Dr. S.L. Beh philipbeh@pathology.hku.hk

• 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

• 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 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

Taken from Colour Atlas of Anatomy – Roden, Yokochi and Lutjen-Drecoll

• 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!!

• 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

• The left coronary trunk gives rise to:-
– Left Anterior Descending (LAD) and the Left
Circumflex (LCX)
• Right Coronary Artery (RCA)

• 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)

• 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.

• 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

• Angina Pectoris
• Myocardial Infarction
• Chronic ischaemic heart disease
– Progressive heart failure consequent to previous myocardial infarction.
• Sudden Cardiac Death

• 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

• 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

• 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.

• 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

• Onset of ATP Depletion
• Loss of contractility
• ATP reduced
– to 50% of normal
– To 10% of normal
• Irreversible injury
• Microvascular injury
• Seconds
• < 2 minutes
• 10 minutes
• 40 minutes
• 20-40 minutes
• > 1 hour

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.

• 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
– 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

• 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

• 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

• Electrocardiogram – Q waves
• Echocardiogram
• Radioisotope studies
• Magnetic Resonance Imaging

Electrocardiogram (ECG) changes

• Contractile dysfunction
• Arrhythmias
• Cardiac rupture
• Pericarditis
• Sudden death
– Invariably this would be due to a lethal arrhythmia (asystole or ventricular fibrillation)

• 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

• 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

• 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.

• 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
Systemic embolisation
Mitral Stenosis
Increased atrial volume and pressure
Right Heart
Failure
Atrial thrombus
Atrial dilatation
Congestion of lungs
Pulmonary
Hypertension

• Degenerative
– Calcific aortic stenosis
– Mitral annular calcification
– Myxomatous degeneration of mitral valves
(mitral valve prolapse)
• Rheumatic fever and rheumatic heart disease

• 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

• 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

• 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)

• 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

• Most important consequence of rheumatic fever
• Inflammatory deformity of valves
– Almost always involve the mitral valve
– Involvement of aortic or other valves also common

• 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

• 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

• 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

• 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

An effective pump
(The heart)
An effective return
(No peripheral pooling)
(Normal blood vessels)
A clear channel

Blood Pressure/Heart Rate
Effective venous and lymphatic return
Intact and unblocked blood vessels

Heart 7%
Arteries 13%
Arterioles and capillaries 7%
Veins
Pulmonary vessels
64%
9%

Plasma
Interstitial fluid
Intracellular fluid
3.0L
11.0L
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)

• 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.

• Hypovoleamia
• Cardiogenic (pump failure)
• Anaphylactic (peripheral pooling) (return failure)
• Septic (Septiceamic) – Complex reasons

• 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

• 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

• 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

• 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

• 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”.

• 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.

• 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

• 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

• 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

• 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.

• Brain
– Hypoxic and ischaemic damage
– Initially found at “boundary” zones
– May also be associated with marked cerebral oedema.

• 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

• 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.

• 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

• 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,

• 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
Physical injuries such as wounds, ruptures of aneurysms, etc
(Hypovoleamic)
Toxins , infection and immunecomplexes (DIC, Anaphylaxis,
Septiceamic)
Peripheral Pooling
Hypoalbumineamia,
Ascites, Renal failure,
(Hypovoleamic)
Septiceamic,
Anaphylaxis
(Capillary pooling)