L5 Regulation of Cardiac function Flashcards
Outline the factors responsible for governing cardiac output.
- CO: HR x SV
2) SV = End diastolic volume —- End systolic volume.
a) Preload (stretch) affects EDV
- This can be reduced by high HR.
b) Afterload (work against aortic pressure) increases ESV (harder to pump out)
c) High Ionotropic state
- increases HR
- decreases ESV bc more force.
Explain the involvement of calcium in cardiac myocyte contraction .
- Myocyte contraction
- Opening of (slow type) L-type Ca2+ channels due to AP depolarsiation causes opening of RyR receptors on SR to increase intracellular Ca2+
- Ca2+ binds to Troponin C to unmask binding sites on thin filaments to allow x bridge cycling to occur
- Ca2+ put back into SR via SERCA, and extruded by Na/Ca exchangers to maintain low levels in diastole
Explain what inotropic state is for heart muscle and what it depends on
Ionotropic state: Force generated at a given sarcomere length depends on
- Magnitude and rate of Ca2+ release from SR on activation. (background removal rate is pretty static)
- Affinity of Troponin C for Ca2+ ions (reliant on current length of sarcomere)
How does the Symp system control cardiac contractility
- Na stimulates B1 adrenoreceptor–> Gs–> adenylate cyclase–> increased cAMP
- cAMP dependent protein kinase A increases
- Resultant phosphorylation of L-type Ca2+ channels, phospholamban, Ryr Troponin I
- Increased opening of L-type channels,
- stimulation of SR on activation and cell membrane Ca2+ pumps,
- faster Ca2+ kinetics and faster X bridge cycling
–> More vigorous and rapid contraction and relaxation of atria + ventricles.
How does the Parasymp system control cardiac contractility
- Ach –> M2 muscarinic receptor–> Gi–> inhibits adenylate cyclase –> decreased levels of cAMP and subsequent phosphorylation cascade
- Gi–> opens K+ channels via By subunit which results in decreased AP duration.
- Negative inotropic effect on mainly Atria
Explain the sarcomere-length tension relationship for cardiac myocytes = what and why
As length increases tension increases up to a point. This is steeper than skeletal muscle because in addition to actin-myosin overlap effects, there is length dependent affinity of Troponin C for Ca2+ ions.
Cardiac myocyte minimum length has limited range bc of connective tissue
Describe the coupling between heart muscle structure and pump function.
At any point in the left or right ventricles cardiac myocytes have a principal orientation which varies in layers across the wall.
3D wall motion which leads to large ejection of blood involves
- circumferential shortening greater than longitudinal shortening
- while the ventricular wall thickens radially.
- significant torsional deformation
- twisting of the apex counter clockwise relative to the base.
Endocardial changes > epicardial .
Compare the effect of symp vs parasymp on cardiac rate and rhythm
Symp:
- increases HR, with relatively slow response to stepwise change in symp stim
-reduces duration of cardiac AP, and acceleration of impulse propagation through AV nodes
Parasymp
-Decreases HR, rapid response to vagal stim
-decreases AP duration in Atrial myoctyes and deceleration of impulse propagation through AV node
Outline the determinants of cardiac oxygen supply
Coronary blood flow x (coronary arterial O2 - coronary mixed venous O2 contents)
- very dependent on coronary blood flow as usually
- Arterial O2 content and coronary O2 extraction is substantial.
Outline the 4 determinants of cardiac oxygen demand.
- Basal metabolism:
- maintenance of cell organelle systems (small) - Mural force development : magnitude and time for which force is sustained in systole.
- May need more in dilation of LV - inotropic state
- number and rate of interactions between contractile proteins –> more force
- altered kinetics of cell function (eg. increased Ca2+ uptake) - HR
- Frequency of force development and also linked with inotropic state
Outline the mechanical, metabolic, and neural/humoral control of the coronary circulation.
Mechanical:
- Blood flow is detemined by perfusion pressure and instantaneous resistance to flow.
Metabolic:
- Vascular resistance is controlled by local factors at the microvascular level linked to O2 supply and demand
Neural/humoral:
- Symp causes vasoconstriction tone normally and is overridden in stress bc of increase in O2 demand (a)
-PS causes transient vasodilation (B2)
Explain the implications of hypoxia for cardiac myocyte homeostasis.
- Reduce O2 = Reduced ATP
2a. Reduced Na/ K pump so reduced resting membrane potential
3a) reduced AP upstroke and magnitude, shortened AP duration
2b) Reduced SR Ca2+ extrusion
3b) increased intracellular Ca2+ in diastole- >impaired relaxation/filling, electrical instability
2c) Local acidosis: causes H+ to compete with Ca2+ on troponin C
3c) decrease inotropic state and CO
