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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. - PowerPoint PPT Presentation
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Cardiovascular Pathology (modification of Dr. Veinot’s presentation)
Michel Dionne MD FRCPCfor
John P. Veinot MD FRCPCProfessor of PathologyUniversity of Ottawa
Pathology and Laboratory MedicineOttawa Hospital
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.
Overview
Atherosclerosis Aneurysms Ischemic heart disease Cardiomyopathies Valvular heart disease Hypertension
The Growing Burden of Heart Disease and Stroke in Canada 2003
Cerebrovascular Disease (15,409)
7%
Accidents/ Poisoning/ Violence
(13,996)6%
Infectious Diseases (2,583)
1%
Diabetes (6,137)3%
Other (33,240)15%
Respiratory (22,026)10%
AMI (20,926)9.5%
Cancer (62,606)29%
Other CVD (20,914)9.5%
Other IHD (21,693)10%
Figure 4-4 Leading causes of death, number and percentage of deaths, Canada, 1999
All Cardiovascular
Disease (78,942)
36%
Source: Health Canada, using data from Mortality File, Statistics Canada
Total Number of Deaths: 219,530Cardiovascular (ICD-9 390-459); Respiratory (ICD-9 460-519); Diabetes (ICD-9 250); Cancer (ICD-9 140-239); Infectious Diseases (ICD-9 001-139); Accidents/Poisonings/Violence (ICD-9 E800-E999)
CVS Anatomy 101
Endothelium
adventitia
intima
media
muscular artery
Aorta
Media of aorta – an elastic artery
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
Atherosclerosis - risk factors
Hyperlipidemia– high LDL
– low HDL Hypertension Smoking Diabetes
Age Male gender Family history/
genetics
Other: physical inactivity, diet, obesity etc.
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.
From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition
Aorta – fatty streaks
Aorta – fibrofatty/atheromatous plaques
Aorta – complicated plaques
Aortic arch vessels –advanced plaques causing severe stenosis
Coronary artery
Atheromatous material – foam cells (lipid laden macrophages) and cholesterol clefts
From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition
Atherosclerosis - complications
Calcification Plaque hemorrhage and rupture Plaque erosion/ulceration Thrombosis Embolization of atheromatous
material (atheroemboli) Aneurysm formation and rupture
Renal infarct from embolization
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
Aneurysm - definition
a localized abnormal dilatation of a vessel
Aneurysm types
Atherosclerotic aneurysms are the most common, but there are other types!
Aneurysms - complications
Stasis of blood Thrombosis
obstruction embolism
Mass effect Rupture
Abdominal Aortic Aneurysm (AAA)
thrombus
Aneurysm rupture
thrombus tear
vessel wall
blood
lumen
AAA rupture
Hemorrhage into surrounding tissue
Dissecting “aneurysm”
Coronary artery aneurysms secondary to vasculitis (inflammation of blood vessels)
Left atrium
Right ventricle
Left ventricle
Right atrium
Pericardium
Right lung
Left lungAortaSVC
Right atrium
Left atrium
Right ventricle
Left ventricle
Interventricular septum
Coronary artery anatomy
http://www.drchander.com/diagnoseCAD.html
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)
Myocardial infarct terminology
Recent MI - about 24 hours old
Contraction band necrosis
Recent MI - about 3 days old
Recent MI - interstitial infiltrate of neutrophils
Recent MI - 5-7 days old
Recent MI - 7-10 days old
Residual necrotic myocytes
Phagocytosis of dead cells at margin of infarct
“Sick” myocytes bordering the infarct
Remote myocardial infarcts
Transmural rupture
Infarct rupture and tamponade
Papillary muscle rupture
Left ventricle aneurysm
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
Atherectomy device
PTCA balloon
Angiogram pre/post PTCA
Aortic valve - normal
Mitral valve - normal
Aortic stenosis - causes
Aortic stenosis causing LVH
Mitral stenosis - rheumatic
Floppy mitral valve - mitral valve prolapse (MVP)
Hypertension
PRIMARY (ESSENTIAL)– 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…
Reno-vascular hypertension
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…
Arteriolo-nephrosclerosis
Brain hypertensive bleed
Hypertensive brain stem bleed
LVH (look familiar?)
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 2006 113:1807-1816
Cardiomyopathy types(clinical/functional/morphologic patterns)
Dilated (DCM) – 90% Hypertrophic (HCM) Restrictive
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
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
Primary dilated cardiomyopathy
Primary myocardial abnormality NO SIGNIFICANT:
– coronary artery disease– valve disease– systemic arterial hypertension– systemic disorder, history of toxin exposure
etc.
Non-specific myocardial degenerative changes
DCM - clinical presentation
Progressive heart failure– systolic dysfunction– 4 chamber dilatation– hypokinesis
Arrhythmias Thromboembolism Sudden death
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
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…
Viral myocarditis and DCM
Enteroviral protease cleaves dystrophin Disrupted dystrophin / sarcoglycan
complex Similar to primary genetic defects found in
DCM
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)
Hypertrophic cardiomyopathy
Disproportionate thickening of the interventricular septum
Myocyte disarray and hypertrophy and interstitial fibrosis
HCM - diastolic dysfunction
ventricular hypertrophy myocyte disarray interstitial fibrosis myocardial microinfarcts
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