Cardiology - Heart Failure: Pathophysiology Flashcards
Heart Failure: Pathophysiology
List the three compensatory mechanisms
- Activation of RAAS and adrenergic nervous systems
- Increased myocyte contractility
- Activation of vasodilatory molecules
Heart Failure: Pathophysiology
Explain the activation of RAAS and adrenergic nervous system in compensatory mechanism
Decreased cardiac output ‘unloads’ baroreceptors in LV, carotid sinus and aortic arch.
–> reduced parasympathetic inhibitory tone to CNS and increased sympathetic tone.
–> pituitary releases ADH resulting in vasoconstriction and increased water retention
–> sympathetic kidney stimulation results in renin release which increases angiotensin II, aldosterone, salt/water retention and vasoconstriction
Heart Failure: Pathophysiology
Explain in compensatory mechanisms the activation of vasodilatory molecules
ANP:Released by cardiac atria in response to atrial distention
BNP:Released by ventricular myocardium when ventricle is overloaded
** NB: increased BNP levels in age, female and post menopause. Decreased BNP levels in obesity.**
Prostaglandins:PGE2 and PGI2
Nitric Oxide
Heart Failure: Pathophysiology
In Cellular Changes in heart failure, what are the stimuli for myocyte alteration
- Mechanical stretch
- Circulating neurohormones: noradrenaline and angiotensin II
- Inflammatory cytokines (ie: TNF)
- Growth factors (ie endothelin)
- Reactive oxygen radicals
Heart Failure: Pathophysiology
What are the cellular changes that happen in the pathophysiology of heart failure (6)
- Myocyte hypertrophy
- Altered contractile properties of myocytes
- Progressive loss of myocytes from necrosis, apoptosis and autophagic cell death
- Beta-adrenergic desensitisation
- Abnoral myocyte metabolism
- Reorganisation of extracellular matrix
Heart Failure: Pathophysiology
How do the contractile properties of myocytes alter?
Reducedsarcoplasmic reticulum calcium uptake due to reduced function of sarcoplasmic reticulum Ca++ ATP.
Sarcoplasmic reticulum leakage of Ca due to hyperphosphorylation ofryanodine receptor
Impaired cross bridging due to reduced expression of alpha-myosin heavy chains and increased expression of beta-myosin heavy chains
What is SERCA2A
Enzyme that regulates Ca uptake in the sarcoplasmic reticulum of cardiac myocytes, and therefore regulates ATP-mediated relaxation
Heart Failure: Pathophysiology
What are the three components of ventricular remodelling?
- Increased LV wall thinning
- Increased LV EDV
- LV dilatation
Heart Failure: Pathophysiology
What does ventricular remodelling result in (4) that contribute to the development of heart failure?
- Hypoperfusion of subendocarcium
- Increased oxidative stress
- Increased expression of stretch-activated genes (ie angiotensin II, endothelin and TNF)
- Mitral regurgitation
What is the timeline of remodelling in heart failure?
Early inflammatory stage: 0-3 days
Late remodelling stage: 7 days
End stage cardiomyopathy: years
What causes increased BNP levels?
Age
Female
Post menopause
What causes decreased BNP levels?
Obesity
On a flow-volume loop what does HFrEF do?
Moves the top dotted line DOWN (decreased emptying)
On a flow volume loop what does HFpEF do?
Moves the bottom dotted line UP (decreased filling)
Which is more specific for heart failure of S3 or S4?
S3 increases diagnosis likelihood by x11
S4 is NOT specific but may be present in diastolic failure
