1. Atherosclerosis

7/29/2019 1. Atherosclerosis

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ClinicianWho applies knowledge and skill to

1. Maintain the state of health of human body

2. Restore the healthy state, if the person is sick

(AL-QANOON)


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Organs

stomach

Tissues

Epithelial,

connective,

Muscle

Cells


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CellThing which can cause injury to cell

Defect in cell function ~tissue ~ organ ~ system

Injurious agents

Ischemia

Chemical agents

Physical agents

Nutritional imbalances

Microbial agents


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Cells

Tissues

Epithelial,

connective,Muscle

Organs

Heart

Blood vessels


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Human body

Systems

CVS,

Blood cell disorders

Respiratory,

GITEndocrine

renal


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Blood vesselsBlood flow

Nutrients (healthy material) towards cells

Waste (toxic) material away from cells


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Blood vessels

Narrowing or complete obstruction ofvessel lumen

Weakening of the vessel wall


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ATHEROSCLEROSIS

Why should we study atherosclerosis ?

What should be studied in atherosclerosis ?


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Transmural myocardial

infarction

Thin fibrous wall

Thin band of collagen

Reduced stroke volume

Aneurysm

Thrombosis


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There has been a previous extensive transmural

myocardial infarction involving the free wall of the

left ventricle.The thickness of the myocardial wall is normal

superiorly, but inferiorly is only a thin fibrous wall.

The infarction was so extensive that, after healing,the ventricular wall was replaced by a thin band of

collagen, forming an aneurysm.

Such an aneurysm represents non-contractile tissue

that reduces stroke volume and strains the remainingmyocardium.

The stasis of blood in the aneurysm predisposes to

mural thrombosis.


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Here is a large remote cerebral infarction. Resolution of the

infarction has left a huge cystic space encompassing much

of the cerebral hemisphere in this neonate.


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This is a normal coronary artery. The lumen islarge, without any narrowing by atheromatous

plaque. The muscular arterial wall is of normal

proportion.


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Causes or risk factors ?

Pathogenesis ?

Components ?Macroscopic & microscopic appearance ?

Clinical significance / complications ?

Prevention ?


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Intima

Media

Adventitia


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Intima

Media

Adventitia


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Properties & Functions of

endothelial cellsMaintenance of permeability barrier

controls the transfer of molecules into the vessel wall

Maintenance of non thrombogenic bloodtissue interface

prostacyclins, thrombomodulins, plasminogen activater

Elaboration of prothrombotic molecules

von willebrand factor, Tissue factor, plasminogen

activater inhibitor


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endothelial cellsExtracellular matrix production

collagen and proteoglycans

Modulation of blood flow

vasoconstrictors Endothelin

vasodilators NO, Prostacyclin


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endothelial cellsRegulation of inflammation and immunity

IL-1, IL-6, IL-8

adhesion molecules

histocompatibilty antigens

Regulation of cell growthplatelet derived growth factor PDGF

fibroblast growth factor FGF

transforming growth factor beta TGF-b


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Properties of smooth muscle

cellsVasoconstriction

Vasodilation

Synthesis of collegan, elastin, proteoglycans

Migration to intimaProliferation after vasculer injury


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Normal to Abnormal


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PATHOGENESIS

Atherosclerosis is considered to be

a chronic inflammatory response ofthe arterial wall initiated by some

form of injury to the endothelium.


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PATHOGENESIS

Injurious agent

endothelial cells

Inflammatory response

atherosclerosis


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Chronic endothelial injury


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chronic endothelial injury - endothelial dysfunction

increased permeability with adhesion of monocytes

and platelets


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PATHOGENESIS

chronic endothelial injuryendothelial dysfunction

increased permeability

insudation of lipoproteins

adhesion of monocytes and platelets

release of factors from platelets and

macrophages


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PATHOGENESIS

Migration of smooth muscle cells from media to

intima

Proliferation of smooth muscle cells

Elaboration of extracelluler matrix

Accumulation of lipids in the cells macrophages

and smooth muscle cells as well as

extracellulerly


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Migration of monocytes into the intima and

their transformation into Macrophages and

Foam cells


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Proliferation of smooth muscle cells in the intima and

elaboration of extracellular matrix, leading to

accumulation of collagen and proteoglycans


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Release of factors from activated platelets,

macrophages, or vascular cells that cause migration

of smooth muscle cells from media into the intima


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Role of Lipid

Increased LDL Cholesterol

Decreased HDL Cholesterol

Increased level of abnormal

lipoproteins


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Role of Lipid

Major lipids in atheroma are

plasma derived

cholesterol

cholesterol esters


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Chronic hyperlipidemia

Impair endothelial cell function

increased production of oxygen free radicals

deactivate nitric oxide ( endothelial relaxing factor)

Lipoprotein accumulate in the intima

thickening of intima

Free radicals generated by macrophages

oxidized LDL

taken by macrophages and form foam cell


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Macrophages

Dysfunctional endothelial cells

Expression on adhesion molecules

Adherence of macrophages

Migration to intima

Foam cell formation


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figure


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1. Atherosclerosis

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