Arteriosclerosis, Arterolosclerosis, Atherosclerosis I Flashcards
What is arteriosclerosis?
Hardening of the arteries
What is atherosclerosis?
Basic lesion is atheroma
Disease of large elastic arteries and large/medium muscular arteries
Prime targets of atherosclerosis?
Aorta, Coronaries, Cerebral Arteries
What is arteriolosclerosis?
Affects mainly arterioles
Associated with chronic hypertension (response to HTN)
Narrowing of lumen
Two forms of arteriolosclerosis?
Hyaline and Hyperplastic
Clinical consequences of arteriosclerosis
Narrowing/Decreased Blood Flow
Weakening/Aneurysm
Thrombosis
Arteriosclerosis/arteriolosclerosis can lead to pulmonary hypertension. What does that do.
Pressure diff of at least 15.
Hyperplasia of art., lumen narrows and vessel loses flexibility.
Eventual Right Heat failure, Pulmonary fibrosis, and possible atherosclerosis of pulmonary vessels.
Who gets hyaline arteriolosclerosis?
Elderly patients, diabetes
Hyaline arteriolosclerosis causes what to happen
Leakage of plasma contents, increased extracellular matrix in smooth muscle layers.
Looks homologous, pink deposits
Seen in kidney as benign nephrosclerosis
Signs of hyperplastic arteriolosclerosis
More acute/severe elevations of BP Characteristic of malignant hypertension Onionskin lesions, concentric laminated thickening of walls Narrowing of lumen thickened BM Necrotizing arteriolitis
What is atherosclerosis?
Progressive disease of the walls of large and medium sized muscular arteries of older adults. Lipid-containing plaques result in narrowing of the vessel lumen, and can also trigger thrombotic/embolic obstruction
Two main features of atherosclerosis?
- Accumulation of cholesterol as a result of insudation and uptake of oxidized LDL by macrophages and smooth musc.
- Substitution of smooth muscle cells for fibroblasts in the healing phase which give rise to a fibrous cap and deposit ECM components
Five main cell types of atherosclerosis
Endothelial Monocyte/Macrophage Lymphocyte Platelet Smooth Muscle
Main steps of atherosclerosis development.
Endothelial cell Injury/activation, adhesion of platelets and monocytes, secretion of inflamm cytokines, migration/proliferation of cells activated by cytokines, which secrete extracellular matrix
Earliest lesions to show up in atherosclerosis
Tiny accumulations leading into fatty streaks
Later in life these will raise and coalesce into plaques
What the deal with plaques in the arteries?
Raised, Show evidence of extracellular lipid accumulation
Evidence of Migration/Proliferation of Smooth Muscle in Intima
Where in vessels should you expect to see atherosclerosis?
Branching points ad ostia in vessels
Effect of atherosclerosis on medium vessels?
Progressive luminal narrowing
Renal, Mesenteric, Cardiac, and CNS ischemia
Effect of atherosclerosis in large vessels (aorta)?
Aneurysm
Thrombotic events associated with fissuring/rupture of the atherosclerotic plaque are associated with…
Acute Infarction
Four major risk factors for atherosclerosis?
Hypertension
Smoking
Hyperlipidemia/Cholesterol Levels
Diabetes
Predictive assessment of cholesterol levels is best determined by…
Cholesterol/HDL ratio
Other than the earlier mentioned main risk factors for athero., what else should you be looking for?
Family History, Age, Sex Obesity/Metabolic Syndrome Stress Lipoprotein (a) Oral contraceptive use Hypothyroidism, hyperuricemia
_______ levels strongly predict the risk f MI
C-reactive proteins
Describe the pathogenesis of athero. origin through smooth muscle migration
Endothelial Cell dysfunction -> Increased vascular permeability/enhanced monocyte binding –> Insudation of lipids –> Migration of Mono –> Secretion of IL1, TNF, PDGF–>Migration of Smooth Muscle
Describe the pathogenesis of athero. from smooth muscle cell migration through when the shit hits the fan.
Migration/Proliferation of Smooth Muscle Cells –> Binding/Accumulation of lipid in macrophages/Smooth muscle cells –> Secretion of ECM and collagen by SMC –> Formation of Fibrous Cap –> Necrosis of Foam cells, further lipid deposits –> narrowed lumen and the shit
What might the shit hitting the fan look like?
Narrowed lumen Loss of elastic tissue Fissuring of the plaque Embolism of lipid debris Thrombosis Hemorrhage
Migrating smooth muscles move from _____ to _____
The media to the intima
What are the lipid filled macrophages and smooth muscle cells called?
Foam Cells
How do macrophages and SMCs get the lipids?
They take in oxidized LDL via scavenger receptors
Examples of things toxic to endothelial cells
Smoking, homocysteine, diabetes
Is accumulated lipid intracellular or extracellular?
BOTH!!
How does accumulation of lipid happen?
- Insudation/Direct deposition from increase vascular perm.
- Binding of lipid to activated mac./SMC receptor
- Necrosis of Mac. and SMC, releasing lipid contents
Most important receptor for binding of lipid to activated cells?
Scavenger receptor binds oxidized lipids
Effect of oxidized lipids on monocytes?
Chemotactic for monocytes
Decrease motility
Increase inflammatory cytokine production
__% of cholesterol is LDL
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