Flashcards in Atherosclerosis Deck (19):
When does diffuse intimal thickening occur?
Result of injury and natural aging process
What happens as a result of injury to the tunica intima?
1. Recruitment of smooth muscle cells2. Smooth muscle cell phenotype is proliferative / synthetic hence ECM elements are elaborated
What is the definition of atherosclerosis?
Form of arteriosclerosis that is characterized by fibrofatty lesions (atheromas) in the tunica intima. These lesions protrude into the vascular lumen thereby producing obstruction and they weaken the tunica media. Obstruction of the vascular lumen leads to ischemia and/or infarction and a weakened media may lead to the development of an aneurysm
How many Americans die each year from IHD?
What are nonmodifiable risk factors for IHD?
1. Age (5x incidence 40-60yo)2. Sex (Men > women until menopause)3. Family history4. Genetics (e.g. familial hypercholesterolemia)
What are modifiable risk factors for IHD?
1. Cholesterol intake2. BP3. Smoking4. Diabetes5. Elevated CRP
What are the key events in the pathogenesis of atherosclerosis?
1. Injury to endothelial cells2. Accumulation of lipoproteins3. Oxidation of LDL 4. Adhesion of blood monocytes5. Platelet adhesion6. Growth factor release and recruitment of smooth muscle cells to subendothelium7. Smooth muscle cell transition from contractile to synthetic8. Accumulation of lipids
What is the effect of CRP on endothelial cells?
Causes them to become pro-thrombogenic and "stickier" for leukocytes
What happens when endothelial cells become injured?
1. Become more permeable2. Synthesize cell adhesion molecules that attach to adluminal plasma membrane3. Decreased NO production
What is the role of LDL when it accumulates post-injury?
Moves across endothelium and enters subendothelial compartment. Macrophages are activated / recruited
What oxidizes LDL in the subendothelial compartment?
Endothelial cells, smooth muscle cells, macrophages
What occurs as a result of decreased NO?
Increased adhesion of platelets and luekocytes
What happens as a result of growth factor release?
Recruitment of smooth muscle cells into subendothelial compartment of tunica intima
What types of smooth muscle cells infiltrate the subendothelial compartment following growth factor release?
1. Smooth myocytes from tunica media passing through fenestrae in internal elastic membrane2. Smooth muscle cell precursors from the blood
What are the frequencies of coronary artery narrowing and thrombosis?
1. LAD (40-50%)2. Right coronary (30-40%)3. Circumflex (15-20%)
What is the wavefront phenomenon of cardiac cell death?
Death occurs in the inner wall of the myocardium (subendomyocardium) and proceeds outward toward the subepicardium
What can result from myocardial ischemia?
1. Arrythmias2. Acute rupture of the cardiac wall or IV septum3. Rupture of papillary muscles4. Ventricular aneurysm
What are the early (acute) microscopic changes in cerebral infarcts?
Eosinophilia of neurons (red neurons)