Flashcards in L25 – Control of the Heart Deck (52):
How is cardiac output calculated?
Stroke volume x Heart rate = cardiac output
Modify which two parameters can change cardiac output?
What is the one parameter that must increase for cardiac output to increase? Why?
Venous return must also increase
Because heart is closed system, can only output the input
What is stroke volume a function of?
Filling and force of contraction
How does contractility and rate of force development related?
rate of force development =contractility
What are the 2 ways that the force of contraction can be increased?
1) Prolong time of contraction at same rate of force development
2) Increase rate of force development but keeping same time of contraction
What ion does contractility depend on?
Intracellular Ca2+ concentration (relating to number of actin- myosin crossbridges formed)
Total force of contraction of ventricles is influenced by intracellular Ca2+ concentration, how?
Increase intracellular Ca2+ conc. > more excitation-contraction coupling > Increase number of actin-myosin crossbridges form > Increase force of contraction
What are the two mechanisms for controlling Force of Contraction in heart?
What is the difference between homeometric and heterometric control of force of contraction in heart ventricles?
Homeometric = change in rate of force development, no change in muscle length, same duration of contraction
Heterometric = change in muscle length, same rate of force development, prolong duration of contraction
What causes change in ventricular muscle length (heterometric control)?
When ventricle walls are more stretched
e.g. increase venous return fills and stretches ventricular wall
What is the main role of heterometric control of contractility?
Protective, prevent overfilling
Which of 2 controls of contractility is intrinsic, which is extrinsic?
Heterometric always INtrinsic - arise from within muscle itself/ autoregulation
Homeometric= INtrinsic OR EXtrinsic - induce by external agent on ventricular muscle
Which mechanism is autoregulatory of venous return volume?
Heterometric control (intrinsic)
Heterometric control changes contractility or not?
No, doesnt change rate of force development
Only prolongs duration of contraction
Does homeometric control change contractility or not?
Yes- Change rate of force development
Same duration of contraction
What do inotrophic and chronotropic refer to ?
Inotrophic = change in contractility
Chronotrophic = change in HR
Explain Inotrophic mechanism/cardiac excitation-contraction coupling, starting with cardiac AP, channels, ion movements... to contraction.
Cardiac AP > Open L-type channels in cell membrane and T-tubule during plateau of AP > Entry of extracellular Ca2+ through Ryanodine receptor by diffusion
> Induce Ca2+ release from sarcoplasmic reticulum > Ca2+ diffuses to contractile protein > Bind to troponin to expose tropomyosin for actin binding/ crossbridge > contraction
Explain how Ca2+ moves out of cardiac cell in diastole.
Removal of AP > Uptake of Ca2+ back to SR by Sarcoplasmic Reticulum Ca-ATPase (SERCA) > detach cross bridge > Ca2+ pumped from SR to extracellular space
Why is it necessary that Ca2+ exits cardiac cell in diastole?
Balances initial Ca2+ entry in AP
What is the main channel used to pump Ca2+ to extracellular space during diastole apart from SERCA?
Ca2+ movement mostly by Na/Ca exchanger
(Na+ moves down through concentration gradient)
How does inotropic mechanism depend on Ca2+ conc. intracellular?
Increased intracellular Ca = increased Ca in SR
More Ca released from SR for excitation- contraction coupling
Increase no. of actin-myosin cross bridges form
Increases force of contraction
How is homeometric mechanism different from sympathetic nerve control on force of contraction?
Homeometric = Increase rate of force development but NO CHANGE in duration of contraction
Whereas Sympathetic nerve DECREASES the time of contraction
Not the same***
How is cAMP important to the sympathetic nerve control of contractility of ventricles?
(think what causes release of cAMP, what channels, receptors and proteins are involved)
Sympathetic nerve release noradrenaline > bind to B1-receptor on ventricular cell membrane
> activate adenyl cyclase > convert intracellular ATP to cAMP > cAMP activates Protein Kinase A > Phosporylate Ca2+ channel in cell membrane
> Increased time in open-state > increased calcium permeability during AP plateau > increase extracellular Ca2+ enter cell > increase contractility
What channels does Protein Kinase A phosphorylate after being activated by cAMP?
SERCA and L-type Ca2+ channels in cell membrane
Sympathetic control of contractility is different from homeometric control because it decreases duration of contraction. How?
Increased rate of Ca uptake into SR because of Protein Kinase A phosphrylating SERCA > more Ca pump from SR to extracellular space during diastole
allows faster relaxation, shortening overall duration of contraction
Sympathetic nerves also produces a minor effect in addition to changing contractility and duration. What is it?
Rate-induced regulation called Treppe effect
Increase in HR causes increase in Force of contraction
Explain Treppe effect as a result of sympathetic nerve control of contractility.
Minor effect of raising HR > less time for diastole > less time for Ca to be pumped from SR to extracellular space > more intracellular Ca > increase force of contraction
Does sympathetic or parasympathetic DIRECTLY affect heart contractility?
ONLY sympathetic can DIRECTLY affect contractility
Parasympathetic can INdirectly affect
How can parasympathetic innervation indirectly change contractility?
only innervates atria and nodal tissues (not ventricles) > cannot influence force but can change heart rate
> change force indirectly by rate-induced regulation, Treppe effect
What does heterometric autoregulation of heart/ Starling's law of the heart concern?
Effect of venous return on force of contraction of the ventricles
How does venous return and contraction of ventricles relate?
Increase venous return = increase preload = increase ventricle filling = increase force of contraction (same contractility/ rate of force development)
What two parameters can cause force of contraction to increase whilst keeping same contractility?
Increase venous return/ preload
Increase arterial pressure/ afterload
How can increase in afterload increase force of contraction but maintain same contractility?
Increase arterial pressure/ afterload > Increase pressure to pump against (higher peripheral resistance > initial drop in stroke volume > increase end-systolic/ residue volume > increase end-diastolic volume > Increase force of contraction
Why is there an optimum length to striated muscle? Remember that force of contraction depends on number of crossbridges formed.
Too long= reduce actin-myosin overlap
Too short = distort filaments, reduce actin- myosin overlap
Optimum = maximum actin- myosin overlap
What length is cardiac muscle usually at in relation to its optimum length? Why?
Slightly shorter than optimum length
Any stretching of cardiac muscle > closer to optimum length > more crossbridges form > Increase force
How is congestive heart failure a result of cardiac muscle fiber property?
Overstretch of cardiac muscle > stretch beyond optimum length > reduce actin- myosin overlap > less force generated > cannot pump out over-filled ventricles > congestive heart failure
Optimum length of muscle and its mechanism is related to which control mechanism?
Heterometric- since there is change in muscle length
What is Cardiac function curve a graphical representation of?
graphical representation of cardiac force of contraction against length of ventricular muscle for the intact heart
What can the cardiac function curve have on its x -axis? (3)
1) Ventricular muscle fiber length
Since length increases with pressure and volume:
2)Left ventricular end-diastolic volume/ pressure
3)Right atrial pressure (indirectly measure ventricular muscle fibre length) (common)
What can the cardiac function curve have on its y-axis? (4)
1)Force of contraction
3)Cardiac output (proportional to force) (common)
How can right atrial pressure be measured to produce cardiac function curve?
Right heart catheterization
How does homeometric increase in force compare to heterometric increase in force on cardiac function graph?
Homeometric has steeper and higher curve
Why does homeometric increase in force have higher and steeper curve in cardiac function graph? (remember properties of homeometric - extrinsic or intrinsic, and no filling)
Homeometric = same duration of contraction, increase rate of force development/ contractility, no change in muscle length
Increase intracellular Ca2+ > change contractility > change slope of cardiac function curve (steeper, higher) > increase force
Explain heterometric increase in force on cardiac function graph. (Heteormetric is always intrinsic)
Not higher and steeper curve like homeometric
Increase muscle length due to more filling > reach optimal muscle length > increase force of contraction
How does the heterometric and homeometric curve compare to normal ?
Heterotrometric : Position of cardiac function curve does not change, but shifted to the right due to higher right atrial pressure, same cardiac output
Homeometric: same right atrial pressure associated with DIFFERENT cardiac output, steeper and higher curve than normal due to increased contractility
Why do both homeometric and heterometric curves dip at high muscle length on the cardiac function graph?
Over-stretch = reduce actin-myosin overlap = reduce cross bridge formation = decrease force
What heart structure resists overstretching of heart to prevent congestive heart failure?
Tough Fibrous pericardium is indistendable
What is the position of the cardiac function curve for a congestive heart failure patient vs normal?
Curve shift to right, higher right atrial pressure
What happens to cardiac function curve if patient has poor contractility e.g. ischaemic scar tissue?
Curve slope becomes shallower
What pathological conditions can likely lead to congestive heart failure?
Heart unable to compensate heart failure by enabling heterometric effect and increasing force of contraction
In hearts with poor contractility e.g. ischaemic scar tissue from MI