Lecture 17: Cardiac Adaption, Acute and Chronic Changes in Loading Conditions that lead to HYPERTROPHY Flashcards
What are the three most important dichotomies for this lecture?
- Pressure-Volume
- Mass-Geometry
- Adaptive-Maladaptive
What does left ventricular size correlate with?
- gender
- overall body size (BSA and height)
This is why we have cardiac index
What are the types of acute changes?
- Volume load (increased stroke volume)
2. Pressure load (increased systolic pressure)
How do you get an acute increase in volume workload?
i. Exercise
ii. Anemia
iii. Regurgitant Valves
This leads to increased stroke volume
How do you get an acute increase in pressure workload?
i. HTN (your ventricle is pushing against a higher afterload)
ii. Valvular stenosis
Leads to increased ventricular systolic pressure to compensate
What is relative wall thickness?
RWT = 2*WT/LVID
WT = Wall thickness
LVID = left ventricular interior diameter
Normal RWT = 0.34
What is cLVH?
Concentric left ventricular hypertrophy
When wall thickness increases but
Internal diameter stays the same
RWT > 0.34
What is eLVH?
Eccentric left ventricular hypertrophy
When wall thickness stays the same
But internal diameter increases
RWT < 0.34
What are the acute compensatory mechanisms for volume and pressure overload?
- Increased cardiac output (SV and HR) for volume overload
2. Increased ventricular systolic pressure for pressure overload
What does the heart do acutely when there is a volume overload?
- Increase end-diastolic volume (EDV)
- ESV is held constant
- Thereby, SV is increased
- Increase heart rate
- Increased contractility
What does the heart do acutely when there is a volume overload?
- Increase end-diastolic volume (EDV)
- ESV is held constant
- Thereby, SV is increased
- Increase heart rate
- Increased contractility
What is the max increase in SV?
180%
What is the max achievable heart rate?
220bpm – age
Example: 22 year old has max heart rate of 198 bpm
What does the heart do acutely when there is a pressure overload?
- Increase systolic ejection pressure (contractility)
- Initiate contraction from higher EDV
Leads to decrease stroke volume initially
This is to compensate for an increased afterload
Increased afterload expected for pressure overload
Limits diastolic filling so higher ESV
NO CHANGE in heart rate
What is ESPVR?
End systolic pressure volume relationship
ESPVR is similar to stress length relationship for muscle
Why does one need to initiate contraction from a higher EDV for a pressure overload?
Because higher EDV = higher preload = greater stretching of the sarcomeres = greater contractility
How does heart increase contractility in a pressure overload compensatory mechanism?
- Increases inotropy through humoral and sympathetic factors!
- contracts at a higher EDV (frank-starling ninja)
What is the metabolic price for volume and pressure overload compensation?
Increase wall stress (not relative wall thickness but wall stress ala Laplace)
Increase wall stress leads to increased myocyte metabolic demands
Greater wall stress = more O2 demand
This happens for BOTH volume and pressure overload
What causes an increase in myocardial oxygen consumption?
- Increased wall stress due to:
i. increased chamber pressure
ii. increased chamber radius
iii. DECREASED wall thickness - Increased contractility
- Increased heart rate
What is the difference between volume and pressure overload acute adaptation?
Volume overload requires more cardiac output so requires increase in HR
Pressure overload only requires you maintain same CO so you don’t have to change HR
What are the limitations to increasing EDV and thus SV? Metabolic costs?
Ventricular compliance
Metabolic cost = increased wall stress
What are the limitations decreasing ESV? Metabolic cost?
Myocardial shortening limit
Metabolic cost = inotropic stimulation
What are limitations to increased inotropic state?
Myocardial properties (amount shortened) Metabolic cost = increased systolic wall stress
What are conditions of chronic VOLUME overload?
- Leaky valves (AR and MR)
- High output states (eg anemia)
Volume overload means your heart is in a situation in which it needs to increase CO
What are conditions of chronic PRESSURE overload?
- Obstructed valves (eg aortic stenosis)
- HTN
Pressure overload means your ventricle has to overcome more pressure to maintain the same CO
What leads to failure of acute adaptation or chronic overload states?
When increased myocyte metabolism cannot be sustained
What is the chronic adaptation for chronic overload?
Hypertrophy
Optimization (minimization of myocyte metabolism)
How does the heart hypertrophy in order to compensate for chronic overload?
- increase in LV mass
2. Changes in LV geometry
How does an increase in myocardial mass decrease myocyte oxygen consumption?
Because the decrease is in consumption at a cellular level
Overall myocardial O2 consumption may be increased, but individual myocyte consumption is decreased because the burden is shared
What type of hypertrophy accompanies PRESSURE overload?
Concentric hypertrophy
In this case, the chamber pressure is increased dramatically
In order to maintain wall stress, one must look to Laplace to figure out how the heart will compensate
Ventricular wall thickness INCREASES to compensate for increase of chamber pressure
Goal is to maintain wall stress value
Radius does not change
What is the end result of pressure overload chronic adaptation?
- increased mass (hypertrophy)
- increased wall thickness (to compensate for increased pressure)
- increase in relative wall thickness (because RWT = 2*WT/radius)
- chamber radius stays the same
What is concentric hypertrophy?
Increase wall thickness to dissipate increased work imposed by increased cavity pressures
Happens in response to pressure overload
What type of hypertrophy compensates for chronic volume overload?
Goal is to maintain wall stress levels
Thus, an increase in chamber radius (due to increased EDV) leads to increased wall thickness
What is the end result for chronic volume overload hypertrophy?
- increase LV mass (hypertrophy part)
- increase LV wall thickness
- increased LV chamber radius
But NOT change in relative wall thickness
What is the difference between the adaptive changes in volume and pressure overload?
There is no change in RWT in volume overload (because chamber radius changes)
But pressure overload, the RWT is greater because radius stays the same while wall thickness increases
Eccentric LVH does not do as good of a job normalizing the wall stress because wall thickness is not as great as concentric
What is eccentric hypertrophy?
When there is no change in relative wall thickness, although there is increased LV thickness, mass, and chamber radius
Just bigger cavity
What is concentric remodeling in HTN?
When there is a normal LV mass with an elevated RWT
Somewhat unique to HTN
What are the characteristics of hypertension?
A combination of pressure and volume overload
Spectrum of LV mass and geometry
How do you make myocytes (myocyte hyperplasia)?
- formation of additional myocytes
- Intrauterine development and the first three months of extrauterine life only
- involves only continued activity of fetal/early genes
How do we normally enlarge the myocytes we got from birth?
- Increase in size of EXISTING myocytes
- Addition of sarcomeres
- in series (increases myocyte length)
- in parallel (increases myocyte diameter)
- Adult forms of protein isomers (eg myosin)
- Augmentation of subcellular components
- mitochondria
- SR
What are the two ways to increase size of myocyte?
- put more sarcomeres in series
2. put more sarcomeres in parallel
What are the interstitial changes in myocardium during normal growth/development?
Interstitium = 20% of myocardial volume
Capillaries must be present
Normal amounts of collagen and cross-linking
What are the abnormal myocyte changes that lead to pathologic hypertrophy?
- additional sarcomeres in series (eccentric hypertrophy)
- additional sarcomeres in parallel (concentric hypertrophy)
- augmentation of subcellular components
i. mitochondria
ii. SR
This is “abnormal” however because all of these components (the additional sarcomeres, mitochondria, etc) are all ABNORMAL
-eg the sarcomeres being added in series/parallel have abnormal protein isomers!
What are the abnormal interstitial changes that lead to pathologic hypertrophy?
- capillary proliferation may not be commensurate with mass; not enough present so can lead to hypoxia
- Exuberant increase in fibrous content
- Decreased efficiency of gas and substrate exchange
What are the limitations of hypertrophied myocardium?
- Abnormal systolic performance
- Abnormal diastolic performance
- Maximal hypertrophy
How is the systolic performance impaired in hypertrophied myocardium?
- decreased achievable active tension
- decreased maximal velocity o active shortening
- slower time to peak tension
- decreased isometric tension production
- decreased systolic tension at given end-diastolic length
You are adding sarcomeres but they are not functioning the right way
How is the diastolic performance impaired in pathologic hypertrophy?
- natural increases in chamber wall stiffness mediated by geometric changes only (increased wall thickness)
- Changes in ventricular insterstitium
i. greater amounts of collagen
ii. enhanced collagen cross-linking - slow Ca uptake into SR due to abnormal Ca channels
- Imparied myocardial oxygen exchange
- myocyte ischemia that leads to diminished
What are the two steps of diastolic performance?
- passive filling
i. ventricular geometry
ii. ventricular compliance - active relaxation
i. related to contraction inactivation
What is the 3 stage model for hypertrophy?
- Acute load stage
- chronic load stage
- End stage
What is the 3 stage model for ACUTE load?
- Circulation changes = increase LV wall stress, transient decline in CO, transient heart failure
- Cardiac changes = acute LV dilatation and increased LV pressure leads to early hypertrophic response
- myocardial changes = activation of early gene products
What is the 3 stage model for CHRONIC load?
Stage associated with adaptive/sub-clinical dysfunction
- Circulation changes = LV wall stress return to almost normal and improved CO (not clinical heart failure)
- Cardiac changes = established hypertrophy, increased fibrous interstitium, decreased capillary density
- Myocardial changes = deposition of abnormal proteins and increase of myofibril content relative to mitochondria
What is the 3 stage mode (end stage)?
Maladaptive and clinical dysfunction stage
- circulation changes = progressive decline in CO, clinical congestive heart failure
- cardiac changes = extensive cardiac hypertrophy, severe interstitial fibrosis, severely decreased capillary density
- myocardial changes = cell death
Why is exercise good while the other activities that hypertrophy the heart is bad?
A matter of degree
The duration of exposure to the activity determines extent of response
Exercise is only for a brief period (unless you want to run 100 miles a day lol)
However if you have chronic pressure/volume overload from HTN, etc, your heart undergoes this type of stress 24/7
Exercise is good but you don’t want to do this 14 hours a day
What type of exercise lead to eccentric LVH? Concentric LVH?
Running = because this is volume overload
Weight lifting = concentric = high static demands or pressure
You can also have mixed hypertrophy in high static and high dynamic demands (basketball)
