ATHEROSCLEROSISBy

Dr. Abdelaty ShawkyAssociate professor of pathology

Histology of the vascular wall

Endothelial cells

• Single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium.

• Endothelial structural and functional integrity is fundamental to the maintenance of vessel wall homeostasis and normal circulatory function.

Smooth muscle cells• SMCs are predominant cellular element of the

vascular media• SMCs are responsible for vasoconstriction and

dilation in response to normal or pharmacologic stimuli.

• SMCs are important elements of both normal vascular repair and pathologic processes such as atherosclerosis

Arteriosclerosis Arteriosclerosis literally means "hardening of the arteries”. It is a

term for thickening and loss of elasticity of arterial walls. Three

patterns are recognized:

1 .Atherosclerosis: the most frequent and important pattern.

2 .Mönckeberg medial calcific sclerosis: is characterized by calcific

deposits in muscular arteries in older people .

3 .Arteriolosclerosis: affects small arteries and arterioles. Is seen

with hypertension and diabetes mellitus.

Atherosclerosis* Definition: Generalized, degenerative arterial disease

characterized by patchy thickening of the intima by

atheromas, which protrude into and obstruct vascular

lumens and weaken the underlying media.

* Risk factors for atherosclerosis:

I. Non-modifiable risk factors:

• Genetic predisposition: Family history is the most important

independent risk factor for atherosclerosis. Certain genetic

disorders are strongly associated with atherosclerosis e.g.,

familial hypercholesterolemia.

• Age: Atherosclerosis manifests in middle and old ages.

• Gender: Atherosclerosis is less common in pre-menopausal

females than males, however is more common in post-

menoapsual females than males.

II. Modifiable risk factors:

• Hyperlipidemia.

• Hypertension.

• Cigarette smoking.

• Diabetes.

• Hyperlipidemia and, more specifically,

hypercholesterolemia—is a major risk factor for

development of atherosclerosis and is sufficient to

induce lesions in the absence of other risk factors. The

main cholesterol component associated with

increased risk is low-density lipoprotein (LDL)

cholesterol (“bad cholesterol”); LDL distributes

cholesterol to peripheral tissues.

• By contrast, high-density lipoprotein (HDL)

(“good cholesterol”) mobilizes cholesterol from

developing and existing vascular plaques and

transports it to the liver for biliary excretion.

• Consequently, higher levels of HDL correlate

with reduced risk.

* Pathogenesis of atherosclerosis:

Response to injury hypothesis:

It considers atherosclerosis to be a chronic

inflammatory response of the arterial wall

initiated by injury to the endothelium.

1. Chronic endothelial injury induced by:

- Hypertension, Hyperlipidaemia, Cigarette

smoking….etc.

- This leads to endothelial dysfunction (increased

permeability to cholesterol, leukocyte adhesion.

2. Accumulation of lipoproteins: mainly LDLin the vessel wall.

3. Adhesion of blood monocytes to the endothelium,

followed by their migration into the intima and their

transformation into macrophages which engulfs the

entering cholesterol and becomes foam cells.

4. Adhesion of platelets to the exposed sub-intimal

collagen.

5. Smooth muscle cell recruitment to the intima due

to release of mitogenic growth factors from activated

platelets and foam cells.

6. Proliferation of smooth muscle cells in the

intima, and elaboration of extracellular matrix,

leading to the accumulation of collagen and

proteoglycans.

Slide 12.13

Chronic endothelial “injury” theory

Endothelial dysfunctionMonocyte adhesion and emigration2

Macrophage activationSmooth muscle recruitment3

How to Make an Atheroma

5, Well-developed plaque.

* Gross and microscopic morphology:

1. Fatty spots: are the earliest lesion of atherosclerosis

as multiple yellow, flat spots less than 1 mm in diameter.

They are composed of lipid-filled foam cells.

2. Fatty streaks: fatty spots coalesce into elongated

streaks, 1 cm long or longer. They are not significantly

raised and thus do not cause any disturbance in blood

flow.

Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal macrophage-derived foam cells ( arrow).

Fatty streak—a collection of foam cells in the intima

Aorta with fatty streaks ( arrows).

3. Atheroma (atherosclerotic plaque): consists of raised patches within the intima, having a soft, yellow, core of lipid, covered by a firm, white fibrous cap.

* Microscopically:

Atherosclerotic plaques have three principal components:

1. Cells, including smooth muscle cells (SMCs), macrophages,

and other leukocytes

2. Extracellular matrix(ECM), including collagen, elastic

fibers, and proteoglycans

3. Lipid (LDL): intracellular (foam cells) and extracellular

(crystals)..

The previously mentioned components are arranged in these layers :

1. Fibrous cap: in the top composed of SMCs and

relatively dense ECM, macrophages, and lymphocytes.

2. Necrotic core: Deep to the fibrous cap , containing

cholesterol clefts, necrotic debris from dead cells, foam

cells and fibrin.

* Sites of atherosclerosis:

• Large elastic arteries e.g., aorta, carotid, and

iliac arteries.

• Large and medium-sized muscular arteries e.g.,

coronary, renal, and popliteal arteries are the

vessels most commonly involved by

atherosclerosis.

* Complications:

1. Rupture, ulceration, or erosion of the luminal

surface of atheromatous plaques.

2. Atheroemboli.

May occur after rupture of atheromatous plaque which

may be fragmented into microemboli.

3. Hemorrhage into a plaque may be initiated by

rupture of either the overlying fibrous cap or the thin-

walled capillaries that vascularize the plaque. A

contained hematoma may expand the plaque or induce

plaque rupture.

4. Thrombosis usually occurs on disrupted lesions

(those with rupture, ulceration, erosion, or

hemorrhage) and may partially or completely occlude

the lumen.

5. Aneurysm: is abnormal dilatation of the

arterial wall which is induced by atrophy of the

underlying media, with loss of elastic tissue,

causing weakness, and potential rupture

6. Calcifications: Atheromas often undergo

calcification.

Please take care of

atherosclerosis