1b// Disorders of Pregnancy and Parturition Flashcards
(99 cards)
1
Q
With what does foetal growth acceleration occur?
A
occurs with changes in support
2
Q
What is foetal growth like in the first trimester?
A
relatively limited
3
Q
What is the foetal demand like on the placenta during the first trimester?
A
low
4
Q
What is the type of embryo nutrition for early embryo (first trimester)?
A
histiotrophic
5
Q
What does histiotrophic mean?
A
reliant on uterine gland secretions and breakdown of endometrial tissues
6
Q
Why may histiotrophic nutrition be beneficial in the early stages of the embryo?
A
it provides nutrients under a low oxygen concentration, so reducing the risk of free radical mediated damage during the sensitive period of organogenesis.
7
Q
What is the nutrition type at the start of the 2nd trimester?
A
haemotrophic
8
Q
What is haemotrophic nutrition?
A
nutrients are delivered to the placenta via maternal blood
9
Q
What are the foetal demands like from the second trimester?
A
increased with pregnancy
10
Q
How is haemotrophic nutrition achieved in humans?
A
through a haemochorial-type placenta where maternal blood directly contacts the foetal membranes (chorionic villi)
11
Q
How would you describe the foetal demand changes on the placenta throughout pregnancy?
A
increased demand as gestational age increases
12
Q
Does branching of chorionic villi increase or decrease with pregnancy?
A
increase
13
Q
Why does branching of chorionic villi increase throughout pregnancy?
A
to increase SA for exchange
14
Q
In weeks 0-13 what are the oxygen levels like for the foetus?
A
low O2- hypoxic
15
Q
What are the oxygen conditions from 13 weeks onwards?
A
higher O2
16
Q
Label.
A
17
Q
What is the intervillous space (lacunae) filled with?
A
maternal blood
18
Q
Why is it important that the intervillous space is filled with maternal blood?
A
It allows absorption of O2 and nutrients and excretion of waste
19
Q
Label.
A
20
Q
What are chorionic villi and what do they provide?
A
provide substantial SA for exchange
finger-like extensions of the chorionic cytotrophoblast, which then undergo branching
21
Q
What are the 3 phases of chorionic villi development?
A
primary
secondary
tertiary
22
Q
What is the primary phase of chorionic villi development?
A
outgrowth of the cytotrophoblast and branching of these extensions
23
Q
What is the secondary phase of chorionic villi development?
A
growth of the foetal mesoderm into the primary villi
23
Q
Label.
A
23
What is the tertiary phase of chorionic villi development?
growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature
23
Label.
24
What surrounds terminal villi?
maternal blood
25
What is the microstructure like of terminal villi?
convoluted knot of vessels and vessel dilation
26
What is the function of the specialised structure of the terminal villi?
slows blood flow enabling exchange between maternal and foetal blood
27
What is the whole structure of the terminal villi coated in?
trophoblast
28
What is the size of the terminal villi during early pregnancy?
150-200ym diameter
approx. 10ym trophoblast thickness between capillaries and maternal blood
aka thicker than late pregnancy
29
What is the size of the terminal villi during late pregnancy?
villi thin to 40ym, vessels move within villi to leave only 1-2ym trophoblast separation from maternal blood
30
Why do the villi thin?
To allow easier exchange between maternal and foetal blood
31
What do spiral arteries provide?
spiral arteries provide the maternal blood supply to the endometrium
32
How is the endovascular EVT formed? (part of spiral artery re-modelling)
extra-villus trophoblast (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endovascular EVT.
33
What does the conversion of the spiral arteries do?
turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow
34
What is the difference of capacity and pressure between unconverted spiral arteries and converted ones?
high pressure, low capacity
to
low pressure, high capacity
35
What is broken down during spiral artery re-modelling to allow the EVT to coat the inside of the vessels?
endothelium and smooth muscle
36
Label.
37
How does spiral artery re-modelling occur?
EVT cell invasion triggers endothelial cells to release chemokines, recruiting immune cells.
Immune cells invade spiral artery walls and begin to disrupt vessel walls.
EVT cells secretion break down normal vessel wall extracellular matrix and replace with a new matrix known as fibrinoid
38
What does failed conversion of spiral artery re-modelling lead to?
smooth muscle remains, immune cells become embedded in vessel wall and vessels occluded by RBCs
39
What do the activated endothelial cells of the spiral arteries produce?
chemoattractant
40
What does the chemoattractant of the endothelial cells of the spiral arteries do?
attract more immune cells, and therefore more immune cells invade vessel wall
41
During failed re-modelling of the spiral arteries, what does the retained smooth muscle lead to?
contractility
42
When are there no more immune cells in the vessel wall during spiral artery remodelling?
when the fibrinoid ECM is complete
42
Do you understand this diagram.
43
What are the consequences of failed spiral artery re-modelling?
unconverted spiral arteries are vulnerable to pathological change including intimal hyperplasia and atherosis
this can lead to perturbed flow and local hypoxia, free radical damage and inefficient delivery of substrates into the intervillous space
44
What does retained smooth muscle allow? And so what happens to blood delivery?
residual contractile capacity-> perturb blood delivery to the intervillous space
45
When can atherosis also occur?
in basal (non-spiral) arteries that would not normally be targeted by trophoblast
46
How does the blood flow change when the spiral artery opens to the intervillous space?
turbulent flow
47
What are some cells in the vessels of the spiral arteries with vascular pathology?
influx of inflammatory cells and immune cells
48
What can happen to foetal cells when there is localized damage near the villous placenta?
apoptosis of foetal cells and they enter the maternal space aka the intervillous space
49
Does this diagram make sense?
50
What is pre-eclampsia?
new onset hypertension (in a previously normotensive woman) BP>-140mmHg systolic and/or >-90mmHg diastolic
51
When does pre-eclampsia occur?
after 20 weeks gestation
(v v rarely happens before)
52
What happens in 30% of cases of pre-eclampsia?
reduced foetal movement and/ or amniotic fluid volume (by ultrasounf)
53
What are some symptoms of pre-eclampsia?
Oedema common but not discriminatory for PE
Headache (in around 40% of severe PE patients)
Abdominal pain (in around 15% of severe PE patients)
Visual disturbances, seizures and breathlessness associated with severe PE and risk of eclampsia (seizures)
54
When is early onset pre-eclampsia?
<34 weeks
55
When is late onset pre-eclampsia?
>34 weeks
56
What happens during early onset pre-eclampsia?
Associated with fetal and maternal
symptoms
Changes in placental structure
Reduced placental perfusion
57
What happens during late onset pre-eclampsia?
* More common (80-90% cases)
* Mostly maternal symptoms
* Fetus generally OK
* Less overt/no placental changes
58
What are the risks to the mother during pre-eclampsia? (4)
* damage to kidneys, liver, brain and other organ systems
* Possible progression to eclampsia (seizures, loss of consciousness)
* HELLP syndrome:Hemolysis, Elevated Liver Enzymes, Low Platelets
* Placental abruption (separation of the placenta from the endometrium)
59
What are the risks to the foetus from pre-eclampsia? (3)
* Pre-term delivery
* Reduced fetal growth(IUGR/FGR)
* Fetal death (500,000/year worldwide)
60
What is HELLP syndrome?
a subtype of pre-eclampsia and it can be fatal
HELLP syndrome:Hemolysis, Elevated Liver Enzymes, Low Platelets
61
What normally happens to the placenta (instead of pre-eclampsia)?
EVT invasion of maternal spiral arteries through decidua and into myometrium
EVT become endothelial EVT
spiral arteries become high capacity
62
What is the general idea of what causes PE?
incomplete remodelling, limited capacity for blood flow leading to placental ischaemia
63
WHat are the placental defects underpinning PE (esp early onset)?
EVT invasion of maternal spiral arteries is limited to decidual/ endometrial layer
spiral arteries are not extensively remodelled
placental perfusion is restricted
placental ischaemia occurs
64
What is PLGF?
placental growth factor
VEGF related, pro-angiogenic factor released in large amounts by the placenta
65
What is Flt1?
soluble VEGFR1
soluble receptor for VEGF-like factors which binds soluble angiogenic factors to limit their bioavailability
66
What is PE in terms of Flt1?
excess production of Flt1 by distressed placenta leads to reduction of available pro-angiogenic factors in maternal circulation, resulting in endothelial dysfunction
67
Do you understand this diagram?
68
What does a healthy placenta do in terms of PLGF and VEGF?
Releases PLGF and VEGF into the maternal circulation. These growth factors bind receptors on the endothelial surface to promote vasodilation, anti-coagulation and ‘healthy’ maternal endothelial cells.
69
What does a pre-eclampsia placenta do in terms of sFLt1, PLGF and VEGF?
Releases sFLT1, which acts as a sponge – mopping up PLGF and VEGF and stopping them binding to the endothelial surface receptors. In the absence of these signals, the endothelial cells become dysfunctional.
70
What are extracellular vesicles?
they are released by cells in danger (they are potent signalling systems)
they are tiny (nano-meter scale) lipid-bilayer laminated vesicles released by almost all cell types
they can influence cell behaviour (locally and at a distance)
71
What do extracellular vesicles contain?
diverse cargos including...
mRNAs
proteins and microRNAs (miRNAs)
72
What are the changes observed in EV number and composition in PE?
overall increase in EVs in the maternal circulation
increase in endothelial derived EVs (indicative of maternal circulation defects)
decrease in placenta-derived EVs
73
What are extracellular vesicles roles?
cell signalling (autocrine, paracrine, endocrine)
homeostasis
74
What are the types of extracellular vesicles? (4)
exosomes
microvesicles
oncosomes (released by tumour cells)
SASP
75
What three things to extracellular vesicles contain?
lipids
nucleic acids
proteins
76
Where do extracellular vesicles (EVs) originate from?
stem cells
apoptotic cells
senescent cells
young/ old donors
77
What is the possible mechanism that links EVs and PE?
* Placental ischaemia induces trophoblast cell apoptosis and EV release
* These enter the maternal circulation
* Act on endothelial cells to induce dysfunction, inflammation and hypercoagulation
* Collectively these may contribute to pre-eclampsia
78
What do EVs from severely pre-eclamptic patients do?
inhibit vasorelaxation of mouse aorta explants vs normotensive EVs
inhibit production of eNOS by human endothelial cells
79
What causes later onset PE?
(mechanism is poorly understood)
in late onset there is little to no evidence of reduced spiral artery conversion
placental perfusion is normal (possibly increased)
current theory: existing maternal genetic pre-disposition to CVD, which manifests during the 'stress test' of pregnancy
80
What are the 3 core causes of abnormal placentation?
genetic factors
maternal/ environmental factors
immunological factors
81
Do you remember most of this diagram?
there are also SNP changes aka changes in gene expression
growth can be limited of the foetus due to abnormal placenta
82
What can be used to test for PE?
PLGR levels alone
or
Flt-1/ PIGR ration
83
Are the tests for PE (with regards to the hormones) sensitive?
high sensitivity (>94%, 20-35wks gestation)
reduced average diagnosis time from 4.1 days to 1.9 days
reduced maternal adverse events and number of nigh spent in high-level neonatal care in test group
84
Describe the tests for PE?
85
Does PE increase risk of late birth or early birth?
early birth
86
What do cfRNA have to do with PE?
Examination of circulation cell free RNA (cfRNA) from liquid biopsy identifies group of tr that are predictive of PE in the first trimester
87
How are small molecule metabolites useful for PE diagnosis?
Examination of small molecule metabolites in urine reveals bio-signature associated with PE before symptom onset
88
What is SGA?
small for gestational age
foetal weight: <10th centile (or 2 SD below pop norm)
89
What is severe SGA?
below 3rd centile or less
90
What are the 3 subclasses for SGA?
* Small throughout pregnancy, but otherwise healthy
* Early growth normal but slows later in pregnancy (FGR/IUGR) (e.g., foetal growth restriction)
* Non-placental growth restriction (genetic, metabolic, infection)
91
What is IUGR?
intrauterine growth restriction (aka foetal growth restriction, FGR)
92
What is the difference between SGA and IUGR?
* SGA considers only the fetal/neonatal weight without any consideration of the in-utero growth and physical characteristics at birth. (not considering growth trajectory)
* IUGR is a clinical definition of fetuses/neonates with clinical features of malnutrition and in-utero growth restriction, irrespective of weight percentile.
* Thus a baby may be IUGR without being SGA if the show features of malnutrition but and growth restriction at birth
* Similarly, a baby with a birth weight less than the 10th percentile will be SGA , not IUGR if there are no features of malnutrition.
aka in IUGR, if the baby has always been small and has been following the growth curve it does not have IUGR
93
What are the differences between symmetrical and asymmetrical IUGR?
features of malnutrition for symmetrical are less pronounced, but instead have more growth insults
94
What are the CV, resp, and neurological implications of FGR/ IUGR?
* Cardiovascular: fetal cardiac hypertrophy, and re-modelling of fetal vessels due to chronic vasoconstriction
* Respiratory: poor maturation of lungs during fetal life, leading to bronchopulmonary dysplasia and respiratory compromise
* Neurological: long term motor defects and cognitive impairments
95
Integrating PE and FGR/ IUGR- what are the common causes?
Genetic causes
Abnormal maternal immunological adaptation
Trophoblast invasion defect
Defective decidualisation
Abnormal maternal systemiv vascular adaptation to pregnancy
Villous placental vulnarability, stress or ageing
