Pregnancy, Parturition and Late Fetal Development Flashcards
(167 cards)
1
Q
What cannabinoid receptors does the fallopian tubes express?
A
CB1
2
Q
What does reduced CB1 receptors indicate?
A
an ectopic pregnancy
3
Q
When are endocannabinoid levels high?
A
during an ectopic pregnancy
4
Q
How do components like THC impact the fallopian tube?
A
- peturb embryo transport
- disrupt the embryo environment
5
Q
How do components like THC disrupt the embryo environment?
A
by altering the balance of endocannabinoids in the fallopian tube
6
Q
Which animal is a good model for humans during pregnancy?
A
the sheep
7
Q
How common is pre-eclampsia?
A
in around 2-4% of pregnancies in the USA and Europe
8
Q
What is the mortality of pre-eclampsia?
A
50,000-60,000 deaths/year
9
Q
What are the risks of PE to the mother during pregnancy?
A
- damage to: kidneys, liver, brain…
- possible progression to eclampsia (seizures, loss of consciousness)
- placental abruption (separation of the placenta from the endometrium)
10
Q
What maternal risk factors may pre-dispose to developing PE?
A
- history/family history of pre-eclampsia
- BMI >30
- Age > 40, and <20
- pregnancy (multiple)
- sub-fertility
- gestational diabetes
- PCOS
- diabetes
- autoimmune disease
- non-natural cycle IVF
11
Q
What are the sub-types of pre-eclampsia?
A
- early onset (<34 weeks)
- late onset (>34 weeks)
12
Q
How do you characterise HELLP syndrome?
A
- haemolysis
- elevated liver enzymes
- low platelets
13
Q
What is the main diagnostic tests done for pre-eclampsia?
A
- Urine Analysis
- Umbilical Artery Doppler velocimetry
14
Q
What are the main characteristics of pre-eclampsia?
A
- > 20 weeks gestation
- sudden, persistant hypertension
- protein uria
15
Q
What are the characteristics of pre-eclampsia?
A
- reduced fetal movement
- reduced amniotic fluid volume
- oedema (not discriminatory)
- new onset hypertension (>140/90)
- > 20 weeks gestation
- headache
- abdominal pain
- visual disturbances
- seizures
- breathlessness
16
Q
What is early onset pre-eclampsia?
A
- <34 weeks
- associated with fetal and maternal symptoms
- changes in the placental structure
17
Q
What is late onset pre-eclampsia?
A
- > 34 weeks
- more common (90%)
- maternal symptoms
- fetus generally OK
- less overt/no placental changes
18
Q
What is a placental abruption?
A
seperation of the placenta from the endometrium
19
Q
What form of nutrition is the early embryo dependent on?
A
histiotrophic
20
Q
What is histiotrophic nutrition?
A
- the derivation of nutrients from the breakdown of surrounding (endometrial) tissues and maternal capillaries
- uterine milk from uterine glands
21
Q
When is the embryo reliant on histiotrophic nutrition?
A
the first trimester
22
Q
When does the embryo swap to haemotrophic support?
A
at the start of the second trimester
23
Q
What is haemotrophic nutrition?
A
derive its nutrients from maternal blood through a haemochorial-type placenta where maternal blood directly contacts the fetal membrane
24
Q
When does the activation of the haemochorial-type placenta happen?
A
12 weeks gestation
25
What happens in the early implantation stage in terms of the origin of the placenta?
- syncytiotrophoblast invades the surrounding endometrial tissue
- secretions of uterine glands and maternal capillary breakdown allows syncytiotrophoblast access to maternal blood
26
What is the function of the amniotic sac?
surrounds and cushions the foetus for it's development through the second and third trimesters
27
What causes the amniotic sac to expand?
secretions from the amnion cells
28
What are the key fetal membranes?
- amnion
- chorion
- allantosis
29
What is a connecting stalk?
- extra-embryonic tissue
| - grows from the embryo to connect the conceptus with the chorion
30
What does the extensive invasion by the syncytiotrophoblasts form?
trophoblastic lacunae
31
What is trophoblastic lacunae?
large spaces filled with maternal blood formed by the breakdown of maternal capillaries and uterine glands
(intervillous/maternal blood spaces)
32
What is the role of the fetal membranes?
- extra-embryonic tissues
| - form a tough but flexible sec that encapsulates the fetus and forms the basis of the maternal-fetal interface
33
What is the amnion?
- inner-fetal membrane
| - forms a closed, avascular sac with the developing embryo at one end
34
Where does the amnion arise from?
epiblast (but does not contribute to fetal tissues)
35
When does the amnion begin to secrete amniotic fluid?
5th week
36
What is the chorion?
- outer fetal membrane
| - high vascularised
37
What does the chorion arise from?
- yolk sac derivatives
| - trophoblast
38
What arises from the chorion?
chorionic villi
| - outgrowth of cytotrophoblast from the chorion that form the basis of the fetal side of the placenta
39
What happens when the amniotic sac expands?
- forces the amnion to come into contact with the chorion
| - they fuze, forming the amniotic sac
40
What are the 2 layers that make up the amniotic sac?
- amnion (inside)
| - chorion (outside)
41
What is the allantois?
- outgrowth of the yolk sac
| - grows along the connecting stalk from the embryo to chorion
42
What arises from the allanosis?
- coated in mesoderm and vascularizes
| - forms the umbilical cord
43
What happens to the cytotrophoblasts when the placenta is developing?
- provides the cells to form syncitiotrophoblasts
- form finger-like projections through the synciotrophoblast layer into the maternal endometrium (primary chorionic villi)
44
What are primary chorionic villi?
finger-like extensions of the chorionic cytotrophoblast, which then undergoes branching
45
What is the role of chorionic villi?
provide substantial surface area for exchange
46
How many stages are there in chorionic villi development?
3
47
What is the primary stage of chorionic villi development?
outgrowth of the cytotrophoblast and the branching of these extensions
48
What is the secondary stage of chorionic villi development?
growth of the fetal mesoderm into the primary villi
49
What is the tertiary stage of chorionic villi development?
growth of the umbilical artery and the umbilical vein into the villus mesoderm, providing vasculature
50
Describe the microstructure of the terminal chorionic villus?
- convoluted knot of vessels
- vessel dilation
- slows blood flow to enhance exchange
- whole structure covered in trophoblast
51
What is the structure of the chorionic villi during early pregnancy?
- diameter: 150-200 micrometers
| - trophoblast thickness: 10 micrometer (between capillaries and maternal blood)
52
What is the structure of the chorionic villi during late pregnancy?
- diameter: thin-40 micrometers
| - trophoblast thickness: 1-2 micrometer (between capillaries and maternal blood)
53
Describe the maternal blood supply to the endometrium?
- uterine artery > arcuate arteries
- arcuate arteries > radial arteries
- radial arteries > basal arteries
- basal artery > spiral arteries during menstrual cycle endometrial thickening
54
Where are radial arteries found?
myometrium and endometrium
55
What is the function of spiral arteries?
provide the maternal blood supply to the endometrium
56
What are extra-villus trophoblasts?
cells coating the villi that invade down into the maternal spiral arteries
57
What happens when extra-villus trophoblasts grow into the spiral arteries?
they become endovascular EVT cells
58
What do endovascular EVT cells do?
- breaks down the endothelium and smooth muscle
| - coats the vessels to form a new endothelial layer
59
What term is used to describe the process of endovascular EVT cells replacing the endothelium of the vessels?
conversion
60
What is the purpose of conversion?
turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow
61
What do the spiral arteries supply?
the intervillus spaces/maternal blood spaces with blood
62
How does oxygen cross the placenta?
diffusional gradient
- high maternal oxygen tension
- low fetal oxygen tension
63
How does glucose cross the placenta?
- facilitated diffusion by transporters on the maternal side and fetal trophoblast cells
64
How does water cross the placenta?
- main site of exchange is placenta
- some exchange crosses the amnion-chorion
- majority by diffusion
- some local hydrostatic gradients
65
How do electrolytes cross the placenta?
large traffic of sodium and other electrolyes
| - diffusion and active energy-dependent co-transport
66
How does calcium cross the placenta?
actively transported against a concentration gradient by Mg ATPase calcium pump
67
How do amino acids cross the placenta?
- reduced maternal urea excretion
| - active transport of amino acids to the fetus
68
What are the physiological changes seen in the mother in regards to oxygen exchange?
- increased cardiac output (30%), by increasing stroke volume and rate
- peripheral resistance decreases by 30%
- pulmonary ventilation increases by 40%
- blood volume increases by 40%
69
How is the placenta/fetus adapted to enhance oxygen exchange?
- placenta consumes 40-60% of oxygen and glucose supplied
- oxygen content and saturation are similar to mternal blood
- embryonic and fetal haemoglobin has a greater affinity for oxygen than maternal haemoglobin
70
How is pre-eclampsia diagnosed?
- persistant hypertension
- proteinuria
- urine analysis
- umbilical artery (Doppler Velocimetry)
71
How can pre-eclampsia be excluded?
placenta growth factor test
72
What are the risks of PE to the fetus during pregnancy?
- reduced fetal growth
- preterm birth
- pregnancy loss/stillbirth
- Placental abruption (separation of the placenta from the endometrium)
73
What happens in the development of a normal placenta?
- EVT invasion of maternal spiral arteries leads to endothelial and smooth muscle breakdown.
- EVT become endothelial EVT and spiral arteries become high capacity
74
What happens in the development of a placenta with a risk of pre-eclampsia?
- EVT invasion of maternal spiral arteries is limited to decidual layer.
- Spiral arteries are not extensively remodelled, thus placental perfusion is restricted.
75
What is Placental Growth Factor (PLGF)?
VEGF related, pro-angiogenic factor released in large amounts by the placenta.
76
What is Fit1 (soluble VEGFR1)?
Soluble receptor for VEGF-like factors which binds soluble angiogenic factors to limit their bioavailabliltiy.
77
What is the Flt1 (souble VEGFR1) and PLGF levels seen in pre-eclampsia?
- excess production of Flt-1 by distressed placenta
| - reduction of available pro-angiogenic factors in maternal circulation, resulting in endothelial dysfuction.
78
What can be used to predict the onset of pre-eclampsia?
- PLGR levels
| - Flt-1/PLGR levels
79
What is the benefit of PLGR?
- triage test
| - rules out pre-eclampsia in the next 14 days in women 20-36weeks and 6days
80
What does a PLGR result of <12 pg/ml mean?
- positive test (highly abnormal)
| - increased risk of preterm delivery
81
What does a PLGR result of >12 pg/ml and <100 pg/ml mean?
- positive test (abnormal)
| - increased risk of preterm delivery
82
What does a PLGR result of >100 pg/ml mean?
- negative test (normal)
| - unlikely to progress to delivery within 14 days of test
83
When is a Flt-1/PlGF ratio test done?
24-36weeks and 6days
84
What does a Flt-1/PlGF ratio of <38 mean?
rules out pre-eclampsia
85
What does a Flt-1/PlGF ratio of >38 mean?
increased risk of pre-eclampsia
86
How can pre-eclampsia be resolved?
only by the delivery of the placenta
87
What is the management plan if <34 weeks?
- preferable to try and maintain the pregnancy if possible for benefit of the fetus
- anti-hypertensive therapies
- corticosteroids to promote fetal lung development before delivery
88
What is the management plan if >37 weeks?
delivery is preferable
89
What are the 3 main approaches to prevent pre-eclampsia?
- weight loss (esp if BMI>35)
- exercise throughout the pregnancy
- low dose aspirin (from 11-14weeks for high risk groups), may delay not prevent
90
What are the long term impacts of pre-eclampsia on maternal health?
elevated risk of:
- CVD
- T2DM
- renal disease
- 1/8 risk of pre-eclampsia in next pregnancy
91
How does the circulatory system mature in late fetal development?
- placenta acts as a site of gas exchange for the fetus
- ventricles act in parallel rather than series
- vascular shunts bypass pulmonary and hepatic circulation (close at birth)
92
How does the respiratory system mature in late fetal development?
- primitive air sacs form in the lungs (at 20 weeks)
- vascularization at 28 weeks
- surfactant production begins around week 20, upregulated towards term
- the fetus spends 1-4hours/day making rapid respiratory movements during REM sleep
93
How does the GI system mature in late fetal development?
- endocrine pancreas functional from start of the second trimester
- insulin from the middle of the second trimester
- liver glycogen is progressively deposited, accelerates towards DD
- large amounts of amniotic fluid swallowed (debris and bile acids form meconium)
94
How does the nervous system mature in late fetal development?
- fetal movements start in the late first T, detectable by the mother from 14 weeks
- stress response from 18 weeks
- thalamus-cortex connections form by 24 weeks
- fetus does not show conscious wakefulness (slow wave / REM sleep)
95
What is thought to cause the further maturation of the organs?
increased corticosteroids
96
What is the purpose of labour?
- safe expulsion of the fetus at the correct time
- explusion of the placenta and fetal membranes
- resolution/healing to permit future reproductive events
97
What are the characteristics of labour?
pro-inflammatory reaction:
- immune cell infiltration
- inflammatory cytokine and prostaglandin secretion
98
How many phases are there to labour?
4
99
What are the 4 phases of labour?
1 - prelude to parturition
2 - preparation for labour
3 - processes of labour
4 - parturient recovery
100
What happens in the first phase of labour?
- contractile unresponsiveness
| - cervical softening
101
When does the first phase of labour happen?
late 1st trimester and onwards
102
What happens in the second phase of labour?
- uterine preparedness for labour
| - cervical ripening
103
What happens in the third phase of labour?
- uterine contraction
- cervical dilation
- fetal and placenta expulsion
(3 stages of labour)
104
What happens in the fourth phase of labour?
- uterine involution
- cervical repair
- breast feeding
105
What is the first stage of labour?
- contractions start
| - cervix dilates
106
What can the first stage of labour be split into?
- latent phase
| - active phase
107
What happens in the latent phase of the first stage of labour?
slow dilation of the cervix to 2-3cm
108
What happens in the active phase of the first stage of labour?
rapid dilation of the cervix to 10cm
109
What is the second stage of labour?
- delivery of the fetus
- commences at full dilation of the cervix (10cm)
- maximal myometrial contractions
110
What is the third stage of labour?
- expulsion of the placenta and fetal membranes
| - post-partum repair
111
What is the role of the cervix?
retains the fetus in the uterus
112
What are the characteristics of the cervix?
- high connective tissue content (rigidity and resistance to stretch)
- bundles of collagen fibres embedded in a proteo-glycan matrix
113
What changes happen to the cervix during labour/delivery?
changes to the collagen bundle structure to soften the cervix to allow dilation
114
When does cervical softening start?
begins in the 1st trimester
115
What happens in cervical softening?
- changes in compliance
| - retains cervical competence
116
When does cervical ripening occur?
weeks and days before birth
117
What happens in cervical ripening?
- monocyte infiltration (macrophages and neutrophils)
- IL-6 and IL-8 secretion
- hylaluron deposition
118
What happens in cervical dilation?
- increased elasticity
- increased hyaluronidase expression (HA breakdown)
- MMPs decrease collagen content
119
What happens in cervical post-partum repair?
recovery of tissue integrity and competency
120
What causes the initiation of labour?
fetus determines the timing of parturition through changes in the fetal HPA axis
121
Why is it believed that the fetus determines the timing of parturition?
- CRH levels rise exponentially towards the end of pregnancy
- decline in CRH binding protein levels
- increased bioavailability of CRH
122
When does CRH exponetially increase in the fetus?
30 days before pregnancy
123
What is the impact of CRH 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 by the placenta)
124
What are progesterone levels during pregnancy?
high progesterone throughout the pregnancy to promote uterine relaxation
125
Is there a shift in the estrogen:progesterone ratio at birth?
- may
- to favour estrogen
- unsure as to why
126
What are the changes seen to progesterone receptors as term approaches?
```
swap from:
- PR-A isoforms (activating)
to:
- PR-B
- PR-C (repressive) isoforms
```
127
What is the result of these changes seen to progesterone receptors as term approaches?
- functional progesterone is withdrawn
| - uterus becomes blinded to progesterone action
128
What are the changes seen to estrogen receptors as term approaches?
increased estrogen receptor alpha expression
129
What is the result of these changes seen to estrogen receptors as term approaches?
uterus is sensitised to estrogen action
130
What is thought to cause these changes in the estrogen/progesteron receptors?
likely: local changes in the E:P ratio in uterine tissues
131
What is oxytocin?
nonapeptide (9aa) hormone synthesized mainly in the utero-placental tissues and pituitary
132
When is oxytocin produced during pregnancy?
at the onset of labour
133
What is thought to trigger the release of oxytocin?
- increased estrogen levels
| - stretch receptors (Ferguson reflex)
134
What is the Ferguson reflex?
- stretch receptors in the cervix and vagina
- hypothalamus by posterior pituitary
- triggers the release of oxytocin by the posterior pituitary
135
What does oxytocin use to signal?
G-coupled oxytocin receptor (OTR/OXTR)
136
What happens to oxytocin expression/signalling pre-labour?
progesterone inhibits OXTR expression so that the uterus can relax
137
What happens to oxytocin expression/signalling labour?
rise in estrogen promotes a large increase in uterine OXTR expression
138
What is the function of oxytocin?
- increases the connectivity of myocytes in the myometrium (syncytium)
- destabilise membrane potentials to lower the threshold for contraction
- enhances the liberation of intracellular Ca2+ ion stores
139
What are the primary prostaglandins that are synthesized during labour?
- PGE2
- PGF2alpha
- PGI2
140
What drives the action of prostaglandins?
- rising estrogen activates phospholipidase A2 enzyme, generating more arachidonic acid for PG synthesis
- estrogen stimulation of oxytocin receptor expression promotes PG release
141
What is the role of PGE2?
- cervix re-modelling
- promotes leukocyte infiltration into the cervix
- IL-8 release
- collagen bundle re-modelling
142
What is the role of PGF2 alpha?
- myometrial contractions
| - destabilises membrane potentials and promotes connectivity of myocytes (with oxytocin)
143
What is the role of PGI2?
promotes myometrium smooth muscle relaxation and relaxation of the lower uterine segment
144
What are the factors that also may be involved in cervix remodelling?
- relaxin
| - nitric oxide
145
What is DHEAS converted to in the placenta?
Estrogen
146
What does oxytocin from the fetus and the mothers pituitary glad stimulate?
- stimulates the uterus to contract
| - stimulates the placenta to make prostaglandins
147
What is the effect of prostaglandins?
stimulate more vigorous contractions of the uterus
148
What would progesterone limit if present during labour?
the increased expression of oxytocin receptors on the uterus, preventing contractions
149
Which part of the uterus drives myometrial contractions?
the fundus, and spread down the upper segment
150
Which parts of the uterus are passive?
- lower segment
| - cervix
151
What muscle cells are present in fundus and upper segment of the uterus?
myometrial muscle cells
152
What do the myometrial muscles form?
syncytium - extensive gap junctions
153
What forms the birth canal?
the lower segment and the cervix being pulled up
154
What causes the passive part of the uterus to be pulled up?
- brachystatic muscle contractions
| - fibres do not return to full length on relaxation
155
What is required before delivery can proceed?
- birth canal formed
| - dilation of the cervix
156
What signals the start of delivery?
the head engages with the pelvic space at 34-38 weeks
157
What happens when the fetus' head engages with the pelvic space?
there is pressure on the fetus causing chin to press against the chest (flexion)
158
What happens to the fetus's position as delivery progresses?
fetus rotates (belly to mothers spine)
159
What is expelled first when the cervix dilates?
head
160
What is delivered after the head?
- shoulders delivered sequentially
| - followed by torso
161
What process happens after the expulsion of the fetus?
placental expulsion and repair
162
What does the rapid shrinkage of the uterus after delivery cause?
- reduction in the area of contact of the placenta to the endometrium
- folding of fetal membranes (peel off the endometrium)
163
What is the impact of clamping the umbilical cord after birth?
stops fetal blood flow to the placenta, and villi collapse
164
What expels the placenta and fetal tissues?
contractions
165
What is the effect of the placenta villi collapse?
hematoma formation between decidua and placenta
166
What happens after the delivery of the placenta?
the uterus remains contracted after delivery to facilitate uterine vessel thrombosis
167
Why does the uterus and cervix return back to non-pregnant state?
- shields the uterus from commensal bacteria
| - restores endometrial cyclicity in response to hormones
