Pathology of Cardiovascular

System

Dr. S.L. Beh

philipbeh@pathology.hku.hk
 Overview
Review of basics
Ischaemic heart diseases
Coronary artery occlusions
Myocardial infarction
Valvular heart diseases
Degenerative valvular diseases
Rheumatic heart disease
Bacterial endocarditis
Shock
Hypovoleamic shock
Cardiogenic shock
Septiceamic shock
Anaphylactic shock
 Review
Atherosclerosis
Epidemiology of coronary artery disease
Physiology of the cardiac cycle
Anatomy of the myocardium
Vascular supply of the myocardium
Taken from Colour Atlas of Anatomy Roden, Yokochi and Lutjen-Drecoll
Taken from Colour Atl
of Anatomy Roden,
Yokochi and Lutjen-
Drecoll
Taken from Colour Atlas of
Anatomy Roden, Yokochi and
Lutjen-Drecoll
Taken from Colour Atlas of Anatomy Roden, Yokochi and Lutjen-Drecoll
Taken from Colour Atlas of Anatomy Roden, Yokochi and Lutjen-Drecoll
 Anatomy of the myocardium
Cardiac muscle cells form a collection of
branching and anastamosing striated muscles.
They make up 90% of the volume of the
myocardium.
Unlike skeletal muscles, they contain ten times
more mitochondria per muscle cell. This reflects
their extreme dependence on aerobic metabolism.
They do not need to rest!!
 Vascular supply of the
myocardium
Predominant blood supply is from the coronary
arteries, which arises from the aorta and runs
along an epicardial route before penetrating the
myocardium as intramural arteries. Effectively a
one-way street flow and supply.
Coronary arterial blood flow to the myocardium
occurs during ventricular diastole; when the
microcirculation in the myocardium is not
compressed by cardiac contraction. The one^way
street only flows within a fixed time span.
Coronary Angiography

L = Left main trunk

A= Anterior descending
C= Circumflex
R= Right coronary
P=Posterior descending
 Areas of supply (perfusion)
The left coronary trunk gives rise to:-
Left Anterior Descending (LAD) and the Left
Circumflex (LCX)
Right Coronary Artery (RCA)
 Areas of perfusion
Left anterior descending (LAD) supplies most of
the apex of the heart, the anterior wall of the left
ventricle and the anterior two-thirds of the
ventricular septum.
Left circumflex branch supplies the lateral wall of
the left ventricle.
The right coronary artery in 80% of the population
supplies the right ventricle, the posterior third of
the ventricular septum and the posterior-basal wall
of the left ventricle. (Right dominant circulation)
 Ischaemic Heart Diseases
This is a generic name for a group of
closely related syndromes that result from
myocardial ischaemia.
In over 90%, this is due to a reduction in
coronary blood flow. (Decrease in supply)
Other conditions arise as a result of
increases in demand e.g. hypertrophy,
shock, increase heart rate, etc.
 Diminished Coronary Perfusion
Fixed coronary obstruction
More than 90% of patients with IHD
One or more lesions that causes at least 75%
reduction of the cross-sectional area of at least
one of the major epicardial arteries.
Coronary atherosclerosis
Coronary atherosclerosis
Coronary atherosclerosis
Coronary atherosclerosis
Taken from Robbins Pathologic Basis of Disease
 Clinical Manifestations
Angina Pectoris
Myocardial Infarction
Chronic ischaemic heart disease
Progressive heart failure consequent to previous
myocardial infarction.
Sudden Cardiac Death
 Angina Pectoris
This is a symptom complex. Symptoms
caused by transient myocardial ischaemia
that falls short of inducing the cellular
necrosis that defines myocardial infarction.
Three variants:-
Stable angina
Prinzmental angina
Unstable angina
 Angina Pectoris
Stable Angina Most common form.
Chronic stenosing coronary atherosclerosis,
reaching a critical level, leaving the heart
vulnerable to increased demand.
Typically relieved by rest or a vasodilator
 Prinzmental Angina
Uncommon pattern
Occurs at rest
Documented to be due to arterial spasm
Unrelated to physical activity, heart rate or
blood pressure.
Generally responds to vasodilators.
 Unstable Angina
Pattern here is the pain occurs with
progressively increasing frequency and
tends to be more prolonged
Associated with disruption of the
atherosclerotic plaque, with superimposed
thrombosis, embolisation or spasm.
Predictor of Myocardial Infarction
Effects of ischaemia on myocytes
Onset of ATP Depletion Seconds
Loss of contractility < 2 minutes
ATP reduced
to 50% of normal 10 minutes
To 10% of normal 40 minutes
Irreversible injury 20-40 minutes
Microvascular injury > 1 hour
 Myocardial Infarction
Transmural Infarction
The ischaemic necrosis involves the full or
nearly the full thickness of the ventricular wall
in the distribution of a single coronary artery.
Usually associated with chronic coronary
atherosclerosis, acute plaque change and
superimposed completely obstructive
thrombosis.
 Myocardial Infarction
Subendocardial infarct
Limited to the inner one-third or at most one
half of the ventricular wall
May extend laterally beyond the perfusion
territory of a single coronary artery
In a majority of cases, there is diffuse stenosing
coronary atherosclerosis.
 Gross changes of myocardial
infarction
Gross changes
None to occasional mottling (up to 12 hours)
Dark mottling (12-24 hours)
Central yellow tan with hypereamic border (3-7
days)
Gray white scar (2-8 weeks)
Varying gross appearance
of myocardial infarction
Recent and Old Myocardial Infarcts
 Microscopic changes of
myocardial infarct
Early coagulation necrosis and oedema;
haemorrhage (4-12 hours)
Pyknosis of nucleic, hypereosinophilia,
early neutrophilic infiltrate (12-24 hours)
Coagulation necrosis, interstitial infiltrate of
neutrophils (1-3 days)
Dense collagenous scar (> 2 months)
Hypereosinophilia
Coagulative necrosis
Interstitial infiltration of neutrophils
 Laboratory detection of
myocardial infarction
This is based on the measurement of
intracellular macromolecules leaked from
the damaged myocytes into the circulation
Creatine kinase particularly the MB
isoenzyme
Lactate dehydrogenase
Troponin Troponin 1 and Troponin T
 Other diagnostic tools
Electrocardiogram Q waves
Echocardiogram
Radioisotope studies
Magnetic Resonance Imaging
Electrocardiogram (ECG) changes
 Acute effects of myocardial
infarction
Contractile dysfunction
Arrhythmias
Cardiac rupture
Pericarditis
Sudden death
Invariably this would be due to a lethal
arrhythmia (asystole or ventricular fibrillation)
 Pathological complications of
myocardial infarction
Infarct extension
Mural thrombus
Ventricular aneurysm
Myocardial rupture
Ventricular free wall
Septal
Papillary muscle
 Infarct extension

Diagram from Robbins Pathologic Basis of Disease

Ruptured
Myocardial
Infarct
Ruptured Papillary muscle
Old myocardial infarct showing evidence of
thinning of ventricular wall replaced by fibrous scar
Fibrous scarring with compensatory hypertrophy of
unaffected ventricular wall
Ventricular wall
aneurysm
 Anatomy of Heart Valves
Aortic valve Commonly tricuspid semi lunar
valves. Can be congenitally bicuspid.
Mitral valve Bi-cuspid flaps supported by
chordae tendinae attached to papillary muscles
Pulmonary valves Tricuspid semi lunar valves
Tricuspid valves Tri-cuspid flaps supported by
chordae tendinae.
Aortic Valves
Mitral Valves
Pulmonary
Valves
Tricuspid Valves
Taken from Colour Atlas of Anatomy Roden, Yokochi and Lutjen-Drecoll
 Response to injury
Mechanical injury superficial fibrous
thickening over preserved architecture.
Inflammation invariably leads to
vascularisation of structure, fibrosis leads to
decrease in size/surface area.
Degenerative changes distortion and
increase in size due to deposits of material
such as calcium salts, cholesterol, etc.
 Effects of valvular disease
Stenosis tightening of the valvular
opening resulting in decreased flow of
blood through the opening.
Incompetence incomplete closure of the
valvular opening, allowing backflow of
blood through the valvular opening
Mixed.
 Effects of valvular disease

Mitral Stenosis

Increased atrial Atrial

volume and pressure dilatation

Systemic
embolisation Congestion
Atrial thrombus
of lungs

Pulmonary
Right Heart Hypertension
Failure
 Common valvular diseases
Degenerative
Calcific aortic stenosis
Mitral annular calcification
Myxomatous degeneration of mitral valves
(mitral valve prolapse)
Rheumatic fever and rheumatic heart
disease
 Calcific Aortic Stenosis
Most frequent of all valvular abnormalities
Calcification induced by wear and tear
Onset in the elderly
50s and 60s in congenital bicuspid individuals
70s and 80s in those with previous normal
valves
Heaped up calcified masses
Aortic Valve Inlet
Looking into
the left
ventricular outlet
Note the three
valvular cusps
and the three
distinct
commissures
(arrows)
Calcific Aortic Stenosis (3 cusps)
Calcific Bicuspid Aortic Valve
 Mitral Annular calcification
Degenerative calcific deposits in the ring of
the mitral valve.
Generally does not affect valvular function,
but can lead to mitral regurgitation
Source of thrombi and emboli, also prone to
infective endocarditis
Most common in women over 60
 Calcification of Mitral Valve Ring

Diagram from Robbins Pathologic Basis of Disease

 Mitral Valve Prolapse
Myxomatous degeneration of valve.
Characteristically ballooning of the valvular cusps
with the affected leaflets thickened and rubbery.
Basis for the change unknown but believed to be
due to developmental anomaly of connective
tissue.
Association with Marfans syndrome (a syndrome
whereby there is a mutation in the gene encoding
fibrillin)
Mitral Valve
Inlet Viewed
from the left
atrium.
Note bicuspid
valve leaflets.
Slight tenting of
the valve
leaflets
suggestive of
early mitral
valve prolapse.
Mitral Valve
Prolapse
Notice
tenting of
valve leaflet
(arrow)
 Rheumatic fever
Once the most common cause of valvular
heart disease in Hong Kong.
It is an acute immunologically mediated ,
multi-system inflammatory disease that
occurs a few weeks after an episode of
Group A (-hemolytic) streptococcal
pharyngitis.
Diagram from Robbins Pathologic Basis of Disease
 Rheumatic Valvulitis

Diagram from Robbins Pathologic Basis of Disease

 Acute Rheumatic Carditis Aschoff Body

Diagram from Robbins Pathologic Basis of Disease

 Chronic Rheumatic Valvular
Heart Disease
Most important consequence of rheumatic
fever
Inflammatory deformity of valves
Almost always involve the mitral valve
Involvement of aortic or other valves also
common
 Characteristics of rheumatic
valvular disease
Acute phase
Foci of fibrinoid degeneration surrounded by
lympocytes Aschoff bodies
Most distinctive within the heart, but widely
disseminated.
Pancarditis
Pericarditis
Myocarditis
Verrucae vegetations (1-2 mm)
 Chronic Rheumatic Disease
of Aortic Valve

Diagram from Robbins Pathologic Basis of Disease

 Characteristics of rheumatic
valvular disease
Chronic
Leaflet thickening
Commissure fusion
Shortening, thickening and fusion of chordae
tendinae
 Chronic Rheumatic Disease of Mitral Valve

Vascularisation)

Diagram from Robbins Pathologic Basis of Disease

 Infective Endocarditis
Colonisation or invasion of heart valves by
microbiologic agent.
Formation of friable vegetations (composed
of thrombotic debris and organisms.
Leads to destruction of underlying cardiac
tissue.
Source of infective embolisation
 Infective endocarditis
Most common sites involve the left heart
valves
Tricuspid valves typically involved in
intravenous drug abusers
Development of infective endocarditis
preventable in patients with valvular
diseases by provision of antibiotic cover for
any surgical or dental procedures.
 Bacteria Endocarditis

Diagram from Robbins Pathologic Basis of Disease

The elements of circulation
An effective pump
(The heart)

An effective return
(No peripheral
pooling)
(Normal blood
vessels)
A clear channel
 The elements of circulation
Blood Pressure/Heart Rate

Effective venous and

lymphatic return
Intact and unblocked
blood vessels
The economics of circulation
 Distribution of blood volume in
the circulatory system

Heart 7%
Arteries 13%
Arterioles and capillaries 7%
Veins 64%
Pulmonary vessels 9%
 Body Fluid Compartments
Plasma 3.0L

Interstitial fluid 11.0L

Intracellular fluid 28.L

Blood volume contains both extracellular fluid (plasma) and

intracellular fluid (fluid in RBC). Average blood volume is
about 8% of body weight, approximately 5L (60% plasma
40% RBC)
 What is shock?
A state of generalised hypoperfusion of all cells
and tissues due to reduction in blood volume or
cardiac output or redistribution of blood resulting
in an inadequate effective circulating volume
A systemic (whole body) event resulting from
failure of the circulatory system
It is at first reversible, but if protracted leads to
irreversible injury and death.
 Causes of shock
Hypovoleamia
Cardiogenic (pump failure)
Anaphylactic (peripheral pooling) (return
failure)
Septic (Septiceamic) Complex reasons
 Hypovoleamic shock
Haemorrhage
External (Chop wounds, Gastro-intestinal
bleeding, etc)
Internal (Hemoperitoneum due to ruptured
aortic aneurysm, ruptured ectopic pregnancy,
etc.
Fluid loss
Dehydration (low intake or excessive loss)
External loss
Internal Bleeding
 Effect of volume loss on
Cardiac Output and Arterial Pressure

Taken from Guyton & Hall Human Physiology and

Mechanisms of Disease
 Stages of hypovoleamic shock
Asymptomatic (< 10%)
Early stage (15-25% loss)
Compensated hypotension
Progressive/Advance Stage
Results when no therapeutic intervention is given for
the early stage, compensatory mechanisms become
harmful. Autoregulation mechanisms breakdown.
Irreversible shock
Irreversible hypoxic injury to vital organs
 Compensated hypotension
Hypotension (low volume or low cardiac output)
Sympathetico-adrenal stimulation (fight or fright)
Release of catecholamines resulting in peripheral
vasoconstriction maintain BP
Activation of renin-angiotensin-aldosterone system and
increased anti-diuretic hormone release
Fluid retention by kidneys, further vasoconstriction
Impaired renal perfusion and perfusion to other organs
with every effort made to maintain perfusion to brain and
heart (auto-regulation)
Taken from Guyton & Hall Human Physiology and Mechanisms of Disease
Splenic Infarct
Infarct of kidney
Replaced by scarred
tissue
Haemorrhagic infarct of lung
 Cardiogenic shock
Failure of myocardial pump.
Intrinsic due to myocardial damage
Extrinsic
Due to external pressure e.g. cardiac tamponade
Due to obstructed flow e.g. thrombosis
 Compensated heart failure
Here the situation is one of a compromised cardiac
pump which has been compensated by an
increase in right atrial pressure ( increased blood
volume caused by retention of fluid ). Thus
cardiac output is maintained.
It may not be noticed as it would have developed
gradually over time. However any strain on the
heart, eg sudden increase in exercise would tip the
balance and lead to a decompensated heart
failure.
 Decompensated heart failure
The pump is so damaged that no amount of
fluid retention can maintain the cardiac
output. This failure also means that the renal
function cannot return to normal, thus fluid
continues to be retained and the person gets
more and more oedematous with eventual
death. In short, failure of the pump to pump
enough blood to the kidneys.
 Anaphylactic shock
Usually due to prior sensitisation
Exposure to specific antigens
Mediated by histamines, complements and
prostaglandins
Vasodilatation of micro-circulation
associated with pooling and fluid
extravasation
 Septic shock
Commonly due to gram-negative endotoxin
producing bacteria. May also accompany
gram-ve bacteria.
Predisposing factors include:-
Debilitating diseases
Complications of instrumentation and treatment
Burns
 Septic shock
Pathogenesis include:-
Inflammatory reaction vasodilatation mediated by
histamines and complements
Disseminated intravascular coagulopathy activation
of clotting factors and platelets together with
consumption of clotting factors
Endothelial damage extensive due to endotoxins
Release of interleukin-1 and TNF-alpha (Tumor
necrosis factor alpha) from macrophages
 Possible mechanisms of septic shock

Taken from Guyton & Hall Human Physiology and Mechanisms of Disease
 Pathological changes
Hypoxic injury to vital organs infarction
Necrosis of tissues
Lysis of cells

The extent of pathological changes is dependent

on the duration of decompensation before death.
In acute deaths, often no significant findings are
found.
 Pathological changes
Brain
Hypoxic and ischaemic damage
Initially found at boundary zones
May also be associated with marked cerebral
oedema.
 Pathological changes
Heart
Focal myocardial necrosis
Subendocardial infarction (vulnerable region of
blood supply)

If there is pre-existing coronary artery diseases,

may also lead to acute transmural myocardial
infarction
 Pathological changes
In cardiogenic shock
Due to previous ischaemic heart diseases the
ventricular chambers may well be dilated and
distended. The walls are often thin and may be
replaced by non-elastic fibrous scars
In intrinsic myocardial diseases leading to
pump failure, the myocardium may be
unusually thickened and rigid.
 Pathological changes
Lungs
Diffuse alveolar damage (adult respiratory
distress syndrome)
Damage to Type 1 pneumocytes and to
endothelial cells oedema as well as hyaline
membrane due to decreased surfactant
production
Haemorrhages, fibrosis, atelectasis and
infection
 Pathological changes
Kidneys
Acute tubular necrosis often associated with
remarkably well preserved glomeruli
 Pathophysiology of
Acute Tubular Necrosis

Taken from Guyton & Hall Human Physiology and Mechanisms of Disease
Acute Tubular
Necrosis,
 Pathological changes
Gastrointestinal tract
Mucosal ischaemia, haemorrhage, necrosis,
gangrene
Liver
Centrilobular necrosis, fatty degeneration
Adrenal glands
Focal necrosis
Diffuse haemorrhagic destruction
 Pump Failure
Cardiogenic Shock

Vessel injury Peripheral Pooling

Physical injuries such as wounds, Hypoalbumineamia,
ruptures of aneurysms, etc Ascites, Renal failure,
(Hypovoleamic)
(Hypovoleamic)
Toxins , infection and immune-
complexes (DIC, Anaphylaxis, Septiceamic,
Septiceamic) Anaphylaxis
(Capillary pooling)