the radius and diameter of the blood vessels if you change the flow by a little bit
What has to happen to the spiral arterioles during pregnancy?
They have to be structurally remodelling in early pregnancy to direct blood to to the intervillus space. - however the remodelling can start pre-pregnancy
How can structural remodelling of the spiral arterioles start pre-pregnancy?
Because during the menstrual cycle there is an extrusion of blood from the uterine organ into the uterine cavity
How do you change the structure of spiral arterioles?
In 2 ways:
either by the extra villus sycitrophoblasts invading the uterine wall and into the lumen of the spiral arterioles
or
they can surround the interstitial dispersing smooth muscle cells that sound the spiral arterioles.
What is taking away the vasoreactivity of the spiral arterioles referred to as?
Interstitial trophoblast invasion or endovasular trophoblast invasion
What is the important task of the extravillous syctitrophobolasts?
To temporality displace the endothelial cells to widen the lumen
What happens when the endothelial cells have been dispersed?
Smooth muscle cells degrade and replaced with fibrinogen which is more elastic than the collagen and elastin
What can you see before pregnancy in histology?
Lots of smooth muscle (brown staining) in the walls of the sprial arterioles
What can you see mid pregnancy in histology?
Brownstaining can be seen further from the lumen of the arterioles (smooth muscle is further away)
What can be seen in pregnancy in histology?
Fibrinogen (purple) which is used to increase blood volume to the interstitial space
When does upstream vascular remodelling occur?
Before pregnancy
When does spiral artery remodelling occur?
Completed 12-16 weeks and has an influence on upstream remodelling because there is a reduction in downstream resistance which facilitates flow from the upstream arteries induced more stress
What does an increase in shear stress stimulate?
Induces more structural and functional remodelling
How does the invasion of sycitrophoblasts stop?
Invasion processed through the endometrium all the way up 1/3 of the endometrium lining and involves maternal immune cell recognition and tolerance
What happens if the invasion of synitrophoblasts goes past 2/3 of the endometrium lining?
Could cause pathophysiological mechanisms and it can be dangerous for the mother
What are defects in uterine or placental blood flow related to? - dysfunction of the regulation of spiral arterioles and upstream arteries
Pre-eclampsia, intra-uterine growth restriction, gestational hypertension and preterm labour
What can pre-eclampsia cause maternally?
5 women per year die in the uk, can cause a haemorrhage
What is pre-eclampsia defined as?
Onset hypertension during pregnancy - hypertension that has occurred during pregancy that wasn’t known before
What is pre-eclampsia usually accompanied by?
Proteinurea
What happens if a mother has pre-eclampsia?
Something has gone wrong with blood pressure management and the kidney
How is pre-eclampsia indicated?
By altercations in vascular fucntion such as uterine artery or umbilical artery Pulsatility.
OR
Altered angiogenic factors in the maternal circulation
What are some examples of angiogenic factors?
sFlt-1 and endoglin - they are both important as they bind growth factors in the plasma
What can sFlt-1 bind to?
The vascular endothelial growth factor (VEGF)
What can endoglin bind to?
TGF-beta
What can an elevation of angiogenic factors in the plasma mean?
The growth factors will not find the receptor on the endothelial cells and it will impair appropriate foetal directed growth mediate remodelling of the arterial systems
What are placenta derived growth factors used for?
A prognostic marker for pre-eclampsia
What can happen to the spiral arterioles and upstream arteries in pre-eclampsia?
Poorly transformed spiral arteries and impaired vasodilation in the upstream arteries
What doesn’t happen in pre-eclampsia that happens in normally pregnancy in terms of reserve?
There is no endothelial dependent reserve
What do adolescent born with pre-eclampsia have?
Higher BP, elevated BMI and alternated heath structure
What is being born prematurely the more important risk factor for?
Getting early onset heart failure
What is the circulation like in paternal circulation?
28mmHg - low pressure,
Where does blood leave to go in placental circulation?
Blood leaves the trophoblasts interface and goes back towards the foetal heart in a single umbilical vein.
How does blood return to the placenta?
Via two umbilical arteries and there is no neuronal innervation of placenta vasaculture
