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 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
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

Seconds < 2 minutes 10 minutes 40 minutes 20-40 minutes > 1 hour

Irreversible injury Microvascular injury

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 volume and pressure Systemic embolisation Atrial dilatation Congestion of lungs Pulmonary Hypertension

Atrial thrombus

Right Heart 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 Arteries 7% 13%

Arterioles and capillaries 7%

Veins
Pulmonary vessels

64%
9%

Body Fluid Compartments

Plasma
Interstitial fluid

3.0L
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
Physical injuries such as wounds, ruptures of aneurysms, etc (Hypovoleamic)

Peripheral Pooling
Hypoalbumineamia, Ascites, Renal failure, (Hypovoleamic) Septiceamic, Anaphylaxis (Capillary pooling)

Toxins , infection and immunecomplexes (DIC, Anaphylaxis, Septiceamic)