Pregnancy, parturition and late foetal development Flashcards
early embryo nutrition?
Histiotrophic
Derivation of nutrients from the breakdown of surrounding tissues
Breakdown of maternal capillaries
Glands within the endometrium provide uterine milk
What happens between first and second trimester?
Rapid increase in rate of growth
what happens in first trimester
limited growth due to histiotrophic nutrition
what is the nutrition in second trimester
haemotrophic
how is histitrophic nutrition supported in the early implantation of the embryo
Syncytiotrophoblast breaks down maternal cells and uses their products to support embryo development
breakdown of maternal capillaries + uterine gland secretions exposes syncytiotrophoblast to maternal blood to derive nutrients from
what is the amnion
Derivative of epiblast - extraembryonic structure
First foetal membrane
Forms the amniotic cavity that goes on to become the amniotic sac
two key foetal membranes
amnion
chorion
what is the chorion
outer membrane surrounding whole conceptus unit
what is the connecting stalk
extra embryonic tissues which grows from the embryo and connects the conceptus with the chorion
What are the trophoblastic lacunae?
Large spaces filled with maternal blood formed by breakdown of maternal capillaries and uterine glands
Become intervillous spaces aka maternal blood spaces
How are trophoblastic lacunae formed?
Breakdown of maternal capillaries and glands
Lumens of the glands and capillaries start to fuse
Create a continuous space where maternal blood can flow
what are the foetal membranes and their function
extraembryonic tissues that form a tough but flexible sac which encapsulates the fetus and forms the basis of the maternal-fetal interface
what happens in the 5th week to amniotic fluid
Amnion begins to secrete amniotic fluid from 5th week – forms a fluid filled sac that encapsulates and protects the fetus
chorion main features
Formed from yolk sac derivatives and the trophoblast
highly vascularized
forms chorionic villi
what are chorionic villi (cell and function)
cytotrophoblast outgrowths from the chorion that form the basis of the fetal side of the placenta
how is the amniotic sac expanded?
fluid accumulation forces the amnion into contact with the chorion, which fuse, forming the amniotic sac
layers of amniotic sac
amnion on the inside
chorion on the outside
what is the allantois
yolk sac outgrowth
grows along connecting stalk embryo-chorion
becomes coated in mesoderm and vascularises
FORMS UMBILICAL CORD
what forms the umbilical cord
connecting stalk
allantois
plus mesoderm cells
what are cytotrophoblast cells
Important in the development of the placenta
form finger-like projections through syncitiotrophoblast layer Into maternal endometrium (primary chorionic villi)
fingerlike projections of cytotrophoblast into endometrium
primary chorionic villi
role of chorionic villi
Provide substantial surface area for exchange (gases and nutrients)
phases of chorionic villi development
primary secondary tertiary
primary phase of chorionic villi development
outgrowth of the cytotrophoblast and branching of these extensions
seconary phase of chorionic villi development
growth of the fetal mesoderm into the primary villi
tertiary phase of chorionic villi development
growth of the umbilical artery and umbilical vein into the villus mesoderm
structure of terminal chorionic villi
convoluted blood vessel comes up through the villus, coated in trophoblast cells
Surrounded by maternal blood
what do the knots of terminal chorionic villi allow
slows blood flow
enables exchange between maternal and foetal blood
how do the villi change from early to late pregnancy
thick to thin
reduced diffusion distance in late pregnancy
blood supply of endometrium
UTERINE ARTERY - ARCUATE arteries - RADIAL arteries - BASAL arteries - SPIRAL arteries
maternal blood supply changes in menstrual cycle
basal arteries spiralise
if no implantation - regression of spiral As
implantation - stabilise
what is spiral artery remodelling
as spiral arteries develop the extra-villi trophoblast cells invade, break down smooth muscle and endothelium of arteries
EVT cells coat inside of spiral arteries
turns spiral artery into low pressure high capacity conduit for maternal blood
what is the process of spiral artery remodelling called
conversion
what do issues in conversion cause
preeclampsia
intra-uterine growth retardation
structure of placenta
maternal arteries and veins supply intervillous space
chorionic villi from foetus act as exchange surface
half moon shape
how does nutrient exchange occur across placenta
Diffusion
Facilitated diffusion
Active transport
how is oxygen exchanged across the placenta
diffusion gradient
high maternal O2 tension, low foetal
how is glucose exchanged across the placenta
facilitated diffusion
by foetal trophoblast cells and maternal transporters
how is water exchanged across the placenta
diffusion
some local hydrostatic gradients
some crosses chorion-amnion
how are electrolytes exchanged across the placenta
diffusion and active transport
how is calcium exchanged across the placenta
active transport by magnesium ATPase calcium pump
transport of amino acids across placenta
reduced maternal urea excretion
active transport
changes in maternal cardiac system
CO increased
peripheral resistance decreased
blood volume increases - erythrocytes and plasma
changes to maternal resp system
pulmonary ventilation increases almost half fold
features of foetal blood O2
foetal O2 tension low
O2 content and sats similar to maternal blood
embryonic/foetal haemoglobins have greater affinity for O2 than maternal haemoglobin
how does the circulatory system mature in foetuses
placenta is main site of gas exchange
ventricles act in parallel
pulmonary and hepatic circulation bypassed until birth
maturation of respiratory system
Primitive air sacs form in lungs around 20 weeks, vascularization from 28
Surfactant production begins around week 20, upregulated towards term
foetus makes rapid respiratory movements during REM sleep, practice for breathing reflex for once it leaves the uterus. - important for diaphragm dev.
maturation of GI tract
endocrine pancreas function from 2nd trimester - insulin mid 2T
liver glycogen progressively deposited – accelerates towards term
Large amounts of amniotic fluid swallowed –debris and bile acids form meconium
what is the meconium
first stool delivered just after birth
formed from amniotic fluid debris and bile acids
maturation of nervous system
movement from late 1T
stress response starts at 18wk
no conscious wakefulness - mostly slow wave or REM sleep
what initiates final maturation f organ systems
increase in foetal corticosteroids
aims of labour
safe expulsion of foetus
placenta, foetal membranes
healing for future reproduction
what chemical has key role in timing and sequence of labour
prostaglandins
stages of partituition
quiescence
activation
stimulation
involution
phase 1 of partiution
prelude
contractile unresponsiveness, cervical softening
phase 2 of partuition
Preparation for labour
Uterine preparedness for labour
Cervical ripening
phase 3 partiuition
Process of labour
Uterine contraction
Cervical dilation
Foetal and placental expulsion
phase 4 partiuition
Uterine involution
Cervical repair
Breast feeding
first stage of labour
contractions start
cervical dilation
stages of first stage of labour
Latent Phase:
Slow dilation of the cervix to 2-3cm
Active Phase:
Rapid dilation of the cervix to 10cm
second stage of labour
foetus delivery
third stage of labour
Delivery of the placenta and foetal membranes
Post-partum repair
cervix structure and role in labour and pregnancy
High connective tissue content:
Provides rigidity
Stretch resistant
Bundles of collagen fibres embedded in a proteoglycan matrix
Changes to collagen bundle structure underlie softening
what is the first cervical change and when is it
softening - first trimester
when does cervical ripening occur
weeks/days before birth
monocyte infiltration and IL-6 IL-8 secretion
hylaluron deposition
how does cervical dilation occur
hyaluronidase enzyme expression increase
hyaluronic acid degrades, matrix metalloproteinases decrease collagen content
role of corticotrophin releasing hormone in pregnancy
Promotes fetal ACTH and cortisol release
Increasing cortisol drives placental production of CRH -> Positive feedback
Stimulates DHEAS production by the fetal adrenal cortex -> substrate for estrogen production
what are progesterone levels in pregnancy and why
high
maintains uterine relaxation
what changes occur in oestrogen and progesterone signalling close to delivery
As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) expressed in the uterus -> functional prog. withdrawal
High levels of P but the receptor changes blind uterus to it
Rise in oestrogen alpha receptor - Uterus sensitised to action of oestrogen
production of oxytocin in labour
Uterine oxytocin production increases sharply at onset of labour
Expression increase is driven by increase in oestrogen levels
Release promoted by stretch receptors as the foetus bears down on the cervix, stretching it -> Ferguson reflex
what is the ferguson reflex
foetus bares down on cervix, stretch receptors cause increased release of oxytocin
oxytocin signalling
via g-coupled oxytocin receptor
OXTR
functions of oxytocin in labour
Increases connectivity of myocytes in myometrium (syncytium)
Destabilise membrane potentials to lower threshold for contraction
Enhances liberation of intracellular Ca2+ ion stores
how does a rise in oestrogen drive prostaglandin action
Rising oestrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
oestrogen stimulation of oxytocin receptor OXGR expression promotes PG release
PGE2 role in labour
cervix re-modelling
Promotes leukocyte infiltration into the cervix, IL-8 release and collagen bundle re-modelling
PGF2 alpha role in labour
myometrial contractions
Destabilises membrane potentials and promotes connectivity of myocytes (with Oxytocin)
role of PGI2 in labour
myometrium
Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segnment
regulation of labour process
foetal CRH - cortisol
placenta CRH + DHEAS (oestrogen produced)
oestrogen acts on myometrium promoting the expression of OXTR and local production of oxytocin
Uterus becomes sensitive to produce the pituitary production of maternal oxytocin - CONTRACTIONS + prostaglandin synth
PGs ripen and soften cervix
process of myometrial contractions
Myometrial muscle cells form syncytium (extensive gap junctions)
Contractions start from the fundus, spread down upper segment
Muscle contractions are brachystatic (fibres dont return to full length on relaxation)
therefore Lower segment and cervix pulled up forming birth canal
how does foetal head position change towards delivery
Head engages with pelvic space 34-38wks
Pressure on fetus causes chin to press against chest (flexion)
how is foetus expelled
Fetus rotates (belly to mother’s spine Head expelled first after cervix dilates Shoulders delivered sequentially (upper first) followed by torso.
what happens after foetal expulsion
placenta expulsion
Uterine shrinkage also causes folding of fetal membranes – peel off the endometrium
Clamping of the umbilical cord after birth stops fetal blood flow to placenta -> villi collapse
Hematoma formation between decidua and placenta
Contractions expel placenta and fetal tissues
how does the uterus undergo repair
Uterus remains contracted after delivery to facilitate uterine vessel thrombosis.
Uterine involution and cervix repair restore non-pregnant state
Shielding uterus from commensural bacteria
Restore endometrial cyclicity in response to hormones
how is preeclampsia diagnosed
During routine check ups:
Check BP
Urine tests
Blood tests
maternal risk factors for preeclampsia
Age Obesity First pregnancy Previous pregnancy with pre-eclampsia/Family history Gestational hypertension or previous hypertension PCOS Renal disease Diabetes Subfertility Autoimmune disease
early onset preeclampsia
less than 34 wk
foetal and maternal symptoms
changes in placental structure
late onset preeclampsia
over 34wk
mostly maternal symptoms
less placental structural changes
symptoms of preeclampsia
high bp when previously normotensive
headaches
proteinuria
upper abdominal pain (less common)
risks to foetus in preeclampsia
reduced growth
stillbirth
neonatal respiratory distress syndrome
preterm birth
risks to mother in preeclampsia
HELLP syndrome
pulmonary oedema
eclampsia
placental abruption
pathophysiology of preeclampsia
failure of normal trophoblast invasion (only in decidual layer)
maladaption of maternal spiral arterioles - placental perfusion restricted
factors associated with preeclampsia
PLFG - proangiogenic, released in large amounts by placenta
Flt1 (soluble VEGFR1) - receptor for VEGF like factors, limits their bioavailability
role of factors in preeclampsia
excess Flt1 leads to reduction of available pro-angiogenic factors in maternal circulation, resulting in endothelial dysfunction
use of PLGR tests alone in PE
triage test
rules out PE in the next 14 days
use of sFlt1:PLGF ratio in PE
under 38 rules out PE
over 38 has increased risk of PE
how is PE managed
only cured by placenta delivery - if over 37wk, deliver, under 34, keep, in between is case by case
anithypertensives
corticosteroids if under 34wk for lung development before delivery
long term impacts of PE
Elevated risk of CV disease, t2DM and renal disease
Roughly 1/8 risk of having pre-eclampsia in next pregnancy (greater if early onset)
prevention of pre-eclampsia
weight loss
exercise - regardless of PE
baby aspirin for high risk groups prevents early onset
