Placenta & Foetal Circulation Flashcards
Why does the placenta need to be inspected following birth?
- a thorough inspection of both the embryonic and maternal sides of the placenta needs to be conducted
- this is to determine whether the placenta is fully intact and ensure no abnormalities are present
When does the foetal period begin and what happens during this time?
- the foetal period begins at the start of week 9 and continues until birth
- it is characterised by maturation of tissues and organs and rapid growth of the body
What are the 2 main roles of the placenta?
- nutrient and gas exchange
- hormone production
- initially hormone production is achieved via the corpus luteum from the oocyte
- the placenta takes over when this begins to regress
What happens to the placenta as the foetus enters week 9 of development?
- the demands of the foetus for nutritional and other factors increase as it enters week 9
- major changes in the placenta occur as it matures to allow for efficient exchange across a thin membrane
- there is an increase in surface area between foetal and maternal compartments to facilitate exchange
- the disposition of foetal membranes is altered as amniotic fluid production increases
What makes up the foetal component of the placenta?
foetal component consists of trophoblast cells and the extraembryonic mesoderm
- trophoblast cells are responsible for forming foetal support tissues
- the extraembryonic mesoderm (chorionic plate) is also part of the support structures
- it is “extraembryonic” so is not formed by the 3 germ layers that develop during gastrulation
What makes up the maternal component of the placenta?
the uterine endometrium
What is placenta praevia?
Can it be screened for?
- an abnormal implantation site leads to the placenta developing over the cervix
- it can be screened for via USS and Doppler can be used to determine whether there is sufficient blood supply
What is placenta accreta and why does it occur?
What is the associated risk with this condition?
- when the embryo implants into the uterine lining, it is important that invasion of support structures only occurs to a certain extent
- it needs to be sufficient to anchor the embryo and provide sufficient amounts of blood to the foetus
- if too much invasion occurs, some placenta can be left within the uterus** after birth, causing **vaginal bleeding
What are some potentially harmful substances that are able to cross the placenta?
- the placenta is efficient at filtering the blood to protect the foetus from harmful substances, but it is not 100% effective
- some harmful factors that can cross the placenta to enter foetal circulation are:
- drugs (e.g. thalidomide)
- alcohol
- some viruses (e.g. HIV, rubella, toxoplasmosis, Zika, CMV)
What part of the placenta is involved in hormone production?
Why can the ovaries be removed from a woman after 4 months of pregnancy without causing an abortion?
- the syncytiotrophoblast takes over from the corpus luteum in hormone production
- ovaries can be removed after the 4th month without causing an abortion as the corpus luteum has become redundant
How does production of hCG vary during pregnancy?
- hCG is produced by the syncytiotrophoblast during the first 2 months of pregnancy
- it supports the corpus luteum and has a role in regulating the mother’s immune response
- so much hCG is produced that it enters the urine and can be used in pregnancy testing
What are the 3 main hormones produced by the syncitiotrophoblast?
- progesterone
- oestrogen
- somatomammotropin
When does the placenta produce progesterone?
- production gradually increases until the end of the 4th month when progesterone production is taken over by the placenta
- at this stage, the placenta produces progesterone in sufficient amounts to maintain the pregnancy if the corpus luteum is damaged / removed
How does production of oestrogenic hormones by the placenta change over time?
What are the roles of these hormones?
- the placenta mainly produces estriol
- production increases throughout pregnancy until just before it ends, when a maximum level is reached
- high levels of oestrogens stimulate uterine growth** and **breast development
What is the role of somatomammotropin (placental lactogen) secreted by the placenta?
- it is a growth-hormone like substance that gives the foetus priority over maternal blood glucose
- this makes the mother somewhat diabetogenic
- it also promotes breast development for milk production
As well as hormone production, what are the other 3 key roles of the syncytiotrophoblast?
- modulating the immune response
- implantation
- breaking down maternal capillaries
What is the main difference between the trophoblast and embryoblast?
Trophoblast:
- the support structures (including placenta) are formed from this layer
- this forms the OCM that will implant into the uterine lining
Embryoblast:
- this forms the ICM that goes on to form the embryo proper
What processes occur on day 7 of development?
- the bilaminar disc is formed from the epiblast and hypoblast cells
- the trophoblast has further differentiated into the cytotrophoblast and syncytiotrophoblast
- the syncytiotrophoblast anchors the embryo onto the uterine lining to allow for implantation
What is the significance of the syncytiotrophoblast cells being multinucleated?
- they are multinucleated as they have lost some of their membranes
- this means that it is more difficult for immune cells to penetrate the syncytiotrophoblast layer to reach the bilaminar disc
How far has the blastocyst implanted by day 9 of development?
- the blastocyst is more deeply embedded in the endometrium
- the penetration defect in the surface epithelium has been closed by a fibrin coagulum
What changes take place in the trophoblast on day 9 of development?
- vacuoles appear within the syncytium
- the vacuoles fuse together to form large trophoblastic lacunae** within the **syncytium
What changes take place in the hypoblast during day 9 of development?
- a wave of flattened cells originating from the hypoblast form the exocoelomic (Heuser) membrane
- this membrane migrates around the entire blastocyst cavity and lines the inner surface of the cytotrophoblast
- Heuser’s membrane together with the hypoblast forms the primitive yolk sac (extracoelomic cavity)
What is meant by the decidual reaction?
When does this occur and what is its purpose?
- the decidual reaction occurs after implantation and involves a change in morphology of the uterine lining
- the uterine lining becomes more vascular and packed with nutrients
- the uterine gland becomes enlarged, allowing for diffusion of nutrients
- the maternal capillaries (sinusoids) become engorged
How far has the blastocyst implanted by day 11-12 of development?
- the blastocyst is completely embedded within the endometrial stroma
- the surface epithelium almost entirely covers the original defect in the uterine wall
- the blastocyst produces a slight protrusion in the lumen of the uterus
How is the arrangement of the trophoblast different on day 11-12 of development?
- the trophoblastic lacunae within the syncytium have enlarged
- lacunar spaces within the syncytium form an interconnected network that is more evident at the embryonic pole
- at the abembryonic pole, the trophoblast still consists mainly of cytotrophoblast cells
During day 11-12 of development, what happens to the syncytiotrophoblast layer?
- the syncytiotrophoblasts penetrate deeper into the stroma and erode the endothelial lining of maternal capillaries
- these capillaries are congested and dilated and are known as sinusoids
- syncytial lacunae become continuous with the sinusoids and maternal blood enters the lacunar system
- the syncytiotrophoblast continues to erode more and more sinusoids causing maternal blood to flow through the trophoblastic system and establishing the uteroplacental circulation
What new population of cells appears during day 11-12 of development?
- cells of the extraembryonic mesoderm appear between the inner surface of the cytotrophoblast and the outer surface of the primitive yolk sac
- these cells are derived from yolk sac cells
- they form a fine, loose connective tissue that eventually develop to form a layer surrounding the entire embryo
What cavities develop within the extraembryonic mesoderm between days 12-13?
- several cavities form within the extraembryonic mesoderm which become confluent to form the chorionic cavity (extraembryonic cavity)
- the chorionic cavity surrounds the primitive yolk sac (except where the germ disc is connected to the trophoblast by the connecting stalk)
How can the extraembryonic mesoderm be further divided?
- the EEM lining the cytotrophoblast and amnion is the the extraembryonic somatic mesoderm
- the EEM lining covering the yolk sac is the extraembryonic splanchnic mesoderm
What can happen around day 13 that can lead to inaccuracy in determining the expected delivery date?
- the surface defect in the endometrium has usually healed by day 13
- occassionally, some bleeding occurs at the implantation site as a result of increased blood flow into the lacunar spaces
- this bleeding occurs near the 28th day of the menstrual cycle so can be confused with normal menstrual bleeding
What happens in the hypoblast around day 13 of development?
- there is a second wave of migration of hypoblast cells that proliferate to form a new cavity within the primitive yolk sac
- this cavity is the secondary / definitive yolk sac
- during its formation, large portions of the primitive yolk sac are pinched off and these portions remain as exocoelomic cysts
- these are found within the extraembryonic coelom or chorionic cavity
What happens to the chorionic cavity around day 13 of development?
- the chorionic cavity increases in size
- the EEM lining the inside of the cytotrophoblast layer is now the chorionic plate
- the only place the EEM traverses the chorionic cavity is in the connecting stalk
- with the development of blood vessels, this stalk becomes the umbilical cord
What changes take place in the trophoblast at the same time the chorionic cavity begins to form (around day 13)?
formation of primary villi
- formation of the extraembryonic mesoderm signals back to the cytotrophoblast layer to induce further proliferation
- the cytotrophoblast proliferates locally to form extensions that grow into the overlying syncytiotrophoblast
- the extensions of cytotrophoblast grow out into the blood-filled lacunae and carry a covering of syncytiotrophoblast with them
What does a primary villus consist of?
- a core of cytotrophoblast cells** with a **covering of syncytiotrophoblast cells
- these extend into the trophoblastic lacunae to form intervillous spaces between the primary villi
How do secondary villi form?
- cells of the extraembryonic mesoderm penetrate the core of the primary villus and grow toward the decidua
- this produces a secondary villus - a core of EEM, covered by a layer of cytotrophoblast cells then a covering of syncytiotrophoblast cells
How does a tertiary villus form?
- extraembryonic mesodermal cells in the core of the villus begin to differentiate into blood cells** and **small blood vessels
- this forms the villous capillary system (chorionic vessels) that play a role in exchanging nutrients with maternal blood within the trophoblastic lacunae
What vessels do the capillaries within the tertiary villi make contact with?
- capillaries within the tertiary villi come into contact with capillaries developing within the chorionic plate** and **connecting stalk
- these vessels establish contact with the intraembryonic circulatory system, connecting the placenta and the embryo
How do the tertiary villi develop even further in the 9th week?
- the tertiary villi continue to mature to form free villi
- these are even further projections of the tertiary villi that further increase the surface area for efficient exchange of nutrients
How does maternal blood pass from the trophoblastic lacunae into the chorionic vessels?
- the chorionic vessels are formed from the extraembryonic mesodermal core of the tertiary villi
- around this core there is a layer of cytotrophoblasts, followed by a layer of syncytiotrophoblasts
- the syncytiotrophoblast cells line the trophoblastic lacunae, which contain blood from the spiral arteries of the uterus
- syncytiotrophoblast cells degrade maternal spiral arteries, which causes blood to leak into the trophoblastic lacuna
When does the transition from secondary to tertiary villi occur?
- when the mesodermal core of the villus differentiates into blood vessels
- chorionic arteries and veins from the embryo will pierce the EEM to develop within it
What is the decidual plate?
Why is it important?
- the decidual plate is part of the uterine lining where the placenta will form
- the cytotrophoblast and syncytiotrophoblast will implant into the uterine lining up to a certain extent
- this implantation usually stops at the decidual plate
What are decidual septa?
- they are wedge-like projections between groups of villi on the maternal side of the placenta
- they partially separate the maternal side of the placenta into regions called cotyledons
What is the difference between a free and an anchoring villus?
Anchoring villi:
- extend from the chorionic plate (EEM + overlying trophoblast layers) to the decidua basalis (decidual plate)
Free villi:
- branch from the sides of the stem villi and through which exchange of nutrients and other factors will occur
What changes occur during endovascular invasion of maternal spiral arteries by the cytotrophoblast?
- endovascular invasion by the cytotrophoblast replaces the epithelial cells in the vessel walls to produce “hybrid vessels”
- this transforms the arteries from being small with high resistance to large with low resistance allowing increased quantities of maternal blood to reach the intervillous spaces
What changes occur in the syncytium around day 21?
- the syncytium becomes thinner** and the **cytotrophoblasts are lost from the villi
- this means that the placental barrier now consists only of the vessel endothelium and the syncytium
What is meant by the junctional zone?
- the junctional zone is a specific layer of the decidua basalis at which the trophoblast stops invading
- at this point, maternal and foetal tissues intermingle
How do tertiary villi develop initially?
How do their characteristics change over time?
- in the early weeks of development, villi cover the entire surface of the chorion
- as the pregnancy advances, villi on the embryonic pole continue to grow and expand and give rise to the chorion frondosum
- this is the “bushy chorion” assoicated with the decidua basalis
- the villi on the abembryonic pole degenerate so this side of the chorion (chorion laeve) is now smooth
When does the embryo bulge into the uterine lumen?
What is the uterine lining at this point called?
- the embryo begins to bulge into the uterine lining during the 2nd month
- the uterine lining covering this bulge is the decidua capsularis
When USS screening is performed during pregnancy, what aspects of the placenta should be assessed?
Why is this important and is it compulsory?
- location
- size
- vascularity / blood flow
- vessels
- undetected placental abnormalities can lead to death of the mother and/or foetus if allowed to deliver spontaneously
- whilst women may not want prenatal screening tests, they should be strongly advised to have an USS to assess the placenta
What are all placental abnormalities associated with?
- vaginal bleeding in the second half of pregnancy
What is the definition of placenta praevia?
What is it directly correlated with?
defined as the placenta overlying the endocervical os
it is directly correlated with the number of previous C-sections
What are the risk factors for placenta praevia?
- previous spontaneous / elective pregnancy terminations
- previous uterine surgery
- increased maternal parity
- increased maternal age
- smoking
- cocaine use
- multiple gestations
- previous placenta praevia
What is the main complication of placenta praevia?
What more serious consequences can this lead to?
- complications are direct consequences of maternal haemorrhage
- blood loss is associsted with:
- increased need for transfusion
- hysterectomy
- maternal death
- sepsis
- thrombophlebitis
- ICU admission
- most of the foetal complications result from pregnancies being premature
How can placenta praevia be detected and managed?
- it can be detected on USS and birth should be via C-section to minimise the risk of bleeding
What is meant by vasa praevia?
- this describes foetal vessels that run through foetal membranes over or near the endocervical os that are unprotected by the placenta or umbilical cord
- these vessels are at risk of rupture when supporting membranes rupture
What are the potential risks of vasa praevia?
- it has a high mortality rate as foetal vessels can tear during spontaenous labour, leading to foetal-neonatal haemorrhage
- it is associated with increased risk of preterm birth
How is vasa praevia detected and managed?
- diagnosed via USS and use of colour Doppler
- delivery via C-section before the onset of labour due to rupture of membranes
What is meant by placenta accreta?
- this occurs when the placenta becomes abnormally adherent to the uterine wall
- there is direct attachment of trophoblast cells to the myometrium without intervening decidua
- usually the trophoblast cells should stop invading the uterus when they reach the decidua basalis
What are the 3 conditions that lie under the spectrum defined as placenta accreta?
Placenta accreta:
- the trophoblast attaches directly to the myometrium with no intervening decidua
- the placenta is attached too deeply into the uterine wall
Placenta increta:
- the trophoblast invades into the myometrium
- the placenta is attached into the uterine muscle
Placenta percreta:
- the trophoblast invades through the myometrium, beyond the serosa and into surrounding structures (e.g. bladder)
What are the risk factors for the placenta accreta spectrum?
- the major risk factor is previous C-section or surgery that may damage the endometrium
- smoking
- IVF
- increased maternal age
- multiparity
- placenta praevia
- a short interval between prior C-section and subsequent pregnancy
What are the main complications associated with the placenta accreta spectrum?
- most maternal complications are the result of maternal haemorrhage:
- disseminated intravascular coagulation
- multiorgan failure
- need for additional surgery (e.g. hysterectomy)
- thromboembolism
- death
- neonatal complications are mainly the result of preterm birth
What arteries deliver blood to the intervillous spaces?
How often does this occur and how is the blood removed?
- around 100 spiral arteries deliver around 150ml of blood to the intervillous spaces
- this blood is replaced 3-4 times each minute
- as the pressure drops within the intervillous spaces, blood flows back into the endometrial veins
In late pregnancy what is the placental barrier comprised of?
Can foetal cells cross this barrier?
- the placental barrier is composed of a syncytial membrane and the endothelial lining of the capillaries within the villi
- there is no mixing of maternal and foetal blood, but sometimes a few foetal cells can cross the thin placental barrier
- these cells are syncytiotrophoblasts that undergo apoptosis and enter the trophoblastic lacuna
- the presence of these cells can be used in prenatal screening
How is thinning of the placental barrier to reduce the diffusion distance acheived?
- loss of the cytotrophoblast cells
- thinning of the endothelial lining of the embryonic vessels
When is the placenta expelled?
What diameter should it be?
- the placenta is expelled around 30 minutes after the neonate
- it should be around 20cm in diameter
What makes up the foetal side of the placenta?
- this consists of the chorionic plate and chorionic vessels that are covered by amnion
- the chorionic vessels converge towards the insertion of the umbilical cord, which is usually central
What makes up the maternal side of the placenta?
- this is characterised by the presence of 15-20 cotyledons (wedge-shaped pieces of septa)
- it must be fully examined after birth to ensure it is intact
- if any part of the placenta is left behind, it can form a connection with the mother’s vascular system and result in haemorrhage
Why do changes in the foetal circulation need to occur after birth?
- there is some mixing of blood within the foetal circulation, which needs to be avoided after birth
- structural / anatomical adaptations that exist in foetal circulation need to close up shortly after birth
What is the role of the ductus venosus?
- umbilical veins carrying oxygenated blood bypass the liver via the ductus venosus
- they enter the inferior vena cava which is carrying poorly oxygenated blood
- the IVC empties into the right atrium, which also receives venous blood from the superior vena cava
What is the role of the foramen ovale and ductus arteriosus?
- blood entering the right atrium from the IVC and SVC passes into the left atrium via the foramen ovale
- the blood then passes into the left ventricle and aorta
- any blood that reaches the right ventricle is ejected into the pulmonary trunk
- as the developing lungs do not require much blood, the majority of this blood bypasses the lungs and enters the aorta via the patent ductus arteriosus
