Transcript Pathology of Cardiovascular System

Pathology of Cardiovascular
System
Dr. S.L. Beh
[email protected]
Overview
• Review of basics
• Ischaemic heart diseases
– Coronary artery occlusions
– Myocardial infarction
• Valvular heart diseases
– Degenerative valvular diseases
– Rheumatic heart disease
– Bacterial endocarditis
• Shock
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Hypovoleamic shock
Cardiogenic shock
Septiceamic shock
Anaphylactic shock
Review
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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 LutjenDrecoll
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
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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
• Loss of contractility
• ATP reduced
– to 50% of normal
– To 10% of normal
• Irreversible injury
• Microvascular injury
• Seconds
• < 2 minutes
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10 minutes
40 minutes
20-40 minutes
> 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
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Electrocardiogram – Q waves
Echocardiogram
Radioisotope studies
Magnetic Resonance Imaging
Electrocardiogram (ECG) changes
Acute effects of myocardial
infarction
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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
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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
volume and pressure
Systemic
embolisation
Atrial thrombus
Right Heart
Failure
Atrial
dilatation
Congestion
of lungs
Pulmonary
Hypertension
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
– 50’s and 60’s in congenital bicuspid individuals
– 70’s and 80’s 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 Marfan’s 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 (ß-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,
ruptures of aneurysms, etc
(Hypovoleamic)
Hypoalbumineamia,
Ascites, Renal failure,
Toxins , infection and immunecomplexes (DIC, Anaphylaxis,
Septiceamic)
Septiceamic,
Anaphylaxis
(Hypovoleamic)
(Capillary pooling)