hdfshds Flashcards
Context/intro
Placenta - protective barrier where nutrient and gas exchange occurs, allowing fetal growth.
Need bigger placenta to have a bigger SA:V for material to transfer
Normal placental structure:
Placental villi extending into maternal blood
Single layer of trophoblast between maternal and fetal blood allowing efficient material exchange - ER talk about immune system? IgG antibodies can pass from the maternal blood into the placenta through the neonatal Fc receptor (FcRn), binds toxins with high affinity - strong neutralising antibody. Provides short term passive immunity while it matures
Spiral artery remodelling - process begins as extravillous trophoblasts originating from the fetus invade the uterine wall and spiral arteries. This process is aided by NK cells and macrophages. These NK cells point their cytoskeleton filaments towards the target cells and release granzymes, specifically targeting cells that need to be destroyed for remodelling. These granzymes activate caspase-3 in target cells which cleaves iCAD into CAD which moves to the nucleus and cuts up DNA, inducing cell death. As well as directly killing cells, uNK cells also produce cytokines, growth factors, angiogenic growth factors, etc (talk about PlGF)
PET
Pre-eclampsia:
What is it - multisystem disorder of endothelial function affecting multiple organs (/placental disease in impaired spiral artery remodelling)
Diagnosis - high blood pressure at/over 20 weeks of gestation along with organ dysfunction and either proteinuria, maternal end-organ dysfunctions (neurological complications, pulmonary oedema, hematological complications, AKI, liver involvement, etc), and uteroplacental dysfunction (or more than one)
Features:
High blood pressure - caused by poor remodelling/excessive vasoconstriction
Proteinuria
Visualised
What is it caused by -
What does it cause to happen:
Infant
Before birth - neonatal death (stillbirth), iatrogenic birth
After birth - NICU admission, prolonged hospital stay, respiratory distress, seizures, infection, neonatal death, deafness/retinopathy
Long term - SEN statementing, chronic lung disease, ischaemic heart disease, cerebral palsy, cardiometabolic programming (“both” section)
Mother - death (1/9, inequality, black women more at risk), maternal kidney injury
Before birth - iatrogenic birth, pulmonary oedema, uncontrolled hypertension (stroke), renal failure, placental abruption (hemorrhage), physiological effects (trauma)
After birth -
Long term - risks in future pregnancies (gestational hypertension, PE), cardiovascular disease, end stage kidney disease, thrombophilia
Both - obesity, diabetes, hypertension, myocardial infarction
What procedures may occur:
Iatrogenic birth
Post-birth - breastfeeding modifies risks after a complicated risk
If at high risk, give aspirin at 75-150mg/day from 12 weeks until birth, reduces the risk of PE
Using animal models -
PET: what is it
- multisystem disorder of endothelial function affecting multiple organs (/placental disease in impaired spiral artery remodelling)
PET diagnosis
Diagnosis - high blood pressure at/over 20 weeks of gestation along with organ dysfunction and either proteinuria, maternal end-organ dysfunctions (neurological complications, pulmonary oedema, hematological complications, AKI, liver involvement, etc), and uteroplacental dysfunction (or more than one)
PET: features
Features:
High blood pressure - caused by poor remodelling/excessive vasoconstriction
Proteinuria
Issues
What does it cause to happen:
Infant
Before birth - neonatal death (stillbirth), iatrogenic birth
After birth - NICU admission, prolonged hospital stay, respiratory distress, seizures, infection, neonatal death, deafness/retinopathy
Long term - SEN statementing, chronic lung disease, ischaemic heart disease, cerebral palsy, cardiometabolic programming (“both” section)
Mother - death (1/9, inequality, black women more at risk), maternal kidney injury
Before birth - iatrogenic birth, pulmonary oedema, uncontrolled hypertension (stroke), renal failure, placental abruption (hemorrhage), physiological effects (trauma)
After birth -
Long term - risks in future pregnancies (gestational hypertension, PE), cardiovascular disease, end stage kidney disease, thrombophilia
Both - obesity, diabetes, hypertension, myocardial infarction
“Treatments” PET
What procedures may occur:
Iatrogenic birth
Post-birth - breastfeeding modifies risks after a complicated risk
If at high risk, give aspirin at 75-150mg/day from 12 weeks until birth, reduces the risk of PE
Using animal models -
FGR (fetal growth restriction):
What is it - small placenta and fetus with failure to reach potential for growth, along with evidence of placental dysfunction
Features:
small placental size
Inefficient syncytium - thicker syncytiotrophoblast (impeding diffusion), reduced cytotrophoblast proliferation, increased placental cell apoptosis, increased syncytial knots (leading to decreased growth and syncytiotrophoblast renewal causing smaller/less branched placentas, unhealthy/damaged ST, and a reduced transfer rate to and from the placenta)
Reduced vasculature, especially in peripheral regions, decreased villous branching, fewer and smaller terminal villi (reduced SA:V)
Increased placental vascular resistance (consrict more than in normal pregnancies - vessels may become constricted and restrict blood flow, poorer physiological function of vessels)
Insufficient spiral artery remodelling (more in PE but still occurs) - reduced flow, high resistance, diastolic notching
Can be visualised by:
Symphysiofundal height - quick, low cost, easily available (everywhere), insensitive/non-specific
2D (umbilical artery doppler) ultrasound - watch blood flow to see if it is FGR (reverse end diastolic flow high risk for stillbirth), takes time, expensive, available in hospitals, better sensitivity, often over-estimates
3D ultrasound - takes longer, even more expensive, looks at fat deposition but not at “real time”, available in research
What is it caused by -
problems with the placenta, IGF?
Single IGF knockout in mice causes reduction to only 60% of wt weight and double IGF knockout they are 30% of wt weight and cannot survive.
Placental specific IGF-2 knockout in mice causes a 50% reduction in SA:V resulting in thicker exchange barriers and reduced passive transport across placenta
ER? Treatments to just increase IGF amount is not amazing treatment - IGF levels must be controlled, high IGF levels in children may cause gigantism and high levels in adults may cause acromegaly (- serious health complication: cardiac issues, joint issues, diabetes, high BP, etc)
Cortisol levels (ER hypothalamus produces ACTH in response to stress which promotes cortisol production from the adrenal gland), cortisol may be helpful in some instances (promoting lung maturation of fetuses) but it has observational evidence to cause lower fetal birth weight. In FGR 11beta-HSD2 (enzyme that converts active cortisol into cortisone) is reduced so more stress is passed to the fetus, potentially impacting birth weight (supported by a study); furthermore, studies have found that it causes reduced IGF-2 expression and angiogenesis
What does it cause to happen:
Infant
Before birth - neonatal death (stillbirth), iatrogenic birth
After birth - NICU admission, prolonged hospital stay, respiratory distress, seizures, infection, neonatal death, deafness/retinopathy
Long term - SEN statementing, chronic lung disease, ischaemic heart disease, cerebral palsy, cardiometabolic programming (“both” section)
Mother - death (1/9, inequality, black women more at risk), maternal kidney injury
Before birth - iatrogenic birth and pre term birth
Both - obesity, diabetes, hypertension, myocardial infarction
What procedures may occur
Iatrogenic births
Risk factors taken into account - largest burden disease is in first time pregnancies in apparently healthy individuals, no previous pregnancy to understand the risk
Using animal models -
FGR - predominantly a fetal manifestation of placental insufficiency
PE - predominantly a maternal manifestation of placental insufficiency
“Treating”:
Pre-pregnancy - weight loss, smoking cessation, control of comorbidities, have kids in your 20s, have kids close together
During pregnancy - Aspirin in those with high risk for PE, calcium/vitamin D, stay active and limit weight gain, tight control of hypertension
Excessive sFlt-1 > PlGF = PE
Normal sFlt-1 with low PIGF = normotensive FGR
Low PAPPA/hCG associated with FGR
PlGF - naturally drop before birth, if this occurs too early or the placental never produced enough
Occurs too early -
Never produced enough - severe
