Atherosclerosis Flashcards
Is tunica intima thickening a normal occurrence?
yes, it is a normal consequence of aging
What is atherosclerosis characterized by?
fibrofatty lesions (atheromas)
Which layer are fibrofatty lesions located?
tunica intima
The fibrofatty 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 infction
A weakened tunica media may lead to the development of..
an aneurysm
What are fatty streaks?
early changes in tunica intima (subendothelial compartment), precursor for development of atheroma
What are the 5 key events in the pathogenesis of atherosclerosis?
1) chronic endothelial “injury”
2) endothelial dysfunction. monocyte adhesion and emigration
3) smooth muscle recruitment
4) macrophages and smooth muscle cells engulf lipid
5) smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid
Hyperlipidemia, hypertension, smoking, homocysteine, hemodynamic factors, toxins, viruses, and immune reactions are all examples of what?
factors that can lead to chronic endothelial “injury”
What is the consequence of chronic endothelial “injury”?
endothelial dysfunction (increased permeability where LDL can get into the subendothelial compartment) and monocyte adhesion and emigration
Where do monocytes emigrate to?
the site of injury, in tunica intima, where they become macrophages
Where do smooth muscles get recruited to?
tunica intima. this is where they shift phenotype from being contractile to proliferative/synthetic
Once macrophages move into tunica intima, what do they do?
they start engulfing oxidized LDL in the subendothelial compartment
What is a foam cell?
macrophages that have engulfed oxidized LDL giving them a foam cell type of appearance. smooth muscle cells can also engulf LDL but macrophages are the PREDOMINANT
When do fatty streaks start to appear?
when macrophages have engorged themselves with oxidized LDL
What is a fibrous cap?
deposition and elaboration of ECM components (collagen fibers) leading to cap over the lesion
When does the lesion become fibrofatty atheroma?
once smooth muscle becomes proliferative, collagen and ECM buildup leading to presence of fibrous cap, and lipid debris in the center
How do leukocytes know to attach to site of injury?
expression of adhesion molecules
What is the normal role of NO (nitric oxide)?
prevents the adhesion of leukocytes and platelets onto the endothelium
How do injured endothelial cells affect NO? What does it lead to?
injured ECs means decreased NO which leads to increased adhesion of leukocytes and platelets
What is the order of the most frequent critical stenosis of coronary arteries?
1) anterior interventricular a. (branch of left coronary a) - most frequent
2) right coronary a.
3) circumflex a. (branch of left coronary a.)
What is the wavefront phenomenon of necrosis (cell death)?
cells die from inner wall of myocardium first then proceed outward
What four things may result from myocardial ischemia or infarction?
1) arrythmias
2) acute rupture of cardiac wall of IV septum
3) rupture of papillary muscles
4) ventricular aneurysm
What is a cerebral infarction?
occlude blood flow to brain
