L11.2 Second hits Flashcards Preview

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Flashcards in L11.2 Second hits Deck (10)
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What are the second hits?

  • Gender → males greater risk than females
  • Improving Diet/Lifestyle → may prevent/improve disease
  • Age → older = ↑risk
  • Pregnancy → increased susceptibility to pregnancy adaptations which may influence next generation


Transgenerational Programming

  • Not limited to affect the first generation
  • Maternal line transmission


Pregnancy adaptations for SGA mothers:

  • SGA F1 pregnant females had impaired glucose tolerance
    • No difference in non-pregnant intraperitoneal glucose tolerance and insulin response test  
      • No metabolic dysfunction
  • Renal adaptations → to Preserves renal function and BP post pregnancy (but unsure what long-term effect may be)
    • ↓nephron deficit
    • ↑glomerular hypertrophy
    • ↓maternal Ma excretion
    • Normal BP


Generations effects on F2 from SGA mothers

  • Absence of low birth weight
  • Delayed nephrogenesis → may have impact later on in life
  • ↑BP in males (exacerbated in F2 compared to F1)
    • Unaffected in females
  • ↓First phase insulin secretion in males and females
    • But ↓b-cell mass in males and ↑b-cell mass in females → may be protective
  • Normal glucose tolerance and insulin sensitivity


Stess from handling rats

  • Maternal stress  from handling rats
  • Exacerbates F2 phenotype
    • Like a third hit


Risk of obesity

  • Obese women → ↑risk of gestational HT, diabetes, preeclampsia


Result of maternal F1 high fat diet

  • ↑body weight, ↑Dorsal fat deposited
  • Exacerbates glucose intolerance 
    • (Mother born small and pregnant develop glucose intolerance)


Effect of exercise

  • Prevents glucose intolerance by improving B-cell mass
  • Increase nephron number
  • Improves obesity


What happens to F2 when dad is born small

transgenic due to post-natal growth/epigenetic programming; altered phenotype only seen in male F2

  • Normal birthweight
  • ↓50% first phase insulin
  • Glucose intolerance → ↑20% glucose (may be from ↓b-cell mass or↓insulin)
  • High BP
  • Renal dysfunction → ↓creatinine clearnace
  • ↑LVWT; no change in LVM and contractility
    • Concentric remodelling 


Smmary of F2 effect from SGA moms

Maternal line → trasngenic due to adverse pregnancy

  • Normal birthweight
  • Decrease 1st phase insulin secretion BUT NORMAL glucose tolerance
  • ↑BP in males and NOT females
  • ↓Nephron number
  • NO CHANGES in cardiac parameters