Pregnancy, Parturition and Late Foetal Development Flashcards
1
Q
What is early embryo nutrition?
A
Histiotrophic
Derivation of nutrients from the breakdown of surrounding tissues
Breakdown of maternal capillaries
Glands within the endometrium provide uterine milk
2
Q
What is limited in the first trimester?
A
Growth
3
Q
What happens between first and second trimester?
A
Rapid increase in rate of growtb
4
Q
What happens in the second trimester?
A
Starts to derive nutrients from maternal blood
Achieved through haemochorial-type placenta where maternal blood directly contacts the foetal membranes
5
Q
What is the second trimester nutrition called?
A
Haemotrophic
6
Q
How is development supported via histitrophic nutrition in the early implantation stage?
A
Syncytiotrophoblast breaks down cells and uses their products to support embryo developement
Breakdown of maternal capillaries and uterine gland secretions exposes syncytiotrophoblast to maternal blood/milk from which it can derive nutrients
7
Q
What is the amnion?
A
Derivative of epiblast
Does not go on to form part of foetus
First foetal membrane
Forms the amniotic cavity that goes on to become the amniotic sac (closed and avascular)
8
Q
What is the second key foetal membrane?
A
Chorion
Outer membrane surround whole conceptus unit
9
Q
What is the connecting stalk?
A
Part of extra embryonic tissues which grows from the embryo and connects the conceptus with the chorion
10
Q
What is the trophoblastic lacunae?
A
Large spaces filled with maternal blood formed by breakdown of maternal capillaries and uterine glands
Become intervillous spaces aka maternal blood spaces
11
Q
How is the trophoblastic lacunae formed?
A
Breakdown of maternal capillaries and glands
Lumens of the glands and capillaries start to fuse
Create a continuous space where maternal blood can flow
12
Q
What are the fetal membranes?
A
extraembryonic tissues that form a tough but flexible sac encapsulates the fetus and forms the basis of the maternal-fetal interface
13
Q
What happens with the amniotic fluid at the 5th week?
A
Amnion begins to secrete amniotic fluid from 5th week – forms a fluid filled sac that encapsulates and protects the fetus
14
Q
What are the main features of the chorion?
A
Formed from yolk sac derivatives and the trophoblast
Highly vascularized
Gives rise to chorionic villi
15
Q
What are the chorionic villi?
A
Outgrowths of cytotrophoblast from the chorion that form the basis of the fetal side of the placenta
16
Q
What is expansion of the amniotic sac caused by?
A
fluid accumulation forces the amnion into contact with the chorion, which fuse, forming the amniotic sac
17
Q
What are the layers of the amniotic sac?
A
Amniotic sac: 2 layers;
amnion on the inside
chorion on the outside
18
Q
What is the Allantois?
A
Outgrowth of the yolk sac
Grows along the connecting stalk from embryo to chorion
Becomes coated in mesoderm and vascularises to form the umbilical cord
19
Q
What forms the umbilical cord?
A
Connecting stalk
Allantois
Additional mesoderm
20
Q
What are cytotrophoblast cells?
A
Important in the development of the placenta
Cytotrophoblast forms finger-like projections through syncitiotrophoblast layer Into maternal endometrium
21
Q
What are the fingerlike projections called?
A
Primary chorionic villi
22
Q
What are the chorionic villi?
A
Provide substantial surface area for exchange (gases and nutrients)
Finger-like extensions of the chorionic cytotrophoblast, which then undergo branching
23
Q
What are the phases of chorionic villi development?
A
Primary
Secondary
Tertiary
24
Q
What happens in the primary phase of chorionic villi?
A
outgrowth of the cytotrophoblast and branching of these extensions
25
What happens in the seconary phase of chorionic villi?
growth of the fetal mesoderm into the primary villi
26
What happens in the tertiary phase of chorionic villi?
growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature.
27
What is the microstucture of terminal chorionic villi?
Blood vessel comes up through the villus
Coated in trophoblast
Surrounded by maternal blood
Convoluted knot of vessels and vessel dilation
28
What does the knot of vessel allow for?
Slows blood flow enabling exchange between maternal and fetal blood
29
How big are the villi in early pregnancy?
150-200µm diameter, approx. 10µm trophoblast thickness between capillaries and maternal blood.
30
How big are the villi in late pregnancy?
villi thin to 40µm, vessels move within villi to leave only 1-2µm trophoblast separation from maternal blood.
Diffusion distance reduced
31
How is the endometrium supplied?
Uterine artery branches give rise to a network of arcuate arteries.
Radial arteries branch from arcuate arteries, and branch further to form basal arteries.
Basal arteries form spiral during menstrual cycle endometrial thickening.
32
What happens to the blood supply during menstrual cycle?
Basal arteries spiralise during menstrual cycle
Implantation does not occur: regression of spiral arteries
Implantation does occur: stabilise and provide the maternal blood supply
33
What happens in spiral artery re-modelling?
As the spiral arteries develop the trophoblast invade the maternal spiral arteries
Outgrowth of trophoblast down into maternal spiral arteries
Known as extra-villus trophoblast cells
34
What forms the endovascular EVT?
Extra-villus trophoblast (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endovascular EVT.
35
What is the role of the endovascular EVT?
Replace the maternal endothelium of the blood vessels
As the e. EVT grow down they break down the maternal endothelium and maternal smooth muscle
Forms a new endothelial layer (foetal EVT)
36
What is the process of going from spiral to non-spiral arteries called?
Conversion
37
What is the affect of conversion?
Turns the spiral artery from a highly convoluted, high pressure vessels
Into a low pressure, high capacity conduit for maternal blood flow
38
What can problems with conversion cause?
Pre-eclampsia
| Intra-uterine growth retardation
39
Describe the placenta
Maternal unit:
Blood supply gives rise to spiral arteries
Spiral arteries supply maternal blood spaces
Drainage from venous system
From the foetal side:
Formation of chorionic villi
Branch and become vascularised
Invasion of fetal circulatory system into chorionic villi that provide the large surface area for exchange between mother and fetus
40
How does nutrient exchange across the placenta occur?
Diffusion
Facilitated diffusion
Active transport
41
How is oxygen exchanged?
diffusional gradient (high maternal O2 tension, low fetal O2 tension)
42
How is glucose exchanged?
facilitated diffusion by transporters on maternal side and fetal trophoblast cells.
43
How is water exchanged?
placenta main site of exchange, though some crosses amnion-chorion. Majority by diffusion, though some local hydrostatic gradients.
44
How are electrolytes exchanged?
large traffic of sodium and other electrolytes across the placenta – combination of diffusion and active energy-dependent co-transport.
45
How is calcium exchanged?
actively transported against a concentration gradient by magnesium ATPase calcium pump.
46
How are amino acids exchanged?
reduced maternal urea excretion and active transport of amino acids to fetus
47
What are the changes observed in the mother's cardiac system?
Maternal cardiac output increases 30% during first trimester (stroke vol & rate)
Maternal peripheral resistance decreases up to 30%
Maternal blood volume increases to 40% (near term (20-30% erythrocytes, 30-60% plasma)
48
What are the changes observed in the mother's respiratory system?
Pulmonary ventilation increases 40%
49
How much glucose and oxygen does the placenta consume?
Placenta consumes 40-60% glucose and O2 supplied
50
What are the features of fetal blood O2?
But although fetal O2 tension is low, O2 content and saturation are similar to maternal blood.
Embryonic and fetal hemoglobins: greater affinity for O2 than maternal hemoglobin.
51
What are the stages of maturation for the circulatory system?
Placenta acts as site of gas exchange for fetus
Ventricles act in parallel rather than series
Vascular shunts bypass pulmonary & hepatic circulation -> close at birth to give the circulatory system we are familiar with
52
What are the stages of maturation for the respiratory system?
Primitive air sacs form in lungs around 20 weeks, vascularization from 28 weeks
Surfactant production begins around week 20, upregulated towards term
Fetus spends 1-4h/day making rapid respiratory movements during REM sleep, practice for breathing reflex for once it leaves the uterus. Also important in development of diaphragm.
53
What are the stages of maturation for the GI system?
Endocrine pancreas functional from start of 2T, insulin from mid-2T
Liver glycogen progressively deposited – accelerates towards term
Large amounts of amniotic fluid swallowed –debris and bile acids form meconium
54
What. is meconium?
First stool which is delivered just after birth
55
What are the stages of maturation for the nervous system?
Fetal movements begin late 1T, detectable by mother from ~14 weeks
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
56
What initiates the final maturation process of the organ systems?
Orchestrated by increase in foetal corticosteroids towards the end of pregnancy
57
What are the aims of labour?
Safe expulsion of the fetus at the correct time
Expulsion of the placenta and fetal membranes
Resolution/healing to permit future reproductive events
58
What characteristics does labour have?
Labour has the characteristics of a pro-inflammatory reaction
Immune cell infiltration
Inflammatory cytokine and prostaglandin secretion
59
What is important in the timing and sequence of labour?
Prostaglandins
60
What are the stages of parturition?
Phase 1: Quiescence
Phase 2: Activation
Phase 3: Stimualtion
Phase 4: Involution
61
What is phase 1?
Prelude to parturition
Contractile unresponsiveness, cervical softening
62
What is phase 2?
Preparation for labour
Uterine preparedness for labour
Cervical ripening
63
What is phase 3?
Process of labour
Uterine contraction
Cervical dilation
Foetal and placental expulsion
64
What is phase 4?
Uterine involution
Cervical repair
Breast feeding
65
What is the first stage of labour?
Contractions start,
| Cervix dilation
66
What can the first stage of labour be broken into?
Latent Phase:
Slow dilation of the cervix to 2-3cm
Active Phase:
Rapid dilation of the cervix to 10cm
67
What is the second stage of labour?
Delivery of the fetus
68
What are the features of delivery?
Commences at full dilation of the cervix (10cm)
| Maximal myometrial contractions
69
What is the third stage of labour?
Delivery of the placenta
Explusion of placenta and fetal membranes
Post-partum repair
70
What is the timings for labour?
Prolonged first stage
Second and third - around an hour
Between 8 and 18 hours for first delivery
Between 5 and 12 for subsewuent
71
What is the role of the cervix?
Cervix has a critical role in retaining the fetus in the uterus.
72
What features of the cervix allow it to function?
High connective tissue content:
Provides rigidity
Stretch resistant
Bundles of collagen fibres embedded in a proteo-glycan matrix
Changes to collagen bundle structure underlie softening, but mechanism unclear.
73
When does cervical softening begin?
Softening – begins in first trimester
| Measurable changes in compliance but retains cervical competence
74
When does cervical ripening occur?
Ripening – weeks and days before birth
Monocyte infiltration and IL-6 and IL-8 secretion
Hylaluron deposition
75
What is cervical dilation?
Dilation – increased elasticity
Increased hyaluronidase expression -> HA breakdown
MatrixMetalloProteinases decrease collagen content
76
What is postpartum repair characterised by?
Recovery of tissue integrity and competency
77
What do we currently think the trigger for labour is ?
Fetus determines timing of parturition through changes in fetal HPA axis
CRH levels rise exponentially towards the end of pregnancy
Decline in CRH binding protein levels, so CRH bioavailability increases
78
What is the role of Corticotrophin-releasing hormone in labour?
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
79
What are levels of progesterone through pregnancy?
High progesterone through pregnancy maintains uterine relaxation
80
What happens to the progesterone:oestrogen ratio around the time of birth?
Serum estrogen:progesterone ratio may shift in favour of estrogen – this is unclear in humans
81
What changes in O and P signalling occurs as delivery approaches?
As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) isoforms
expressed in the uterus -> functional prog. withdrawal
High levels of P but the receptor changes blind the uterus to the increasing levels
Rise in Estrogen Receptor - Uterus is sensitised to the action of oestrogen
Alpha expression
82
What is oxytocin?
Nonapeptide (9aa) hormone synthesized mainly in the utero-placental tissues and pituitary.
83
What happens to uterine oxytocin during 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 bares down on the cervix, stretching it -> Ferguson reflex
84
How does Oxytocin signal?
Signals through G-coupled oxytocin receptor (OTR / OXTR)
85
What happens re the OXRT pre-labour?
Pre-labour: progesterone inhibits OXTR expression -> uterus relaxed
86
What allows for an increase in OXTR expression?
Rise in estrogen promotes large increase in uterine OXTR expression
87
What are the functions of oxytocin?
Increases connectivity of myocytes in myometrium (syncytium)
Destabilise membrane potentials to lower threshold for contraction
Enhances liberation of intracellular Ca2+ ion stores
88
What does oxytocin work in conjunction with?
Prostaglandins
89
What are the primary PGs synthesised during labour?
PGE2, PGF2alpha and PGI2
90
How do rising oestrogen levels drive PG action?
1. Rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
2. Estrogen stimulation of oxytocin receptor expression promotes PG release.
91
What is PGE2 involved with?
cervix re-modelling
| Promotes leukocyte infiltration into the cervix, IL-8 release and collagen bundle re-modelling
92
What is PGF2 alpha involved with?
myometrial contractions
| Destabilises membrane potentials and promotes connectivity of myocytes (with Oxytocin)
93
What is PGI2 involved with?
myometrium
| Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segnment
94
What are other factors important for cervix remodelling?
peptide hormone relaxin and nitric oxide (NO) implicated in cervix re-modelling
95
What is the integrated hypothesis for the regulation of labour?
CRH by foetal pituitary
Cortisol by foetal adrenals
Placenta also produces CRH and DHEAS which is converted to oestrogen
Oestrogen acts on myometrium promoting the expression of the oxytocin receptor
Uterus becomes sensitive to produce the pituitary production of maternal oxytocin and that triggers contractions
Oestrogen promotes local production of oxytocin which stimulates contractions and prostaglandin production
PGs mediate myometrial contractions and help to soften the cervix to ensure dilation can occur
96
What happens in the non-labouring state?
Progesterone inhibits the production of these oxytocin receptors that keeps the myometrium quiescent
Stops contractions occurring prematurely
97
How do the myometrial contractions work?
Myometrial muscle cells form a syncytium (extensive gap junctions)
Contractions start from the fundus, spread down upper segment
Muscle contractions are brachystatic –fibres do not return to full length on relaxation
This causes lower segment and cervix to be pulled up forming birth canal
98
What happens to foetal positioning towards the end of term?
Head engages with pelvic space 34-38wks
Pressure on fetus causes chin to press against chest (flexion)
99
How is the foetus expelled?
Fetus rotates (belly to mother’s spine
Head expelled first after cervix dilates
Shoulders delivered sequentially (upper first) followed by torso.
100
What occurs to allow for placental expulsion?
Rapid shrinkage of the uterus after fetal delivery causes area of contact of placenta with endometrium to shrink
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
101
How is the uterus repaired?
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
