Pathology Of Atherosclerosis

Types of blood vessels

• Arteries:
– Elastic arteries: Aorta and large arteries
– Muscular arteries: Smaller arteries
• Arterioles:
– Smallest elements of arterial system.
• Capillaries:
– Tiniest blood vessels.
• Venules
• Veins
• Lymphatics
Normal structure

Endothelium

Very thin intima

Internal elastic lamina

Media

External elastic lamina

Adventitiae
 Arterial Sclerosis

Hardening

Atherosclerosis Medial Calcific Arteriolosclerosis

Sclerosis Small vessels
Large Blood Vessels
Media
Intima Full thickness

Hyaline Hyperplastic
Atherosclerosis
• A disease of large and medium-sized
elastic arteries.
• Charcterized by the ccumulation of
smooth muscle cells and lipids within the
intima producing irregular thickening of the
wall and narrowing of the lumen
• The lesion is called Atheroma
WHAT IS ATHEROMA?
Morphology

• Three types of lesion are recognised

• Fatty streaks
– Linear elevations composed of lipid laden macrophages

• Fibrolipid plaque
– Bigger lesions with fat and fibrosis, and with fibroblasts presents

• Complicated lesion
– Narrowing
– Endothelial erosion with thrombosis
– Plaque rupture and fissuring (bleeding)
– Aneurysm formation
Fatty streak Fibrolipid plaque Complicated plaque
Stages of Atheroma - Aorta
Coronary Atherosclerosis:
Atheroma Coronary Artery:
Atheroma Coronary Artery:
Atheroma Coronary Artery:

Calcification
Atheroma with Thrombosis:
Atheroma Aorta:
Atheroma Aorta:
Atherosclerosis
• Major complications of atherosclerosis:
– ischemic heart disease
– myocardial infarction
– stroke
– gangrene of extremities

• Ischemic heart disease is the leading cause

of death in this country.
WHY IS

ATHEROMA

IMPORTANT?

Major clinical

effects from

its complications
 Coronary Atheorsclerosis

LCx
•Left Coronary Artery.
•Anterior Descending (LAD)
•Left Circumflex (LCx) LAD
•Right Coronary Artery.
Coronary Narrowing in Atherosclerosis:
 Sites of severe atherosclerosis
1. Abdominal aorta and Iliac arteries

3. Proximal coronary arteries

5. Thoracic aorta, Femoral & popliteal arteries

7. Internal carotid arteries

9. Vertebral, basilar & middle cerebral arteries

Sites affected by atheroma
Vessels often affected.
Lower abdominal aorta/iliac > coronary >
popliteal > desc thoracic aorta > int. carotid and
circle of Willis.

Vessels relatively spared (except at ostia)

Upper extremity > renal > mesenteric > aortic
arch.
 Risk factors for atherosclerosis
• Any factor associated with a doubling in
the incidence of ischemic heart disease
has been defined as a risk factor.
Risk factors for atherosclerosis
Major

Non-modifiable: Potentially controllabe:

• Increasing age • Hyperlipidemia
• Hypertension
• Male gender
• Cigarette smoking
• Family history
• Diabetes
• Genetic
abnormalities
 Risk factors for atherosclerosis
Minor, non-quantitated factors:

3. Obesity
4. Physical inactivity
5. Stress(type A personality)
6. Homocysteine
7. Postmenopausal estrogen deficiency
8. High carbohydrate intake
9. Alcohol
10. Lipoprotein (a)
11. Trans unsaturated fat intake
Hyperlipidaemia

• Atherosclerotic plaques rich in cholesterol

• Experiments in animals

• Genetic disorders

• Higher mortality from IHD

• Treatment reduces mortality

Hypertension
• Increased IHD (Ischaemic heart
disease)
• Increased CVD (Cerebro-vascular
disease)
• Higher BP, greater the risk
• Antihypertensive treatment reduces
incidence of IHD/CVD
Diabetes
• Increased atherosclerosis at autopsy
• 2x incidence of myocardial infarction
• Increased incidence of cerebrovascular
disease
• 10-150x incidence of peripheral
vascular disease
Smoking

• Mortality up to 200% higher

• Degree of atherosclerosis greater
• Cessation followed by reduction in risk
Mortality from atherosclerosis in various countries

Deaths per 100000

600

500

400

300
Mortality
200

100

0
NI UK FIN AUS USA GER FRA JPN
 Complications of
atherosclerosis

• Acute arterial occlusion leading to ischemic

necrosis (infarction / gangrene)
• Chronic occlusion leading to tissue / organ
atrophy
• Aneurysm formation
• Embolism
Theories of Atherosclerosis
• Inflammation theory of Virchow (1856)

• Thrombogenic or encrustation theory

(Rokitansky)

• Insudation or perfusion theory

• Monoclonal hypothesis of atherogenesis

• Reaction to Injury Hypothesis

Pathogenesis of Atheroma I
Endothelial cell damage
– Mechanical and Haemodynamic forces
– Sheer stress
– Turbulence
– Branching
– Hypertension
– Cigarette smoking

Smooth muscle proliferation

– Growth Factors - endothelial, macrophages, platelets
– Loss of growth inhibitors
Pathogenesis of Atheroma II
Macrophages
– Possess VLDL & LDL receptors > foam cell
– Produce cytokines
– Toxic oxygen molecules

Hyperlipidaemia
– ↑ concentration gradient.
– ↑ Foam cells
– Toxic to endothelial cells.
– Oxidised lipids are very reactive,
• leading to injury, necrosis, chemotaxis and continuing
inflammation.
Pathogenesis of Atheroma III
Other Factors

• Infections (viral, bacterial, other)

• Immunological factors

• Genetic predispositions