9. Heart failure - pathophysiology Flashcards
Which 4 main neurohormonal systems does decreased CO as a result of HF activate/inhibit?
activates:
1- sympathetic nervous system - NA release
2- Renin-Angiotensin-Aldosterone system
3- ADH
inhibits:
4- natriuretic hormones
What causes activation of the SNS in HF?
low CO sensed by baroreceptors
How does NA release in SNS activation initially improve CO?
- increased HR and contractility
- vasoconstriction
- renin release and RAAS activation
Why are the long term effects of SNS activation in HF deleterious?
Chronic high [NA] causes:
- downregulation/uncoupling of beta-adrenergic receptors… decreased contractility and CO
- direct cardiotoxicity: myocyte apoptosis and necrosis… decreased contractility and CO
- long-term vasoconstriction and increased HR/inotropy cause increased wall stress… increased myocardial oxygen demand and LV hypertrophy… decreased contractility and CO
- reduced heart rate variability (decreased paraSNS and increased SNS) - increased risk of arrhythmias
What causes activation of the RAAS in HF?
i) decreased CO causes decreased kidney perfusion
ii) SNS induction of renin from macula densa/JGA
Which 2 types of receptor does AngII act on?
AT1R - deleterious effects via vasoconstriction and sodium/water retention - key role in organ damage
AT2R - positive effects via stimulation of NO production and consequent vasodilation
Why are the long term effects of RAAS activation in HF deleterious?
Leads to elevated levels of AngII:
1- potent vasoconstrictor… increased afterload… decreased CO
2- promotes LV hypertrophy and myocyte dysfunction
3- promotes aldosterone release… Na+/H2O retention
4- increases SNS activity
How does AngII activation of AT1R affect the brain?
Causes atherosclerosis… stroke… death
How does AngII activation of AT1R affect the kidney?
Causes decreased GFR, increased proteinuria, increased aldosterone release and glomerular sclerosis… renal failure… death.
How does AngII activation of AT1R affect the heart?
Causes LV hypertrophy, fibrosis, remodelling and apoptosis… MI and HF… death.
How does AngII activation of AT1R affect the blood vessels?
a) Causes vasoconstriction, vascular hypertrophy and endothelial dysfunction…
b) … hypertension…
c) … stroke, HF/MI and renal failure…
d) … death.
What are the effects of ADH increase in HF?
- increased H2O retention
- tachycardia
- increased systemic resistance
Long term lead to decreased CO.
How does ADH mediate increased water retention in the kidney?
Acts on V2 receptors in the collecting duct, leading to increased expression of aquaporin-2 and increased water retention.
What term decribes low Na+?How is this caused?
- hyponatraemia
- results from H2O in excess of Na+ retention, due to increased water intake or increased water reabsorption by action of ADH on V2 Rs
What causes ANP and BNP release and what is the general effect of this?
- Released by atrial/ventricular myocyte stretch (i.e. high BP).
- Oppose the RAAS by promoting Na+/H2O loss and vasodilation.
How do ANP/BNP act to oppose the RAAS?
- Inhibit secretion of renin and aldosterone.
- Constrict afferent and vasodilate efferent arterioles to kidneys.
- Decrease Na+ reabsorption in collecting duct.
- Systemic arterial and venous vasodilation?
What is endothelin secreted by and what are its actions?
- Secreted by vascular endothelial cells.
- Potent system and renal vasoconstrictor acting via autocrine (local) activity… activated RAAS.
Name 3 chemical mediators that might attenuate the effects of NA/RAAS.
- Prostaglandins E2 (stimulated by NA and RAAS) - vasodilator of afferent renal arterioles
- Nitric oxide - vasodilator produced by endothelial cells
- Bradykinin - promotes naturesis and vasodilation via NA and stimulates prostaglandin production
Which enzyme produces NO and how is the activity of this changed in HF?
- NO synthase
- may be blunted in HF
Explain how increased Na+/H2O retention affects HF.
Increased retention… increased blood volume… increased preload… ventricular dilation and increased heart wall stress… decreased SV and CO… decreased renal perfusion… increased retention…
Explain how increased vasoconstriction affects HF.
Vasoconstriction… increased systemic vascular resistance… increased outflow resistance…impaired LV function… decreased SV and CO.
