Cardiovascular Pathology (modification of Dr. Veinot’s presentation)

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Cardiovascular Pathology (modification of Dr.
Veinots presentation)

• Michel Dionne MD FRCPC
• for
• John P. Veinot MD FRCPC
• Professor of Pathology
• University of Ottawa
• Pathology and Laboratory Medicine
• Ottawa Hospital

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Overview

• Atherosclerosis
• Aneurysms
• Ischemic heart disease
• Cardiomyopathies
• Valvular heart disease
• Hypertension

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CVS Anatomy 101
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Endothelium
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muscular artery
intima
media
adventitia
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Aorta
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Media of aorta an elastic artery
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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

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Atherosclerosis - risk factors

• Hyperlipidemia
• high LDL
• low HDL
• Hypertension
• Smoking
• Diabetes

• Age
• Male gender
• Family history/ genetics

Other physical inactivity, diet, obesity etc.
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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.

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From Robbins and Cotran Pathologic Basis of
Disease, 8th Edition
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Aorta fatty streaks
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Aorta fibrofatty/atheromatous plaques
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Aorta complicated plaques
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Aortic arch vessels advanced plaques causing
severe stenosis
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Coronary artery
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Atheromatous material foam cells (lipid laden
macrophages) and cholesterol clefts
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From Robbins and Cotran Pathologic Basis of
Disease, 8th Edition
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Atherosclerosis - complications

• Calcification
• Plaque hemorrhage and rupture
• Plaque erosion/ulceration
• Thrombosis
• Embolization of atheromatous material
  (atheroemboli)
• Aneurysm formation and rupture

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Renal infarct from embolization
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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

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Aneurysm - definition

• a localized abnormal dilatation of a vessel

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Aneurysm types
Atherosclerotic aneurysms are the most common,
but there are other types!
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Aneurysms - complications

• Stasis of blood
• Thrombosis
• obstruction
• embolism
• Mass effect
• Rupture

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Abdominal Aortic Aneurysm (AAA)
thrombus
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Aneurysm rupture
blood
lumen
tear
thrombus
vessel wall
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AAA rupture
Hemorrhage into surrounding tissue
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Dissecting aneurysm
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Coronary artery aneurysms secondary to vasculitis
(inflammation of blood vessels)
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Left lung
SVC
Aorta
Left atrium
Pericardium
Right atrium
Right lung
Left ventricle
Right ventricle
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Left atrium
Right atrium
Left ventricle
Right ventricle
Interventricular septum
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Coronary artery anatomy
http//www.drchander.com/diagnoseCAD.html
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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)

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Myocardial infarct terminology
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Recent MI - about 24 hours old
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Contraction band necrosis
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Recent MI - about 3 days old
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Recent MI - interstitial infiltrate of neutrophils
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Recent MI - 5-7 days old
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Recent MI - 7-10 days old
Residual necrotic myocytes
Phagocytosis of dead cells at margin of infarct
Sick myocytes bordering the infarct
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Remote myocardial infarcts
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Transmural rupture
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Infarct rupture and tamponade
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Papillary muscle rupture
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Left ventricle aneurysm
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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

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Atherectomy device
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PTCA balloon
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Angiogram pre/post PTCA
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Aortic valve - normal
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Mitral valve - normal
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Aortic stenosis - causes
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Aortic stenosis causing LVH
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Mitral stenosis - rheumatic
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Floppy mitral valve - mitral valve prolapse (MVP)
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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

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Reno-vascular hypertension
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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

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Arteriolo-nephrosclerosis
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Brain hypertensive bleed
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Hypertensive brain stem bleed
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LVH (look familiar?)
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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 1131807-1816

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Cardiomyopathy types(clinical/functional/morphol
ogic patterns)

• Dilated (DCM) 90
• Hypertrophic (HCM)
• Restrictive

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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

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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

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Primary dilated cardiomyopathy

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

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Non-specific myocardial degenerative changes
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DCM - clinical presentation

• Progressive heart failure
• systolic dysfunction
• 4 chamber dilatation
• hypokinesis
• Arrhythmias
• Thromboembolism
• Sudden death

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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

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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

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Viral myocarditis and DCM

• Enteroviral protease cleaves dystrophin
• Disrupted dystrophin / sarcoglycan complex
• Similar to primary genetic defects found in DCM

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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)

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Hypertrophic cardiomyopathy
Disproportionate thickening of the
interventricular septum
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Myocyte disarray and hypertrophy and interstitial
fibrosis
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HCM - diastolic dysfunction

• ventricular hypertrophy
• myocyte disarray
• interstitial fibrosis
• myocardial microinfarcts

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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