1a Pregnancy, Parturition and Late Fetal Development Flashcards
During the first trimester, why is embryo-fetal development relatively slow?
Because the embryo is dependent on histiotrophic nutrition
what is histiotrophic nutrition?
The derivation of nutrients from the breakdown of surrounding tissues
How does the syncytioblast invading the endometrium provide histiotrophic nutrition?
Invaded and breaks down local tissues, and used products to fuel development of the embryo
When does the switch from histiotrophic to haemotrophic nutrition occur?
At the start of the second trimester
How is haemotrophic nutrition achieved?
through haemochorial - type placentas where the materal blood is directly in contact with the fetal membranes
When is the haemochorial-type placenta activated?
Around 12th week of gestation
What is the amnion derived from?
Epiblast
What does the amniotic cavity become?
The amniotic sac
What does the amniotic sac do?
surrounds and cushions fetus during 2nd and 3rd trimester
What is the chorion?
The second fetal membrane which surrounds the whole conceptus unit
What is the connecting stalk?
Links the developing embryo unit to the chorion
What are the trophoblastic lacunae?
Large spaces filled with maternal blood formed by the breakdown of maternal capillaries and uterine glands
What are the intervillous spaces that are formed when maternal capillaries break down?
Maternal blood spaces
What are fetal membranes?
Extra-embryonic tissues that form a tough but flexible sac that encapsulates the fetus and forms the basis of the maternal-fetus interface
What is the amnion?
The inner fetal membrane which arises from the epiblast, and forms an enclosed, avascular sac with the developing embryo at one end
When does the amnion start to secrete amniotic fluid?
From 5th week - forms a fluid filled sac that encapsulates and protects the fetus
Which fetal membrane is highly vascularised?
Chorion
What is the chorionic villi?
Outgrowths of the cytotrophoblast from the chorion that forms the basis of the fetal side of the placenta
How does the amniotic sac form?
Expansion of the amniotic sac by fluid accumulation forces the amnion into contact with the chorion, which fuse forming the amniotic sac
What is the allantois?
An outgrowth of the yolk sac which grows along the connecting stalk from embryo to chorion
How does the umbilical cord form?
Coated in mesoderm and vascularises to form the umbilical cord
What is found on the inside and outside of the amniotic sac?
Amnion on the inside, chorion on the outside
Where do the primary chorionic villi project to?
they project through the syncitiotrophoblast layer into the maternal endometrium
What happens in the primary stage of chorionic villi development?
outgrowth of the cytotrophoblast and branching of these extensions
What happens in the secondary stage of chorionic villi formation?
Growth of the fetal mesoderm into the primary villi
What happens in the tertiary phase of chorionic villi development?
Growth of the umbilical artery and umbilical vein into the villus mesoderm providing vasculature
Describe the microstructure of the terminal villus?
A convoluted knot of vessels and vessel dilation
Why is the terminal villus knotted?
Slows the blood flow, allowing exchange of material between maternal and fetal blood
What coats the entire terminal villus structure?
the trophoblast
What is the approx diameter of the terminal villus during early pregnancy?
150-200 micrometers in diameter
What is the approx diameter of the terminal villus during late pregnancy?
the villli thin to 40 micrometers
What happens to the thickness of the trophoblast that surrounds the terminal villi as you move from early to late pregnancy?
10 micrometers to 1-2 micrometers
What forms from the branching of uterine arteries?
Arcuate arteries
What branches from the arcuate arteries?
Radial arteries
What do the radial arteries branch to form?
Basal arteries
During menstrual cycle endometrial thickening what do the basal arteries form?
Spiral Arteries
What happens to the spiral arteries if implantation does not occur?
The spiral arteries regress
What do the spiral arteries do?
provide the maternal blood to the endometrium
How does the endovascular EVT form?
The EVT cells (Extra-villus trophoblast) cells coating the villi invade down into the maternal spiral arteries
What is meant by the process of conversion?
When the spiral artery is converted into a low pressure, high capacity conduit maternal blood flow
How is glucose transported across the placenta?
Facilitated diffusion by transporters on maternal side and fetal trophoblast cells
How is water transported across the placenta?
Placenta is the main site for exchange, through some crosses the amnion-chorion
Majority is through diffusion, though some local hydrostatic gradients
How are electrolytes transported across the placenta?
Large traffic of sodium and other electrolytes across the placenta - through a combination of diffusion and active energy dependant co-transport
How is calcium transported across the placenta membrane?
Actively transported against a concentration gradient by magnesium ATPase calcium pump
How are amino acids transported across the placenta?
Reduced maternal urea excretion and active transport of amino acids to fetus
How does maternal cardiac output change during the first trimester?
Increases by 30% during first trimester (through increases in stroke volume and rate)
How does maternal peripheral resistance change through pregnancy?
Decreases up to 30%
How does maternal blood volume change near term?
blood volume increases by 40% near term
How does maternal pulmonary ventilation change during pregnancy?
Increases
How much glucose and oxygen supplied by the mother does the placenta consume?
40-60%
How is the affinity for O2 different between maternal and fetal haemoglobin?
HbF has a higher affinity for Oxygen than Maternal Hb
Why does the placenta consume so much glucose and oxygen?
it is a highy metabolic tissue
What process reduces maternal vessel pressure and increases capacity?
Spiral Artery remodelling
What is the role of the placenta?
A site of gas exchange for the foetus
Vascular shunts bypass pulmonary and hepatic circulation. What effect does this have?
Allows the placenta to drive oxygenated blood around the body
At what point do primitive air sacs form in the lungs?
Around 20 weeks
When does surfactant production begin?
Around week 20
Why does the foetus spend a large proportion of their day making rapid respiratory movements?
It is practice for breathing when it comes out the womb
What is the meconium?
The first stool which is delivered after birth
What forms the meconium?
The large amount of amniotic fluid which the foetus swallows - contains debris and bile acids which form the meconium
When do thalamus-cortex connections form in the foetus?
By 24 weeks
When can fetal movements be detected?
Approx 14 weeks
What increases towards the end of pregnancy that is responsible for the organ maturation and changes seen?
Corticosteroids
What is the definition of labour?
The safe expulsion of the foetus at the correct time, including the placenta and the fetal membranes
What is important to ensure can occur after labour?
The resolution and healing of the uterus to permit future reproductive events
What two events that occur during labour are characteristic of a pro-inflammatory reaction?
Immune cell infiltration
Inflammatory cytokine and prostaglandin secretion
What does prostaglandins do during labour?
Orchestrate the timing and sequence of the events of labour
What are the three stages of labour?
- Contractions start and cervical dilation
- Delivery of fetus
- Delivery of the placenta
What are the two stages of the first labour stage?
The latent phase and active phase
What occurs during the latent phase?
Slow dilation of the cervix to 2-3 cm
What occurs during the active phase of labour?
Rapid dilation of the cervix to 10cm
When does the second stage of labour commence?
When the cervix is fully dilated to 10cm
What occurs during the second stage of labour?
Maximal myometrial contractions - intense and frequent
What occurs during the third stage of labour?
Expulsion of the placenta and fetal membranes
How does the time the mother is in labour change between her first and second pregnancy?
Decreases
8-18 h to 5-12 h
What does the high connective tissue content of the cervix allow?
Provides rigidity and stretch resistance, both help keep the cervix closed
Describe the tissue structure of the cervix?
Bundles of collagen fibres embedded in a proteo-glycan matrix
What changes occur to the cervix near delivery time?
Changes to the collagen bundles underlie the softening of the cervis
What are the three processes the cervix undergoes?
Softening
Ripening
Dilation
When does softening of the cervis occur?
Begins in the first trimester
Describe the process of spiral arery remodelling?
- Extravillus throphoblast cells are shed off he chorionic villi
- They invade fown the spiral arteries, displacing the maternal endothelium by forming a new one, and thus remodelling the spiral arteries
- This process increases the diameter if the blood vessels and makes them not spiral, lowering the pressure and increases blood flow to the placenta
When does ripening of the cervix occur?
Weeks. days before birth
What occurs during ripening of the cervix?
Monocyte infiltration
IL-6 and IL-8 Secretion
Hyaluron deposition
What acts to decrease collagen content during dilation of the cervix?
Matrix metalloproteinases
What occurs during the dilation phase of cervical remodelling?
Increase hyaluronidase expression, which leads to HA breakdown
Why is post partum repair of the cervix so important?
It ensures that the mother is able to have another pregnancy - recovery of tissue integrity and competency
Which two immune cells are present in larger quantities during labour?
Macrophages and neutrophils
How is labour initiated?
The fetus determines the timing of parturition through changes in the fetal HPA axis
Levels of what hormone rise exponentially towards the end of pregnancy?
Corticotrophin-Releasing Hormone (CRH)
How do CRH levels increase towards the end of pregnancy?
There is a decline in CRH binding protein so this means the amount of free, circulating CRH that is bioavailable and therefore free to circulate increases
What functions do CRH have in labour?
Promote fetal ACTH and cortisol release
What affect does increasing cortisol production have on the placenta?
Drives placental production of CRH, resulting in a positive feedback look, as CRH promotes fetal cortisol production
What affect does cortisol have on the fetal adrenal cortex?
Stimulates DHEAS production - this is a substrate for oestrogen production
Why is it important that progesterone remains high throughout pregnancy?
High progesterone maintains uterine relaxation
Describe the shift in progesterone receptor subtypes which occurs in the uterus as term approaches? And what effect does this have
There is a switch from PR-A isoform (activating) to PR-B and PR-C (repressive) isoforms, which leads to functional progesterone withdrawal
PR = Progesterone receptor
Despite the levels of progesterone still being high, this switch in receptor type blinds the uterus to the actions of progestone - meaning the endometrium is able to start to degrade and release the baby etc etc
What does functional progesterone withdrawal involve?
The blinding of the uterus to progesterone action and sensitization to eostrogen action
What affect does functional progesterone withdrawal have on the overall estrogen:progesterone radio?
MAY shift in favour of oestrogen, increase ratio - this is not 100% clear
There is an increase in the expression of what receptor during pregnancy?
Estrogen Receptor Alpha
Where is nonapeptide hormone synthesized?
Mainly in the utero-placental tissues and the pituitary
How does uterine oxytocin production change towards the onset of labour?
it increases sharlpy
What drives the increase in uterine oxytocin production?
Increase in oestrogen levels
What is meant by the Ferguson reflex?
the fetal distension of the cervix stimulates a series of neuroendocrine responses, leading to oxytocin production.
What affect does a rise in oestrogen have on uterine OXTR?
Oestrogen promotes a large increase in uterine OXTR
What are the functions of Oxytocin to enable labour?
- Increases connectivity of myocytes by promoting the function of gap junctions
- Destabilise membrane potentials to lower the threshold needed for contraction
- Enhances the liberation of intracellular Ca2+ ion stores
What are the three primary prostaglandins that are synthesized during labour
PGE2, PGF2Alpha and PGI2
How does rising oestrogen drive prostaglandin action?
Activates phospholipase A2 enzyme, which generates more arachidonic acid for PG synthesis
Stimulation of oxytocin receptor expression prmotoes PG release
what affect does PGE2 have?
Promotes leukocyte infiltration into the cervix, collagen bundle remodelling and IL-8 release which all contribute to cervix remodelling
What affect does PGF2alpha have on labour?
Promotes myometrial contractions alongside oxytocin by destailising membrane potentials and promoting connectivity of myocytes
What affect does PGI2 have?
Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segment
Why is the relaxation of lower uterine segments so important during labour?
Allows blood flow to return to the uterus and placenta to ensure there is blood flow to the foetus
The levels of which two peptide hormones increase sharply towards the end of pregnancy?
Relaxin and Nitric oxide
what stimulates the placenta to make prostaglandins?
Oxytocin
Where do myometrial contractions originate?
The fundus
What is meant by brachystatic contractions, as shown by the myometrial contractions?
The muscle fibres do not return to full length apon relaxation
How does the birth canal form?
The brachystatic contractions of the myometrium causes the lower segment and cervix to be pulled up, forming the birth canal
Which segment of the uterus contributes to contraction?
The upper segment
At what stage does the head of the baby engage with the fetal space?
34-38 weeks
What is meant by flexion of the fetal head?
When pressure on the fetus causes the chin to press up against the chest
Which part of the baby is expelled first during birth?
The head after the cervix dilates
What is birthed after the head of the fetus?
The shoulders (upper shoulder first) followed by the torso
What affect does uterine shrinking have on the fetal membranes?
Causes them to fold and peel away from the endometrium
What affect does clamping the umbilical cord at birth have?
Stops fetal blood flow to the placenta, causing the villi to collapse
What effect does the collapse of the villi have
Causes a hematoma formation between the decidua and placenta
Contractions of the uterus expell what?
The baby, placenta and fetal tissues
Why does the uterus remain contracted after delivery?
To facilitate uterine vessel thrombosis (interuterine bleeding)
What occurs to repair non-pregnant state?
Uterine involution and cervix repair
What does uterine involution and cervical repair involve?
Sheilding uterus from commensural bacteria and restoration of endometrial cyclicity in response to hormones
What is endometrial cyclicity?
The endometrium undergoes cyclic changes each month, under the overall control of fluctuating levels of estrogen and progesterone. This hormone dependent endometrial remodelling is a continuum of structural and functional changes that make up the menstrual cycle.
Describe the hormone changes which occur towards the end of term?
- There is a switch in progesterone receptor from PA-A isoforms to PR-B and PR-C isoforms which are repressive
- This essentially blinds the uterus to the actions of progesterone despite the levels being high
- There is also an increase in estrogen receptors which allows the uterus to become sensitized to the estrogen
Describe the integrated hypothesis for the regulation of labour?
- Fetal production of CRH increases
- This trigger the Fetal adrenal gland to increase Cortisol production
- This fetal cortisol then enters into the placenta and increases the production of maternal CRH
- The cortisol also stimulates the production of placental DHEAS
- This is is then converted into Oestrogen, casing oestrogen levels to rise
- Once oestrogen levels rise, this causes the sensitivity of the OTXR in the uterus to increase = contractions
- Also, the rising oestrogen causes an increase in the fetal and maternal production of Oxytocin - leading to vigorous contractions and prostaglandin synthesis
