Pregnancy, Parturition and Late Fetal Development Flashcards
First trimester Fetal growth
Limited as nutrition is histiotrophic - reliant on uterine gland secretion and breakdown of endometrial tissues
Second trimester Fetal growth
Switch to haemotrophic support at start of second semester
Achieved through haemochorial type placenta where maternal blood directly contacts the fetal membranes around 12 weeks gestation
Primary chorionic villi
Cytotrophoblasts form finger like projections through syncytiotrophoblast layer into maternal endometrium
Oxygen exchange across placenta
Diffusion gradient (high maternal O2 tension, low Fetal O2 tension)
Glucose exchange across placenta
Facilitated diffusion by transporters on maternal side and Fetal trophoblast cells
Water exchange across placenta
Placenta main site of exchange though some crosses amnion-chorion. Majority by diffusion, though some local hydrostatic gradients
Fetal expulsion
Head engages with pelvic space 34-38 weeks
Pressure on fetus causes chin to press against chest
Fetus rotates so belly is to mother’s spine
Head expelled first after cervix dilation
Shoulders delivered subsequently followed by torso
Origins of placenta
Amniotic cells begin to secrete into amniotic sac causing formation and expansion
Chorion - outer membrane surrounding conceptus unit
Connecting stalk - links developing embryo unit to chorion - begins to develop
Trophoblastic lacunae - large space filled with maternal blood formed by breakdown of maternal capillaries and uterine glands - become intervillous spaces aka maternal blood spaces
Fetal membranes
Extraembryonic tissues that form tough but flexible sac, encapsulates fetus and forms basis of maternal-fetal interface
Amnion (inner) forms closed, avascular sac with developing embryo at one end and secretes amniotic fluid from 5th week - forms fluid filled sac that encapsulates and protects fetus
Chorion (outer) highly vascularised, gives rise to chorionic villi which is an outgrowth of cytotrophoblast from chorion that form the basis of Fetal side of placenta
Allantois- outgrowth of yolk sac, grows along connecting stalk from embryo to chorion and becomes coated in mesoderm and vascularises to form umbilical cord
Chorionic villi
Provide substantial surface area for exchange
Undergo branching
Three phases of chorionic villi development
Primary - outgrowth of cytotrophoblast and branching of these extensions
Secondary - growth of Fetal mesoderm into primary villi
Tertiary - growth of umbilical artery and umbilical vein into the villus mesoderm, providing Vasculature
Terminal chorionic villus
Convoluted knot of vessels and vessel dilation
Slows blood flow enabling exchange between maternal and Fetal blood
Whole structure covered in trophoblast
150-200 micrometer in diameter and 10 micrometers trophoblast thickness in early pregnancy
40 micrometers and 1-2 micrometer in late pregnancy
Maternal blood supply to endometrium
Uterine artery branch into arcuate artery in myometrium which turn into radial arteries and then basal arteries in the endometrium which also turn to spiral arteries
Spiral artery remodelling
Extra-villus trophoblast cells coating the villi invade down into maternal spiral arteries, forming endovascular EVT
Endothelium and smooth muscle is broken down - EVT coats inside of vessel
Conversion - turns spiral artery into low pressure high capacity conduit for maternal blood flow
Electrolyte exchange across placenta
Large traffic of sodium and other electrolytes across placenta - combination of diffusion and active-energy dependent co-transport
Calcium exchange across placenta
Actively transported against concentration gradient by magnesium ATPase calcium pump
Amino acid exchange across placenta
Reduced maternal urea excretion and active transport of amino acids to fetus
Maternal changes
Maternal cardiac output increases 30% during first trimester
Maternal peripheral resistance decreases up to 30%
Maternal blood volume increases to 40%
Pulmonary ventilation increases 40%
Placenta and fetus oxygen exchange
Placenta consumes 40-60% glucose and O2 supplied
O2 content and saturation are similar to maternal blood
Embryonic and fetal hemoglobins have greater affinity for O2 than maternal
Circulatory system maturation
Placenta acts as site of gas exchange
Ventricles act in parallel rather than series
Vascular shunts bypass pulmonary and hepatic circulation > close at birth
Respiratory system maturation
Primitive air sacs form in lungs around 20 weeks, vascularisation from 28 weeks
Surfactant production starts around 20 weeks, unregulated towards term
Fetus spends 1-4hours/day making rapid respiratory movements during REM sleep
GI system maturation
Endocrine pancreas functional from start of 2T, insulin from mid-2T
Liver glycogen progressively deposited - accelerated towards term
Large amounts of amniotic fluid swallowed - debris and bile acids form meconium
Nervous system maturation
Fetal movements begin late 1T, detectable by mother from ~14 weeks (2T)
Stress responses from 18 weeks, thalamus-cortex connections form by 24 weeks
Fetus does not show conscious wakefulness- mostly in slow-wave or REM sleep
System development changes
Orchestrated by Fetal corticosteroids
Surfactant production and liver glycogen both occur in parallel with corticosteroids
Labour
Safe expulsion of fetus at correct time
Expulsion of placenta and Fetal membrane
Resolution/healing to permit future reproductive events
Pro-inflammatory reactions - immune cell infiltration and inflammatory cytokines and prostaglandin secretion
Phases of labour
Phase 1 - quiescence - prelude to parturition - contractile unresponsive, cervical softening
Phase 2 - activation - preparation for labour - uterine preparedness for labour, cervical ripening
Phase 3 - stimulation - process of labour - uterine contraction, cervical dilation, Fetal and placenta expulsion
Phase 4 - involution - parturient recovery - uterine involution, cervical repair, breast feeding
Stages of labour
First stage
-contractions start and cervix dilation
-latent phase - slow dilation of cervix to 2-3 cm
-active phase - rapid dilation of cervix to 10 cm
Second stage
-delivery of fetus
-commences at full dilation of cervix
-maximal myometrial contractions
Third stage
-delivery of placenta
-expulsion of placenta and Fetal membranes
-post-partum repair
Remodelling of cervix
Critical role in retaining foetus in uterus
High connective tissue content
-provides rigidity
-stretch resistant
Bundles of collagen fibres embedded in proteoglycan matrix
Changes to collagen bundle structure underlie softening, but mechanism unclear
Stage of remodelling cervix
Softening - first trimester - measurable changes in compliance but retains cervical competence
Ripening - weeks and days before birth - monocyte infiltration and IL6 and IL8 secretion, hylaluron deposition
Dilation - increased elasticity - increased hyaluronidase expression - HA breakdown, MMPs decrease collagen content
Post-partum repair - recovery of tissue integrity and competency
Corticotrophin releasing hormone and initiation of labour
Fetus determines timing of parturition through changes in Fetal HPA axis
CRH level rises exponentially towards end of pregnancy
Decline in CRH binding protein levels, so CRH bioavailability increases
CRH functions in labour
Promotes ACTH and cortisol release
Increasing cortisol drives placental production of CRH - positive feedback
Stimulates DHEAS production by Fetal adrenal cortex - substrate for estrogen production
Estrogen and progesterone at labour
High progesterone through pregnancy maintains uterine relaxation
As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) isoforms in uterus - functional progesterone withdrawal
Rise in estrogen receptor alpha expression
Uterus becomes blinded to progesterone action and sensitised to estrogen action
Lead to local changes in E:P ratio in uterine tissue
Oxytocin
Nonapeptide hormone synthesised mainly in uterine-placental tissues and pituitary
-uterine oxytocin production increases sharply at onset of labour
-expression increase is driven by increase in estrogen levels
-release promoted by stretch receptors - Ferguson reflex
-signals through G-coupled oxytocin receptor (OXTR)
-rise in estrogen promotes large increase in uterine OXTR expression
Ferguson reflex
As fetus starts to bear down on cervix, stretch receptors in cervix and in vagina signal up to hypothalamus and firing of hypothalamus onto posterior pituitary triggers release of oxytocin into maternal circulation where it can act back on uterus and myometrium
Oxytocin functions
Increase connectivity of myocytes in myometrium (syncytium)
Destabilise membrane potentials to lower threshold for contraction
Enhance liberation of intracellular Ca2+ ion stores
Prostaglandins
Rising estrogen levels drive prostaglandin action in uterus
-rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
-estrogen stimulation of oxytocin receptor expression promotes PG release
-peptide hormone relaxin and nitric oxide implicated in cervix remodelling
Primary prostaglandins
PGE2 - cervix remodelling - promotes leukocyte infiltration into cervix, IL8 release and collagen bundle remodelling
PGF2alpha - myometrial contraction - destabilises membrane potential and promotes connectivity of myocytes (with oxytocin)
PGI2 - myometrium - promotes myometrial smooth muscle relaxation and relaxation of lower uterine segment
Regulation of labour
Production of CRH by Fetal pituitary acts on Fetal adrenal to produce cortisol
Cortisol is transferred to placenta for more production of CRH - positive feedback loop
CRH acting on adrenal also promotes production of DHEAS, which in placenta is converted to oestrogen
Oestrogen acts on myometrium promoting the expression of oxytocin receptor so uterus becomes sensitive to pituitary production of maternal oxytocin and that triggers contractions
Oestrogen also promotes oxytocin production which stimulates contraction and promote prostaglandin production, which go on to stimulate more vigorous contractions
In non labour state progesterone inhibits production of oxytocin receptors to keep myometrium quiescent
Myometrial contractions
Contraction starts at Fundus, spread down upper segment
Muscle contractions are brachystatic - fibres do not return to full length on relaxation
Causes lower segments and cervix to be pulled up forming birth canal
Placental expulsion
Rapid shrinkage of uterus after Fetal delivery causes area of contact of placenta with endometrium to shrink
Uterine shrinkage also causes folding of Fetal membranes - peel off endometrium
Clamping of umbilical cord after birth stops Fetal blood flow to placenta - villi collapse
Haematoma formation between decidua and placenta
Contractions expel placenta and Fetal tissue
Placental repair
Uterus remains contracted after to facilitate uterine vessel thrombosis
Uterine involution and cervix repair resorted non-pregnant state
-shielding uterus from commensural bacteria
-restore endometrial cyclicity in response to hormones
