Athersclerosis Flashcards
What is ATHEROSCLEROSIS?
Chronic inflammatory disease of the inner layer (tunica intima) of arteries causing narrowing and hardening of the arteries
What is the cause of ATHEROSCLEROSIS?
Due to the accumulation lipid garbage (atheroma) followed by fibrosis
In which arteries does Atherosclerosis occur?
Medium (muscular) arteries (especially coronary and cerebral) and large elastic arteries (aorta) and it favors branch points
WHAT are some of the causative agents that cause the initial injury to endothelial cells that begin the ATHEROSCLEROTIC pathogenesis?
- Hemodynamic stress
- Carbon Monoxide
- Hyperglycemia
- Hypercholesterolemia
- Chlamydia
- Cytomegalovirus
What does the first step of ATHEROSCLEROSIS involve?
Injury to the endothelial cells cause impairment to the permeability barrier, the release of inflammatory cytokines, increased adhesion of monocytes, decreased secretion of vaso dilators nitric oxide and prostacyclin, and decreased release of antithrombotic substances
What is the second step of the Atherosclerotic pathogenesis?
Accumulation of LDL in the Tunica intima
How does the LDL get trapped in the intima?
By binding to extracellular matrix proteoglycans whose production is increased in hypertension
What happens to the LDL once trapped in the Intima?
Modified by Oxidation, glycation, and other processes
What is the role of the modified LDL?
Promotes leukocyte recruitment and foam cell formation (steps 3 & 4)
Why do Macrphages become overstuffed with LDL
Because they take up LDL via scavenger receptors which lack the feedback mechanism of LDL receptors
What is step 3 of the ATHEROSCLEROTIC process?
Leukocyte recruitment into the tunica intima
What molecules mediate the recruitment of Leukocytes into the intima?
Endothelial expression of Leukocyte adhesion molecules LAM, monocyte chemotactic protein 1, interferon inducible protein 10 and IL8
Besides leukocyte recruitment whatelse happens in step 3?
Recruitment of smooth muscle cells into the intima
What molecules mediate the recruitment of SMOOTH muscle cells into the intima?
- PDGF,
- TNF-alpha
- TGF-beta
- IL-1
Where do smooth muscle cells normally reside?
The Tunica media
What change do smooth muscle cells undergo once the find themselves in the Tunica Intima?
They become phagocytic
What is step 4 of Atherosclerotic pathogenesis?
The formation of foam cells
How does the formation of foam cells begin?
- Transformation of monocytes to macrophages
2. Phagocytosis of modified LDL via scavenger receptor
What is the final step of atherosclerotic
ECM deposition occurs due to smooth muscle cell production of ECM mediated by;
- IL-1
- TNF-alpha
- TGF-beta
- FGF
What is the irreversible component of Atherosclerosis?
The laying down of collagen
What are the earliest signs/lesions in atherosclerosis?
Fatty streaks, which are deposits of lipid in the Tunica intima, this is reversible
What is an ATHEROMATOUS plaques?
0.3-1.5 cm raised yellow-white fibrofatty lesions composed of soft grumous yellow lipid core called an atheroma covered by a firm white fibrous cap of variable thickness
What are Atheroma composed of?
Primarily composed of amorphous eosinophilic debris, cholesterol clefts, fibrin, smooth muscle cells, and foam cells.
What is the fibrous cap of Atheroma composed of?
Collagen and proliferating smooth muscle cells, macrophges and lymphocytes
What is the natural progression of Athromas?
Gradual conversion to fibrous tissue
What is one of the later features of Atherosclerosis?
Neovascularization
What is Neovascularization as pertaining to Atherosclerosis?
It is an ingrowth of capillaries from the outer layer (Tunica adventitia) through the middle layer (Tunica Media) into the Tunica intima
What are the features of these abnormal new blood vessels?
- Prone to rupture
2. Cause intraplaque hemorrhage that can rapidly increase the degree of arterial stenosis
What are the complications of Atherosclerosis?
- Calcification
- Fissures (cracks in the surface)
- Ulceration
- Rupture
- Atheroembolism
- Superimposed thrombosis
Which kinds of Atherosclerotic plaques are most dangerous?
Atherosclerotic plaques with a large atheroma which is loose and semi-liquid, and a thin fibrous cap are vulnerable to rupture and in turn thrombosis
What are the three factors that predispose to thrombosis?
- Endothelial injury
- Hypercoagulability
- Abnormal blood flow (both stasis and Turbulent flow)
Where is Stasis more prone to cause thrombosis?
In veins more than areteries except where arteries have aneurysms.
What does Thrombosis due to plaque rupture particularly lead to?
Particularly likely to proceed to full fledged total 100% occlusion of an artery
What is the most fearsome complication of atherosclerosis?
Superimposed thrombosis which leads to total occlusion and transmural (full thickness) MI
What drugs are therapeutic against superimposed thrombosis?
- Asprin
2. Clopidogrel (Plavix)
What is a vulnerable plaque?
Atherosclerotic plaque with large loose atheromatous core and a THIN fibrous cap, prone to rupture and occlusive superimposed thrombosis
