Atherosclerosis Flashcards
Artery classification based on size
- large & medium arteries: >2 mm in diameter (aorta)
- small arteries: 100um to 2 mm in diameter
- arterioles: 20-100 um in diameter
Artery classification based on tunica media composition
- large & medium: multiple layers of smooth muscle
- small arteries: few layers of smooth muscle
- arterioles: 1-2 layers of smooth muscle
Atherosclerosis key points
- 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
arteriosclerosis definition
hardening of arteries
Three forms of ateriosclerosis
- Monckeberg medial calcific sclerosis: deposits of calcium in muscular arteries, which do not encroach lumen, of older individuals
- atherosclerosis
- ateriolosclerosis: only arterioles and is unique to chronic HTN
Literal translation of atherosclerosis
hardening of the arteries w/ gruel-like deposits
Nonmodifiable risk factors for atherosclerosis
age, male, family history, genetics
Controllable risk factors for atherosclerosis
hyperlipidemia, HTN, smoking cigs, diabetes mellitus
Most important risk factor for atherosclerosis
HYPERLIPIDEMIA
Stages of atherosclerotic plaque development
- endothelial dysfunction
- fatty streak formation
- plaque growth and maturation
- unstable fibrous plaque
Endothelial dysfunction pathology
- begins w/ injury to epithelium
- increased permeability to lipids followed by adhesion & emigration of monocytes
Fatty streak formation pathology
- 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
Plaque growth and maturation pathology
- 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
Unstable fibrous plaque pathology
- 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
Pathogenesis of atherosclerosis
- chronic inflammatory response of arterial wall
- initiated by endothelial injury
- sustained interactions among; lipoproteins, macrophages, T lymphocytes & smooth muscle
Major factors that contribute to atherosclerotic plaque formation
Shear stress, oxidative stress, chronic inflammation & growth factors, neovascularization & apoptosis
Shear stress
- reduction in shear stress occur at regions of turbulent blood flow at branch points, initiate endothelial injury
Oxidative stress
- oxidation of lipoproteins contributes to fatty streak formation by attracting macrophages, which ingest oxidized lipoproteins
Chronic inflammation & growth factors
- 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
Neovascularization & apoptosis
- 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
Match stages to major factors in plaque formation
- shear stress:endothelial dysfunction
- oxidative stress: fatty streak formation
- chronic inflammation & growth factors:plaque growth & maturation
- neovascularization & apoptosis:unstable plaque
Common sites of atherosclerosis
- abdominal aorta, arteries that supply heart (coronary) and brain (carotid)
- MYOCARDIAL INFARCTION, CEREBRAL INFARCTION, AORTIC ANEURYSM
Aneurysm definition
localized abnormal dilation of a blood vessel or wall of heart
True vs. false aneurysms
- 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
Aneurysm causes
- ATHEROSCLEROSIS is most common
- cystic medial degeneration, tertiary syphilis, infection, & trauma
Epidemiology of atherosclerotic aneurysms
- age range: rare before 40
- male>female
Location of aortic aneurysms
- abdominal aorta
- may involve origins of renal & mesenteric arteries or common iliac arteries
Complications of aortic aneurysms
- rupture, obstruction of adjacent vessels, embolism from atheroma or mural thrombus
Atherosclerosis significance
- 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.
