A L3.2 Cardiac hypertrophy

Question 1

What is the timing of normal heart growth

Answer 1

• Heart parallels growth of body
• Doubles size after 6 months
• Triples after 1 year

Question 2

Macroscopic heart growth

Answer 2

• Ovoid → spheroid
• Due to change in L (40ml) & R(20ml) V size
• Thickening of walls & ↑ in capacity

Question 3

Microscopic heart growth

Answer 3

• 1st few months - hyperplasia
• After - hypertrophy (LV - 20µm; RV - 16µm)
• Changes in composition:
  
  • ↑proportion of fibroendothelial cells
  • Myocardial cells cannot replicate

Question 4

Factors controlling/needed for the growth of the heart

Answer 4

• # of cells - depends on how many cells divide in utero & 1st few month
• Hypothalamic-pituitary axis
  
  • GH/IGF
  • Thyroxine
• Mean mass ~159g

Question 5

Factors with correlation to heart size

Answer 5

• Lean body mass → important determiniant of heart size
  
  • Due to exercise (which ↑heart size)
• BP → ↑ BP = harder to pump blood
• ANGII/catecholamines → causes growth of cardiovascular cells
  
  • To cope with effects of such hormones
• Family history

Question 6

Extrinsic growth determinants

Answer 6

• Hemodynamic: things affect vol/pressure
  
  • SV & systolic wave form
• Non-hemodynamic
  
  • Hormones (ANG II)
  • Neural (NA)

Question 7

Intrinsic growth determinants

Answer 7

• Genetic
• Autocrine/paracrine

Question 8

Causes of hypertrophy

Answer 8

• Myocardial infarction (some cardiac cells die → rest have extra load)
• Hypertension
• Valve disease (valve lesions → ↑pressure loads on ventricles)
• Obesity (vol load on ventricles - more blood need to pump around, also affects BP)
• Unknown

Question 9

3 phases of cardiac hypertrophy

Answer 9

• Is on a spectrum
• Development (stress of heart)
• Compensated (coping)
• Decompensated (failure - cells under pressure → fail eventually → more cells under pressure)

Question 10

How does the developmental phase arise?

Answer 10

• From:
  
  • Pre-load (How much heart filled - EDV)
  • After-load (What ventricles pump into = BP)
    
    • Both ↑strain on walls

Question 11

2 patterns of hypertrophy

Answer 11

1. Concentric (diameter of lumen unchanged)
   
   • Thicker walls related to PRESSURE overload
2. Eccentric (diameter of lumen ↑)
   
   • VOLUME overload

Question 12

Cellular compensatory response

Answer 12

• ↑myocardial cell size (>20 µm)
• ↑# of fibroendothelial cells (esp ~epicardial vessels - i.e voronary A into heart)
  
  • However, this ↓space of A to dialate → limits O2 supply into heart muscles
• ↑intersitital matrix

Question 13

Subcellular compensatory response

Answer 13

• Regression to fetal pattern of gene expression
• ↑mito → ↑energy
• ↑myofibril → better contraction
• ↑SR → ↑EC coupling
• Low to high transition of ATPase myosin (more efficient contraction)

Question 14

Effect of the compensated responses

Answer 14

• Normalised strain on individual sarcomeres & cells
• Normal CO BUT
  
  • ↓tension at given length → ↓actin-myosin interaction
  • Develop tension more slowly → ↓ ability of actin to activate myosin ATPase

Question 15

Consequences of decompensated hypertrophy

Answer 15

• ↓work rate : mass ratio
• Sympatomatic deterioration
• Heart failure
• Death
• Electrical instability (fibrillations)