Atherosclerosis is caused by plaques made of lipid and fibrous tissue building up in the vessel walls. It is the most common type of arteriosclerosis. The plaques can rupture, leading to thrombosis and blockages that cause issues like heart attacks or strokes. Risk factors include hyperlipidemia, hypertension, smoking, and diabetes. Macrophages play a key role by taking up lipid in the plaques. Atherosclerosis can affect arteries throughout the body and cause peripheral vascular disease, mesenteric ischemia, or cerebrovascular disease in addition to coronary artery disease.

1. Pathogenesis of
Atherosclerosis
P SAI KRISHNAN
SHRI B M PATIL MEDICAL COLLEGE

2. Atherosclerosis
Arteriosclerosis (hardening of the arteries)
3 types:
1.Atherosclerosis (athero=porridge) plaques
of lipid and fibrous tissue in vessel
wall
Less important forms of arteriosclerosis
2. Medial calcification (Monck berg)
3. Small vessel (arteriolosclerosis)

6. Atheromatous Plaque,
Macroscopic
 Distribution: Abdominal aorta> coronary >
popliteal > descending thoracic >internal carotid
> circle of Willis.
 Spared: upper extremities, renal, mesenteric
(except ostia).
 Fibrous cap (white), deeper portion (grumous,
yellow).
 3 - 15 mm diameter, raised, coalesce.
 Scanty to numerous

7. Atheromatous Plaque
Histology
 Fibrous cap: Smooth muscle, WBC,
connective tissue, collagen, elastic,
proteoglycans.
 Core: lipid debris, cholesterol, cholesterol
esters, foam cells ( smooth muscle and
macrophage), fibrin, plasma proteins, T-
cells.
 Periphery: neovascularisation, chronic
inflammation.

8. Effects of Atheromatous Plaque
Different effects in narrow (coronary) and wide
(aorta) vessels
Clinically silent
Most plaques have no effect.
Calcification: Identify on imaging.

9. Complicated plaques
Fissure
Ulcerate: atheroemboli.
Thrombosis: occlude, embolism
Haemorrhage: occlude.
Consequences
Stenos: Ischaemia, atrophy.
Occlude (by thrombus or haemorrhage): Infarct.
Aneurysm: pressure effects, leak (rupture)

10. Fatty streak
Possible precursor of atheroma.
 Spot (1mm), Streak (1x10mm).
 Composition: Macrophages filled with lipid (foam
cells) later smooth muscle cells with lipid droplets,
extracellular lipid, T-lymphocytes, proteoglycans,
collagen, elastin.
 Incidence: More frequent with high milk/fat diet:
 10% first decade, 30% third decade,
 May recede, persist or convert to fibrous plaque
 Distribution: Aorta - unlike atheroma, Coronary
arteries - like atheroma.

12. Intimal Cushion
 White areas of diffuse intimal thickening
composed of intimal smooth muscle and
matrix (little collagen, no lipid), gelatinous
lesion.
 Degenerate effect of blood pressure and
time.
 But occur at ostia (atheroma sites).

13. Monck berg's Calcific
Medial Sclerosis
 Calcification of medium or small arteries
 Both sexes, over 50
 Arteries: Femoral, radial, ulnar, genital.
 Cause: vasotonic factors, adrenaline, nicotine.
 Effect: none, visible in imaging

14. Arteriolosclerosis
 Hyaline change in vessel walls.
 Pathogenesis - plasma leakage, smooth muscle
matrix.
 Associations - hypertension, diabetes, age.
 Benign - hyaline narrowing.
 Hyper plastic - onion skin (fibrinoid necrosis).
 Sites: Kidney, gall bladder, intestine, periadrenal,
pancreatic.

15. Theories of Atherogenesis
 Virchow - imbibation
(lipid theories)
Rokitansky - encrustation
(thrombotic theories)

16. Atherosclerosis Risk Factors
Hyperlipidemia. LDL (low density lipoprotein)
Hypertension: 160/95 Vs 140/90,- Risk X 5. Increases: Atheroma, IHD, CVD. Risk decreases with
therapy.
Cigarettes: More AS, more sudden death, Risk increased by 70-200%. Decreases after
cessation.
Diabetes: More AS, MI x 2, Increased CVD, PVD risk increased x 8-150.
Other: Physical activity, stress, obesity, oral contraceptives, hyperuricemia, high carbohydrate
intake, male, age, family history, homocystinemia.
Multiple Factors: More than additive.
NOTE: IHD ischaemic heart disease, CVD cerebrovascular disease, PVD peripheral vascular
disease AS atherosclerosis, MI myocardial infarction,

17. Role of lipid in
Atherosclerosis
1. Found in plaque
2. Experimentally raised lipid -> AS
3. Hyperlipidemia -> AS
4. Populations with high lipids -> high AS rate
5. Treat Hyperlipidemia - decrease AS.

18. Risk of Atherosclerosis
 High: Raised LDL (70% cholesterol),
triglyceride and VLDL.
 Low: Raised HDL.
 Risk increases with increased cholesterol level
(risk x 5 with cholesterol increase 220 to 265)
 Increased intake cholesterol and triglycerides
- increases serum cholesterol.
 Omega 3 fatty acids (fish) protective

19. Intimal dysfunction
 Cause: Mechanical, Haemodynamic stress, Immune
complex, Radiation, Chemotherapy.
 Association: Hypertension, Stress, Cigarettes.
 Effect: Increased intimal permeability, adhesion,
smooth muscle proliferation, atheroma (if
hyperlipidemia )

21. Macrophage
 Family: Monocyte, histiocyte, macrophage,
epithelioid cell, giant cell, granuloma
 Monocyte adhere, migrate, phagocytes
 Have scavenger receptor - modified VLDL
receptor (Lipid internalized, hydrolyzed, esterifies
-> lipid droplet).
 Monocyte produce: IL-1, TNF (increased
adhesion), chemo taxis factors, toxic O2, PDGF,
TGFbeta -> smooth muscle

22. Smooth muscle
proliferation
 Origin: From media (or myointima)
 Stimulus: PDGF (from platelets, macrophages,
endothelial and smooth muscle cells), FGF, EGF, TGF.
 Inhibit: Heparin, TGF-B.
 Result: Smooth muscle cells produce extracellular
matrix and foam cells (atheroma)

23. Arterial Injury
Permeability increases.
Adhesion of platelets, monocytes
Factors released
Smooth muscle migrates to intima, proliferates
and produces extracellular matrix, collagen,
elastin, proteoglycans
Monocytes - phagocytose
Lipid deposited

24. Ischaemic Heart Disease
Epidemic

Causes 80% of cardiac mortality
 Peaked in US in 1960s, 40% decline
since
 Different patterns in some Western
countries
 Cause of decline: Changing
lifestyle (diet, smoking, exercise)
 Better therapy (CCU, thrombolysis,
arrhythmia therapy, CABG,
angioplasty)

25. Atherosclerotic Coronary Artery
Disease:
Clinical Syndromes
 Silent Infarct
 Angina Pectoris
 Myocardial Infarct
 Chronic Ischaemic Heart Disease
 Sudden Death

26. Aneurysms
 Localised abnormal dilation of vessel.
 Types: Saccular, fusiform, cylindroid, dissection.
 Complications: Pressure, thrombus, rupture.
 Etiology: Atherosclerosis, cystic medial necrosis,
syphilis, trauma (arteriovenous aneurysm), PAN,
infections, (mycotic), congenital (berry).

27. Atherosclerotic Aneurysm
 Males of 50+, frequently (50%) hypertensive
 Abdominal aorta (between renal artery and aortic
biforcation). (Thoracic aorta, renal, mesenteric
arteries)
 Complications;
 Rupture (if >6 cm, 50% rupture in 10 years)
 surgical mortality 50% (unruptured 5%)
 Compression - ureter, vertebrae
 Occlusion (thrombus, pressure)
 Embolism
 Abdominal mass

28. Atherosclerosis
Peripheral vascular disease
 Pain (claudication)
 Ischaemic changes
 Gangrene
 General atheroma
risk factors
 But 100 times more
frequent in diabetes

29. Atherosclerosis
Mesenteric ischaemia
 Coeliac, superior
mesenteric artery)
 Aymptomatic
 Intestinal angina
(pain after food)
 Intestinal ischaemia
 Bloody diarrhoea
 Infarction/gangrene
 obstruction

30. Athersclerosis
Cerebrovascular disease
 Thrombosis (embolism,
haemorrhage are other
import factors in stroke)
 Sites of thrombotic
occlusion:carotid
bifurcation, middle
cerebral and basilar
arteries)
 Transient ischaemic
attack (TIA),
cerebrovascular
accident (CVA),
(stroke)

31. In Brief