CARDIOVASCULAR SYSTEM

AORTA: ANEURYSM

1.    What is the organ shown?
 
Abdominal aorta at bifurcation of common iliac arteries (into external and internal iliac arteries).

2.    What are the associated lesions seen?
 
a.    Aneurysm (fusiform dilatation).
b.    Atherosclerosis.
c.    Mural thrombus.

3.    What are the likely complications?
 
a.    Rupture of aneurysm leading to massive bleeding.
b.    Impingement on adjacent structures.
c.    Occlusion of proximate vessels by either extrinsic pressure or superimposed thrombosis.
d.    Embolism from mural thrombosis.

4.    What is the pathogenesis of the lesion?
 
Atherosclerosis causes arterial wall thinning through medial destruction secondary to intimal plaque. 
 
Proliferation of smooth muscle cells in the intima and elaboration of extracellular matrix under the influence of cytokines and other growth factors secreted by endothelial cells and macrophages leads to accumulation of collagen and proteoglycans. Gradual collagenous replacement of muscle in the medial weakens the arterial wall and decreases its elasticity and strength to withstand the high pressure of arterial blood flowing through it.

5.    Name 3 other causes of this condition.
 
a.    Syphilis: now rare, the spirochaete causes an inflammatory destruction of the media with fibrous replacement. 
b.    Mycotic aneurysm due to seeding of vessel wall by septic embolic from a distant site, e.g. infective endocarditis.
c.    Cystic medial degeneration, e.g. in Marfan's syndrome.

6.    Name 2 other common sites where this condition can develop.
 
a.    Abdominal aorta just below the ostia of the renal arteries.
b.    Arch and descending parts of the thoracic aorta.

7.    What is the risk of rupture in this patient and what would you suggest for him?
 
a.    Size of aneurysm is probably > 5cm: risk of rupture of 5 - 10% per year.
b.    Operation to replace aneurysm with prosthetic arterial channels. Mortality of 5% compared to 50% if left untreated.

AORTA: ATHEROMA

Abdominal aorta of a 70-year-old Indian man with a history of hypertension and ischaemic heart disease.

1.    Describe the gross morphological features shown.
 
Multiple raised yellowish-white plaques seen within the intima, some are fissured, ulcerated with possible hemorrhage into more than one plaques on the left of the specimen. 

2.    What are the components of the lesion (s) seen and how are they organized?
 
Atherosclerotic plaques have three principal components:
 
a.    Cells: smooth muscle cells, macrophages and other leukocytes.
b.    Connective tissue extracellular matrix: collagen, elastic fibers, and proteoglycans.
c.    Intracellular and extracellular lipid deposits.
 
Organization of plaque (from lumen inwards):
 
a.    Superficial fibrous cap: smooth muscle cells with a few leukocytes and relatively dense connective tissue.
b.    Cellular are beneath: mixture of macrophages, smooth muscle cells and T lymphocytes.
c.    Deeper necrotic core: disorganized mass of lipid material, cholesterol cleft, cellular debris, lipid-laden foam cells, fibrin & thrombus.
d.    Periphery: proliferation small blood vessels.

3.    Where else is this lesion commonly found? Name 3 sites.
 
a.    Coronary arteries.
b.    Popliteal arteries.
c.    Descending thoracic aorta.
d.    Internal carotid arteries.
e.    Vessels of the circle of Willis.

4.    Give a summary of the pathogenesis of this lesion.
 
The "Response to injury hypothesis" considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by some form of injury to the endothelium:
 
a.    Chronic injury to endothelium due to mechanical stress, toxins such as cigarette smoke, etc. leads to endothelial dysfunction with increased endothelial permeability and increased leukocyte adhesion.
 
b.    Adhesion of blood monocytes to the endothelium, followed by migration of monocytes into the intima and their transformation into macrophages and platelets to focal areas of denudation.
 
c.    Insudation of lipoproteins, mainly LDL into the vessel wall where they are taken up by the macrophages forming foam cells.
 
d.    Release of factors from activated platelets and macrophages cause migration of smooth muscle cells from media into intima.
 
e.    Proliferation of smooth muscle cells in the intima and elaboration of extracellular matrix, leading to accumulation of collagen and proteoglycans.
 
f.    Collaginzation of the intima forms a dense fibrous cap to the plaque which is now hard and white (fibrolipid plaque).

5.    What are the risk factors for this condition?
 
a.    Non-modifiable risk factors: increasing age, male gender, family history, genetic abnormalities.
b.    Modifiable risk factors: hyperlipidaemia, hypertension, cigarette smoking, diabetes.

6.    What are the complications that can arise?
 
a.    Reduction of blood flow through arteries due to decreased size of lumen leading to ischaemic heart disease, peripheral vascular disease and cerebrovascular disease.
 
b.    Predisposition to thrombosis: if the fibrous cap over an atheromatous plaque breaks down, collagen fibers in the abnormal intima are exposed to the thrombogenic substances, e.g. Hageman factor in circulating blood (triggering off the intrinsic pathway of the coagulation cascade) and this initiates the formation of a thrombus. This thrombus may suddenly complete the occlusion of an already narrowed coronary artery leading to myocardial infarct.
 
c.    Weakening of vessel wall and aneurysm formation: severe atheroma in the intima eventually leads to thinning of the media, loss of smooth muscle cells and elastic fibers, and progressive replacement by non-contractile inelastic collagen. The media becomes functionally incompetent and this leads to generalized dilatation of the artery over the years to form an aneurysm. 

AORTA: DISSECTING ANEURYSM

A 67-year old man with a past history of hypertension collapses in the A&E department after complaining of severe chest pain and shifted down his back.

1.    What is the diagnosis?
 
Dissecting aneurysm: dissection of blood along the laminar planes of the aortic media, with the formation of a intramural blood-filled channel.

2.    What are the predisposing conditions for its formation?
 
a.    Connective tissue disorders: Marfan's syndrome, Ehlers-Danlos syndrome.
b.    Congenital heart disorders: bicuspid aortic valves, coarctation of aorta.
c.    Complication of therapeutic or diagnostic arterial cannulation.

3.    Where is it usually found?
 
a.    90%: within 10cm of the aortic valve.
b.    Descending thoracic aorta just distal to the origin of the left subclavian artery. 

4.    What are the possible outcomes?
 
a.    External rupture: massive fatal haemorrhage into the thoracic cavity.
 
b.    Retrograde spread towards the heart with rupture into the pericardial cavity leading to fatal hemopericardium.
 
c.    Internal rupture, with blood tracking back into the lumen by rupturing through the inner media and intima, to produce a double-channelled aorta. 

INFECTIVE ENDOCARDITIS

1.    Describe the gross morphological features shown. What is your diagnosis?
 
This is a picture of the heart showing irregular, friable, bulky vegetations on the mitral valve eroding into the adjacent aortic wall producing a yellow abscess. 
Diagnosis: Infective endocarditis.

2.    What are the common pathogens?
 
a.    Acute infective endocarditis: staphylococcus aureus.
b.    Subacute infective endocarditis: streptococcus viridans, enterococcus faecalis, staphylococcus epidermidis.

3.    How was the lesion developed?
 
Inflammatory damage to the heart valves leads to:
 
a.    Valve collagen is exposed, causing thrombus deposition. The thrombus develops as exophytic nodules or irregular warty growths on the valve leaflets forming vegetations.
b.    Inflammation and thrombus formation on the valve causes organization with collagenous scarring. This causes physical distortion to the valve cusps and renders them mechanically and functionally abnormal. 

4.    What are the clinical outcomes of this condition?
 
a.    Stenosed valves leading to valvular insufficiency with eventual left heart failure.
b.    Embolic to spleen, kidneys, heart, and brain with infarction or metastatic infection (septic emboli).
c.    Deposition of immune complexes in the afferent arterioles of the glomerulus cause glomerulonephritis. 

 
5.    Name some risk factors of this condition.
 
a.    Valvular pathology: mitral valve prolapse, bicuspid aortic valve, degenerate calcific stenosis.
b.    Others: neutropenia, IV drug abuse.

CHRONIC RHEUMATIC VALVULITIS

1.    Describe the gross morphological features shown. What is your diagnosis?
 
This is a picture of the heart showing fibrous thickening of mitral valve cusps with shortened and thickened chordae tendinae.
Diagnosis: Rheumatic heart disease.

2.    What is the pathogenesis of this condition?
 
Inflammatory damage to the heart valves secondary to host anti-streptococcal antibodies that are cross-reactive to cardiac antigens in childhood. Damage to valves heals by progressive fibrosis, with fibrous thickening of the valve leaflets and associated chordae tendineae. The valve leaflets become thickened, fibrotic and shrunken, often with fusion and there is frequent secondary deposition of calcium. 

3.    What is the major criteria for its diagnosis?
 
Jones criteria:
 
a.    Carditis. 
b.    Erythema marginatum.
c.    Sydenham chorea.
d.    Subcutaneous nodules.
e.    Migratory large joint polyarthritis.

4.    What are the clinical outcomes of this condition?
 
a.    Left atrial hypertrophy and atrial fibrillation secondary to atrial dilatation.
b.    Chronic pulmonary congestion.
c.    Right ventricular hypertrophy.
d.    Congestive heart failure.
e.    Increased risk of developing infective endocarditis.

 
5.    What are the histological features in the acute phase?
 
Aschoff bodies: foci of necrosis of collagen with fibrin deposition, surrounded by lymphocytes, macrophages and occasional plump modified histiocytes called Anitschkow cells. 

RIGHT VENTRICULAR HYPERTROPHY

1.    What is your diagnosis? 
 
Right ventricular hypertrophy due to cor pulmonale (note that left ventricle is not markedly thickened).

2.    What are the causes?
 
a.    Lung parenchyma diseases: chronic obstructive pulmonary disease, pulmonary fibrosis, bronchiectasis.
b.    Pulmonary vessel diseases: recurrent pulmonary thromboembolism, primary pulmonary hypertension, Wegener granulomatosis.
c.    Disorders of chest wall: kyphoscoliosis, neuromuscular disorders.
d.    Disorders inducing pulmonary constriction: metabolic acidosis, hypoxaemia, chronic altitude disease.  

LEFT VENTRICULAR HYPERTROPHY

1.    What is your diagnosis? Name a feature supportive of it.
 
Left ventricular hypertrophy. Circumferential thickening of the left ventricular to more than twice its normal maximal thickness of 1.5cm. 

2.    What is the usual cause?
 
Systemic hypertension produces left ventricular pressure overload and the heart hypertrophies to cope with the increased pressure. 

3.    What can this lead to?
 
In time, the increased thickness of the left ventricular wall imparts a stiffness that impairs diastolic filling leading to left ventricular failure.

4.    What are the associated biochemical changes?
 
a.    Pressure overload stimulate the stretched myocytes to enlarge.
b.    Gene expression changes with reappearance of fetal isoforms of contractile proteins requiring less energy and having a slower sustained rate of contraction than adult forms.
c.    Proto-oncogenes are expressed encoding growth factors, which also result in increased interstitial fibrous tissue. 

MYOCARDIAL INFARCT

A 74-year-old man collapses at home after complaining of severe chest pain and breathlessness. 

1.    What is your diagnosis? Describe the lesion shown.
 
Myocardial infarct. This is the left ventricular wall which has been sectioned lengthwise to reveal a large recent myocardial infarction. The center of the infarct contains necrotic muscle that appears yellow-tan. Surrounding this is a zone of red hyperemia. Remaining viable myocardium is reddish- brown. 

2.    What are the likely histological features?
 
a.    Disintegration of dead myofibrils with interstitial infiltrate of neutrophils and macrophages. 
b.    Phagocytosis of dead myofibrils by macrophages.
c.    Formation of fibrovascular tissue with laying down of fibrin and collagen in the area of infarct. 

3.    The left anterior descending artery was found to be completely stenosed. Relate the pathology to the clinical outcome.
 
a.    Rupture, fissure and ulceration of an existing atheromatous plaque exposed the subendothelial collagen to thrombogenic substances in the circulating blood, triggering off thrombosis.
b.    The formation of a superimposed thrombus on the plaque leads to complete occlusion of the coronary vessel.
c.    Sudden disruption of blood supply to the myocardial muscles leads to myocardial infarct. 

4.    Suggest a biochemical marker that can be used to diagnose this condition accurately. What are the advantages and disadvantages associated with their use?
 
Troponins T and I myocardial proteins responsible for the contraction mechanism are released following membrane damage during severe ischaemia starting in 3 hours with a peak at 14 hours; followed by slow dissociation and degradation of myofilaments leading to continuous release over 3 - 5 days. They are both an early and late marker and is cardiac specific. However, they lack specificity in co-existing skeletal muscle damage. 

5.    What can be done for this patient if he had been seen 1 hour after the onset of his symptoms?
 
Thrombolytic therapy with the use of streptokinase or tissue-type plasminogen activator to dissolve the thrombus that initiated the acute MI, to re-establish blood flow to the area at risk of infarction and to rescue ischaemic musles.

6.    What are the complications that can arise had the patient survive?
 
a.    Contractile dysfunction leading to cardiogenic shock and death.
b.    Arrhythmias.
c.    Myocardial rupture with hemopericardium and cardiac tamponade.
d.    Mural thrombus formation and emboli to the brain, kidneys and spleen.
e.    Ventricular aneurysm.

PERICARDITIS

1.    Describe the lesion shown.
 
The organ shown is the heart with its encasing pericardium. The pericardium is 'carpet' or 'rug-like' and has a shaggy, necrotic yellowish loose exudate giving it a 'bread-and-butter' appearance. 

2.    Name a few causes of this condition.
 
a.    Transient pericarditis 2 - 3 days after MI. 
 
b.    Post-operative, following open-heart surgery. The pericarditis is diffuse, involving the entire pericardial surface, and heals by fibrosis, largely obliterating the pericardial cavity.
 
c.    Bacterial pericardial, usually associated with severe bacterial infection of the lungs. An important cause is pulmonary TB, producing tuberculous pericarditis. Healing by fibrosis became heavily calcified and rigid, producing restriction to cardiac filling.
 
d.    Malignant pericarditis, usually due to infiltration of the pericardium by local spread from a primary bronchial tumor. Less commonly the cause is blood-borne metastases from a distant site.

 
3.    What are the complications in the long-term?
 
Healing of acute lesions can lead to resolution or pericardial fibrosis ranging from a thick, pearly, non-adherent epicardial plaque, to thin, delicate adhesions; to massive adhesions:
 
a.    Adhesive mediastinopericarditis is clinically significant: the pericardial sac is obliterated, and the parietal layer is tethered to mediastinal tissue. The heart thus contracts against all the surrounding attached structures, with subsequent hypertrophy and dilatation.
 
b.    Constrictive pericarditis: marked by thick (up to 1cm), dense fibrous obliteration, often with calcification of the pericardial sac that encases the heart, limiting diastolic expansion and restricting cardiac output.

4.    What are the clinical signs present in this condition?
 
a.    Right heart failure with severe ascites and hepatosplenomegaly.
b.    Tachycardia.
c.    Hypotension.
d.    Pulsus paradoxus: fall of systolic blood pressure of > 10mmHg on inspiration.
e.    Kussmaul's sign: high JVP which paradoxically rises with inspiration. 

BRAIN INFARCT

1.    Describe the lesion shown. What is the diagnosis?
 
Cystic cavity at the left basal ganglia with loss and distortion of tissue architecture. The normal white matter is replaced by a shaggy, irregular, fibrotic material. 
Diagnosis: infarct of basal ganglia.

2.    Name a few causes of this condition.
 
a.    Thrombotic occlusions due to atherosclerosis: common sites of involvement are the carotid bifurcation, origin of middle cerebral artery and at either end of the basilar artery.
b.    Lacunar infarcts: small, silt-shaped, areas of infarction less than 1cm in maximal diameter found in patients with hypertension and diabetes, being caused by hyaline arteriosclerosis.
c.    Embolism to brain: cardiac mural thrombi from MI, valvular disease and atrial fibrillation.
d.    Arteritis of small and large vessels in syphilis, TB, toxoplasmosis and CMV encephalitis, the latter two being seen in the immunocompromised.

 
3.    What is the biochemical basis for hypoxic injury?
 
Excitatory amino acid neurotransmitters such as glutamate, released during ischaemia, cause cell damage by overstimulation and persistent opening of specific membrane channels, N-methyl-D-aspartate and kainate receptors. This may cause cell death through an uncontrolled influx of calcium ions.

4.    How does the lesion heals?
 
Liquefactive necrosis: liquefaction completely digests the dead cells. The end result is transformation of the tissue into a liquid viscous mass.

BRAIN HEMORRHAGE

1.    Describe the lesion shown. 
 
A large brownish red hematoma effaces the basal ganglia, with compression of adjacent brain parenchyma. Blood has ruptured into the lateral ventricles.

2.    What is its pathogenesis?
 
Hypertension is the most common underlying cause of primary brain parenchymal haemorrhage. Hypertension causes accelerated arterosclerosis in larger arteries; hyaline arteriolosclerosis in smaller vessels and in severe cases, proliferative changes and frank necrosis of arterioles. Arteriolar walls affected by hyaline change are weaker than are normal vessels and are more vulnerable to rupture. In some instances, chronic hypertension is associated with the development of minute aneurysms, termed Charcot-Bouchard microaneurysms which may rupture under high blood pressure.

3.    What other sites are commonly affected?
 
a.    Putamen.
b.    Thalamus.
c.    Pontine tegmentum.
d.    Cerebellar hemispheres.

4.    How does death occurs?
 
a.    Uncontrollable bleeding leading to global ischaemia, compromise of vital brain functions and brain death.
b.    Raised intracranial pressure leading to tonsillar herniation through the foramen magnum.