🐣Dev and Ageing🐣 - Disorders of Pregnancy & Parturition Flashcards
How does foetal growth change over the course of gestation?
Embryo-foetal growth during the first
trimester is relatively limited
Accelerates over the course of gestation
How does the support required by the foetus change over pregnancy?
Low foetal demand on the placenta in first trimester - embryo nutrition is histiotrophic
Start of 2nd trimester - switch to haemotrophic support
Foetal demands on the placenta increase with pregnancy
What is histiotrophic nutrition?
Reliant on uterine gland secretions and breakdown of endometrial tissues for nutrients
How is haemotrophic support achieved in humans?
Achieved in humans through a haemochorial-type placenta where maternal blood directly contacts the foetal membranes (chorionic villi)
How does the foetus increase its demand on the placenta through pregnancy?
Outline the structures shown here
- Bilaminar Embryonic Disc (Yes, this is the actual embryo)
The bilaminar disc is the earliest form of the embryo at this stage.
It consists of two layers:
Epiblast: Forms the actual embryo and later gives rise to all tissues of the fetus. It also contributes to the formation of the amniotic cavity.
Hypoblast: Forms extraembryonic tissues, contributing to structures like the yolk sac (which supports early nutrition before the placenta fully develops). - Amnion & Amniotic Cavity (Protects the embryo)
The amnion is a thin membrane that encloses the amniotic cavity, a fluid-filled space that cushions and protects the developing embryo.
This will expand as the embryo grows, eventually surrounding the entire fetus during pregnancy. - Blastocoel (A temporary cavity)
The blastocoel is a fluid-filled cavity inside the embryo at this stage.
It will later be displaced as the yolk sac and other embryonic structures form. - Cytotrophoblast (Inner trophoblast layer, provides structure)
The cytotrophoblast is a layer of stem-like cells that continually divide and provide new cells for the growing trophoblast.
It maintains the structure of the developing placenta. - Syncytiotrophoblast (Outer trophoblast layer, invades the uterus)
This is a multinucleated outer layer that aggressively invades the uterine lining (endometrium) to establish the placenta.
It:
Secretes enzymes that break down maternal tissue, allowing implantation.
Produces hCG (human chorionic gonadotropin), which is essential for maintaining pregnancy and is the hormone detected in pregnancy tests.
Forms the early connection with maternal blood supply.
How does the early embryo derive nutrition?
Embryo implants into the placenta
Syncytiotrophoblasts invade endometrium - uses breakdown products from tissue to support embryo
Breakdown of maternal capillaries results in the syncytiotrophoblasts being exposed to the maternal blood
Outline the placental structure
What are the chorionic villi?
Provide substantial surface area for exchange
Finger-like extensions of the chorionic
cytotrophoblast, which then undergo branching
What are the phases of chorionic villi development?
Primary: outgrowth of the cytotrophoblast and branching of these extensions
Secondary: growth of the foetal mesoderm into the primary villi
Tertiary: growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature.
What is a terminal villus?
Smallest, most developed branch of a chorionic villus
Convoluted knot of vessels and vessel dilation
Slows blood flow enabling exchange between maternal and foetal blood
Outline the terminal villus microstructure
Whole structure coated with trophoblast
Early pregnancy: 150-200µm diameter, approx. 10µm trophoblast thickness
between capillaries and maternal blood.
Late pregnancy: villi thin to 40µm, vessels move within villi to leave only 1-2µm trophoblast separation from maternal blood
i.e. become thinner, trophoblasts leaves less space between foetal and maternal blood by the end
What are spiral arteries?
Spiral arteries provide the maternal blood supply to the endometrium
They supply blood to the decidua (maternal portion of the placenta) and the developing embryo
What is spiral artery remodelling?
Extravillous trophoblast (EVT) cells that coat the villi, invade down into maternal spiral arteries, forming endovascular EVT
Endothelium and smooth muscle is
broken down – EVT coats inside of
vessels
Conversion: turns the spiral artery into a
low pressure, high capacity conduit for
maternal blood flow
What is the purpose of spiral artery remodelling?
Makes the vessels low pressure and high capacity for maternal blood flow
What is the mechanism behind spiral artery remodelling?
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 cell secretions break down extracellular matrix of vessel wall - replaced with fibrinoid
How can spiral artery conversion fail?
Smooth muscle remains
Immune cells become embedded in vessel wall - vessels become occluded by RBCs
What are the consequences of failed spiral artery remodelling?
Unconverted spiral arteries are vulnerable to pathological change including intimal hyperplasia and atherosis
Leads to perturbed flow - local hypoxia, free radical damage, inefficient deliver of substrates to intervillous space
Retained smooth muscle - residual contractile capacity - perturbed blood flow
What is pre-eclampsia?
New onset hypertension (in a previously normotensive
woman) BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic
Occurring after 20 weeks’ gestation
What are some characteristic feature of pre-eclampsia?
Oedema common, but not discriminatory for PE
Headache (~40% severe cases)
Abdominal pain (~15% severe cases)
Visual disturbances, seizures, breathlessness associated with severe PE
Risk of eclampsia (seizures)
How can pre-eclampsia be categorised?
Early onset <34 weeks
Late onset >34 weeks
Outline early onset pre-eclampsia
Associated with foetal and maternal symptoms
Changes in placental structure
Reduced placental perfusion
Outline late onset pre-eclampsia
More common (80-90%)
Mostly maternal symptoms - foetus generally OK
Less overt/minimal placental changes
What are the risks of pre-eclampsia to the mother?
Damage to kidneys, liver, brain and other organ systems
Possible progression to eclampsia (seizures, loss of consciousness)
HELLP syndrome - Haemolysis. elevated liver enzymes, low platelets
Placental abruption (separation of placenta from endometrium)
What are the risks of pre-eclampsia to the foetus?
Pre-term deliver
Reduced foetal growth
Foetal death (500,000/year worldwide)
What is the underlying mechanism behind pre-eclampsia?
Incomplete spiral artery remodelling - EVT invasion limited to decidual/endometrial layer
Placental perfusion restricted - placental ischaemia occurs
How does incomplete spiral artery modelling lead to the systemic effects seen in pre-eclampsia?
PLGF - placental growth factor
VEGF related, pro-angiogenic factor released in large amounts
FIt-1 (soluble VEGFR1)
Soluble receptor for VEGF-like factors (such as PLGF) which binds them to limit their bioavailability
PE - excess production of FIt-1 by distressed placenta - reduction of available pro-angiogenic factors, resulting in endothelial dysfunction
Compare a healthy and pre-eclamptic placenta in terms of its relationship with pro-angiogenic factors
What are Extracellular vesicles?
EVs are tiny (nano-meter scale) lipid-bilayer laminated vesicles released by almost all cell types
Contain diverse cargos, including mRNAs, proteins, microRNAs - can influence cell behaviour
What role do EVs serve 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
What is the proposed mechanism for EVs role in PE?
Placental ischaemia induces trophoblast cell apoptosis - EV release
These enter maternal circulation - act on endothelial cells
Induces endothelial dysfunction, inflammation and hypercoagulation
Collectively contributes to PE
What causes late onset PE?
Although >80% PE cases are late onset, the underlying mechanisms are poorly
understood
In late onset PE there is little no evidence of reduced spiral artery conversion
Placental perfusion is normal (possibly increased?)
Current theory: existing maternal genetic pre-disposition to cardiovascular disease,
which manifests during the ‘stress-test’ of pregnancy
What can be used to test for PE?
PLGF levels alone or Flt-1/PLGF ratio
High sensitivity (>94%, 20-35 weeks gestation)
Reduced average diagnosis time from 4.1 to 1.9 days
Reduced maternal adverse events and number of night spent in high-level neonatal care in test group
What is “Small for Gestational Age” (SGA)?
Foetal weight: <10th centile (or 2 SD below pop norm)
Severe SGA: 3rd centile or less
Can be subclassified into 3 groups:
Small throughout pregnancy, but otherwise healthy
Early growth normal but slows later in pregnancy (FGR/IUGR)
Non-placental growth restriction (genetic, metabolic, infection)
What is IUGR/FGR
Intrauterine Growth Restriction/Foetal Growth Restriction (same condition)
What is SGA vs IUGR/FGR?
SGA considers only the fetal/neonatal weight without any consideration of the in-utero growth and physical
characteristics at birth
IUGR/FGR has clinical features of malnutrition and in-utero growth restriction
A baby with a birth weight <10th percentile will be SGA, but not IUGR if no features of malnutrition
What are the implications of IUGR/FGR?
Cardiovascular - foetal cardiac hypertrophy, remodelling of foetal vessels due to chronic vasoconstriction
Respiratory - poor maturation of lungs, leads to bronchopulmonary dysplasia + respiratory compromise
Neurological - long term motor defects and cognitive impairments
What are the links between PE and FGR/IUGR?
