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Flashcards in Atherosclerosis Deck (38)
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What is the general definition of arteriosclerosis?

• thickening and loss of elasticity of arterial walls
Note: there are three subtypes, including "arteriosclerosis" aka the same name as the general type


What is Mönkeberg medial calcific sclerosis?
What age group is affected?

• calcific deposits in the muscular arteries
• in persons older than age 50
• do not encroach the vessel lumen


What is arteriosclerosis (subtype)?

• small arteries and arterioles
• thickening of the wall with narrowing of the lumen
• downstream ischemia (possible)
Note: Most common in hypertension, diabetes mellitus


What is Atherosclerosis?

• large arteries
• localized thickening of the wall with lumen narrowing


What are the word roots of atherosclerosis?

Athere: gruel
sclerosis: hardening


What are the qualities of artheriosclerosis...
What is the root cause?
Which arteries are affected?
Who is affected?
When does it become symptomatic?

• chronic inflammatory disease
• large arteries
• affects every human being
• progresses with age
• asymptomatic until a certain stage


What is the epidemiological importance of Atherosclerosis?

Consequences - contributes to more mortality and serious morbidity in the Western world than any other disorder.

* more than 50% of all deaths!
(This is preventable with a plant-based diet and daily exercise)


Important Chart on ppt slide 5 (some details are listed here)
What are the stages of atherosclerosis...
Type I initial
Type II fatty streak
Type III intermediate
Type IV atheroma
Type V fibroatheroma
Type VI complicated plaques

Type I initial: isolated macrophage foam cells
Type II fatty streak: mainly intracellular lipid accumulation (reversilbe)
Type III intermediate: Type II changes and smal extracellular lipid pools
Type IV atheroma: Type II changes and core of extracellular lipid
Type V fibroatheroma: lipid core and fibrotic layer, or multiple lipid cores and fibrotic layers, or mainly calcific, or mainly fibrotic
Type VI complicated: surface defect, hematoma-hemorrhage, thrombus, symptoms become apparent here.


Biochem recap. Lippincott page 235
What is the five step mechanism for deposition of cholesterol on the arterial walls?
Note: these steps will be repeated for this class later in this set.

1) in response to endothelial injury (caused at least in part by oxidized LDL) monocytes adhere to endothelial cells >> move to the intima (sub endothelium) >> transformed into macrophages
2) Macrophages consume excess oxidized lipoprotein >> become foam cells
3) Foam cells accumulate, releasing growth factors and cytokines that stimulate the migration of smooth muscle cells from the media to the intima >> there, they proliferate, produce collagen, take up lipid, and become foam cells
4) blood LDL has two fates >>
a) become oxidized cholesterol under the influence of superoxide, nitric oxide, hydrogen peroxide and other oxidants
b) remain un-oxidized LDL under the influence of Vit E, Vit C, B-carotene, and other antioxidants
5) Foam cells take up oxLDL in an unregulated fashion >> oxLDL receptors never become down-regulated OR Foam cells take up LDL in a regulated fashion >> LDL receptors are down regulated and stop taking up LDL


See slide 7 for fatty streaks pictures
Where do fatty streaks occur?
In whom do they occur?
In what vessel are they most prominent?
Are they reversible?
What are they the precursor to?

Fatty Streaks
• foam cells
• Children of all populations
• Most prominent in aorta branches to smaller vessels
* Reversible
* Probably the precursor of


What is Atheroma?

In pathology, an atheroma is an accumulation and swelling in artery walls made up of (mostly) macrophage cells, or debris, and containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.


What are the key processes in Atheroma?

intima thickening
lipid accumulation


What are the features of atheroma?

• raised focal lesions
• initiate into the intima >> Extends to involve media
• protrude into and obstruct the vascular lumen
• weaken the underlying tunica media
• soft grumous core of lipids (cholesterol and CE)
• covered by endothelium or a fibrous cap.


people in their 30s and 40s (even some in their 20s)
Fat accumulation, proliferation of myointimal cells
Extends to involve media
As it enlarges, the center tends to undergo necrosis
Usually asymptomatic


What is a Fibroatheroma?
Slide 10 has histo stain

Atheroma plus the production of Collagen
Fibrofatty plaque


What is the stage of atherosclerosis that clinical manifestations appear?

Type VI: Complicated Plaques


What are the clinical complications of complicated plaques?
See slide 13 and 14for histology of complicated plaque

• Calcification
• Ulceration
• Thrombosis
• Hemorrhage into plaque
Severe artery destruction may lead to aneurysm and atheroemboli


Normal artery >> Fatty Streak >> Fibroplaque >> advanced vulnerable plaque >> leads to what main three clinical fates?

See slide 15 for schema of atherosclerosis.

1) Stenosis - narrowing of the vessel lumen results in ischemia
2) Occlusion - total closure of the vessel lumen
a. Thrombosis on plaque
b. Hemorrhage into plaque
c. Atheroembolus
Results in - Myocardial infarct, Cerebral infarct, Gangrene
3. Aneurysm formation - rupture, massive hemorrhage


What are the possible fates of Occlusion of blood vessel?

blood may break through the occlusion and cause:
a. Thrombosis on plaque
b. Hemorrhage into plaque
c. Atheroembolus
Results in - Myocardial infarct, Cerebral infarct, Gangrene


What is an aneurysm?

An aneurysm or aneurism (from Greek: aneurusma "dilation") is a localized, blood-filled balloon-like bulge in the wall of a blood vessel.


Where do aneurysms commonly occur?

Aneurysms can commonly occur in arteries at the base of the brain (the circle of Willis) and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart.


What are the risks of an aneurysm?

When the size of an aneurysm increases, there is a significant risk of rupture, resulting in severe hemorrhage, other complications or death. Aneurysms can be hereditary or caused by disease, both of which cause the wall of the blood vessel to weaken.


Note: definitive cause of atherosclerosis has not been established

Note: definitive cause of atherosclerosis has not been established


What is the Endothelial Injury Hypothesis?

• Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to endothelium


According to the endothelial injury hypothesis, how do lesions progress?

• lesion progression sustained by interaction between
• modified (oxidized) lipoproteins
• monocyte-derived macrophages
• T-lymphocytes
• the normal constituents of arterial wall
• endothelial cells,
• smooth muscle cells,
• matrix


This class: What are the steps in pathogenesis in Artherosclerosis? (Details will follow next)

1) Chronic endothelial injury
2) Endothelial disfunction (permeability and WBC interaction)
3) migration of smooth muscle into intima
4) Foam cell formation
5) Fibrous cap formation


What are the causes of chronic endothelial injury?

Hemodynamic Factors
Immune Reactions (aka inflammation)


What are the causes of endothelial dysfunction? (basic)

Increased permeability
leukocyte adhesion
monocyte adhesion


What are the causes of endothelial dysfunction? (detailed)

• Expression of adhesion molecules
• Increased permeability
• Secretion of cytokines, growth factors
• Subendothelial accumulation of lipoproteins (LDL) and their oxidation
• Adhesion of monocytes (leukocytes) to activated endothelium and their emigration into the arterial intima, where they become macrophages.
• Adhesion of platelets to the Edothelial Cells and liberation of active lipids (PGI2, PAF) that enhance vascular permeability and factors that stimulate proliferation of Smooth Muscle Cells and collagen production


Explain step 3 migration of smooth muscle cells into the intima.

Migration of smooth muscle cells into the intima under the influence of chemotactic factors released from activated platelets, macrophages and endothelium. Macrophage activation.


Explain the formation of the foam cells.

Macrophages and smooth muscle cells engulf lipids and become foam cells.
- LDL and oxidized LDL are taken up via their receptors and accumulate into the cytoplasm. Uptake at higher rate than breakdown.
(Note: from lippincott, it says that LDL uptake has negative feedback, but oxLDL uptake has no neg feedback and continues unregulated)