ATHEROSCLEROSIS

Dr .Vijaya.K
Professor and HOD
Department of Pathology
MIMS,Vikarabad
 Arteriosclerosis

Thickening and
loss of elasticity
of arterial walls
Hardening of the
arteries
 Three patterns of arteriosclerosis

• Atherosclerosis
– The dominant pattern of arteriosclerosis
– Primarily affects the elastic and large to
medium sized muscular arteries
• Monckeberg medial calcific sclerosis
• Arteriolosclerosis –small arteries and
arterioles (hypertension and DM)
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
 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
AHA Classification of atherosclerosis

Fig. 11.7
Pathogenesis of atherosclerosis
Normal Artery
 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
 Major components of plaque
• Cells -SMC, macrophages and other WBC

• ECM -Collagen, elastin, and PGs

• Lipid -Cholesterol (Intra/extracellular)

• Calcification
 Two major processes in plaque
formation

• Intimal thickening -SMC proliferation and

ECM synthesis

• Lipid accumulation
• https://youtu.be/f2e5M-cLaG8
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
 Response to injury hypothesis (I)

1. Chronic EC injury
– EC dysfunction
– Increased permeability
– Leukocyte adhesion (via VCAM-1)
– Thrombotic potential
Response to injury hypothesis (II)

2. Accumulation of LDL (cholesterol)

3. Oxidation of lesional LDL
4. Adhesion & migration of blood
monocytes; transformation into
macrophages and foam cells
5. Adhesion of platelets
6. Release of factors from platelets,
macrophages and ECs
Response to injury hypothesis (III)

7. Migration of SMC from media to intima

8. Proliferation of SMC
9. ECM production by SMC
10. Enhanced lipid accumulation
Intracellular (SMC and macrophages)
Extracellular
Response to Injury
Endothelial Dysfunction
Initiation of Fatty Streak
Fatty Streak
Fibro-fatty Atheroma
 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
 Consequences of plaque
formation
Generalized
 Narrowing/Occlusion

 Rupture

 Emboli

 Leading to specific problems:

 Myocardial and cerebral infarcts
 Aortic aneurysms

 Peripheral vascular disease

 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
Fatty Streak-Aorta
Fatty Streak-Coronary Artery
Consequences of
Atherosclerosis
 Altered Vessel Function

 Vessel change  Consequence

 Plaque narrows  Ischemia, turbulence
lumen
 Aneurysms, vessel
 Wall weakened rupture
 Narrowing, ischemia,
 Thrombosis embolization
 Athero-embolization
 Breaking loose of
plaque
 Loss of elasticity  Increase systolic
blood pressure
 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
 ATHEROSCLEROSIS:
Pathology, Pathogenesis, Complications, Natural History
Fibrous Plaques Complicated Lesions
Complicated Lesions
 Neovas.
Fibrous cap Elastin membrane Calcification
Cholesterol clefts destroyed Inflam. cells
Hemorrhage into Plaque
Ulceration/Hemorrhage/Cholesterol Crystals
Complicated Lesion/Calcification
Foam Cells/Cholesterol Crystals
Cholesterol Crystals/Foam Cells
Thrombosis/Complicated Lesion
Complicated Lesion/Ulceration/Thrombosis
Common Consequences of
Atherosclerosis in Specific
Vessels
 Aorta

 Aneurysm
 Pulsatile abdominal mass
 Abdominal pain

 Bleeding

 Atheroembolization
 Narrowing of lumen
 Usually not a problem
Aortic Aneurysm
Aortic Aneurysm
 Coronary Arteries

 Ischemic heart disease

 Angina pectoris
 Myocardial infarction
Coronary Artery Atherosclerosis
Coronary Artery Atherosclerosis
 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
 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
 Renal Artery

 Progressive ischemic atrophy of

kidney leads to gradual kidney failure
(nephrosclerosis)
 Renal hypertension due to decreased
perfusion
 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
 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
Normal Artery
 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
Thank you