Pathogenesis of hypertrophy Flashcards
a. Define cardiac hypertrophy and remodeling b. Define and describe morphologic patterns of pathologic cardiac hypertrophy c. Describe the adaptive response by a heart muscle cell to a prolonged increased workload d. Compare and contrast pathologic and physiologic cardiac hypertrophy
What causes cardiac hypertrophy -general
Prolonged increase in workload
Hearts response to prolonged changes in workload
-remodels
Remodelling
The adaptive response of the heart to physiologic or pathologic stimuli
What does the process of remodeling involve
- alterations at cellular, biochemical and molecular levels in the myocytes, vasculature and interstitium
- ultimately leading to changes in size, shape and function of the heart
Causes of physiologic hypertrophy (2)
- exercise
- pregnancy
Causes of pathologic hypertrophy (3)
- hypertension
- valve disease
- infarction
Consequences of pathologic hypertrophy (4)
- increase dysfunction after ischemia
- increase infarct size
- sudden death
- heart failure
MOA normal heart –> pathologic hypertrophy
1) Pressure overload
2) Volume overload
3) Loss of contractile mass
Causes pressure overload
- hypertension
- aortic stenosis
Causes volume overload
- septal defects
- valvular regugitation
Causes of loss of contractile mass
-myocardial infarction
Law of laplace explanation of cardiac hypertrophy
- Wall tension /stress is proportional to Pxr/h
- if pressure increases due to a biomechanical stress (i.e. pressure overload) then to balance out and maintain wall tension thickness (h) of myocardial wall will increase = cardiac hypertrophy (negative feedback to wall tension/stress)
Two patterns of remodeling
1) pressure overload –> concentric remodeling
2) volume overload —> eccentric remodelling
Relative wall thickness
The ratio of LV wall thickness to diastolic diameter
Relative wall thickness in cocentric and eccentric hypertrophy
- increase RWT in concentric (like wall growing in)
- decrease RWT in eccentric (like wall growing out)
MOA cardiac hypertrophy -what is happening to the cells
-increased cell size
Pressure overload hypertrophy vs. volume overload hypertrophy
-difference in way the individual cells grow in
response to different stimuli
a) pressure overload
-increase length 5%
-increase x sectional area 150% (more like a square)
b) volume overload
-increase length 30%
-increase cross sectional area 50%
(which if look at the shape a rectangle - makes sense that it grows outwards)
Cardiac hypertrophy response to a stimulus
- 2 changes included in growth
1) Quantitative changes
- structural changes i.e. size
2) Qualitative changes
- non structural changes (properties)
* * a hypertrophied heart is not just a big normal heart!
Myocardial adaptations in pathologic cardiac hypertrophy
- decrease SR Ca2+ ATPase
- Increase ANP/BNP expression
3) Expression NE/EPI receptors
4) Increase glycolysis
5) Decrease FA oxidation
6) Increase beta MHC on contractile protein
* many of changes in gene expression are reminiscent of the gene expression profile in fetal hearts
MOA myocardial cell changes to get cardiac hypertrophy
1) Stimulus
-biomechanical stimuli
-neurohumoral stimuli
2) Receptors
activated by biomechanical stimuli
-stretch-sensitive receptors
activated by neurohumoral stimuli (hormones, cytokines, growth factors)
-surface receptors
3) Both stretch-sensitive and surface receptors activate the signal transduction pathway leading to..
a) gene transcription
b) protein synthesis/degradation
4) Net effect = cardiac hypertrophy
Representative stimuli of cardiac myocyte hypertrophy
a) hormones
- Ang II
- endothelin-1
- norepinephrine/epinephrine
b) peptide growth factors
- insulin like growth factor 1
c) cytokines
- cardiotrophin-1
Effects of prolonged exercise
Physiologic hypertrophy
Hemodynamic response to acute exercise in endurance training (4)
1) increase o2 consumption
2) increase CO
3) Increase systolic bp
4) Decrease peripheral vascular resistance
Hemodynamic response to acute exercise in strength training
1) Slight increase O2 consumption
2) Slight increase in CO output
3) Increase in systolic bp (more than endurance)
4) Increase peripheral vascular resistance
