1. Pathology of Atherosclerosis
John P. Veinot MD, FRCPC
Professor of Pathology and Laboratory Medicine
University of Ottawa
Ottawa Hospital
CHEO
EORLA

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3. Objectives State the prevalence and complications of atherosclerosis.
List and describe the risk factors for the formation of atherosclerosis.
Describe the pathogenesis of atherosclerosis.
List the consequences of atherosclerosis and the organs affected.
Describe the treatment and prevention of atherosclerosis

4. Veinot Cardiac teaching page
Veinot Cardiac teaching page

5. (medium sized muscular artery)
Layers of the blood vessel wall
adventitia
Coronary artery
(medium sized muscular artery)
intima
media

6. Atherosclerosis
Disease of large and medium sized arteries (elastic and muscular), particularly:
aorta, iliac, coronary, popliteal, carotid, circle of Willis
Develop intimal lesions called atheromas or atheromatous plaques which:
protrude into the lumen resulting in stenosis (narrowing of lumen) and possibly occlusion (lumen blocked)
can weaken the underlying media, possibly leading to aneurysm formation

7. Leading causes of death, by sex 2009
Rank
Number %
Total, all causes of death
238,418
100
Malignant neoplasms (cancer) 1
71,125
29.8
Diseases of heart (heart disease) 2
49,271
20.7
Cerebrovascular diseases (stroke) 3
14,105
5.9
Chronic lower respiratory diseases 4
10,859
4.6
Accidents (unintentional injuries) 5
10,250
4.3
Diabetes mellitus (diabetes) 6
6,923
2.9
Alzheimer's disease 7
6,281
2.6
Influenza and pneumonia 8
5,826
2.4
Intentional self-harm (suicide) 9
3,890
1.6
Nephritis, nephrotic syndrome and nephrosis (kidney disease) 10
3,609
1.5
Notes: Causes of death are coded to the 10th revision of the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10).
Sources: Statistics Canada, CANSIM table and Catalogue no X.
Last modified:

9. Atherosclerosis - Risk Factors
Age
Male gender
Family history/ genetics
Hyperlipidemia
high LDL
low HDL
Hypertension
Smoking
Diabetes
Other: physical inactivity, diet, obesity, homocysteine, Lp(a) (altered form of LDL) etc.

10. Coronary Artery Disease - gender

11. Liver

13. Atherosclerosis - Pathogenesis
Chronic endothelial injury* resulting in dysfunction
increased permeability
increased adhesion of leukocytes (monocytes and lymphocytes) and platelets
accumulation of lipids in intima
Migration of monocytes into intima leading to formation of foam cells (lipid-laden macrophages)
Release of cytokines and growth factors result in smooth muscle cell migration into intima, proliferation of smooth muscle cells, deposition of extracellular matrix (e.g. collagen)
* From hemodynamic forces, hyperlipidemia, HTN, smoking, homocysteine etc.

14. From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition

15. From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition

16. Injured Endothelial Cell
Healthy
anti-thrombotic
barrier
NO - vasodilator
LDL uptake
factors - mitogens
Injured
pro-coagulant
permeable
poor dilation
factors released - chemotaxis

17. Smooth Muscle Cell Types
Contractile
myofibrils
responsive to vasoactive mediators
Synthetic
RER and Golgi
LDL receptors
migration - cytokines
secretes connective tissue matrix

18. Atherosclerosis - Macrophage
LDL receptor - oxidizes lipid
Free radicals - further injury
Growth factors - chemotaxis acts on smooth muscle

19. Atherosclerosis - Pathology

20. Aorta – fatty streaks

21. Foam cells

23. Aorta – fibrofatty/atheromatous plaques

25. Aorta – complicated plaques

27. Coronary artery

28. Atherosclerosis - Complications
Calcification
Plaque hemorrhage and rupture
Plaque erosion/ulceration
Thrombosis
Embolization of atheromatous material (atheroemboli)
Aneurysm formation and rupture

31. Atherosclerosis effects
Degree of stenosis / narrowing
time of stenosis development
collaterals
demand of organ

32. Atherosclerosis- Major Consequences
Symptomatic disease most often affects the heart, brain, kidneys and lower extremities
Heart: angina and myocardial infarction
Brain: cerebral infarction (stroke)
Aorta (particularly abdominal):
Aneurysms
Stenosis of ostia of major branches leading to visceral ischemia
Lower extremities: peripheral vascular (arterial) disease – claudication, gangrene

34. Myocardial infarcts

36. AAA RUPTURE

39. Renal infarcts from embolization

40. Splenic infarcts

41. Ischemic Heart Disease - Interventions
Non-surgical
Thrombolysis
PTCA / stenting
Atherectomy
Rotablation
Stem cells
Surgical
Coronary Artery Bypass Grafting (CABG) – typically using saphenous vein grafts and/or internal thoracic arteries
Endarterectomy
Stem cells

42. Peripheral Arterial Disease – Interventions
Endarterectomy surgery (e.g. carotid endarterectomy)
Aneurysm repair using synthetic graft (e.g. AAA repair)
Bypass using synthetic graft (e.g. femoral-popliteal bypass)
Stents/ atherectomy/ stem cells

45. PTCA angioplasty balloon

46. Angiogram pre/post PTCA

49. Recommended textbooks
Robbins and Cotran - Pathologic Basis of Disease, 9th edition. Kumar, Abbas, & Aster.  Philadelphia: Elsevier, 2015 
Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 7th edition / David Strayer, Emanuel Rubin,Jeffery Saffitz and Alan Schiller (eds).  Philadelphia:  Wolters Kluwer, 2015