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ATHEROSCLEROSIS

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Arteriolosclerosis small arteries and arterioles (hypertension and DM) ... Fatty Streak-Coronary Artery. Consequences of Atherosclerosis. Altered Vessel Function ... – PowerPoint PPT presentation

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Title: ATHEROSCLEROSIS


1
ATHEROSCLEROSIS
MEDS 520, 2007
WWAMI Medical Program, MSU
2
General Comments
  • Arteriosclerosis
  • Thickening and loss of elasticity of arterial
    walls
  • Hardening of the arteries
  • Greatest morbidity and mortality of all human
    diseases via
  • Narrowing
  • Weakening

3
Three patterns of arteriosclerosis
  • Atherosclerosis
  • The dominant pattern of arteriosclerosis
  • Primarily affects the elastic (aorta, carotid,
    iliac) and large to medium sized muscular
    arteries (coronary, popliteal)
  • Monckeberg medial calcific sclerosis
  • Arteriolosclerosis small arteries and arterioles
    (hypertension and DM)

4
Non-Modifiable Risk Factors
  • Age
  • A dominant influence
  • Atherosclerosis begins in the young, but does not
    precipitate organ injury until later in life
  • Gender
  • Men more prone than women, but by age 60-70 about
    equal frequency
  • Family History
  • Familial cluster of risk factors
  • Genetic differences

5
Modifiable Risk Factors(potentially controllable)
  • Hyperlipidemia
  • Hypertension
  • Cigarette smoking
  • Diabetes Mellitus
  • Elevated Homocysteine
  • Factors that affect hemostasis and thrombosis
  • Infections Herpes virus Chlamydia pneumoniae
  • Obesity, sedentary lifestyle, stress

6
AHA Classification of atherosclerosis
Fig. 11.7
7
Pathogenesis of atherosclerosis
8
Normal Artery
9
Atherosclerosis
  • A disease of the intima
  • A disease of the intima
  • A disease of the intima
  • Atheromas, atheromatous/fibrofatty plaques,
    fibrous plaques
  • Narrowing/occlusion weakness of wall

10
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12
Major components of plaque
  • Cells (SMC, macrophages and other WBC)
  • ECM (collagen, elastin, and PGs)
  • Lipid Cholesterol (Intra/extracellular)
  • (Often calcification)

13
Two major processes in plaque formation
  • Intimal thickening (SMC proliferation and ECM
    synthesis)
  • Lipid accumulation

14
Response to injury hypothesis
  • Injury to the endothelium
  • (dysfunctional endothelium)
  • Chronic imflammatory response
  • Migration of SMC from media to intima
  • Proliferation of SMC in intima
  • Excess production of ECM
  • Enhanced lipid accumulation

15
Response to injury hypothesis (I)
  • 1. Chronic EC injury (subtle?)
  • EC dysfunction
  • Increased permeability
  • Leukocyte adhesion (via VCAM-1)
  • Thrombotic potential

16
Response to injury hypothesis (II)
  • Accumulation of LDL (cholesterol)
  • Oxidation of lesional LDL
  • Adhesion migration of blood monocytes
    transformation into macrophages and foam cells
  • Adhesion of platelets
  • Release of factors from platelets, macrophages
    and ECs

17
Response to injury hypothesis (III)
  • Migration of SMC from media to intima
  • Proliferation of SMC
  • ECM production by SMC
  • Enhanced lipid accumulation
  • Intracellular (SMC and macrophages)
  • Extracellular

18
Response to Injury
19
Endothelial Dysfunction
20
Initiation of Fatty Streak
21
Fatty Streak
22
Fibro-fatty Atheroma
23
Summary of Atherosclerotic Process
  • Multifactorial process (risk factors)
  • Initiated by endothelial dysfunction
  • Up regulation of endothelial and leukocyte
    adhesion molecules
  • Macrophage diapedesis
  • LDL transcytosis
  • LDL oxidation
  • Foam cells
  • Recruitment and proliferation of smooth muscle
    cells (synthesis of connective tissue proteins)
  • Formation and organization of arterial thrombi

24
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25
Consequences of plaque formation
  • Generalized
  • Narrowing/Occlusion
  • Rupture
  • Emboli
  • Leading to specific problems
  • Myocardial and cerebral infarcts
  • Aortic aneurysms
  • Peripheral vascular disease

26
Is Atherosclerosis Reversible
  • Primate experiments
  • High fat diet discontinued atherosclerotic
    lesions regress
  • Humans
  • Decrease fat and caloric intake (wars, famine,
    wasting disease), atheromas decrease.
  • Angiography after cholesterol lowering, plaque
    size decreases
  • What has to happen for plaques to regress?
  • LDL lowered
  • Mac ingest lipids
  • Reverse cholesterol transport, depends on HDL

27
Fatty Streak-Aorta
28
Fatty Streak-Coronary Artery
29
Consequences of Atherosclerosis
30
Altered Vessel Function
  • Vessel change
  • Plaque narrows lumen
  • Wall weakened
  • Thrombosis
  • Breaking loose of plaque
  • Loss of elasticity
  • Consequence
  • Ischemia, turbulence
  • Aneurysms, vessel rupture
  • Narrowing, ischemia, embolization
  • Athero-embolization
  • Increase systolic blood pressure

31
Late Changes
  • Calcification
  • An example of dystrophic calcification
  • Cracking, ulceration, rupture
  • Usually occurs at edge of plaque
  • Thrombus formation
  • Caused by endothelial injury,ulceration,
    turbulence
  • Organization of thrombus
  • More thrombus
  • Encroachment
  • Weakens vessel wall
  • Bleeding
  • Ulceration, cracking and angiogenesis

32
ATHEROSCLEROSIS Pathology, Pathogenesis,
Complications, Natural History
33
Complicated Lesions
Fibrous Plaques
34
Complicated Lesions
35
Neovas. Calcification Inflam. cells
Fibrous cap Cholesterol clefts
Elastin membrane destroyed
36
Hemorrhage into Plaque
37
Ulceration/Hemorrhage/Cholesterol Crystals
38
Complicated Lesion/Calcification
39
Foam Cells/Cholesterol Crystals
40
Cholesterol Crystals/Foam Cells
41
Thrombosis/Complicated Lesion
42
Complicated Lesion/Ulceration/Thrombosis
43
Common Consequences of Atherosclerosis in
Specific Vessels
44
Aorta
  • Aneurysm
  • Pulsatile abdominal mass
  • Abdominal pain
  • Bleeding
  • Atheroembolization
  • Narrowing of lumen
  • Usually not a problem

45
Aortic Aneurysm
46
Aortic Aneurysm
47
Coronary Arteries
  • Consequences of coronary artery atherosclerosis
    discussed next lecture

48
Coronary Artery Atherosclerosis
49
Coronary Artery Atherosclerosis
50
Carotids and Cerebral Circulation
  • Atherosclerosis with thrombosis can lead to brain
    infarction
  • Red or white
  • Coagulative or liquefactive
  • Can lead to transient ischemic attacks (TIA), if
    narrowing is aggravated by mural thrombus or
    vasospasm

51
Celiac and Mesenteric Arteries
  • Narrowing primarily at aorta bifurcation
  • Ischemia uncommon because of collateral
    circulation
  • Ischemia can occur if more than 1 artery severely
    affected - ischemic entercolitis

52
Renal Artery
  • Progressive ischemic atrophy of kidney leads to
    gradual kidney failure (nephrosclerosis)
  • Renal hypertension due to decreased perfusion

53
Iliac and Femoral Arteries
  • Aneurysms
  • Vessel occlusion by plaque and thrombus
  • Ischemia of leg muscles, especially during
    exercise (intermittent claudication)
  • Ulcers of skin of legs and feet
  • Gangrene of feet

54
Atherosclerotic Disease
  • Prevalence
  • 6 million Americans with CAD
  • 3 million Americans have had strokes
  • Mortality
  • 1.5 million deaths/yr in US due to myocardial
    infarction
  • 0.5 million deaths/yr in US due to strokes

55
Normal Artery
56
Pathogenesis of Atherosclerosis
  • Cause?
  • Current hypothesis Response to Injury
  • Initiated by endothelial dysfunction
  • Disease of the intima
  • Intimal thickening
  • Intra- and extra-cellular lipid accumulation
  • Chronic Inflammation
  • Basic Lesion is termed atheroma, fibro-fatty
    plaque, or atheromatous plaque
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