L7.1 Cardiomyocyte growth remodelling Flashcards Preview

Cardio Phys > L7.1 Cardiomyocyte growth remodelling > Flashcards

Flashcards in L7.1 Cardiomyocyte growth remodelling Deck (15):
1

Concentric cardiac hypertrophy

  • Thick walls, Decrease lumen size
  • Fatter myocytes → failure is 'pathological'
  • From resistance exercise/hypertension

2

Eccentric cardiac hypertrophy

  • Wall thickness maintained, Increase lumen size
  • Longer myocytes → maintained function 'physiological'

3

Why is there a cardiac hypertrophic response?

  • Hypertrophy is the response to altered mechanical conditions
  • Compensatory mechanism to decrease wall stress (Load per cell)
  • Optimise thermodynamic state

4

Physiological hypertrophy

  • Athletes adaptation to CV training
    • Remodeling in ~50% of athletes
    • Endurance → Increase in LVEDV = increase in LVWT
    • Resistance → Increase in LVEDV < Increase in LVWT
  • Remodeling is reversible/benign when training stops

5

Determinants of LVEDV

  • Body size (50%)
  • Type (14%) - Endurance > Resistance
  • Sex & age (11%)
  • 'Others' (25%) - genetic factors (e.g. endogenous trophic influences)

6

Pathological hypertrophy (relatively irreversible): Chronic

  • Hypertension (load & stretch)
  • Renal disease (Increase BV)
  • Hormonal disturbance (RAS, SNS)

7

Pathological hypertrophy: Acute

  • Valve disease (rigidity, obstruction, backflow)
  • Infarction

8

When are different chambers affected by hypertrophy?

  • LV = from systemic load effect
  • LV + RV = trophic influences (i.e. hormone mediator)

9

What leads to dysfunction and failure?

  • Dispropotionate increase in myocardiocyte width size → dysfunction and failure

10

Subcellular 'remodeling' pathology

  • Transition of a (fast) → b (slow) MyHC
  • Changes in Ca transport
  • Decrease in Vmax to economise on energy
  • Reactivation of fetal & embryonic expression patterns
    • Adaptive process to make energy utilisation better → but ultimately are short term adaptations and will decompensate

11

Changes in Ca transport during contraction

  • Decrease L-type (generally position next to RyR → triggers SR Ca release maximally)
  • Increase T-type (When moving twds failing state)
    • Not optimally positioned
    • Ca directly acts on myofilaments → less Ca release from SR → Decrease EC coupling
    • May have a lower threshold for activation (more energy efficient)
  • Decrease SR Ca release channels
  • But Ca current is still maintained

12

Changes in Ca transport during relaxation

  • Decrease SERCA
    • Delay Ca reuptake (don't need fast MyHC → more energy efficient)
  • Increase Na/Ca exchanger
    • Increase reliance on Na/Ca exchange → relaxation associated with depol → arrhythmia
  • Increase Na/H exchanger
    • To deal with acid loading

13

Ca/H handling changes

  • Shifts to increase dependence on extracellular Ca cycling (enhanced Na/Ca exchange Ca influx)
  • Increase capacity to export acid
  • Prolonged Ca signals
  • Delayed relaxation (diastole beat compromised)

14

Outcome of compensation

  • Chronic exposure to growth promoting agents
    • Increase heart muscle mass & WT
    • Arrhythmia vulnerability
    • Functional decompensation & failure

15

What attributes to decompensation?

  • Hypertrophy → myocyte loss → failure
    • Loss through necrosis, apoptosis autophagy