Chronic/ repetitive injury

Injury
Mechanical Denudation
Hemodynamic force
Immune complex deposition
Irradiation
Chemicals
Hyperlipidemia

Non-Denuding
Endothelial Dysfunction
Permeability
Enhanced leukocyte
adhesion
Alteration of gene products

Role of Inflammation
Initiate, progression, development of complications
Early arthrosclerosis endothelial cells express VCAM-1
(binds leukocytes, monocytes, lymphocytes)

Monocytes differentiate to macrophages & foam cells

Elaborate growth factors leading to SMC proliferation

T lymphocytes lead to activation of cellular, humoral

immunity
Role of Lipids
Major lipids in atheromatous plaque

Plasma derived cholesterol

Cholesterol esther
Production of super oxide, other free radicals

Impairs endothelial function

Forms oxidized LDL

Anti oxidants (-carotene, Vitamin E) protects arterosclerosis
formation
Genetic/ acquired defects in lipoprotein metabolism

Natural History & Its Sequelae

Common sites
Aorta (abdomen > thoracic)
Coronary arteries
Popliteal arteries
ICA, vessels of circle of Willis
Spare

Vessels of upper extremities

Mesenteric arteries

Renal arteries (except at their ostia)

Fatty Streaks
Earliest lesion of arterosclerosis
Composed of lipid-filled foam cells
Begin as

Multiple yellow

Flat spots < 1mm in diameter

Coalesce into elongated streaks ( 1cm long)

Contain small amounts of T lymphocytes, extracellular lipids
Commonly found in children (as early as < 1 year of age)

Fatty Streaks
Pathology & Complications

Role of Smooth Muscle Cells

SMC migrate (media intima)
Proliferate & deposit ECM components
Convert fatty streak into mature atherosclerotic lesions
(stabilize atherosclerotic plaques)

Progression

Morphology
Atherosclerosis

Intimal thickening

Lipid accumulation
Atheromatous plaque

Raised focal lesion in intima

Soft yellow grumous core of lipid

Covered by a firm white fibrous capsule

Coronary Narrowing
(Atherosclerosis)

Atheroma Coronary
Artery

Complications of Atherosclerotic Plaques

Calcification
Rupture, ulceration, erosion

Exposure of highly thrombogenic substance Thrombus

formation
Haemorrhage

Due to rupture of plaque/ thin wall capillaries

(that vascularise plaque)
Thrombosis

Superimposed thrombus formation

Partially/ completely occluded lumen

Aneurysmal dilatation

Atrophy of underlying media

Loss of elastic tissue

Cause weakness, potential rupture

Calcification

Calcification

Calcification
Severe coronary
atherosclerosis
Extensive calcification
Lumen is narrowed

Ulceration
Components of Atheromatous Plaque
Smooth muscle cell, Macrophage, Leukocytes
Collagen, Elastic fibers, Proteoglycans
Intracellular, extracellular lipid deposits

Ulceration

Ulceration

Ulceration
(Severe atherosclerosis of
aorta)
Atheromatous plaques
Ulceration
Mural thrombus
Ulceration
Severe atherosclerosis,
ulceration

Severe atherosclerosis
Ulceration, thrombosis
Haemorrhage

Coronary Atherosclerosis
Haemorrhage - atheromatous
plaque
Narrow arterial lumen

Thrombosis

Thrombosis
Pink-to-red recent thrombosis
Narrowed coronary artery
Cholesterol clefts
(open, needle-like spaces)

Coronary Thrombosis
Occlusive, dark red thrombus
Atherosclerosis
(Produce acute MI)

Atherosclerosis
Narrowing of coronary artery

Coronary Thrombosis
Dark red thrombus (in lumen)
Yellow tan plaques of
atheroma
Narrow coronary artery
Thrombus occludes it
completely

Atherosclerosis
Organization, recanalization of
previous thrombosis
Recent thrombus in small
lumen

Aneurysm
Localized abnormal dilatation of blood vessel/ wall of heart
Causes

Ahterosclerosis

Cystic medial degeneration of arterial media

Most common AS aneurysm AAA (abdominal aortic aneurysm)

Aneurysm
(abdominal aorta)
Atrophy of tunica media

Aortic Aneurysm

Aortic Aneurysm
Rupture tract
Wall of aneurysm is thin
Lumen filled with thrombus

Ruptured

(layered, unorganized)