Lecture 8: Cardiac Dysfunction and pharmacological treatment Flashcards
What is observed in MI on ECG?
Elevated ST segment
Necrosis current
How many hospital admissions are their for heart failure?
12000 per year.
Whats the mortality rate of heart failure post diagnosis?
20% dead at 6 months and 30% by 12.
5 years @ 50%
When does HF occur in moaris?
15-20 years earlier
What is the main cause of heart failure?
Coronary Artery Disease
Is heart failure restricted to the heart?
No it has multiorgan effects
Describe the NYRA classification of HF
Class 1 = No symptoms Class 2= Slight limitation of physical activity with fatigue, palpations, angina, dysnopea, comfortable at rest Class 3= marked limitation of physical activity, + class 2 Class 4= Unable to be physically active without discomfort, symptoms of cardiac insufficiency may be present at rest.
Whats the ACC classification?
Stage A: Patient at high risk for HF, no structural changes of heart
Stage B: Heart structure changes with no symptoms
Stage C: Heart structure changes with past/present HF symptoms
Stage D: End stage disease patient who requires specialist treatment.
Do different stages change treatment?
Each stage has a different drug treatment strategy.
What is heart failure characterised by?
- Progressive cardiac dysfunction
- Breathlessness
- Tiredness
- Neurohormonal activation
- Oedema (lungs, legs)
- Sudden death (myocytes stretch, alters electrical pathway, arrhythmia)
- Enlarged heart
How does the body respond to a decreased CO in HF?
- Increased TPR (to maintain BP), increased sympathetic tone (baroreflex)
- RAA activation to raise blood volume, BP, venous return, filling pressures
Describe the changes in VR/CO RAP curve in HF;
Following HF i.e caused by MI. CO/ VR drops. Both curves shift down and to the right as since the heart cannot pump (systolic HF) the RAP increases (causes dilation).
Baroreflex is initiated. Curves both shift up.
RAA is activated and this eventually results in a compensated heart failure (as CO never returns to normal) (curves shift up to just below normal)
A decompensated heart failure could occur where despite baroreflex and RAA CO never returns.
Why does RAP increase in heart failure?
It is an attempt to utilise the frank starling mechanism to increase CO. The heart does not respond well and dilates.
A viscous loop develops.
Describe the problems with heart failure
- Low CO
- Inadequate tissue perfusion
- Volume overload
Cardiac remodelling;
- Enlarged ventricles
- Spherical shape
- Reduced efficiency (EF)
What can be observed at a macroscopic level in heart failure?
- Loss of muscle mass
- Altered chamber size and shape
- In-coordinated contraction and abnormal contraction timing
What happens at a microscopic level in heart failure?
- Myocyte changes (cell thining, lengthening, hypertrophy, necrosis, apoptosis)
- Disorganized muscle fibre orientation and myocyte slippage
- ECM inflammatory cell infiltrates, fibroblast expansion and fibrosis.
What happens at an intracellular in HF?
- Disorganized cytoskeleton
- Impaired nexus junctions
- Contractile protein structural and functional derangements
- Altered EC coupling and Ca homeostasis
- Reduced efficiency of intracellular transduction pathways
- Altered energy metabolism
- neonatal expression pattern
In long term HF what are so major cellular markers?
T tubules shorten
Less DHPR - RYR2 alignment
Decreased SERCA activity (inc Ca)
NCX upregulated
Whats a novel treatment to combat t tubule shortening?
Can use drugs to activate FKB12.6 to align DHPR with RYR2 for Ca spark
Increase Ca sensitivity of tropomyosin
Deactivate NCX or reverse it
therefore increase inotropy
How is noradrenalin receptors altered in HF?
NA uses B1. But in HF B3+4 are upregualted while beta one is downregulted.
Therefore g protein levels altered, cAMP levels change and inotropy isnt maintained.
What must be done to excel in the test and exam?
Read the extra literature given….. plus link it all together. Show big picture thinking.
