Lecture 30 - Pathology Of Atherosclerosis

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 Sclerosis

Arteriolosclerosis Small vessels

Large Blood Vessels Media

Full thickness

Intima

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 •Left Coronary Artery. •Anterior Descending (LAD) •Left Circumflex (LCx)

•Right Coronary Artery.

LCx LAD

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: • • • •

Increasing age Male gender Family history Genetic abnormalities

Potentially controllabe: • Hyperlipidemia • Hypertension • Cigarette smoking • Diabetes

Risk factors for atherosclerosis Minor, non-quantitated factors: 3. 4. 5. 6. 7. 8. 9. 10. 11.

Obesity Physical inactivity Stress(type A personality) Homocysteine Postmenopausal estrogen deficiency High carbohydrate intake Alcohol Lipoprotein (a) 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