10/29 - Atherosclerosis

Front 1

The kinds of blood vessels that are normally affected by atherosclerosis.

Back 1

Elastic and muscular arteries.

Front 2

Define atherosclerosis.

Back 2

Accumulation of lipids in the wall of arteries beneath sites of endothelial injury.

Front 3

Histologic location of atheromas.

Back 3

Intima and subintimal layer

Front 4

Principle arteries in which atherosclerosis is found

Back 4

Aorta, coronary arteries, cerebral arteries

Front 5

Definition of arteriosclerosis.

Back 5

"Hardening of arteries"
All inclusive terms, mixing pathologies of atherosclerosis, medial calcific sclerosis, and arteriolosclerosis

Front 6

Definition of arteriolosclerosis.

Back 6

Hyalinizing, hyperplastic, or necrotic processes affecting small arteries.

Front 7

Different varieties of atherosclerotic lesions.

Back 7

Fatty streak
Atheromatous plaque
Complicated plaque

Front 8

Earliest visible atherosclerotic lesion.

Back 8

Fatty streak.

Front 9

Point at which you start seeing fatty streaks in an individual.

Back 9

At birth!

Front 10

Point at which fatty streaks are visible in coronary arteries.

Back 10

Puberty

Front 11

Composition of fatty streak.

Back 11

Foam cells

Front 12

Foam cells.

Back 12

Lipid-laden macrophages and lipid-laden smooth-muscle cells.

Primary component of atherosclerotic lesions.

Front 13

Location of foam cells in a fatty streak.

Back 13

Intima

Front 14

Fatty streaks are often first found concentrated around these.

Back 14

Flow dividers in thoracic aorta (descending aorta)

Front 15

Atherosclerotic lesion that can disappear.

Back 15

Fatty Streak

Front 16

Description of atheromatous plaque.

Back 16

Elevated plaque composed of a fibrous cap overlying a localized deposit of lipids.

Front 17

Components of an atheromatous plaque

Back 17

Fibrous cap
Lipid deposit with cholesterol and cholesterol esters
Proliferating smooth muscle cells and CT at the margin of the lipid.
Neovascularization along base

Front 18

Steps that transform an atheromatous plaque into a complicated plaque.

Back 18

1. Dystrophic calcification w/in media or plaque
2. Ulceration with local loss of endothelium, exposing collagen
3. Thrombus forms from platelets exposed to collagen
4. Thrombus ruptures (thrombosis) --> vascular occlusion.

Front 19

Complication caused by weakening of vessel's media following complicated plaque rupture

Back 19

Aneurysm or external rupture

Front 20

Preferred sites of atherosclerosis

Back 20

Intimal irregularities and sites of turbulent flow

Front 21

Mechanism(s) of compensation for atherosclerotic obstruction

Back 21

Increased arterial diameter
Formation of collateral vessels

Front 22

Vasoconstriction can occur at sites of atherosclerosis due to what activity.

Back 22

Exercise

Front 23

Mechanism of localized vasoconstriction at sites of atherosclerosis.

Back 23

decreased local NO-prostaglandin secretion
Increased endothelin production

Front 24

General characteristics of stable atherosclerotic lesions.

Back 24

Circumfrential
Avascular
Collagen Rich
Lipid Poor

Front 25

General characteristics of unstable atherosclerotic lesions.

Back 25

Eccentric
Protruding
Lipid-rich
Easily ulcerated
Vascular

Front 26

4 hypotheses for pathogenesis of atherosclerosis

Back 26

1. Endothelial Injury
2. Lipid Infiltration
3. Unification of 1 & 2
4. Atherosclerosis as an Inflammatory Disease

Front 27

Ligand on platelets responsible for triggering cascade of inflammation

Back 27

CD40L

Front 28

Evidence that CD40-CD40L plays a role in atherosclerosis

Back 28

Antibody disruption of CD40-CD40L can inhibit initiation of atherosclerosis.
Patients with unstable angina exhibit high serum levels of CD40L.

Front 29

Effect of CD40-40L interaction.

Back 29

Destabilizes atherosclerotic lesion by triggering a cascade of inflammation involving endothelial cells, connective tissue cells, monocytes, and lymphocytes.

Front 30

Evidence suggesting viruses might be involved in atherosclerotic pathogensis

Back 30

Marek virus --> plaques in chickens
Virsuses cause vasculitis (prerequisite of atherosclerosis)
Herpesvirus, CMV have been found in plaques
Antiviral prophylaxis can lead to inhibition of atherosclerosis

Front 31

Early steps in formation of atherosclerotic plaques beginning with endothelial injury.

Back 31

1. Platelets exposed to collagen --> release ADP, aggregate
2. Tissue thromboplastin released, activates extrinsic coagulation
3. Platelet aggregation promoted by local reduction of endothelial derived PGI2
4. Depletion of endothelial cell-derived plasminogen activator
5. Intrinsic coagulation initated by adherent platelet release of Platelet Factor 3, vasoconstriction and platelet aggregation promoted by release of Factor 4 and TxA2
6. Thrombin (hence fibrin) is deposited
7. Lipids derived from platelets and red blood cells are sequestered in the lesion

Front 32

Late effects of endothelial injury

Back 32

1. PDGF induces proliferation of smooth muscle cells in subintima
2. Collagen from fibroblasts, GAGs from smooth muscle cells (secondary to PDFG) --> enlarging of obstruction.
3. Damaged arterial wall permeable to lipids, get trapped in the media
4. Ineffective/incomplete endothelial regeneration leads to sequestration of lipids.

Front 33

Lipid infiltration hypothesis.

Back 33

1. Increase concentration of serum LDL --> increased rate of cholesterol infiltration into arterial wall.
2. Endothelial cells, smooth muscle cells, macrophages increase uptake of lipid. Only partial degradation occurs.
3. Necrosis + local proliferation of lipid-containing smooth muscle cells --> release of lipids

Front 34

The link between endothelial injury and lipid infiltration in the unification theory.

Back 34

Injury to endothelium produced by increased plasma LDL levels

Front 35

C-reactive protein

Back 35

Acute phase reactant, circulating marker of inflammation.
Enhances inflammation and lipid accumulation
Elevated in persons with unstable angina, indicator of myocardial injury.

Front 36

Morphological change in smooth muscle cell distribution likely responsible for irreversible legion.

Back 36

Migration from media into subintima.

Front 37

Plasma LDL-C level below which atherosclerosis rarely develops

Back 37

160mg/dL

Front 38

Plasma LDL-C level below which atherosclerosis is absent

Back 38

80 mg/dL

Front 39

HDL change with exercise

Back 39

Increase

Front 40

Change of lipid fractions of arterial wall with age

Back 40

Increase

Front 41

Enzyme in macrophages that degrades VLDL and chylomicrons

Back 41

Lipoprotein lipase

Front 42

Effect of oxidized LDL in arterial wall.

Back 42

Locally toxic (to endothelium especially)
Chemotactic for macrophages --> rapid production of foam cells

Front 43

Consequences of gradual atherosclerotic occlusion

Back 43

Cerebral ischemia ('senile' dementia)
Myocardial ischemia (angina pectoris)
Renal ischemia (hypertension)

Front 44

Consequences of sudden atherosclerotic occlusion.

Back 44

Thrombosis --> Myocardial infarction, Cerebral infarction (stroke)
Embolism --> Cerebral infarction, renal infarction

Front 45

Embolism vs. Thrombosis

Back 45

Thrombosis = local blockage by thrombus/clot
Embolism = piece of a thrombus/clot that has broken off of a thrombosis, migrated elsewhere (brain = stroke, renal infarction)

Front 46

Complications following burst of atherosclerosis.

Back 46

Aortic/cerebral aneurysm
Rupture/leaking of aneurysm --> hemorrhage

Front 47

Most important risk factors for atherosclerosis per the Framingham study

Back 47

Hyperlipidemia, hypertension