PREGNANCY, PARTUITION AND LATE FETAL DEVELOPMENT Flashcards
How does the embryo get its nutrition in the first trimester?
Histiotrophic - from breakdown of surrounding tissue
Uterine gland secretions (uterine milk) and breakdown of endometrial tissues
How does the embryo get its nutrition at the start of the 2nd trimester and why does this allow for an uptick in foetal growth?
Haemotrophic
Haemochorial-type placenta where maternal blood directly contacts the fetal membranes (chorion)
What does the amniotic cavity do?
Expands to become amniotic sac to surround and cushion the foetus for development
What do amniotic cells do and when?
Secrete amniotic fluid to expand the amniotic cavity from 5th week
What is the connecting stalk?
Links the embryo unit with the chorion once embryo is fully implanted.
What are the trophpblastic lacunae?
Large spaces filled with maternal blood formed by breakdown of maternal capillaries and uterine glands
They become intervillous spaces aka maternal blood spaces
What is the chorion and what does it give rise to?
Highly vascularised outer fetal membrane formed from the yolk sac derivatives and the trophoblast
Gives rise to chorionic villi
What is the allantois?
Outgrowth of yolk sac which grows along the connecting stalk from embryo to chorion
Becomes coated in mesoderm and vascularises to form the umbilical cord along with connecting stalk and additional mesoderm
What forms the umbilical cord?
Allantois, connecting stalk and additional mesoderm
How is the amniotic sac formed?
Expansion of amniotic cavity by fluid accumulation forces amnion into contact with the chorion which fuse together
2 layers: amnion and chorion
What are chorionic villi and their function?
Extensions of chorionic cytotrophoblast which undergo branching
Increases SA for exchange of gases and nutrients
What are the 3 phases of chorionic villi development and explain them?
Primary - outgrowth of cytotrophoblasts through syncitiotrophoblast layer into maternal endometrium
Secondary - growth of fetal mesoderm into primary villi
Tertiary - growth of umbilical artery and umbilical vein into the villus mesoderm
Gives a maternal-fetal blood interface with maternal blood spaces surrounding the villi
Describe the microstructure of the terminal villus
Convoluted knot of vessels
Whole structure coated with trophoblast
How is blood flow optimised at the terminal villus?
Convoluted knot of vessels and vessel dilation slows blood flow enabling more exchange between maternal and fetal blood
What is the diameter of the terminal villi in early pregnancy compared to late pregnancy?
150-200 um diameter early pregnancy
40 um in late pregnancy
What is the trophoblast thickness between terminal villi capillaries and maternal blood in early pregnancy compared to late pregnancy?
10 um early preg
1-2 um late preg
Describe the maternal blood supply to the endometrium
Uterine artery –> arcuate arteries –> radial arteries –> basal arteries which form spiral arteries during menstrual cycle endometrial thickening
Which arteries provide the maternal blood supply to the endometrium
Spiral arteries
Describe the process of spiral artery re-modelling
Extra-villus trophoblast (EVT) cells which coat the villi invade down into maternal spiral arteries becoming endovascular EVT
Endothelium and smooth muscle is broken down with EVT coating the inside of vessels forming new endothelial layer
Spiral artery had now been broken down and converted into a low pressure, high capacity conduit to feed maternal blood spaces
What nutrients are exchanged across the placenta and how?
O2 - simple diffusion
Glucose - facilitated diffusion
Water - majority diffusion, some local hydrostatic gradient
Electrolytes - diffusion and active co-transport
Calcium - active transport by magnesium ATPase calcium pump
Amino acids - active transport (reduced maternal urea excretion)
Where is water exchanged from maternal to fetus?
Placenta main site
Some crosses amnion-chorion
What changes occur to the mother in order to facilitate the ability to supply oxygen to the fetus?
Cardiac output increases 30% in 1st trimester
Peripheral resistance decreases up to 30%
Blood volume increases 40%
Pulmonary ventilation increases 40%
How much of the oxygen/glucose from the mother does the placenta itself consume before the fetus?
40-60%
How is the fetus able to maintain similar O2 content and saturation despite low O2 tension?
Embryonic and fetal hemoglobins have a greater affinity for O2 than maternal hemoglobins
What are the differences in the circulatory system between a fetus and a developed human?
- Placenta acts as site of gas exchange (not lung)
- Ventricles act in parallel rather than series (same
circulatory loop) - Vascular shunts bypass pulmonary and hepatic
circulation allowing heart to pump oxygenated blood
from placenta with increased efficiency
What are some landmarks during the development of the respiratory system in a fetus?
Primitive air sacs - 20 weeks
Vascularisation - 28 weeks
Surfactant production - 20 weeks
How does the fetus practice for the breathing reflex when born and help develop their diaphragm?
Fetus spends 1-4 hr/day making rapid respiratory movements during REM sleep
What are some landmarks during the development of the gastrointestinal system in a fetus?
Endocrine pancreas function - 2nd trimester
Insulin production - mid 2nd trimester
Liver cell - 23 days
Liver glycogen progressively deposited - accelerates towards end
Large amounts of amniotic fluid swallowed - debris and bile acids form meconium
What is the meconium?
1st stool delivered after birth
What are some landmarks during the development of the nervous system in a fetus?
Fetal movements - late 1st trimester, detectable by mother ~14 weeks
Stress response - 18 weeks
Thalamus-cortex connections - 24 weeks
Fetus doesn’t show conscious wakefulness
Mostly in slow-wave or REM sleep
What co-ordinates organ maturation in fetuses?
Fetal cortico-steroids
What are the aims of labour/parturition?
Safe expulsion of fetus at correct time
Expulsion of placenta and fetal membranes
Resolution/healing to allow future reproductive events
In what way does labour have the characteristics of a pro-inflammatory reaction?
- Immune cell infiltration into reproductive tract
- Cytokine and prostaglandin secretion to orchestrate the
timing and order of events of labour
What occurs in the 1st stage of labour?
Latent phase: slow dilation of cervix to 2-3 cm
Active phase: rapid dilation of cervix to 10 cm
Contractions start
0-14 hours
What occurs in the 2nd stage of labour?
Delivery of fetus commencing at full dilation of cervix
Maximal myometrial contractions
14-16 hours
What occurs in the 3rd stage of labour?
Expulsion of placenta and fetal membranes
Post-partum repair
16 hours onwards
What features does the cervix have to help keep the fetus in the uterus?
High connective tissue content:
- stretch resistant, rigidity
Collagen fibres embedded in proteo-glycan matrix
What allows the cervix to dilate?
Changes to collagen bundle structure underlie softening but mechanism still unclear
Describe the changes the cervix undergoes throughout pregnancy
Softening (1st trimester)
- increased compliance but still retains competence
Ripening (weeks/days before birth)
- monocyte infiltration, IL-6/8 secretion
- hylaluron deposition
Dilation (increased elasticity)
- increased hyaluronidase expression –> HA breakdown
- MMPs decrease collagen content increasing elasticity
Post-partum repair
- recover tissue integrity and competency
How does the fetus determine the timing of parturition?
Through changes in fetal HPA axis
How does fetal corticotrophin-releasing hormone behave in pregnancy and its role?
CRH levels rise exponentially towards end of pregnancy
Decline in CRH binding protein so more bioavailability
Initiates labour/parturition
What functions does fetal corticotrophin-releasing hormone have in pregnancy?
- Promotes fetal ACTH and cortisol release
- Increasing cortisol +ve feedback on placental CRH
- Stimulate DHEAS production by fetal adrenal cortex
(substrate for oestrogen production)
How do oestrogen and progesterone behave in pregnancy and their role?
High progesterone throughout pregnancy to maintain uterine relaxation
Local changes to O:P ratio in uterine tissues important for downstream processes
How does the O:P ratio change?
As term approaches:
- Switch from progesterone receptor A (PR-A, activating)
to PR-B/C (repressive) in uterus causing functional
progesterone withdrawal
- Rise in oestrogen receptor alpha expression
Uterus becomes blinded to progesterone action and sensitised to oestrogen action
How does oxytocin behave in pregnancy and why?
Uterine oxytocin production increases sharply at onset of labour driven by increase in placental oestrogen
Pituitary oxytocin release promoted by stretch receptors (FERGUSON REFLEX)
What does oxytocin bind to?
G-coupled oxytocin receptor (OTR/OXTR)
What allows the uterus to be relaxed pre-labour
High levels of progesterone inhibiting OXTR receptor
What does the large increase in oestrogen do?
Increases uterine OXTR expression increasing oxytocin signalling
What are the functions of oxytocin?
Increases connectivity (gap junctions) of myocytes in myometrium Destablises membrane potentials to lower contraction threshold Helps free intracellular Ca2+ stores aiding contraction of myocytes of myometrium
What are the primary prostaglandins synthesised during labour?
PGE2, PGF2alpha, PGI2
Whats the relationship between oestrogen and prostaglandin?
Rising oestrogen levels:
- Activates phopholipase A2 enzyme making more
arachidonic acid for PG synthesis
- Stimulates OXTR expression promoting PG release via oxytocin signalling
What is the role of PGE2?
Cervix remodelling:
- Leukocyte infiltration into cervix
- IL-8 release
- Collagen bundle remodelling
What is the role of PGF2alpha?
Myometrial contractions:
- Destabilises membrane potentials
- Promotes connectivity of myocytes with oxytocin
What is the role of PGI2?
Myometrium:
- Myometrial smooth muscle relaxation allowing blood
flow to return to uterus/placenta
- Lower uterine segment relaxation between myometrial
contractions
What factors other than PGE2 are implicated in cervix re-modelling?
Relaxin Nitric oxide (NO)
How do uterine contractions work?
Only upper uterus (fundus, upper segment) contributes to contractions whereas lower segment and cervix don’t.
The myometrial muscle cells form gap junctions becoming a syncytium
Contractions start from fundus and spread down upper segment.
Contraction is brachystatic
Causes lower segment and cervix to be pulled up forming birth canal
What does brachystatic mean?
Muscle fibres don’t return to full length on relaxation
Describe the process of fetal expulsion
Head engages with pelvic space - 34-38 weeks
Pressure on fetus causes chin to press to chest
Fetus rotates belly to mother’s spine
Head expelled first after cervix dilates
Shoulders delivered next followed by torso
List the steps of placental expulsion
- Uterus rapidly shrinks after fetal delivery causing are of
contact between placenta and endometrium to shrink. - Fetal membranes fold and peel off endometrium.
- Umbilical cord clamped stopping fetal blood flow to
placenta causing villi collapse. - Triggers hematoma between decidua and placenta.
- Contractions expel placenta and fetal tissues.
How is the uterus repaired after birth?
Uterus remains contracted after delivery to facilitate uterine vessel thrombosis
Uterine involution and cervix repair to non-pregnant state:
- Shields uterus from commensural bacteria of repro tract
- Restore endometrial cyclicity in response to hormone
