Pregnancy, Parturition and Late Fetal Development Flashcards
how much embryonic growth occurs in the first trimester
why
very limited amount growth- surprising considering the change from single celled zygote to complex embryo with body plan + major organ systems in place
embryo is dependent on histiotrophic nutrition in the 1st trimester = derivation of nutrients from the breakdown of surrounding endometrial tissues + from uterine gland secretions (uterine milk)
give example of histiotrophic nutrition
peri-implantation period
syncytiotrophoblasts → invading endometrium surrounding embryo → breaking down the tissues + capillaries → the breakdown products fuel embryo development
also receiving nutrition from uterine gland secretion
and syncytiotrophoblasts are breaking down maternal capillaries → allows them to get some nutrition from maternal blood (but fetal membranes are not in contact with maternal blood)
how does rate of fetal growth change from 1st to 2nd trimester
why
significantly increases
change from histiotrophic nutrition to hemotrophic nutrition at the start of 2nd trimester
haemotrophic nutrition = fetus derives its nutrients from the maternal blood
how is haemotrophic nutrition achieved in humans
humans have a haemo-chorial type placenta - maternal blood is directly in contact with the fetal membranes (chorion)
what specific event causing the switch in nutrition between the 1st and 2nd trimester
activation of the haemo-chorial type placenta around the 12th week of gestation
allows the switch from histiotrophic to haemotrophic nutrition (large increase in fetal growth can now occur)
what is the amnion
amnion is derived from epiblasts
other epiblast derived cells form the fetus
amnion is the first of the fetal membranes and forms roof of amniotic cavity which will become amniotic sac
how does the amnion contribute to amniotic sac formation
from 5th week of gestation amniotic cells secrete fluid into the amniotic cavity causes it to expand and start to form sac which encapsulates and protects the fetus
as the amniotic sac expands with fluid accumulation → forces amnion into contact with chorion → they fuse → forms amniotic sac
what are the fetal membranes
extra-embryonic tissues which form a tough but flexible amniotic sac which encapsulates the fetus and forms the basis of the maternal fetal interface
amnion - innermost
chorion - outermost membrane
allantois - grows along connecting stalk from embryo to chorion
what is the connecting stalk
extra embryonic structure which connects the chorion to the embryo
what are the trophoblastic lacunae
how do they form
large spaces surrounding the embryo unit which are filled with maternal blood
syncytiotrophoblasts break down maternal capillaries + uterine glands → lumens of the capillaries and glands fuse → create continuous space through which maternal blood can flow and come into contact with syncitiotrophoblast
they become filled with maternal blood as they develop → later become intervillous spaces
label the diagram
what are the fetal membranes derived from
what do they form
amnion:
derived from epiblasts
forms closed, avascular sac with developing embryo at one end
chorion:
derived from yolk sac and trophoblasts
highly vascularized
forms chorionic villi - outgrowths of cytotrophoblasts which form basis of fetal side of placenta
allantois:
derived from yolk sac
becomes coated in mesoderm + vascularizes to form umbilical cord
might be part of embryonic bladder
what is the structure of the amniotic sac
2 layers which are fused together
amnion on inside
chorion on outside
what forms the umbilical cord
combination of connecting stalk, allantois and the mesoderm which coats it
as the allantois grows along connecting stalk it becomes coated in mesoderm which then becomes vascularized = umbilical cord
how are cytotrophoblasts relevant in placenta development
(remember trophoblast divided into invasive syncytiotrophoblast and proliferative cytotrophoblast which give rise to more syncytiotrophoblasts)
continues to provide cells which will form syncytiotrophoblasts
outgrowths of cytotrophoblasts form (cytotrophoblast layer sits on outside of chorion)
the outgrowths are finger like projections through syncytiotrophoblast layer into maternal endothelium = primary chorionic villi
label the image
what direction do the outgrowths grow
what is the function of the chorionic villi
provide a large surface area for exchange of gases+nutrients etc between the mother and fetus
describe the development of chorionic villi
what is the function of this
primary phase - outgrowths of cytotrophoblasts form which then undergo branching
secondary phase - growth of the fetal mesoderm into the primary chorionic villi
tertiary phase - growth of umbilical artery and vein into the mesoderm within the villus, provides vasculature
the villi grow into the maternal blood spaces → allows close contact between maternal and fetal blood for exchange, the villi provide large surface area for exchange
what is the structure of the terminal chorionic villi
why
blood vessel is a convoluted knot of vessels with some areas of dilatation
this slows down the bloodflow through the terminal villus - gives time for exchange between maternal and fetal blood
how does the structure of chorionic villus change over pregnancy
early in pregnancy:
villi have large diameter 150-200 micrometres
thick layer of trophoblasts separating fetal capillaries and maternal blood is around 10 micrometres thick
later in pregnancy:
villi diameter has decreased to 40 micrometres
capillaries within villi move so that layer of trophoblasts separating them from maternal blood is 1-2 micrometres
much shorter diffusion distance later in pregnancy
describe the maternal blood supply to the endometrium
ovarian and uterine artery fuse and give rise to number of branches of arcuate arteries (in the myometrium)
arcuate arteries then give rise to radial arteries (which pass through myometrium and stop at junction of endometrium)
radial arteries branch further to form basal arteries
basal arteries form spiral arteries
how does the blood supply to the endometrium vary depending on implantation
during menstruation the basal arteries grow and spiralise to form spiral arteries → supply blood to thickened endometrium → if implantation does not occur there is vasoconstriction + regression of these spiral arteries → endometrium is shed
if implantation does occur → spiral arteries are stabilised and provide maternal blood supply to fetus (in intervillous space)
label the diagram
which vessels may not always be present
why
spiral arteries - depending on stage of menstrual cycle or if pregnant
if pregnant or in luteal/proliferative and secretory phase = present
menstruation = not present
how do the spiral arteries change after implantation
they undergo extensive remodelling during placental development = conversion
extra-villus trophoblasts (on the outside of the villi) start to invade down into maternal spiral arteries → forms endovascular extra-villus trophoblasts, by doing the capillaries de-spiralise and open up to form straight channels
as the endovascular EVT forms it breaks down the maternal endothelium of the spiral arteries and the underlying smooth muscle and forms a new endothelium made up of EVT cells
conversion = process by which spiral arteries are changed from highly convoluted, high-pressure vessels into lower pressure, straighter, high capacity conduits
allows large flow of blood into the maternal blood spaces
summarise conversion
why is it clinically relevant
change of spiral arteries to non-spiral, low pressure, high capacity conduits
problems in conversion are thought to underlie IUGR and pre-eclampsia
what do the spiral arteries do in pregnancy
they supply the maternal blood spaces/intervillous spaces with blood → exchange of gases and nutrients with fetus then occurs through villus
label this structure
describe the exchange occurring
spiral arteries fill intervillous spaces/maternal blood spaces with maternal blood (some of the blood drains away in the venous system)
substances can be exchanged with fetus across their highly vascularized chorionic villi - large surface area for exchange between maternal blood + chorionic villi
what are the possible mechanisms for nutrient exchange across the placenta
simple diffusion - depends on size, shape, charge of molecule + concentration gradient
facilitated diffusion - depends on number of transporters + concentration gradient
active transport - depends of energy-dependent co-transporters
what are the main molecules crossing the placenta
how do they do it
what changes to the maternal circulation occur during pregnancy
what is the O2 partial pressure in the fetus
what are the implications of this
oxygen partial pressure in fetus is much lower than in maternal
this would suggest that fetal Hb saturation would be much lower than maternal
but fetal saturation and O2 content is very similar to maternal
this is because the embryo and fetus have different forms of haemoglobin which have higher O2 affinity than adult/maternal haemoglobin
what are the features of the cardiovascular system in the 2nd and 3rd trimester
(organ systems are in place by end of 1st trimester, but they mature and develop in 2nd and 3rd)
complete circulatory system in place by the end of 1st trimester
but some major differences compared to CV system in neonates:
placenta acts as site of gas exchange (not lungs)
ventricles act in parallel rather than in series → driving blood together around the same circulatory loop → achieved by presence of vascular shunts which bypass pulmonary and hepatic circulation (close at birth)
shunts allow body to drive oxygenated blood from around the body more efficiently, especially to head → ensures that it is well oxygenated + has nutrients needed for tissue development
what stimulates organ maturation as pregnancy progresses
increase in fetal corticosteroids towards end of pregnancy → responsible for the final maturation of each of the organ systems
exponential increase in corticosteroids → increased surfactant production + liver glycogen deposition
what are the phases of labour
Phase 1 - Quiescent:
Late in 1st trimester onwards
uterus is not contracting but there are some cervical changes
Phase 2 - Activation
some uterine activity
further cervical developments → preparations for cervix to dilate
Phase 3 - Stimulation
uterine contraction
cervical dilation
3 stages of labour occur
Phase 4 - Involution
uterine involution - restored to its original size
repair of cervix
start of lactation
what are the stages of labour
what phase do they occur in
3rd Phase
what is the timing of the stages of labour
1st stage - contractions and cervical dilation = 14 hours
much longer than stages 2 and 3
separated equally between latent and active phases
2nd stage = 1-2 hours
fetal descent and delivery
3rd stage = 1-2 hours
placenta delivery
1st delivery = overall takes 8-18 hours
2nd delivery = 5-12 hours
how does the cervix undergo remodelling
Softening begins in 1st trimester:
maintains cervical competence (stays closed) but it has has a measurable change in compliance
days or weeks before birth Ripening occurs:
extensive monocyte (macrophages and neutrophils) infiltration into cervix and IL-6 and IL-8 secretion
hyaluronan deposition
when labour starts cervical dilation occurs:
increased hyaluronidase expression → breaks down hyaluronan deposited in ripening
immune cell influx → production of large amounts of matrix metalloproteinases → breakdown collagen → increase elasticity
post-partum repair:
recovery of tissue integrity + competence (ensures women is able to go through pregnancy again with closed cervix which can then undergo remodelling around birth)
what is the endocrine regulation of labour
not sure of the exact mechanism - current thinking is fetus determines timing of delivery through changes in the hypothalamo-pituitary-adrenal axis
close to birth there is an exponential increase in production of CRH by fetal pituitary and a concomitant decrease in production of CRH binding protein → increased bioavailability of CRH
increased CRH → stimulates ACTH release → acts on fetal adrenal cortex → stimulates cortisol release
cortisol binds to placenta → drives placental production of CRH → placental CRH acts on fetus to further increase cortisol production (+ve feedback)
CRH also stimulates production of DHEAS by fetal adrenal cortex → DHEAS is used as a substrate to allow greater oestrogen production by placenta
describe progesterone levels during pregnancy
why is this necessary
describe estrogen levels during pregnancy
progesterone levels increase steadily during pregnancy
progesterone is produced by placenta - high levels are needed to maintain pregnancy + uterine relaxation until labour occurs
(falls following delivery)
estrogen levels also increase steadily during pregnancy
increased estrogen : progesterone ratio close to term
(but over pregnancy more progesterone than estrogen)
what happens to estrogen and progesterone levels during labour
approaching delivery there is a switch in progesterone receptor subtypes expressed on the uterus
switch from A isoforms (activating) to B and C isoforms (repressive)
leads to functional progesterone withdrawal → levels of progesterone are still high but change in receptor isoforms means that the uterus is blinded to the action of progesterone
at the same time there is an increase in estrogen receptor alpha expression in uterine tissue
leads to uterus becoming sensitised to estrogen action
ultimately leads to local shift in estrogen : progesterone ratio in uterine tissues - increased ratio (more estrogen less progesterone)
what stimulates release of prostaglandins in labour
rising estrogen levels drive prostaglandin production in 2 ways:
rising estrogen activates phospholipase A2 enzyme → generates more arachidonic acid for PG synthesis
estrogen stimulation of oxytocin receptor expression promotes PG release (through oxytocin signalling)
what are the effects of prostaglandin release
PGE2 - acts on cervix
PGF2alpha - acts on myometrium
PGI2 - acts on myometrium
draw flow chart of the regulation of labour
explain the process of myometrial contraction
myocytes in upper uterine segment formed a syncytium (due to oxytocin binding) → gap junctions allow the contractions to be transmitted across the whole upper segment
contractions start at fundus → spread down upper segment → action of the contractions it to pull up + apart the lower segment + cervix → forms open birth canal (cervix is dilated and lower segment is passive)
lower segment + cervix are pulled up because the contractions are brachystatic - after contraction the muscle fibres do not become completely relaxed, so they retain some shortening (don’t return to full length on relaxation)
each contraction progressively pulls the lower segment + cervix up and apart until full 10cm dilation is reached (birth canal is formed)
describe the process of fetal expulsion from uterus
head engages with cervix at 34-38 weeks
onset of labour - myometrial contractions put pressure on hindquarters of fetus + pressure of head on cervix → head flexion = causes chin to press against chest
as labour progresses - fetus rotates, so that belly faces mother’s spine → head is expelled first after cervical dilation → shoulders are delivered sequentially (upper first) → torso
(once shoulders are out fetus is delivered quite quickly)
how are the placenta and fetal membranes delivered
rapid shrinkage of uterus after fetus has been delivered → area of contact of placenta with endometrium starts to shrink
at the same time uterine shrinkage causes folding of fetal membranes (which were stretched before) → fetal membranes peel off endometrium
umbilical cord is clamped after birth → stops fetal blood flow to placenta → chorionic villi collapse → haematoma formation between decidua and placenta
haematoma + ongoing myometrial contractions → expel placenta + fetal membranes from uterus
