Artherosclerosis Flashcards
What happens to the vascular wall normally as we age? How does it occur?
Diffuse intimal thickening due to the recruitment of smooth muscles cells from the tunica intima. These then secrete ECM
What is atherosclerosis?
is a form of arteriosclerosis that is characterized by fibrofatty lesions (aka atheromas) in the tunica intima
What is an atheroma?
A fatty lesion comprised of oxidized LDL produced by atherosclerosis.
What forms over atheromas?
A fibrous cap d/t elaboration of ECM
What are the precursors of Atheromas? What type of stain would you use to highlight them?
Fatty streaks that can be highlighted by Sudan Red
Where do atheromes occur?
In areas of turbulent blood flow such as at point of bifurcation
What are the cells that have a foamy cytoplasm that are present in ateromes?
Macrophages
What are the four major, non-modifiable risk factors for atherosclerosis?
Increasing age
Family history
Male
Genetic abnormalities
What are the five major modifiable risk factors for atherosclerosis?
Hyperlipidemia Cigarette smoking C-reactive protein HTN DM
The incidence of MI increases how many times between the ages of 40 and 60?
5x
When does the risk of MI for men and women become equal?
70-80 years of age
What are the guidelines for:
- Total cholesterol
- LDL
- HDL
- Triglycerides
- < 200 mg/dL total
- < 130 mg/dL LDL
- > 45 mg/dL HDL
- Triglycerides < 150 mg/dl
What is the clinical significance of CRP in terms of heart disease?
Endothelial cells become prothrombotic, and increase their adhesiveness for WBCs
What is the significance of smoking in terms or artherosclerosis?
> 1 ppd = 200% risk increase
What is the significance of DM in terms of MIs?
2x more likely to get a MI with DM
What is the first step in the pathogenesis of atherosclerosis?
Injury to the endothelium, leading to
1. increased permeability and
- endothelial cell synthesis of cell adhesion molecules on lumen side
How do endothelial cells become injured?
Hyperlipidemia
HTN
Smoking
Homocysteine etc
What is the second key event of the development of athreosclerosis?
Accumulation of LDL and monocytes in the endothelium
What is the third step of the pathogenesis of atherosclerosis, after monocytes and LDL accumulate?
Smooth muscle cells migrate into the intima and macrophages are activated
Where do the smooth muscle cells that migrate into the endothelial compartment come from? What change do they undergo when they get there?
Come from the tunica media and blood.
transition from their contractile phenotype into a proliferative-synthetic phenotype
What role do the macrophages play in the development of atherosclerosis?
Ingest LDL and oxidize it
What is the dominant foam cell type in artherosclerosis?
Macrophages
Smooth muscle cells contribute other, smaller part
What is the fifth step the pathogenesis of atheroscleorsis, after macrophages have engulfed LDL?
Smooth muscle proliferation, and resulting collagen and other ECM deposition
What forms that cap of a fibrofatty atheroma? The center?
Cap of collagen
Center = lipid debris
What is perhaps the most important step (the step that may be a target for drug therapy) in the formation of atheromas?
LDL oxidation by macrophages
What role does NO play in atherosclerosis? How is it brought about?
injured endothelial cells results in decreased nitric oxide, which normally prevents platelets from sticking
What is the most frequently involved coronary artery in MIs?
LAD (40-50%)
What is the 2nd most frequently involved coronary artery in MIs?
Right coronary (30-40%)
What is the 3rd most frequently involved coronary artery in MIs?
Circumflex artery (15-20%)
What is the wavefront phenomenon of cardiac necrosis?
Cell death occurs in the inner wall of the myocardium (subendomyocardium) and proceeds outward toward the subepicardium
What is the cause of te wavefront phenomenon?
Increased work of the inner layer of the myocardium
What is the chemical basis for using the stain triphenytetrazolium in looking at a sample of necrotic heart tissue?
Binds to LDH heart isozyme that will not be expressed in dead tissue (obviously)
What are the histological characteristics of necrotic heart tissue?
Lots of blue staining collagen and red staining muscle that remains
Myocardial ischemia and infarction may result in what four things?
a. Arrythmias
b. Acute rupture of the cardiac wall or IV septum
c. Rupture of papillary muscles
d. Ventricular aneurysm
What are the four steps that occur in a cerebral infarction on a microscopic level?
Eosiniphilia of neurons
Neutrophils infiltrate to clean
Macrophages infiltrate (10 days out)
Reactive gliosis
