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Atherosclerosis

Specific form of arteriosclerosis affecting primarily the intima of large and medium sized muscular arteries and is characterized by fibrofatty plaques or atheromas

Atheroma

Athero: soft lipid rich material in the center of atheroma


Sclerosis: referring to CT in the plaques

Major Risk Factors

1.) Dyslipidaemias


2.) Hypertension


3.) Smoking due to reduced level of HDL, deranged coagulation system & accumulation of carbon monoxide


4.) Diabetes Mellitus


5.) Age


Sex: women less affected due to oestrogen & HDLs which are antiatherogenic


6.) Sex: women less affected due to oestrogen & HDLs which are antiatherogenic


7.) Genetic Factors


Minor Risk Factors

1.) Developed countries


2.) Obesity


3.) Use of exogenous hormones


4.) Physical inactivity


5.) Stressful lifestyle


6.) Patients with homocystinuria


7.) Elevated C reactive protein

2 major risk factors which act together to produce endothelial injury:

1.) Haemodynamic stress from hypertension


2.) Chronic Dyslipidaemias

IL-1 and TNF-a lead to local synthesis of growth factors each having a role in plaque evolution:

1.) PDGF and FGF: stimulate proliferation and migration of smooth muscle cells from media to intima


2.) TGF-b and IFN: regulate synthesis of collagen by smooth muscle cells


NO and endothelin released from endothelial cells also also facilitate smooth muscle proliferation

Role of blood monocytes in plaque formation:

Plasma LDL upon entering intima undergoes oxidation


Oxidized LDL formed in the intima:


-for monocytes, oxidized LDL attracts, proliferate, immobikize and activates the monocytes and oxidized LDL is taken up by scavenger receptors on monocyte to transform to LIPID LADEN FOAM CELL


-oxidized LDL is cytotoxic and death of foam cell by apoptosis releases lipid to form lipid core of plaque

Morphological Features of Atherosclerosis

Fatty streaks: flat or elevated and yellow


Microscopically- foam cells, lipid containing elongated smooth muscle cells and lymphoid cells


Gelatinous Lesion


Atheromatous Plaque: fully developed atherosclerotic lesion


microscopic Morphology of Atheromatous Plaque

1.) Superficial luminal part of the fibrous capbis covered by endothelium, smooth muscle cells, dense CT and ECM containing proteoglycan and collagen


2.) Cellular area under cap contains microphages, foam cells, lymphocytes and smooth muscle cells


3.) Deep central soft core: extracellular lipid material, cholesterol cleft, fibrin and foam cells

Complicated Plaques

Pathologic changes that occur in fully developed atheromatous plaques

Changes that occur in complicated plaques:

Calcification


Ulceration


Thrombosia


Haemorrhage


Aneurysmal Dilatation