Lecture 9 Theme B Flashcards
What are some other words for ischemic heart disease?
coronary artery disease
coronary heart disease
heart disease
What are the symptoms of ischemic heart disease?
None until eventually angina develops.
How is angina pectoris felt?
lactate and adenosine activate pain nerve endings in the heart
What is cardiac ischaemia?
Coronary flow is inadequate to maintain steady state metabolism.
What are the factors that contribute to an increased oxygen demand?
ventricular wall stress:
increase in intraventricular pressure means more strength needed from contraction. Wall thickness increase decreases oxygen per gram but increases overall oxygen demand.
Heart rate increase
increase contractility meas more energy is expended to exhibit inotropic effect.
What are the factors that influence oxygen supply?
Diastolic pressure because coronary flow is highest in this period.
Coronary resistance is modulated by vascular tone of that artery. Vessel obstruction
Oxygen carrying capacity depends on Hb level and oxygen saturation and
What are the kinds of factors that influence coronary vascular tone?
Metabolic factors: Constrictors include oxygen, dilators include adenosine, lactate, H+, and CO2.
Endothelial factors:
Constrictors include endothelin - 1, dilators include nitric oxide and prostacyclin.
Neural/hormonal factors:
alpha-1 receptor is a constrictor and beta-2 is a dilator.
How does atherosclerosis occur?
Streaks of fatty tissue form on the outer edges of the coronary blood vessel,
Fatty tissue gets penetrated by muscle cells.
Fibrous scar tissue forms above the plaque, this starts to occlude the vessel. This also reduces coronary artery elasticity.
When a plaque is stable the lipid core within it expands and smc’s proliferate. As a result the bulge grows.
Vulnerable plaque results from rupture of the plaque cap and so as a result collagen is exposed for thrombosis.
How does plaque obstruction affect the flow?
90% : Basal ischemia
100% : Total occlusion
What are the heart responses to myocardial infarction?
Partially hibernation occurs in some heart cells and this is maintained.
Some cells end up being stunned for a while before dying.
What is an infarct?
irreversible necrosis of myocardium due to prolonged intense ischemia.
What is cardiac stunning?
prolonged contractile depression
What is cardiac hybernation?
Heart suppresses itself metabolically until it gets its blood flow again.
What is the main cause of a myocardial infarction?
90% of MI’s are due to plaque rupture which leads to thrombus formation.
What does MI pain feel like?
MI pain feels like angina in 75% of cases but causes no pain in 25% of cases.
How is an MI diagnosed?
Heart releases intracellular macromolecules into the serum which can be used to diagnose a myocardial infarction.
What happens to myocytes in heart cells during an MI?
ischaemia results in a decrease in activate of ATP pumps and exchangers causing sodium to build up in the cell as well as calcium (due to Na/Ca exchanger)
What happens to the heart 1 - 2 minutes after MI?
ATP drops and heart stops contracting
What happens to the heart 10 minutes after MI?
@50% ATP, cell swells due to osmotic gradient, RMP drops, arrhythmias result.
What happens to the heart 20 - 24 minutes after MI?
Irreversible cell injury
What happens to the heart 1 - 3 hours after MI?
Interstitial oedema and disruption.
What happens to the heart 4 - 12 hours after MI?
Neutrophil infiltration
What happens to the heart 4-12 hours after MI?
neutrophil infiltration which results in necrosis after a few hours
What happens to the heart after a few days of experiencing an MI?
Extensive phagocytosis of myocytes, fibroblasts, and connective tissue.
dead tissue is resorped and fibrosis/scarring is complete.
What is the way to fix/prevent ischemia?
reperfusion (reopening blood vessel)
What are the negative effects that reperfusion can cause?
H+ is flushed away by reinstated blood flow.
H+ flushed rapidly out of the cell and exchanged with Na+.
Na+ buildup within cell causing opposite direction flow of Ca/Na exchanged.
Ca buildup in the cell followed by overload.
Why is calcium overload caused by early reperfusion a bad thing?
Contraction can be so immense that it can cause cell death.
Fatal arrhythmias
Cardiomyocyte death
How can Ca triggered problems be reduced (in ischemia/reperfusion)?
CAMK2 is upregulated to produce proteins that handle Ca++ and Na+.
CaMK2 inhibition reduces reperfusion pathologies in the heart.
What is the normal physiological stimulus that results in activation of CAMK2?
Sudden increase in calcium concentration.
