Heart Failure Flashcards
What are triads?
Terminal cisternae of the SR is intimately associated with the t-tubule. In cardiac cells, the terminal cisternae are more discrete and tend to appear as double structures, aka dyads.
Ionic basis of an AP?
High K+ inside cell. High Na+ outside cell.
VGCC and VG Na channels are opened, depolarising cell membrane. Repolarisation brought about by delayed increase in K+ permeability repolarises cell as K+ leave cell.
3 classes of ion translocating proteins?
1) Ion pumps
2) Ion exchangers
3) Ion channels
Why is the pacemaker potential extended?
Prevents tetany
Prevents re-entrant arrhythmias
Who first proposed that extracellular calcium is essential for cardiac contraction?
Sydney Ringer, 1883
Describe excitation-contraction coupling?
T-tubulues = L-type Ca2+ channels aka DHP-R
SR = Ryanodine-R = CICR
T-tubules dive down from cell surface, carrying wave of AP. The DHP-R are voltage-activated and so open. In skeletal muscle this directly open the ryanodine-R via a physical link aka voltage-induced calcium release. In Cardiac muscle there is no physical link but there is CICR
Ca is then removed via SERCA and the sarcolemmal Na/Ca exchanger.
What is the Ca-Tension relationship?
Increased Ca increased tension in a fibre, the sensitivity can be modulated by drugs.
Describe the length-tension relationship
Increasing length initially increases the tension developed by a fibre as it facilitates the overlap, increasing the number of cross-bridges formed. Past a certain point, the overlap begins to diminish again. Only accounts for 20% in cardiac muscle. Increasing sarcomere length increases Ca sensitivity AND maximall activated force. The Ca-Tension curve is shifted to the left due to an increase in the sensitivity of troponin for Ca. The increase in the “height” of the Ca-Tension relationship is mediated by the effects of myofilament overlap.
What law does the length-tension relationship explain?
Frank-Starling Law of the Heart
What is the force-frequency relationship?
Increase the frequency, increase the force until a plateau is reached due to increased SR Ca.
What happens to the force-frequency relationship in the failing heart?
Seen to become negative, due to down-regulation of SERCA and an upregulation of Na/Ca exchanger and a subsequent elevation of intracellular Na. This results in more Ca extrusion between beats and less Ca cycling through the SR. This is one of the reasons why failing hearts dont response to beta-blockers.
Define heart failure
Heart failure in an inability to meet CO demands to support the needs of the tissues OR able to do so but only at the expense of an increased filling pressure.
Describe RHF
Impaired RV pumping reduces output of both ventricles so CO falls. System venous pressure rises because RV end-diastolic pressure is increased (RV backs up) but circulatory reflexes tend to maintain mean pulmonary artery, LV end diastolic and aortic pressures near normal
Describe LHF
Reduced output of both ventricles. Pulmonary venous pressures increases because LV end diastolic pressure increases. Circulatory relfexes maintain aortic pressure near normal. Elevated pulmonary venous pressure may cause a rise in pulmonary artery pressure.
Describe congestive HF
Failure of LV -> failure RV.
Fall in CO, elevation of PV pressure due to elevated LV end diastolic pressure, elevation pulmonary artery pressure because the lungs “back up” and elevated systemic venous pressure because the RV backs up. Aortic pressure maintained near normal by circulatory reflexes.
3 primary causes HF?
Volume overload
Pressure overload
Contractile dysfunction - IHD, MI, pregnancy, cardiomyopathies
What is the Law of LaPlace? What does it show?
P = 2SW / R
Where SW = Tension
S = wall stress W = wall thickness R = radius P = output pressure
When the heart gets bigger to accomodate pressure or volume overload, it must increase the amount of work it does (S) or the wall thickness (W). Early stages of HF = increase in W.
