Development and Ageing Flashcards
How do we diagnose preeclampsia?
New onset hypertension BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic
20 weeks gestational age +
What happens normally in placental development in terms of maternal spiral arteries?
Extra-villus trophoblast (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endovascular EVT.
Endothelium and smooth muscle is broken down – EVT coats inside of vessels
What 2 ways can we detect PE with?
PLGR alone (20 weeks - 36 weeks 6 days):
<12pg/ml - Test positive- Highly abnormal - increased risk for preterm delivery
12 - 100 pg/ml - Test positive- abnormal- increased risk for pre term delivery
> 100 pg/ml - Test negative- normal - unlikely to progress to delivery within 14 days of test
sFLT1/ PLGR ratio (24 weeks to 36 weeks 6 days):
< 38 rule out pre- eclampsia
>38 rule in pre - eclampsia
What are the stages from chorionic villi to fetal artery and vein?
Primary: outgrowth of the cytotrophoblast and branching of these extensions
Secondary: growth of the fetal mesoderm into the primary villi
Tertiary: growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature.
What causes failure in placenta plantation? (7)
-smooth muscle remains (increased contractility)
-spiral artery remodeeling does not penetrate myometrium
-immune cells become embedded in vessel wall - vaso-occlusion - reduced placental perfusion - placental ishcaemia
- intimal hyperplasia and atherosis—>vessels occluded by RBCs
- free radical damage
-localised tissue damage
- local hypoxia
Types of small for gestational age
Small throughout pregnancy, but otherwise health
Early growth normal but slows later in pregnancy (FGR/IUGR)
Non-placental growth restriction (genetic, metabolic, infection)
Symmetrical IUGR
Asymmetrical IUGR
Describe the mechanisms of Barker et al proposal of devellopmental origins of health and disease
The idea is that in response to maternal malnutrition, the fetus has predictive adaptive response in expectations of a nutrition poor environment. When they are born and the environment isn’t nutrition poor, they are then maladapted and increase risk of cardiovascular events
What challenges could the fetus face in utero that as life long impacts on health?
Epigenetics
Organ size/ structure
Hormonal effects
What placental enzyme is linked to glucocorticoid mismanagement?
11BHSD2 - due to low glucocorticoid exposure
How does hormonal effects impact Dohad
In environments of maternal stress; stress hormones are released. Therefore there is an increase in glucocorticoid and a downregulation of 11BHSD2 ( a placental enzyme that regulates GCs). This means there is a higher fetal exposure to glucocorticoids. This leads to changes in growth, cell number, organ size, gene expression (epigenetics), HPA axis. eventually impacts aduly lifestyle
Explain the way epigentics impacts DoHaD
Epigenetics influenced by post translational modification of histones, DNA methylation, non- coding regions
Maternal/ Paternal stress:
Adaptation in terminally differentiated cell numbers- cardiomyocytes, neuronal cells e.g leading to increase risk of cardiovasuclar and neurovascular events
Fetal Growth restriction
Increase capacity to store energy - obesity
Changes metabloic activity- Increase risk of diabetes
What are the three main points along fetal development where epigenetics is thought to play a massive role
Gametogeneis
Early development
Organogensis and fetal growth
Examples of in utero programming affecting organ developmental
fetal hypoxia - reduced number of nephrons - increased risk of hypertension and renal disease
fetal undernutrition - reduced beta cells, and reduced insulin sensitivity of muscles, impaired glucose ocntrol in adulthood increased risk fo diabetes
How can future generations be affected by in utero changes
Primordial germ cells undergo epigenetic modification in utero , leading to adaptation in the egg/sperm which can then be passed down to the next generation
What factors influences prenatal growth
Prenatal:
Genetics - maternal determines size at birth
Endochrine - Insulin and IGF
IGF 2 embryonic growth
IGF 1 later fetal and infant growth
Nutritional - Placental insufficiency - nutrition and growth horome
Maternal diet
Environment - Uterine capacity
Mostly placental sufficiency
What influences post natal growth
Postnatal:
Genetics - largely determines height
Sex XY boys taller than XX girls
Endochrine - Human Growth Hormone
Nutritional - Excessive food intake - obesity
Poor nutrition - delayed pubarche
Starvation
Environment- Socioeconomic status
Chronic illness
Altitude
Emotional status
