C L9.2 Developmental origins of cardiovascular diseases Flashcards Preview

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Flashcards in C L9.2 Developmental origins of cardiovascular diseases Deck (15)
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What is fetal growth determined by?

  • Fetal growth is determined by multiple factors including genome and env
    • 15% genotype
    • 2% sex


What are the hormonal factors controlling growth?

  • IGF, thyroids, insulin → promote growth
  • Glucocorticoids → inhibits fetal growth
  • GH → minimal control


What is intrauterine growth restriction (IUGR)

  • Low term birth weight (<2.5g) (2% of term babies)
  • Small-for-gestational age
    • <2SD below population mean
    • 10% of babies
  • 2-3 times normal perinatal mortality


Why are babies born small?

  • Causes: (↓delivery across placenta → distinct from being born premature)
    • Uteroplacental insufficiency (mainly in western society)
    • Maternal undernutrition (mainly in third world countries)
      • May have trimester specific effects
    • Maternal disease states
    • Genetic factors


What are the risks associated with babies born small?

  • Babies born small have a risk of developing adult disease


Fetal adaptations to improve survivability

  • Exposure of the fetus to a suboptimal environment causes adaptations that may help the fetus to survive in the short term but leads to increased susceptibility of developing some diseases in adulthood
  • Independent of level of obesity or exercise
    • i.e. obese people can give birth to IUGR babies


What are the critical programming periods and what is the significance of these periods being affected?

  • Timing, duration, nature
    • Preimplantation/implantation/organogenesis/prepartum maturation/suckling/after weaning/after puberty
    • Different stages affected will have different outcomes


In what parameters are adults who were born small susceptible to?

  • Organs
    • Heart, vasculature, kidney, brain
  • Systems
    • RAS, HPA (hypothalamis-pituitary-adrenal) axis
  • Alterations
    • ↓ cell numberes
    • Altered organ structure/"set-points"/hormone sensitivity


Characteristics of individuals born small

  • Have a higher mortality rates of CV diseases
  • Greater risk of non-fatal coronary heart disease & stroke
  • Altered HPA Axis
    • Higher plasma cortisol levels
    • Altered mineralo & glucocorticoid R.
    • Greater HPA axis responsiveness to stress
      • Altered renal function → hypertension


Difference in cardiomyocytes in fetus of mothers exposed to maternal stress?

  • ↓fetal body weight and relative heart weight
  • ↑mononucleated cardiomyocytes & ↓binucleated cardiomyocytes → retarded maturation
    • Implications in CV functions


How are the features of human IUGR models imitated?

  • Bilateral uterine vessel ligation → uteroplacental insufficiency


What are the results in animal models with imitated IUGR?

  • Offspring born small
  • Alters maternal endocrine env (↓progesterone)
  • Impairs mammary dev, early lactogenesis (↑milk protein genes)
    • ↓milk quality and quantity during lactation
    • Compromise postnantal growth with consequence for adult disease devlopment


Are there gender specific differences?

  • Dev hypertension:
    • Males at 6 months; Female don't dev even by 18months
    • Males have reduced cardiomyocytes numbers → causes hypertension


What is accelerated growth?

  • 90% small babies have accelerated growth in first 6 months
    • Independently associated with increased risk of adult diseases
  • Early accelerated growth → protective against disease
  • Late accelerated growth → detrimental (after 1 year)


Results of the intervention study on the effect of nutrition on babies born from IUGR

  • Cross-fostering  → restricted males onto control mothers
    • Improves postnatal body weight due to early accelerated growth
    • Cardiomyocyte numbers restored (prevents development of hypertension)