Development and Ageing Flashcards
How does placental support for the foetus change throughout pregnancy
During first trimester: growth is limited, there is low foetal demand on placenta and the nutrition is histiotrophic: therefore reliant on uterine gland secretions and brakdown of endometrial tissue
2nd trimester onwards: fetal demand increases as switches to haemotrophic support. This happens due to a hameochorial-type placental where materanl blood directly contacts babies chorionic villi.
Describe the different cells involved in the early implantation stage
Syncytiotrophoblasts: grow out from the implanted embryo to break down uterine glands, maternal capillaries and endometrial tissue for nutrients
Cytotrophoblasts: proliferative form of syncytiotrophoblasts, important to form chorionic villi
What is chorionic villi
Finger like extentions of the chorionic cytotrophoblast
Describe the phases of chorionic villi development
Primary: outgrowth of the cytotrophoblast and branching of these extensions (forms villi)
Secondary: foetal mesoderm grows into the primary villi
Tertiary: umbilical artery and vein grow into the villus mesoderm
How does the chorionic villi’s terminal villus microstructure change throughout pregnancy
Early pregnancy: 150-200 micrometers diameter, 10 micrometres trophoblast thickness
Late pregancy: villus thinner only 40 micrometres, 1-2 micrometres trophoblast thickness
villi gets thinner and the distance between maternal blood and babies blood decreases
Describe spiral artery remodelling
Extra-villus trophoblast (EVT) cells coating the chorionic villi, invade through the decidua and myometrium, down into the maternal spiral arteries, there they becomes known as endovascular EVT cells. EEVT cells activate endothelial cells to release chemokines to recruit immune cells. The immune cell invasion triggers the breakdown of smooth muscle around the vessels and the ECM in the wall of vessels so that EVT coats the inside of the vessels. once inside EVT cells replace the ECM with fibrinoid. This makes the spiral arteries a low pressure and high capacity conduit for blood flow
Describe failed spiral artery conversion
Retain smooth muscle so arteries stay spiralled and have contractibility, which affects blood delivery to the IVS
high chance of occlusion
Immune cells surround the wall of unconverted vessel and embed causing an atherosclerotic process, immune cells from plaques- intima hyperplasia
Leads to peturbed/turbulent flow (where goes from thin artery to thick) and local hypoxia, free radical damage and inefficient delivery of substrates from intervillous space
What is the criteria for pre-eclampsia diagnosis
New onset hypertension, 140 and above systolic, 90 and above diastolic
After 20 weeks of gestation
Some have:
proteinuria
reduced fetal movement
less amniotic fluid volume
oedema
headache
abdominal pain
What symptoms are associated with severe preeclampsia/ risk of eclampsia
visual distrubances, seizures, breathlessness
What are the two subtypes of preeclampsia
- Early Onset: less than 34 weeks, get fetal and maternal symptoms, placental structure chnages, reduced placental perfusion
- Late Onset: over 34 weeks, maternal symptoms, foetus and placenta are okay
What are the risk factors for preeclampsia
previous pregnancy with preeclampsia
BMI over 30
Fx
Over 40 yrs, under 20
Previous hypertension
diabetes, PCOS, autoimmunity
IVF
What risk does preeclampsia pose to
(1) the mother
(2) the foetus
1) damage to kidney, liver ,brain, other organs
progression to eclampsia
HELLP syndrome: hemolysis, Elevated liver enzymes, low platelets
placental abruption (placenta separates from endometrium)
2) pre term delivery, reduced fetal growth, fetal death
Describe what placental defects can cause preeclampsia
EVT cells only invade to decidual layer as the EVT cells dont switch from proliferative to invasive. Spiral arteries are therefore, not remodelled and placental perfusion restricted as muscle remains in tact and chorionic villi cannot draw enough blood
Placenta makes lots of PLGF, some VEGF, little Flt1.
PLGF (VEGF related) are pro-angiogenic, released into maternal circulation to bind to VEG-F receptors on endothelial cells to make them vasodilate and release anticoagulants.
Flt1 is a soluble receptor for VEGF-like factors , binds to them and limits bioavailability. High Flt-1 reduces pro-angiogenic factors causing endothelial dysfunction. Preeclampsia placentas release sFlt-1, takes up PLGF and VEGF stopping them reaching endotherlial cells
What causes late onset preeclampsia
women may have a predisposition to cardiovascular disease, the stress of pregnancy causes it to manifest
What tests are used to predict onset of preeclampsia
PLGF: if levels are smaller than 12 its a positive test and highly abnormal, if 12-100 its a positive test and abnormal so inc risk for preterm delivery
sFlt-1/PLGF ratio: is ratio is over 38 then increased risk
tests can only be used week 20-35
What is the management of preeclampsia
delivery of placenta
if less than 34 weeks, maintain pregnancy for fetus
is over 37 try to deliver
regular monitoring
anti-hypertensives
magnesium sulphate to prevent seizures
corticosteroids if before 34 weeks to promote babies lung developement
Three ways to prevent preeclampsia
Reduce BMI
Exercise throughout pregnancy (is effective even if BMI doesnt change)
Low dose asprin from 11-14 weeks for high risk groups
What are the 4 long term risks of preeclampsia
risk of CVD
T2D
renal disease
future preeclampsia (esp if early onset)
How is Small for Gestational Age defined
if fetal weight is under 10th centile (2DS under norm)
Severe SGA if 3rd centile or under
What are the three groups of SGA
1) small throughout pregnancy but healthy
2) early growth but slows later in third trimester (FGR/IUGR)
3) non-placental growth restriction like infections or genetic issue
What is different between SGA and Interuterine Fetal Growth Restriction
SGA- fetal neonatal weight, not in-utero growth or physical characteristics at growth
IUGR- clinical definitions of fetuses with signs of malnutrition and in-utero growth restriction regardless of weight percentile
What are the two types of IUGR and their characteristics
Symmetrical IUGR: earlier in gestation, genetic disorder or infection, reduced cell number but normal cell size, reduced weigh, length and head circumference, poor prognosis, less malnutrition
Asymmetrical IUGR (big head): later in gestation, utero-placental insufficiency, normal cell number but reduced cell size, low weight bu length and head circumference normal, big head and small body, good prognosis, more malnutrition
What does IGFR cause
Cardiovascular: fetal cardiac hypertrophy, remodelling of fetal vessels
Resp- poor lung maturation,
Neurological- motor defects and cognitive impairments
What is the Barker hypothesis
DOHaD (developmental origins of health and disease) hypothesis, low birth weight and being small at 2yo who then put on weight rapidly inc risk of coronary events.
Rate of BMI change not BMI at a point in time
