Atherosclerosis Flashcards
What is Myocardial Ischemia?
Lack of Oxygen to the heart muscle due to narrowing of the coronary artery.
Angina?
A temporary chest pain/discomfort.
Myocardial infarction?
Cell death/necrosis of the heart tissue
Monocytes?
Mature into macrophages which are germ eating cells.
Macrophages?
Fight against infections – phagocytic cell.
Lymphocytes?
20-30% of the WBC …. play a role in immunity
Thrombogenic?
Promotes blood coagulation (blood clotting)
Proliferation?
Rapid production of new parts or cells.
Arterial walls?
Adventitia- outermost
media - middle
Intima - innermost
Endothelial Cell Functions?
Permeable Barrier - limits large molecules from entering endothelial cell.
NO Production - vasodilation
Produces Anti-thrombotic molecules
Inhibits SMC proliferation
Secretes chemokines (immune function)
What is the mechanism to to produce NO?
L-arginine > eNOS > L-citrulline
NO benefits?
- Vasodilation
- Immune Function
- Decreased permeability
- anti-thrombotic
- inhibit SMC Proliferation
What are some theories for Endothelial Dysfunction?
- Physical Forces
(Laminar flow is disrupted, reducing NO production) - Toxic Chemical Environment
(Cigarettes, high LDL, high BP, diabetes)
What blocks the NO production mechanism?
ROS (reactive oxidative species)
Lipoproteins
LDL > correlates with atherosclerosis
HDL > protects against atherosclerosis
Endothelial Permeability and LDL
LDL accumulates in the intima and is oxidized. This modification leads to inflammatory response
What happens when there’s mLDL in the intima?
Macrophages and leukocytes accumulate where the mLDL is and it leads to foam cell (when the macrophages engulf the mLDL)
What happens when foam cells accumulate in the cell?
Fatty streak
What is the transition process from a fatty streak to a fibrous plaque.
SMC migrate from the media, into the injured intima, where the SMC proliferates and secretes fibrous connective tissue.
What does the fibrous plaque consist of?
SMC mass, accumulation of leukocytes, and foam cells. Also the development of a fibrous cap of extra cellular matrix with embedded SMCs
What leads to a plaque rupture?
Hemodynamic shear forces, vasoconstriction, and circulating substances.
Thrombus forms at a site of rupture.
What’s the difference between a stable and unstable plaque?
The unstable plaque has a larger fatty core and a thin fibrous cap, whereas the stable plaque has a smaller fatty core and a thicker fibrous cap. Unstable plaque is more prone to sudden rupturing.
What is the pathogenesis of atherosclerosis?
Endothelial dysfunction > accumulation of mLDL in the intima and leukocyte recruitment > foam cells form and fatty streak > SMC migration from media to intima leading to SMC proliferation > plaque formation rupture and thrombosis formation.
What is an ischemia?
Imbalance between oxygen supply and demand due to limited blood supply.
Reasons include: fixed vessel narrowing and endothelial dysfunction
Proximal coronary arteries vs. Distal vessels?
Proximal - subject to atherosclerosis and stenotic plaques
Distal - usually free of plaque development (it adjusts vasomotor tone to metabolic needs)
Why does endothelial dysfunction lead to Inappropriate Vasoconstriction?
When atherosclerosis leads to endothelial dysfunction, there is a reduced release of vasodilators so vasoconstriction occurs. This causes reduced coronary flow and contributes to ischemia.
Why does Endothelial dysfunction leads the to the loss of antithrombotic properties?
Endothelial dysfunction leads to decreased NO release so there’s reduced antithrombotic properties. This impaired NO release also leads to platelet aggregation (platelets clumping together) which has vasoconstrictor effects.
What is the consequences of ischemia?
Reduced O2 supply leads to reduced atp production and more metabolic accumulation. This causes reduced ventricular function.
What is stunned myocardium?
Stunned myocardium is acute ischemia in the absence of necrosis. This results in prolonged systolic dysfunction.
What is hibernating myocardium?
It’s chronic ventricular dysfunction. It occurs due to a persistently reduced blood supply. No irreversible damage.
What is myocardial infarction ?
Occurs after 30 mins of ischemia, when damage becomes irreversible.
Angina?
A temporary chest pain/discomfort.
What is stable angina?
It’s predictable discomfort during exercise or emotional caused by FIXED PLAQUE.
What is unstable angina?
An acceleration of symptoms (stable to unstable). There’s an increase in frequency, severity and duration of ischemic episodes. It’s associated with a rupture of an unstable plaque.
What is variant angina?
It occurs in a minority of patients. Coronary spasms.
What is silent Ischemia?
Lack of O2 in absence of pain. Occurs in 40% of patients with stable angina.
What is syndrome X
It’s when patients have symptoms of angina but have no evidence of atherosclerotic stenosis.
