Pathophysiology of Heart Failure Flashcards
Features of HF
- Caused by myocardial injury which results in loss of cardiac muscle or dysfunction of cardiac muscle.
- Results in adaptive neurohumoral changes and remodeling of the heart that may be compensatory initially, but ultimately result in ongoing myocardial injury.
- Causes symptoms of oedema, dyspnoea and fatigue.
- If left untreated, it usually results in a progressive decline in cardiac function and an increase in symptoms.
Causes of HF
- Ischaemic heart disease
- HTN (commonly a factor)
- Cardiomyopathies
- Valvular heart disease
- Others: thyrotoxicosis, drugs, myocarditis, HIV
What happens in acute heart failure?
- Stroke volume and cardiac output falls as a result of reduced contractility.
- Consequently, ejection fraction will be reduced, and ESV will be increased.
- There will be an increase in preload (EDV) as the heart fills in subsequence cycles which will help to partially preserve the SV.
- However, ejection fraction will remain low.
Falls in stroke volume and CO are partially offset at the expense of having higher filling pressure. But CO is still lower than it was before.
Blood pressure and tissue blood flow will fall if there was no ability to compensate.
Compensatory mechanisms in response to acute cardiac failure.
Heart fails → CO and MAP fall precipitously
Within seconds berareflex is strongly activated → SNS activated and PNS inhibited → increased venous return, TPR and CO.
Wihtin hours fluid retention → increased venous return and CO
Weeks and months collateral angiogenesis and cardiac hypertrophy → improved coronary perfusion and variable recovery of cardiac function.
We can say that in systolic HF, the BP is maintained at the expense fo:
- Increased LV filling pressure
- SYmpathetic and RAS mediated vasoconstriction in non-critical organs
Short term adaptations to heart failure
- Frank-Starling mechanism
- Activation of sympathetic nervous sytem
- Activation of the renin-angiotensin-aldosterone system
2 and 3 lead to vasocontriction in non-critical circulations preserving flow to brain and heart.
Sympathetic nervous system and the CVS
- Increases HR
- Increases cardiac contractility
- Reduces venous capacitance increasing venous return
- Increased constriction of resistance vessels
Long term adaptations to HF resulting from fluid overload
Volume overload (e.g. in mitral or aortic regurgitation) initially leads to a dilated myocardium, with some hypertrophy normalising wall stress. When myocardial failure sets in, the degree of dilation exceeds the degree of hypertrophy.
All the mechanisms have achieved is to maintain BP and critical organ perfusion. However:
- The underlying disease process still exists
- We have normalised CO at rest, but not with exertion
- *The compensatory mechanisms come with a long term cost and over time result in further injury to the heart. *
Complications of increasing EDV by renal salt and water retention
Increasing LV EDV will increase filling pressure in the left ventricle and also the left atrium and in the pulmonary veins. This increases the pressure back to the pulmonary capillaries. The balance of Starling’s forces favour increased fluid shift from pulmonary capillary to pulmonary interstitium. The result in pulmonary oedema and dyspnoea.
Forward failure
Fall in cardiac output and resultant tissue perfusion.
Results clinically in fatigue (particularly on exertion).
Backward failure.
Increas in filling pressure and resultant oedema.
Results clinically in dyspnoea.
Sympathetic NS in HF
Beneficial
- Fall in CO leads to increased central sympathetic outflow and increased plasma noradrenaline levels
- Increased SNS activity attempts to restore contractility and maintain BP.
Negative
- Over time sustained SNS activity adversely effects excitation-contraction coupling and appears to enhance apoptopic pathways causing further myocardial damage and a ‘vicious cycle’ ensues.
- Can also predispose to arrhythmias.
- Infusion of catecholamines harmful in HF whereas beta blockade beneficial.
Renin-Angiotensin-Aldosterone system in HF
Positives
- Activated via SNS (and also sensors in the kidney that detect poor renal perfusion)
- Maintains BP by vasoconstriction (increased TPR) and increased Na and H20 retention (increases preload)
Negatives
- Excessive venous pressures cause oedema (pulmonary or peripheral)
- Long term activation of the RAS causes remodeling of the heart with hypertrophy but also fibrosis and apoptosis.
- Can sitmulate increased production of reactive oxygen species and proinflammatory cytokines.
Ventricular remodeling in HF
Ventricular remodeling occurs with dilatation and hypertrophy initially.
This is adaptive at first and helps to reduce wall stress and reduce the O2 consumption of individual myocytes.
Over time the hypertrophy becomes disorganised, with loss of normal arrangement of myofibrils, apoptosis of some cells ad replacement of fibrous tissue.
At a cellular level, there are alterations in gene expression that result in abnormal protein expression and function including:
- Contractile proteins (eg reversion to fetal myosin heavy chain)
- EC coupling (eg decreased Ca channels and SERCA expression)
Decompensated heart failure
If renal perfusion pressure falls too low, then the kidney makes so little urine that it cannot match output of salt and water to normal dietary input.
Fluid retention will begin as input>output and will continue indefinitely unless CO increases.
Progressive fluid retention leads to oedema and overstretching of the heart.
This is decompensated heart failure, and will lead to death if untreated.
Natriuretic peptides
There are mechanisms that oppose fluid overload:
- Pressure volume changes in atria and ventricles promote release of natriuretic peptides
- Stretch of ventricles releases mainly BNP
- Stretch of atria releases both ANP and BNP
These peptides promote natriuresis and thus limit the Na and water retention. They also cause vasodilatation.
In heart failure the natriuretic effects of ANP and BNP are outweighed by the Na conservation effects of the RAAS.
BNP is a biomarked used increasingly to assess the progression of heart failure and effectiveness of treatment.
Chronic overload hypertrophy
Pressure and volume overload produce different adaptations.
Pressure
- Sarcomeres added in parallel
- Concentric hypertrophy
Volume
- Sarcomeres added in series
- Eccentric hypertrophy
