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Flashcards in Heart Failure Deck (44)
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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.


Effects of pressure overload?

Acute increase in wall stress, which leads to a thickening of the ventricle walls. During compensated phase therefore, wall stress normalised by concentric hypertrophy. When dilation begins to develop, R increases and wall stress increases.


Effects of volume overload?

Initially leads to ventricular dilation. Some hypertrophy can normalise wall stress. However, when the heart begins to fail, the degree of dilation exceeds the degree of hypertrophy and wall stress increases.


What is concentric hypertrophy?

Hypertrophic growth without overall enlargement. Increased W, decreased R.


What is eccentric hypertrophy?

Hypertrophic growth WITH overall enlargement.


What is the immediate effect of a fall in CO?

Baroreflex activation

Increases peripheral resistance, increases HR, contractility and returns BP to normal. Renal artery constriction in intended to retain salt and water and help maintain BP. Activation of RAAS. Increased TPR and water retention help increase CVP and therefore restore CO via FS mechanism, but at cost of raised LVEDP. Release of ANP may occur, which vasodilated and diureses but the effect is overwhelmed.



Describe the RAAS.

Angiotensinogen -1-> AT 1 -2-> AT 2 -> Release aldosterone

1 = renin
2 = ACE

AT 2 = vasoconstrictor
Aldosterone = salt and water retention


Describe the growth of cardiac myocytes

Grow by hypertrophy rather than proliferation.

Concentric hypertrophy = cells get fatter
Eccentric hypertrophy = cells get longer

Cells appear to revert back to neonatal "program" of genetics


What are the detrimental effects of hypertrophy?

Suseptibility to ischaemia, arrhythmias, sudden death and pushes heart towards HF. It increases O2 consumption/demand and the capillaries become inadequate to meet the demands, lack of vascular reserve (problem during exercise for eg).


Why is lack of vascular reserve a problem for the hypertrophied heart?

Leads to focal ischaemia, fibrosis and collagen deposition. Makes the heart stiffer and therefore reduces contractility.


What happens to the hydrostatic and oncotic pressures in the lungs?

Normally, the colloidal oncotic pressure is higher than the capillary pressure -> net loss of fluid from lungs but not a problem as we breathe humidifed air.

In HR, fluid movement is rev
ersed, hydrostatic pressure is increased and becomes > than colloidal oncotic pressure. This leads to a net gain of fluid by the lung -> congestion.


How does the cardiac myocyte sense overload?

Mechanical stretch of tissue - direct stretch of myocyte and non-myocytes (eg VSMCS), release of paracrine factors eg FGF, TGF, IGF-1

Systemic neurohormonal activation - sympathetic activation, release or hormones and NTs eg alpha and beta agonists, renin, AT-1, GH, aldosterone


What are integrins?

Family of cell surface receptors which link ECM to cellular cytoskeleton at focal adhesion complexes (FACs). They sense mechanical stretch. Stabilise the cytoskeleton and directly activate gene expression. Couple to a variety of signalling molecules including Focal Adhesion Kinase (FAK), Src kinase, small G-proteins (Rho and Ras) and ERK/JNK kinases.


Role of stretch-activated ion channels?

Stretch activated Ca channels, activate Ca dependent kinases and phophatases

Na/H exchange regulates intracellular pH and causes alkalinisation. Blockade causes stress-induced ERK activation and protein synthesis.