Pathology of Cardiovascular System Dr. S.L. Beh [email protected].

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– 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





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




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

• Irreversible injury• Microvascular injury

• Seconds• < 2 minutes

• 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

• 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


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

Atrial dilatation

Atrial thrombus Congestion of lungs

Pulmonary HypertensionRight Heart

Failure

Systemic embolisation

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


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.


Rheumatic Valvulitis


Acute Rheumatic Carditis – Aschoff Body


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


Characteristics of rheumatic valvular disease

• Chronic– Leaflet thickening– Commissure fusion– Shortening, thickening and fusion of chordae

tendinae

Chronic Rheumatic Disease of Mitral Valve

Vascularisation)


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


The elements of circulationAn effective pump

(The heart)

(Normal blood vessels)

A clear channel

An effective return

(No peripheral pooling)

The elements of circulation

Blood Pressure/Heart Rate

Intact and unblocked blood vessels

Effective venous and lymphatic return

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)


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


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.


• 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


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 immune-complexes (DIC, Anaphylaxis, Septiceamic)

Peripheral Pooling

Hypoalbumineamia, Ascites, Renal failure,

(Hypovoleamic)

Septiceamic, Anaphylaxis

(Capillary pooling)

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Pathology of Cardiovascular System Dr. S.L. Beh [email protected].

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