Unit 4: Path - Blood Vessels > Atherosclerosis > Flashcards

Atherosclerosis Flashcards

(37 cards)

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1
Q

What collects in an atherosclerotic plaque?

A

Inflammatory/immune cells, smooth muscle cells, lipids, connective tissue

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2
Q

What are the three stages of atherosclerotic plaque formation?

A
  1. Initiation and formation
  2. Adaptation
  3. Clinical
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3
Q

What is a genetic predisposition that can accelerate atherosclerotic plaque formation in the first decade of life?

A

Homozygous Familial Hypercholesterolemia

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4
Q

Where do atherosclerotic lesions generally form?

A

Where shear stress is low but fluctuates rapidly

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5
Q

What gene expression increases at sites prone to plaque development? What cells do these genes help recruit?

A
  • Vascular Cell Adhesion Molecule (VCAM-1)
  • Intercellular Adhesion Molecule (ICAM-1)
  • Proinflammatory Genes

Monocytes/Macrophages

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6
Q

What factors does lipid accumulation depend on?

A

Disruption of the integrity of the endothelial barrier through cell loss and/or cell dysfunction

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7
Q

Describe the relationship betwixt LDL and atherosclerosis.

A
  1. LDL carries lipids into the intima
  2. Macrophages containing lipids enter intima and undergo necrosis.
  3. Lipids collect and contribute to plaque formation
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8
Q

What is the likely effect of oxidized lipoproteins in the evolution of atherogenesis?

A

Ox. lipos. induce tissue damage and recruit macros which can transform the normal anticoagulant vascular surface to a procoagulant one

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9
Q

When a thrombus forms on the early atherosclerotic plaque, what 3 things can occur?

A

Thrombus may

  1. Grow
  2. Lyse
  3. or become organized and incorporated into the plaque
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10
Q

What occurs when the plaque separates the intima from the nutrient-rich blood?

A

Intima undergoes ischemic necrosis. Macros as well as platelets release angiogenic factors causing new vaso vasorum to form

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11
Q

What cytokine is a key regulator of ECM deposition in atherosclerotic plaques?

A

TGF-Beta

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12
Q

Describe the adaptation stage of atherosclerosis

A
  • Plaque protrudes into lumen and the wall of the artery remodels to maintain lumen size
  • Once the plaque occupies half of the lumen, remodeling can no longer compensate and the arterial lumen becomes stenotic.
  • “Clinically silent”
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13
Q

How can hemorrhage occur in the atherosclerotic plaque?

A

Fragile new vessels are formed within the plaque and can rupture

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14
Q

What are the two precursor lesions of atherosclerosis?

A
  1. Fatty Streaks - Intra/Extracellular lipid accumulation
  2. Intimal Cell Mass (“cushions” - White, thickened areas at branch points in the arterial tree, NO LIPID
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15
Q

What is the characteristic plaque of atherosclerosis? Characteristics?

A

The fibroinflammatory lipid plaque; Well defined borders, irregular shape

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16
Q

What is a more advanced lesion than a fibroinflammatory lipid plaque?

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A

Fibrofatty plaques

17
Q

What separates the lumen of the blood vessel from the necrotic center of the atherosclerotic plaque?

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A

The fibrous capsule

18
Q

What is an important contributor to plaque growth and subsequent complications?

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A

Neovascularization

19
Q

What are the possible states of a complicated atherosclerotic plaque?

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A
  • Calcification
  • Fissure
  • Hemorrhage
  • Mural Thrombosis
  • Erosion
  • Ulceration
  • Aneurysm
20
Q

What causes the formation of a mural thrombus?

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A

Abnormal blood flow around the plaque

21
Q

What major cytokine within the necrotic center of the plaque is thrombogenic?

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A

Tissue Factor

22
Q

What are complications of atherosclerosis?

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A
  • Acute Occlusion
  • Chronic Narrowing of the Vessel Lumen
  • Aneurysm Formation
  • Embolism
23
Q

What is restenosis? What causes it?

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A

Following percutaneous transluminal coronary angioplasty, stenosis again occurs; Intimal hyperplasia due to SM proliferation

24
Q

What are risk factors for atherosclerosis?

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A
  • HTN
  • Dyslipidemias
  • Smoking
  • Diabetes
  • Increasing Age
  • Male Sex
  • Physical Inactivity
  • Stress
  • Homocysteine
  • C-reactice protein
25
What are the four major components of cholesterol metabolism?
* Chylomicrons * Very Low Density Lipoproteins * LDLs * High Density Lipoproteins
26
What are the lipoproteins in the major cholesterol metabolic pathways?
B apolipoproteins
27
Describe the exogenous cholesterol pathway. What apolipoprotein is used?
Fat/cholesterol is ingested and absorbed by the intestine. Chylomicrons containing **apoB-48**. * Chylos acquire apoCII and apoE from HDL and transport lipid from intestine to liver * Chylos get processed to remnants and are removed by the liver
28
Describe the endogenous pathway. What lipoproteins are used?
* The liver secretes lipoproteins containing **apoB-100**. * Liver VLDL acquires apoCII and apoE from HDL * LPL hydrolyzes TGs on VLDL * VLDL -\> IDL -\> LDL * LDL taken up and catabolized
29
What two lipoproteins are associated with HDL? What two major functions are associated with HDL?
apoAI and apoAII 1. Reservoir for mainly apolipoproteins apoCII and apoE 2. **Reserve Cholesterol Transport** - interaction with cells in the transport system to carry extrahepatic cholesterol, including that in the arterial wall, to the liver for ultimate removal from the body
30
What happens if there is a defect in cholesteryl ester transfer and exchange?
Dyslipoproteinemia, increaseed inctracellular cholesteryl ester concentrations and premature atherosclerosis
31
What is the relationship betwixt ischemic heart disease and HDL cholesterol levels?
Inverse relationship
32
What apolipoproteins are contained by LDL?
apoB-100
33
What role does oxidized LDL play in atherogenesis?
Ox LDL is atherosclerotic, toxic to vascular wall cells and are also chemotactic for macrophages
34
What is the genetic defect in familial hypercholesterolemia? What is the outcome of homozygotes?
LDL receptor mutation on chromosome 19; Generally death of CAD by age of 20
35
A patient presents with lesions on his skin and tendons as shown below. What are the lesions? What condition does he likely have? What ocular lesion might he have? Where else can lesions form?
LDL Xanthomas; Familial Hypercholesterolemia; Arcus Lipoides; Extensor surface of elbow and knees
36
What is Lipoprotein (a) and what is its role in the pathogenesis of atherosclerosis?
LDL-like particle to which glycoprotein apo(a) is attached; Lp (a) is associated with increased risk of atherosclerosis of the coronary arteries and larger cerebral vessels in both men and women
37
What genotype of apoE is associated with type III hyperlipidemia and premature atherosclerosis?
E2/2
Unit 4: Path - Blood Vessels
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