Regulation of Cardiac Mechanical function Flashcards
Inotropy, Chronotropy, Lusitropy, Dromotropy
Inotropy - contractility of myocardium
Chronotropy - firing rate of SA node
Lusitropy - relaxation of myocardium
Dromotropy - conduction velocity of AV node
Calcium and contraction
During AP, calcium enters the cell through L type receptors
-this binds to Ryr receptors and allows the release of calcium from SR
-calcium then binds to tropnin C allowing actin and myosin to interact and then get contraction
-then calcium is removed from cell by NA/Ca pump and this is a passive process
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inotropic state
- amount of Ca in SR
- rate and amount released from SR
- affinity of troponin C for CA, sacromere - length dependednt calcium sensitivyt of troponin C
Sympathetic stimualation and inotropic state
Sympathetic system activated - adrenaline and noradrenaline
b1 receptor - bind and results in phosphorylation of calcium channels to allow more calcium in
-also phosphorylates the Ryr receptors, -to increase rate that SR takes calcium into the cell - (increased luisotropy - muscle relaxation - to increase filling)
-also increases the sensitivy of troponin for calcium binding - get a more rapid contraction and more rapid relaxation
-shortenes AP duration
parasympathetic stimulaiton
- acetyl choline binds to muscarinic receptor
- m2 receptor - stimulates GI which inhibits this process- decrease cAMP - no phosphorylation
- these things turn off
- connects to potassium chanel - increases its activity to get more K out of cell - shortes AP duration
force sarcomere length relationship
- the further apart the sarcomeres are - the increased active force produced, passive force increases but stops increasing so much at a certain part
- has no decending limb - because of high passive stiffness
- steeper ascending limb - becauase of actin/myosin overlap
- also has length dependent specificity of tropnonin C
Hypoxic state
Reduced ATP • reduced Na+/K+ pump • reduced Na+ & K+ transmembrane concentration gradients • hyperkalaemia (é[K+]o) • reduced resting membrane potential • reduced action potential upstroke speed and magnitude • shortened APD • reduced Na+/Ca2+ exchange • reduced myosin head detachment (ATP required for relaxation) • reduced sarcolemmal Ca2+ extrusion • increased cytoplasmic Ca2+ • impaired relaxation/filling • electrical instability • reduced pH (acidosis) • H+ competes with Ca2+ on Troponin-C • reduced inotropic state • reduced nexus junction coupling (slows conduction)
How are heart muscle cells lined up?
- all overlap in a specific organisaiton so that when they contract, they line up and make the walls bigger - increase volume to pump so less volume for blood and it is pumped out
- alot of collagen in the heart
- Deformation during cardiac cycle - circumferential shortening, longitudinal shortening, torsion, transmural shear, radial wall thickening
what changes can structural heart disease make?
- remodelling of ventricles - myocardial infarction and heart failure, hypertension lead to changes in cardiac geometry and myocyte arangement that reduces the effectiveness of mechanical function of the heart
- systemic hypertension leads to LV myoctye hypertrophy and wall thickening
- increased amount of collagen - stifened heart and reduced effectivenes of cardiac filling
where are sympathetic nerves found?
and parasymapthetic
sympathetic ganglion - superior, middle cervical ganglion adn inferior stellate ganglion
pns - vagus nerve
what happens when increase SNS in heart?
- 3 main changes
- what does it result in?
- adrenaline and noradrenaline released
- b1 receptors in heart -SA and AV nodes - in heart have many sympathetic nervous fibers here
- get increase in decrease in HR
- decrease of action potential length , increase propgation to AV node
- increase in inotropic state
- slower response to parasympathetic control
what does this result in
- pressure in atria and ventricles increase (due to increased contraction)
- increase in blood ejection
- end systolic volume reduced so SV increased
- rapid filling occurs due to relaxation of muscle - to increase the end diastolic volume
Parasympathetic control
- acetyl choline to Muscarnic M2 receptor
- decrease heart rate (rapid compared to sympathetic)
- AP duration decrease, decrease propagation to AV node
- inotropic state reduced (not much parasympathetic supply to ventricles)
speed of sns vs pns
- autonomic blockade results in an increase in HR and reduction in cardiac inotropic state
- shows that at rest hr is controlled by pns and contracitlre state managed by sns
- HR is more sensitive to vagal activity than sumapthetic activity
Why are responses different?
-and why can pns effect HR beat to beat
- SA and AV node are rich in cholinesterases which break down ach, thus ach released at nerve terminals is rapdily hdyrolised and can get pns activity stoped
- ach rapid because binds to m2 receptors and causes direct inhibiton of phosphorylation
- sns slwo- becuase noradrenaline release is slower, and requires a second messenger to get phsoprohlation
- termination of sns is slow due ot reuptake of nuetrnasmitter to remove it (weather as ach is broekn down by teh enzyems faster)
- pns - can effect beat to beat by sns cannot as its slower
Demand of oxygen from heart
- basal metabolism
- Afterload - force development - pressure and geometry (if pressure increases then need to develop more force e.g hypertension, heart failure)
- inotropic state - increase oxygen required
- increase HR - requries more oxygen
