Download AV Septal Defects

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
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Overview
 Atherosclerosis
 Aneurysms
 Ischemic
heart disease
 Cardiomyopathies
 Valvular heart disease
 Hypertension
Figure 4-4
Leading causes of death, number and percentage of
deaths, Canada, 1999
Respiratory (22,026)
10%
Other IHD (21,693)
10%
AMI (20,926)
9.5%
Other (33,240)
15%
Diabetes (6,137)
3%
Infectious Diseases
(2,583)
1%
All
Cardiovascular
Cerebrovascular
Disease
Disease (15,409)
(78,942)
7%
36%
Other CVD (20,914)
9.5%
Cancer (62,606)
29%
Accidents/
Poisoning/ Violence
(13,996)
6%
Total Number of Deaths: 219,530
Cardiovascular (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)
Source:
Health Canada, using data from Mortality File, Statistics Canada
The Growing Burden of Heart Disease and Stroke in Canada 2003
CVS Anatomy 101
Endothelium
muscular artery
intima
media
adventitia
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
Age
Male
gender
Family history/
genetics
Hyperlipidemia
– high LDL
– low HDL
Hypertension
Smoking
Diabetes
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
blood
lumen
thrombus
tear
vessel
wall
AAA rupture
Hemorrhage into
surrounding tissue
Dissecting “aneurysm”
Coronary artery aneurysms secondary to
vasculitis (inflammation of blood vessels)
SVC
Left lung
Aorta
Left atrium
Pericardium
Right lung
Right
atrium
Left
ventricle
Right
ventricle
Left atrium
Right
atrium
Left
ventricle
Right
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
“Sick” myocytes
bordering the infarct
Phagocytosis of dead
cells at margin of infarct
Residual necrotic
myocytes
Remote myocardial infarcts
Transmural
rupture
Infarct rupture and tamponade
Papillary muscle rupture
Left ventricle
aneurysm
Ischemic heart disease interventions
Non-surgical
Surgical
thrombolysis
 PTCA / stenting
 atherectomy
 rotablation


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 nonspecific but may be diagnostic
 Most require clinicopathological correlation
 Many mimics and secondary diseases
 Molecular diagnosis / genetics developing