1. Cardiovascular Pathology (modification of Dr. Veinot’s presentation)
Michel Dionne MD FRCPC
for
John P. Veinot MD FRCPC
Professor of Pathology
University of Ottawa
Pathology and Laboratory Medicine
Ottawa Hospital

2. You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation online or distribute it without the permission of the author.

3. Overview Atherosclerosis Aneurysms Ischemic heart disease
Cardiomyopathies
Valvular heart disease
Hypertension

5. CVS Anatomy 101

6. Endothelium

7. muscular artery
intima
media
adventitia

8. Aorta

9. Media of aorta – an elastic artery

10. 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

11. Atherosclerosis - risk factors
Hyperlipidemia
high LDL
low HDL
Hypertension
Smoking
Diabetes
Age
Male gender
Family history/ genetics
Other: physical inactivity, diet, obesity etc.

12. Atherosclerosis - pathogenesis
Chronic endothelial injury* resulting in endothelial 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 etc.

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

14. Aorta – fatty streaks

16. Aorta – fibrofatty/atheromatous plaques

17. Aorta – complicated plaques

18. advanced plaques causing severe stenosis
Aortic arch vessels –
advanced plaques causing severe stenosis

19. Coronary artery

20. Atheromatous material – foam cells (lipid laden macrophages) and cholesterol clefts

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

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

23. Renal infarct from embolization

24. 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

25. a localized abnormal dilatation of a vessel
Aneurysm - definition
a localized abnormal dilatation of a vessel

26. Aneurysm types
Atherosclerotic aneurysms are the most common, but there are other types!

27. Aneurysms - complications
Stasis of blood
Thrombosis
obstruction
embolism
Mass effect
Rupture

28. Abdominal Aortic Aneurysm (AAA)
thrombus

29. Aneurysm rupture
blood
lumen
tear
thrombus
vessel wall

30. AAA rupture
Hemorrhage into surrounding tissue

31. Dissecting “aneurysm”

32. Coronary artery aneurysms secondary to vasculitis (inflammation of blood vessels)

33. Left lung
SVC
Aorta
Left atrium
Pericardium
Right lung
Right atrium
Left ventricle
Right ventricle

34. Left atrium
Right atrium
Left ventricle
Right ventricle
Interventricular septum

35. Coronary artery anatomy

36. Coronary artery atherosclerosis
affects the epicardial arteries; tends to be more pronounced in the proximal portion of these vessels
can involve 1, 2 or all 3 of the main vessels +/- their large branches
if degree of obstruction is significant, can result in angina (pain from myocardial ischemia)
an atherosclerotic plaque can become unstable (acute plaque lesion):
intraplaque hemorrhage
plaque rupture or erosion resulting in thrombosis
acute plaque lesions can result in an “acute coronary syndrome” (unstable angina, myocardial infarct)

39. Myocardial infarct terminology

44. Recent MI - about 24 hours old

45. Contraction band necrosis

46. Recent MI - about 3 days old

47. Recent MI - interstitial infiltrate of neutrophils

48. Recent MI days old

49. Recent MI - 7-10 days old “Sick” myocytes bordering the infarct
Phagocytosis of dead cells at margin of infarct
Residual necrotic myocytes

50. Remote myocardial infarcts

52. Transmural rupture

53. Infarct rupture and tamponade

54. Papillary muscle rupture

55. Left ventricle aneurysm

56. Ischemic heart disease - interventions
Non-surgical
thrombolysis
PTCA / stenting
atherectomy
rotablation
Surgical
Coronary Artery Bypass Grafting (CABG) – typically using saphenous vein grafts and/or internal thoracic arteries
endarterectomy

57. Atherectomy device

58. PTCA balloon

60. Angiogram pre/post PTCA

64. Aortic valve - normal

65. Mitral valve - normal

66. Aortic stenosis - causes

67. Aortic stenosis causing LVH

68. Mitral stenosis - rheumatic

69. Floppy mitral valve - mitral valve prolapse (MVP)

70. Hypertension PRIMARY (ESSENTIAL) SECONDARY
Genetic and environmental factors
Defects in sodium homeostasis, vascular smooth muscle structure, regulation of vascular tone
SECONDARY
renal disease
vascular disease
endocrinopathies
drugs
neurogenic etc…

71. Reno-vascular hypertension

72. Hypertension - complications
enhance other diseases (risk factor)
small vessel changes
scarring/sclerosis
microaneurysms
large vessel changes
ectasia / aneurysms / aortic regurgitation
dissection
vessel rupture
cardiac hypertrophy
etc…

73. Arteriolo-nephrosclerosis

74. Brain hypertensive bleed

75. Hypertensive brain stem bleed

76. LVH (look familiar?)

77. Cardiomyopathy - definition
Heterogenous group of diseases of the myocardium associated with mechanical or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic.
Cardiomyopathies are either confined to the heart or are part of generalized systemic disorders often leading to cardiovascular death or progressive heart failure related disability.
Circulation :

78. Cardiomyopathy types (clinical/functional/morphologic patterns)
Dilated (DCM) – 90%
Hypertrophic (HCM)
Restrictive

79. Primary cardiomyopathy (confined to the heart) - etiology
Genetic
e.g. HCM, ARVC, mitochondrial defects, channelopathies (e.g. LQTS)
Acquired
e.g. due to myocarditis (inflammation of the myocardium)
Mixed
Idiopathic

80. Secondary cardiomyopathy (part of generalized systemic disorder) – examples of etiologies
Amyloidosis
Hemochromatosis
Sarcoidosis
Medication/Toxin induced - e.g. cancer chemotherapy, alcoholism
Autoimmune diseases - e.g. SLE, rheumatoid arthritis
Infections
Endocrine disorders - e.g. hypothyroidism
Neuromuscular diseases - e.g. muscular dystrophies
Storage diseases - e.g. glycogen storage disease
Nutritional deficiencies - e.g. thiamine

81. Primary dilated cardiomyopathy
Primary myocardial abnormality
NO SIGNIFICANT:
coronary artery disease
valve disease
systemic arterial hypertension
systemic disorder, history of toxin exposure etc.

86. Non-specific myocardial degenerative changes

87. DCM - clinical presentation
Progressive heart failure
systolic dysfunction
4 chamber dilatation
hypokinesis
Arrhythmias
Thromboembolism
Sudden death

88. Familial (genetic) DCM
About 30 % of DCM
Often asymptomatic LV dilatation at detection - minority progress
Examples:
muscular dystrophy
mitochondrial defects - maternal inheritance
inherited metabolic disorders

89. Cardiomyopathy – genetic abnormalities
Dilated - cytoskeletal elements largely affected
dystrophin - X-linked, some muscular dystrophies
lamin
desmin
actin
etc…
mitochondrial genes
Hypertrophic - contractile elements affected (sarcomeric genes)
myosin
troponin
tropomyosin
myosin binding protein C
etc…

91. Viral myocarditis and DCM
Enteroviral protease cleaves dystrophin
Disrupted dystrophin / sarcoglycan complex
Similar to primary genetic defects found in DCM

93. Hypertrophic cardiomyopathy
a genetic disease; autosomal dominant, variable penetrance
phenotype variations even with same mutation - ? environmental influences
myocardial hypertrophy (thickened myocardium)
diastolic dysfunction
sub-aortic obstruction
sudden death (60% of deaths are sudden)

94. Hypertrophic cardiomyopathy
Disproportionate thickening of the interventricular septum

95. Myocyte disarray and hypertrophy and interstitial fibrosis

96. HCM - diastolic dysfunction
ventricular hypertrophy
myocyte disarray
interstitial fibrosis
myocardial microinfarcts

99. Cardiomyopathy - summary
Gross and histopathologic findings are non- specific but may be diagnostic
Most require clinicopathological correlation
Many mimics and secondary diseases
Molecular diagnosis / genetics developing