Atherosclerosis

Question 1

Artery classification based on size

Answer 1

• large & medium arteries: >2 mm in diameter (aorta)
• small arteries: 100um to 2 mm in diameter
• arterioles: 20-100 um in diameter

Question 2

Artery classification based on tunica media composition

Answer 2

• large & medium: multiple layers of smooth muscle
• small arteries: few layers of smooth muscle
• arterioles: 1-2 layers of smooth muscle

Question 3

Atherosclerosis key points

Answer 3

• disease of LARGE AND MEDIUM ARTERIES
• atherosclerotic lesions develop in and are confined to the INTIMAL LAYER, which is narrow zone of extracellular matrix b/w endothelium & tunica media

Question 4

arteriosclerosis definition

Answer 4

hardening of arteries

Question 5

Three forms of ateriosclerosis

Answer 5

1. Monckeberg medial calcific sclerosis: deposits of calcium in muscular arteries, which do not encroach lumen, of older individuals
2. atherosclerosis
3. ateriolosclerosis: only arterioles and is unique to chronic HTN

Question 6

Literal translation of atherosclerosis

Answer 6

hardening of the arteries w/ gruel-like deposits

Question 7

Nonmodifiable risk factors for atherosclerosis

Answer 7

age, male, family history, genetics

Question 8

Controllable risk factors for atherosclerosis

Answer 8

hyperlipidemia, HTN, smoking cigs, diabetes mellitus

Question 9

Most important risk factor for atherosclerosis

Answer 9

HYPERLIPIDEMIA

Question 10

Stages of atherosclerotic plaque development

Answer 10

1. endothelial dysfunction
2. fatty streak formation
3. plaque growth and maturation
4. unstable fibrous plaque

Question 11

Endothelial dysfunction pathology

Answer 11

• begins w/ injury to epithelium

- increased permeability to lipids followed by adhesion & emigration of monocytes

Question 12

Fatty streak formation pathology

Answer 12

• accumulation of lipids/monocytes in arterial intima cause fatty streaks
• monocytes transform into macrophages, which ingest lipids
• smooth muscle cells of tunica media invade plaque
• FIRST STAGE AT WHICH PLAQUE CAN BE RECOGNIZED GROSSLY AND MIRCROSCOPICALLY

Question 13

Plaque growth and maturation pathology

Answer 13

• plaque grows as lipids, macrophages & smooth muscle accumulate
• FORMATION OF FIBROUS CAP INTERPOSED B/W INNER CORE OF PLAQUE AND VASCULAR LUMEN
• fibrous cap forms protective barrier b/w blood and core of plaque, which contains clotting factors

Question 14

Unstable fibrous plaque pathology

Answer 14

• plaque becomes VASCULARIZED, results in plaque instability and increases risk of hemorrhage from microvessels w/in plaque and rupture through the fibrous cap
• blood is exposed to clotting factors, which results in thrombus formatiion

Question 15

Pathogenesis of atherosclerosis

Answer 15

• chronic inflammatory response of arterial wall
• initiated by endothelial injury
• sustained interactions among; lipoproteins, macrophages, T lymphocytes & smooth muscle

Question 16

Major factors that contribute to atherosclerotic plaque formation

Answer 16

Shear stress, oxidative stress, chronic inflammation & growth factors, neovascularization & apoptosis

Question 17

Shear stress

Answer 17

• reduction in shear stress occur at regions of turbulent blood flow at branch points, initiate endothelial injury

Question 18

Oxidative stress

Answer 18

• oxidation of lipoproteins contributes to fatty streak formation by attracting macrophages, which ingest oxidized lipoproteins

Question 19

Chronic inflammation & growth factors

Answer 19

• T lymphocytes & macrophages (chronic inflammation), together w/ platelets attracted to injured endothelium produce growth factors (platelet derived growth factor [PDGF])
• PDGF stimulate proliferation & migration of smooth muscle into plaque

Question 20

Neovascularization & apoptosis

Answer 20

• new vessels formed are weak & susceptible to rupture/hemorrhage
• same time cells w/in plaque undergo apoptosis further weakening plaque and increasing chance of rupture

Question 21

Match stages to major factors in plaque formation

Answer 21

• shear stress:endothelial dysfunction
• oxidative stress: fatty streak formation
• chronic inflammation & growth factors:plaque growth & maturation
• neovascularization & apoptosis:unstable plaque

Question 22

Common sites of atherosclerosis

Answer 22

• abdominal aorta, arteries that supply heart (coronary) and brain (carotid)
• MYOCARDIAL INFARCTION, CEREBRAL INFARCTION, AORTIC ANEURYSM

Question 23

Aneurysm definition

Answer 23

localized abnormal dilation of a blood vessel or wall of heart

Question 24

True vs. false aneurysms

Answer 24

• true: entire wall bulges outward and wall integrity is maintained
• false: wall is ruptured, results in hematoma formation on outer surface & adjacent extravascular tissue confines hematoma and creates localized bulge

Question 25

Aneurysm causes

Answer 25

• ATHEROSCLEROSIS is most common

- cystic medial degeneration, tertiary syphilis, infection, & trauma

Question 26

Epidemiology of atherosclerotic aneurysms

Answer 26

• age range: rare before 40

- male>female

Question 27

Location of aortic aneurysms

Answer 27

• abdominal aorta

- may involve origins of renal & mesenteric arteries or common iliac arteries

Question 28

Complications of aortic aneurysms

Answer 28

• rupture, obstruction of adjacent vessels, embolism from atheroma or mural thrombus

Question 29

Atherosclerosis significance

Answer 29

• cardiovascular disease (CVD) no. 1 cause of death in U.S.
• atherosclerosis accounts for 3/4 of all deaths from CVD
• KEY POINT: as the leading cause of CVD, atherosclerosis accounts for nearly 30% of all deaths/year in U.S.