Week 2 - Ischaemic Heart Disease, Myocardial Infarction & Atherosclerosis

Question 1

Outline ischaemic heart disease.

Answer 1

• Leading cause of mortality and morbidity - clinically presents as chest pain (angina).
• Myocytes have a continuous need of O2 - myocytes generate energy almost exclusively through mitochondrial oxidative phosphorylation, therefore cardiac function is strictly dependent upon the continuous flow of oxygenated blood through the coronary arteries.
• Lack of O2:
- 1-2 min → loss of function (of myocytes = pain) - reversible.
- 20-40 min → coagulation necrosis (muscle dies) - irreversible
• Cell viability can be preserved if myocardial blood flow is restored before irreversible injury occurs → rationale for early diagnosis of MI and for prompt intervention by thrombolysis or angioplasty to salvage myocardium at risk.
• IHD: imbalance in supply vs. demand (decreased O2 vs increased need). Myocardial ischaemia - imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements.

Question 2

Describe the aetiology of ischaemic heart disease.

Answer 2

• 90% IHD due to decreased coronary blood flow (causing reduced perfusion to cardiac tissue).
- 90% of cases due to coronary atherosclerosis (excess fat deposition in vessel causing block → reduced coronary blood flow).
• Non coronary causes <10%:
- Decreased aortic diastolic pressure - AS, AR, CHF.
- Increased intraventricular pressure - MS, hypertension.
- Increased right atrial pressure - COPD (back pressure).
• 10% (increased demand):
- Cardiomyopathy - hypertrophic - muscle too thick → normal coronary artery unable to supply sufficient O2.
- Hypertension - increased demand.
- Shock - diminished blood volume.
- Severe anaemia - diminished oxygen carrying capacity.
- Lung disorders - decreased O2.
• Somatic and autonomic/visceral pain.

• Ischaemia - decreased blood flow, without tissue injury.
• Infarct - decreased blood flow, with tissue injury.

Question 3

Explain the pathogenesis of ischaemic heart disease.

Answer 3

• Normal: increased stress with sufficient supply of blood and nutrition (O2) → cardiac myocytes increase in size (adaptation - hypertrophy).
• Ischaemia: decreased blood supply → ischaemic damage → reversible myocyte injury → irreversible cell injury → cell death.

1. There is an obstruction to the blood flow in the coronary arteries.
   - Due to atherosclerosis, atheroma, thrombosis, embolism, rupture or haemorrhage.
2. The obstruction leads to diminished coronary perfusion → ischaemic cell injury → release chemical mediators → chest pain (angina).
3. If obstruction is prolonged and cell death (necrosis) occurs → myocardial infarction
   - Characterised by inflammation, granulation tissue & healing by fibrous scarring.

Question 4

Outline the mechanism of myocyte injury.

Answer 4

• Coronary artery blocked → decreased blood supply to mitochondria → decreased oxidative phosphorylation (dependent mechanisms stop) → decreased ATP:

• Decreased Na+/K+ pump → influx of Ca2+, H2O and Na+, K+ efflux → cell swelling, ER swelling → loss of function (cell is still alive but develops a lot of vacuoles and swelling because of damage).
• Stimulates anaerobic glycolysis → increased lactic acid and decreased pH → ischaemic pain, acidity and stimulation of inflammation.
• Decreased pH also leads to clumping of nuclear chromatin → infarction.
• Cell swelling also leads to detachment of ribosomes → protein synthesis blocked.

See diagram *EXAM HINT.

Question 5

Identify the clinical presentations of ischaemic heart disease.

Answer 5

• There are 4 clinical presentations depending on amount of coronary vessel which has been blocked and whether or not cell death has occurred:

• Angina pectoris.
• Acute MI.
• Chronic IHD with CHF.
• Sudden cardiac death.

• <70% blocked - asymptomatic.
• 70-75% blocked - angina.
• 90% blocked - fixed stenosis, chronic IHD.
• >90% blocked - MI, SCD.
NB: If plaque changes - unstable angina, rupture, fissure, ulcer.

ACS = unstable angina, acute MI, SCD.

Question 6

Provide a brief overview of the clinical presentations of ischaemic heart disease.

Answer 6

• Coronary atherosclerosis:

• ~70% cases asymptomatic.
• ~30% cases symptomatic (>75% block).

1. Angina pectoris:
   • Stable - fixed fibrotic plaque 90%.
   - Stable atherosclerotic narrowing of coronary artery. Pain caused by imbalance in coronary perfusion relative to myocardial demand. Relieved by rest.
   • Unstable - plaque disruption 10%.
   - Advanced atheroma prone to complications (i.e. disruption of atherosclerotic plaque).
   • Variant - temporary spasm.
   - Spasm of coronary arteries (may not be atheroma). Occurs at rest.

Acute plaque change (inflammation) - sudden disruption of partially occlusive plaque leads to acute MI or SCD depending on size of block (ACS).

Acute MI:
• Following coronary block - prolonged ischaemia causes death of the heart muscle.
• Loss of myocyte function: 1-2 min. Necrosis: 20-40 min.
• Diagnosis - symptoms, ECG changes, serum CK-MB and troponins.
• Note: Gross and histologic changes of infarction requires hours to a day to develop even though cell is dead.

SCD:
• Sudden, unexplained death of previously fit person usually due to IHD.
• Usually the consequence of a lethal arrhythmia (ventricular fibrillation).
• Often significant narrowing of coronary arteries & coronary thrombosis in 50% of cases.
• Other causes include: abdominal aneurysm, dissecting aortic aneurysm, pulmonary embolism.
• Morphologically, marked coronary atherosclerosis.

2. Chronic IHD: >75% + heart failure.

Question 7

Outline chronic ischaemic heart disease - ischaemic cardiomyopathy.

Answer 7

• Progressive heart failure due to chronic ischaemia (+/- infarction).
• Gross: LV dilation and hypertrophy (dead tissue - heart is weak, pressure causes dilation).
• Myocardium - multiple grey white scars (old MI - evidence of past MI).
• Evidence of atherosclerosis.
• Patchy white scars in endothelium - mural thrombi.
• Microscopy: myocyte hypertrophy and vacuolisation, fibrosis.
• Clinical: progressive, chronic heart failure over years. Episodes of angina, MI, arrhythmia etc. - causes morbidity and mortality.
• Chronic ischaemia - gradual development of block with/without any sudden MI.
• Essentially progressive heart failure secondary to ischaemic myocardial damage. In most instances, there is a history of previous MI. In this setting, chronic IHD appears when the compensatory mechanisms (e.g. hypertrophy) of residual viable myocardium begin to fail. In other cases, severe obstructive CAD can cause diffuse myocardial dysfunction without frank infarction.

Question 8

Outline myocardial infarctions.

Answer 8

• Part of ischaemic heart disease → death of myocardial tissue.
• The vast majority of MIs are caused by acute coronary artery thrombosis. In most instances, disruption of pre-existing atherosclerotic plaques serves as the nidus for thrombus generation, vascular occlusion and subsequent transmural infarction of the downstream myocardium.

• Severe chest pain which develops suddenly & generally lasts for several hours.
• Pain is often accompanied by profuse sweating, nausea and vomiting.
• The ECG provides a guide as to which coronary artery is narrowed:
- Infarcts with ST elevation (STEMI) require emergency treatment.
- Infarcts with no ST elevation (non-STEMI) indicates infarct is limited to subendocardial zone of myocardium.
• Rise in cardiac enzyme (i.e. troponin) levels.

Question 9

What are the 3 types of infarct?

Answer 9

1. Subendocardial infarct - partial infarct/obstruction. Infarct is less than half the thickness of muscle - seen clinically as NSTEMI.
2. Transmural infarct - when the complete artery is blocked/obstructed → whole thickness - seen clinically as STEMI.
3. Multiple small/microscopic infarcts - block in small branches of coronary artery causes microscopic infarcts - seen clinically as normal because infarcts are small and do not affect electrical signals.

• Partial thickness (subendocardial) infarct → partial obstruction → NSTEMI.
• Full thickness (transmural) infarct → whole artery blocked → STEMI.

Question 10

Differentiate between transmural, subendocardial and microscopic infarcts.

Answer 10

• Transmural infarctions involve the full thickness of the ventricle and are caused by epicardial vessel occlusion through a combination of chronic atherosclerosis and acute thrombosis. Transmural MIs typically yield ST segment elevations on the ECG and can have a negative Q wave with loss of R wave amplitude. (STEMI).
• Subendocardial infarctions are MIs limited to the inner third of the myocardium. These infarcts typically do not exhibit ST segment elevations or Q waves on the ECG tracing. The subendocardial region is most vulnerable to hypoperfusion and hypoxia. Thus, in the setting of severe coronary artery disease, transient decreases in O2 delivery (as in hypotension, anaemia or pneumonia) or increases in O2 demand (as with tachycardia or hypertension) can cause subendocardial ischaemic injury. This pattern can also occur when an occlusive thrombus lyses before a full thickness infarction can develop.
• Microscopic infarcts occur in the setting of small vessel occlusions and may not show any diagnostic ECG changes. These can occur in the settings of vasculitis, embolisation of valve vegetations or mural thrombi or vessel spasm due to elevated catecholamines - either endogenous (e.g. extreme stress or pheochromocytoma) or exogenous (e.g. cocaine).

Question 11

Outline the progression of ischaemic damage in the myocardium.

Answer 11

• When there is a block in the blood vessel → the area affected will become ischaemic.
• The irreversible injury of ischaemic myocytes first occurs in the subendocardial zone. This region is especially susceptible to ischaemia because it is the last area to receive blood delivered by the epicardial vessels and also because it is exposed to relatively high intramural pressures which act to impede the inflow of blood.
• With more prolonged ischaemia, a waveform of cell death moves through other regions of the myocardium, with the infarct usually achieving its full extent within 3-6 hours.
• In the absence of intervention, the infarct can involve the entire wall thickness (transmural).
• A very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle (diffusion of oxygen and nutrients from the ventricular lumen).

Question 12

Identify the major vessels commonly affected in MI.

Answer 12

• Origin of coronary arteries - the left and right coronary arteries arise from the root of the aorta just above the cusps of the aortic valve.

• Common sites of block:
1. Left coronary artery - left anterior descending (anterior interventricular) branch (40-50%).
• Supplies anterior left ventricle, anterior 2/3 septum and apex circumferentially.
• Anterior infarction/sudden death.
• ECG changes (i.e. ST elevation for MI) in anterior chest leads V1-V6.

2. Right coronary artery - posterior interventricular branch (30-40%).
   • Supplies posterior left ventricle, posterior 1/3 septum and right ventricle wall.
   • Inferior infarction.
   • ECG changes in leads II, III, aVF.
3. Left coronary artery - left circumflex branch (15-20%).
   • Supplies lateral left ventricle except the apex.
   • Lateral infarction.
   • ECG changes in leads I, aVL, V5, V6.

See diagram *EXAM HINT.

Question 13

Outline the morphology of MIs.

Answer 13

• The gross and microscopic appearance of an MI depends on the age of the injury. Areas of damage progress through a highly characteristic sequence of morphologic changes from coagulative necrosis to acute and chronic inflammation, to fibrosis. Myocardial necrosis proceeds invariably to scar formation without any significant regeneration.

Summary:
• Necrotic myocardium elicits acute inflammation (typically most prominent 1-3 days after MI), followed by a wave of macrophages that remove necrotic myocytes and neutrophil fragments (most pronounced 5-10 days after MI).
• The infarcted zone is progressively replaced by granulation tissue (most prominent 1-2 weeks after MI), which in turn forms the provisional scaffolding upon which dense collagenous scar forms. In most instances, scarring is well advanced by the end of the 6th week but the efficiency of repair depends on the size of the original lesion.
• Healing requires the migration of inflammatory cells and ingrowth of new vessels from the infarct margins. Thus, an MI heals from its borders towards the centre and a large infarct may not heal as fast or as completely as a small one.

Question 14

Describe the morphology of an MI <4 hours.

Answer 14

• Gross: normal.

* Microscopy: normal. Loss of LDH or glycogen can be seen only on special stains/ultrastructure.

Question 15

Describe the morphology of an MI 4-24 hours.

Answer 15

• Gross: dark area (little pale areas) surrounded by erythema and oedema.
• Microscopy: karyolysis (dissolution of cell nucleus)/pyknotic nucleus, myocyte necrosis, congestion, acute inflammatory cells (neutrophils). Formation of contraction bands.

Question 16

Describe the morphology of an MI 3-7 days.

Answer 16

• Gross: central pale/yellow area with haemorrhagic border.

* Microscopy: obvious necrosis of muscle, plenty of neutrophils and haemorrhage, few macrophages.

Question 17

Describe the morphology of an MI >3 weeks (old).

Answer 17

• Gross: thin wall, multiple white scar. Bulging of scar part (aneurysm).
• Microscopy: loss of muscle tissue replaced by pale fibrous tissue (collagen).

Question 18

Differentiate between an acute and chronic MI.

Answer 18

Acute (1-3 days):
• Gross: reddish brown colour (hemorrhagic), no significant loss of muscle mass.
• Microscopy: inflammation, necrosis of muscle fibres, formation of contractile bands.

Chronic (weeks-months):
• Gross: loss of muscle mass (thin wall), whitish grey scar, no haemorrhage, thrombus (no dark regions).
• Microscopy: granulation tissue, fibrosis.

Question 19

Identify the clinical features of MIs.

Answer 19

• Severe, crushing substernal chest pain.
• Can radiate to neck, jaw, epigastrium or left arm.
• Associated pain typically lasts >20 mins to hours and not relieved by nitroglycerin or rest (in contrast to angina pectoris).
• Anxiety/distress.
• Diaphoretic.
• Nausea.
• Pallor
• Dyspnoea.
• Palpitations.
• Rapid, weak pulse (pulse may increase or decrease).
• BP may increase or decrease.
• Minority of cases - atypical signs and symptoms or may even be asymptomatic. ‘Silent’ infarcts common in patients with underlying diabetes (in which autonomic neuropathic may prevent perception of pain) and in elderly patients - may present with pulmonary oedema, epigastric pain and vomiting, confusion, stroke, hyperglycaemic state, post-op hypotension or oliguria.

Question 20

Identify the acute complications of MIs.

Answer 20

• Complications occur in 75% of cases.

Acute complications:
• Heart failure.
• Sudden cardiac death (due to lethal arrhythmia).
• Arrhythmias (effect electrical/conduction signals).
• Extension of infarction or re-infarction (dead tissue stimulates more inflammation).
• Congestive heart failure (heart unable to sufficiently support life).
• Cardiogenic shock (may develop with massive MIs - severe pump failure).
• Pericarditis (full thickness (transmural) infarctions lead to fibrin deposits on the outside of pericardium within pericardial sac) - Dressler’s syndrome.
• Mural thrombosis - embolisation (loss of heart function - blood coagulates on dead tissue causing mural thrombosis and embolisation).
• Myocardial wall rupture (most common) → tamponade (3-10 days).
• Papillary muscle rupture - MR (similar to myocardial wall rupture).

Question 21

Identify the chronic complications of MIs.

Answer 21

• Chronic IHD - CHF (development of scar).
• Arrhythmias (if affects conduction system).
• Ventricular aneurysm (dilation of ventricles).
• Mural thrombosis.
• Papillary muscle contraction - MR (when it is healed by scarring, the scar contracts and contraction of papillary muscles can lead to mitral regurgitation).

Question 22

Describe ischaemic mitral regurgitation.

Answer 22

• When there is an infarction or rupture → there is no contraction so mitral valve cannot close properly causing mitral regurgitation.
• MI, LVH, dilated CMP, myocarditis.

Question 23

Outline the management of MIs.

Answer 23

• Measures to prevent atherosclerosis (e.g. antiplatelet/antihypertension therapy).
• Patients with history of arrhythmias can have a pacemaker/defibrillator implanted.
• Coronary bypass.

Question 24

What is atherosclerosis?

Answer 24

• Chronic inflammatory disease of large and medium sized arteries due to endothelial injury.
• Characterised by sub-endothelial lipid deposit, inflammation and fibrosis (plaque).
- Inflammation + lipid deposit + fibrosis form plaque AKA atheroma → obstruction of blood vessel. Common factor is endothelial injury and deposition of fat.
• Lifestyle/non communicable disease.
• End result of diabetes, hypertension, smoking and hyperlipidaemia.
• ‘Athero’ (fat) and ‘sclerosis’ (hardening).
• Hardening of arteries with fat deposition.
• Clinically known as macroangiopathy.
• Not seen in veins or capillaries.
• Major cause of death and disability (IHD, MI, stroke, HT, diabetes etc.)

• Characterised by the presence of intimal lesions called atheromas. Atheromatous plaques are raised lesions composed of soft lipid cores (mainly cholesterol, cholesterol esters, with necrotic debris) covered by fibrous caps.
• Atheromatous plaques can mechanically obstruct vascular lumina and are prone to rupture, resulting in catastrophic vessel thrombosis. Plaques also weaken the underlying media, sometimes leading to aneurysm formation.

Question 25

Outline the aetiology of atherosclerosis.

Answer 25

• Exact cause is unknown (idiopathic). Trauma in endothelium associated with risk factors.
• Starts early in life <10y - asymptomatic.
• Symptoms and complications later in life >30-40y.
• Endothelial damage is the first step.
• Plaque starts at bifurcations (trauma)* - blood hits bifurcation causing trauma → endothelial injury - location of plaque formation.

• Risk factors (not aetiology):
1. Non modifiable
- Age, male, family history, genetic.
2. Modifiable
- Hyperlipidaemia, hypertension, smoking, diabetes mellitus, lifestyle, obesity.
3. Additional
- CRP (inflammation), hyperhomocysteinaemia (vit B12), metabolic syndrome (syndrome X), pro-coagulants.
• Risk factors have a multiplicative effect - more risk factors promote greater formation.

Question 26

Describe CRP as a risk factor of atherosclerosis.

Answer 26

• CRP is an inflammatory mediator - suggestive of inflammation in the body.
• Inflammatory mediators in blood damage endothelium.
• Atherosclerosis - disease of inflammation. If these mediators are increased → risk factor.
• The higher the CRP level, the higher the risk of atherosclerosis.
• Can be due to any cause e.g. streptococcal infection.
• CRP secreted by cells within atherosclerotic plaques can activate endothelial cells, increasing adhesiveness and inducing a prothrombotic state.

Question 27

Explain the pathogenesis of atherosclerosis.

Answer 27

1. LDL enters intima through intact endothelium.
   - Entry of excess lipids into endothelium - increases when endothelium damaged.
2. Initimal LDL is oxidised into pro-inflammatory lipids.
   - Oxidised in intima - strong inflammatory mediators.
3. Oxidised LDL causes adhesion and entry of monocytes and T lymphocytes across endothelium.
   - Inflammatory mediators activate monocytes to bind and enter blood vessel wall.
4. Monocytes differentiate into macrophages and then consume large amounts of LDL, transforming into foam cells.
   - When macrophages cannot handle the load of lipids, they disintegrate and release fat - forms a lipid pool.
5. Foam cells release growth factors (cytokine), that encourage atherosclerosis.
   - Activated macrophages also release growth factors → fibrous and smooth muscle cell proliferation → chronic inflammation (rupture if macrophages release more inflammatory mediators - severe inflammation with lipid pool).

IFN-γ, TNF-α, IL-1, IL-6, IL-12

6. Chronic inflammation (atheroma plaque).

Question 28

Differentiate between inflammation and healing in the pathogenesis of atherosclerosis.

Answer 28

1. Endothelial injury.
2. LDL entry and oxidisation in intima.
3. Platelet and monocyte activation → foamy macrophages → inflammation → IL, CRP.

• Inflammation: WBC, proteinases, rupture → lipid pool → ulceration → complications.
• Healing → SMC and fibroblast proliferation.
• More healing → stable/chronic IHD.
• More inflammation → unstable/ACS.

Question 29

Outline the stages of an atheroma.

Answer 29

• Dot → streak → soft plaque → hard plaque → complicated.

• Starts early in life → asymptomatic because blood vessel is still able to supply sufficient blood.
• Grows over years → symptoms. Stable angina in beginning in 90% of cases.
• Increased inflammation with less healing → plaque tends to rupture → leads to unstable angina with formation of thrombus.

Question 30

What are the 2 different types of plaques?

Answer 30

• 2 types of plaque:

• Fibrous - stable with healing (fibrosis).
• Complicated - with more inflammation and breakdown causing thrombosis.

Stable plaque (90%):
• Small lipid core.
• Low inflammation (IL-4, IL-13).
• Thick fibrous cap.
• High SMC. 
• Slow progressive.
• Pain on exercise.

Unstable plaque (10%)
• Large lipid core.
• Severe inflammation (IFN-γ).
• Thin fibrous cap.
• Low SMC.
• Rapid change.
• Pain at rest.

Question 31

Outline the 2 ways macrophages can be activated.

Answer 31

• Tissue macrophages can be stimulated by 2 pathways:
1. Classic pathway (M1) - TH1 lymphocytes - due to IFN-γ activating inflammation and tissue injury (ROS, proteases etc.). Inflammatory mediators produce inflammation. Therefore, macrophages activated through classic pathway leads to more inflammation and unstable plaque. The plaque is more inflamed and can breakdown because there are plenty of macrophages causing complications. Unstable plaque → unstable angina clinical features.

2. Alternate pathway (M2) - TH2 lymphocytes - stimulation of macrophages by anti-inflammatory mediators (IL-4, IL-13) which prevent inflammation and produce growth factors → this induces more fibrous tissue and SMC proliferation → makes plaque stable (does not break down easily). Although the plaque is obstructing, it is chronic obstruction - gradual increase in size but no acute changes. Stable plaque → stable angina clinical features.

• Plaque is a balance between inflammation and repair.

• If more inflammation → unstable plaque.
• If more healing → stable plaque.
• Stable plaque can progress to unstable and unstable plaques can reverse back to stable.

Question 32

Describe the morphology of atherosclerosis.

Answer 32

Gross:
• Fatty dots.
• Fatty streak.
• Soft plaque (fatty atheroma plaque) - foamy macrophages, thin endocardium, necrosis.
• Hard plaque - cholesterol crystals, fibrous cap, calcium, necrosis, inflammatory cells.
• Complicated plaque - inflammation, ulceration, thrombus.

Microscopy:
• Normal area of tunica media and tunica intima, separate from plaque.
• Fibrous cap.
• T lymphocytes.
• SMC.
• Macrophages containing fat.
• Areas of lipid pool/deposit.
• Cholesterol crystals.

See diagram *EXAM HINT.

Question 33

What are the complications of atherosclerosis?

Answer 33

In the organ supplied:
• Ischaemia/infarction (decreased/no blood supply).
- Heart - IHD, MI, SCD.
- CNS - stroke.
- Renal - atrophy, infarction, secondary hypertension.
- Limb - PVD (claudication).
- GIT - ischaemic enteritis (infarction).

In the artery (macroangiopathy):
• Progressive block (most common which leads to chronic ischaemia).
• Thrombosis, thromboembolism (due to acute changes in plaque).
• Aneurysm - fusiform, dissecting, berry etc. (inflammation with macrophage induced proteases weakens arterial wall → leads to abnormal dilation of artery).
• Rupture - haemorrhage (wall rupture leading to haemorrhage.
• Narrowing and hardening.
• Fibrosis and calcification.

Question 34

Identify the clinical features and management of atherosclerosis.

Answer 34

Clinical:
• Ranges from benign symptoms to life threatening diseases.
• Atherosclerosis in large arteries (i.e. carotids, iliac, aorta) may be detected as bruit.
• Commonly affects aorta, iliac, coronary and renal arteries (determines symptoms).

Management:
• Primary prevention - modify risk factors through diet and lifestyle.
• Secondary prevention
- Correct modifiable risk factors (eg. smoking, hypertension etc.)
- Common medications used
o HMG-CoA reductase inhibitors (lower cholesterol).
o Aspirin (inhibit platelet aggregation).
o BP medication (if BP over 140/85).
o Beta-blockers (if patient has history of MI).
• Surgical intervention - aim to reduce severity of lesions, remove thrombus or bypass severely occluded artery. Include percutaneous angioplasty or surgical bypass.

Question 35

What is an aneurysm?

Answer 35

• Congenital (e.g. Marfan’s) or acquired (e.g. atherosclerosis - many causes) dilations of blood vessels or the heart.
• Localised abnormal dilation of a blood vessel or heart chamber usually due to a weakened vascular (or cardiac) wall as a result of impaired connective tissue structure/function.
• As walls are weakened, this allows blood to pool in the cavity.
• 2 types - true and false.

Question 36

Differentiate between true and false aneurysms.

Answer 36

True aneurysms:
• Involve all 3 layers of the artery (intima, media, adventitia) or the attenuated wall of the heart.

False aneurysms:
• Result when a wall defect leads to the formation of an extravascular haematoma that communicates with the intravascular space.
• The wall is ruptured, creating a collection of blood (haematoma) bounded externally by adherent extravascular tissues.

Question 37

Outline the classification of aneurysms.

Answer 37

• Saccular/berry (true): discrete outpouchings often with a contained thrombosis (unilateral - single wall).
• Fusiform (true): circumferential dilation of the vessel, most commonly involve the aortic arch, abdominal aorta or the iliac arteries (bilateral - both walls).
• Dissecting (false): pressurised blood gains entry to the arterial wall through a surface defect and then pushes apart the underlying layers (blood is forced through tear in the aortic intima to create a blood-filled place in aortic media - ‘false lumen’).

• Aneurysms and dissections are important causes of stasis and subsequent thrombosis. They also have a propensity to rupture.

Question 38

Describe aortic aneurysms.

Answer 38

• Aneurysms can occur in any blood vessels from arterioles to aorta.
• Aortic is more common clinically. 2 types - AAA and TAA. Both of these cause pulsating swelling, pain (fusiform or saccular).
• Also divided into type A and B:
- Type A - proximal or extending into distal (DeBakey types). Proximal lesions involving the ascending aorta with or without involvement of the descending aorta (DeBakey type I or II respectively). Type A proximal, dangerous, common (hypertension). TAA - interscapular.
- Type B - only distal - AAA due to atherosclerosis. Proximal due to many causes. Distal lesions usually beginning beyond the subclavian (DeBakey type III). Type B distal to subclavian, less dangerous (atherosclerosis).

Question 39

Explain the pathogenesis of aneurysms.

Answer 39

• Localised weakness in wall.
• Commonest cause is atherosclerosis - inflammation of intima, macrophages secrete proteases which break down the tissue (macrophage mediated proteolysis).
• Cystic medial degeneration is the most common pathogenesis - abnormal elastic fibres and supporting fibrous collagen in arterial wall making it weak → dilates. Produces small cyst like spaces of necrosis.
• Atherosclerosis*: (abdominal/AAA) - inflammation, MMP’s - degeneration.
• Inflammatory AAA: IgG4 disease. Plasma cells, steroid therapy (excess IgG4 and plasma cells, immune abnormality. Patients usually respond to steroid therapy, not common).
• Hypertension*: (TAA) - compression of vasa vasorum - ischaemia. Excess BP presses on wall of blood vessel → compression of small blood vessels supplying vasa vasorum - causes ischaemia then (CM) degeneration (vast vasorum supplies blood vessel wall).
• Mycotic (infective): sepsis, SBE.
• Syphilis: (TAA) - endarteritis - vaso vasorum. Endarteritis - infection/inflammation of vaso vasorum causing necrosis. Usually results in proximal type of TAA → dilation of roof of aorta causing aortic valve incompetence.
• Marfan’s Syndrome: (thoracic/TAA) - defective fibrillin, TGF-β and elastic fibers (substrate for the development of all these collagen and elastic fibres - abnormal elastic fibres).
• Ehlers-Danlos Syndrome: (TAA) - altered collagen cross-linking (abnormality of collagen and elastic fibres cross linking - weakness of blood vessel wall resulting in the same aneurysm formation).

Question 40

Identify the complications of aneurysms.

Answer 40

• Fatal haemorrhage - weakness in wall, therefore aneurysm can rupture → patient bleeds to death because high pressure vessels.
• Ischaemic organ damage - iliac (leg - claudication), renal (kidney - very common - renal artery affecting kidney causing secondary hypertension), mesenteric (GIT infarctions), vertebral (damage to spinal cord), cerebral (stroke - berry aneurysm common in Circle of Willis).
• Mural thrombosis/embolism - commonest due to abnormal dilation/blood stagnation - thrombus (obstruction to blood flow) or separate (embolism) - block in distal branch.
• Surrounding organ compression - swelling compressing on surrounding organs (impingement on adjacent structures).

Question 41

What are the clinical features of aneurysms?

Answer 41

Fusiform:
• Lower abdominal aorta and iliac arteries.
• Pulsatile abdominal mass.
• Lower limb ischaemia.
• Rupture leading to retroperitoneal haemorrhage.

Saccular/berry:
• Cerebral arteries.
• Subarachnoid haemorrhage.
• Stroke.

Dissecting:
• Aorta and major branches.
• Loss of peripheral pulses.
• Haemopericardium.
• External rupture.

Question 42

What is the difference between a embolus and a thrombus?

Answer 42

• An embolus is a mass in the vascular system able to become lodged within a vessel & block its lumen. Types include: atheroma, platelet, infective, fat, gas, amniotic fluid, tumour, foreign substance.
• A thrombus is a solid mass of blood formed within the vascular system during life.

Question 43

Outline thromboembolism and provide some common examples.

Answer 43

• There are 3 disposing factors that result in thrombi formation:
- Changes in the intimal surface of the vessel.
- Changes in the pattern of blood flow.
- Changes in the blood constituents.
• Arterial thrombosis usually due to atheroma → systemic emboli.
• Venous thrombosis usually due to stasis (95% leg veins) → pulmonary emboli.
• Clinical features depend on the final destination of emboli (i.e. heart, lungs etc.)

Pulmonary thromboembolism:
• Normally occurs when emboli from deep vein thrombosis becomes lodged in lungs.
• Small emboli may occur unnoticed.
• Large emboli may cause respiratory deficiency and cardiac problems (chest pain, dyspnoea, infarct).

Systemic thromboembolism:
• Arises in the arterial system with thrombi originating from the heart or atheromatous plaque.
- Atrial fibrillation causes blood to stagnate & thrombosis to occur.
- Thrombi may come from vegetations on the heart (e.g. in infective endocarditis).
- Thrombi may form on areas of cardiac muscle which has died as a result of an MI.
• Effects of emboli depend on size and final destination e.g. cerebral infarct, renal infarct, ischaemic bowel, ischaemic foot (dry gangrene).