VIVA: Pathology - Cardiovascular system Flashcards
What are the risk factors for abdominal aortic aneurysm?
Age >60
Male
Smoking
HTN*
Atherosclerosis*
Diabetes mellitus
Family history
Connective tissue disease (e.g. Marfan’s, Ehlers-Danlos)
Vasculitis
Trauma
Congenital
Infection
Inflammation
*needed to pass + two others
Describe the pathogenesis of an aneurysm
- Aneurysms can occur when the structure or function of the connective tissue within the vascular wall is compromised
- Atherosclerotic plaque in intima compresses media, with degeneration and weakness of the wall and cystic medial degeneration
- Local inflammation (proteolytic enzymes with collagen degradation, role of matrix metalloproteinases)
- Loss of vascular smooth muscle cells
- Inappropriate synthesis of non-elastic ECM
What is the definition of cardiomyopathy?
Heterogenous group of diseases of the myocardium that is associated with mechanical and/or electrical dysfunction* that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation*
Primary cardiomyopathies can be congenital or acquired
Secondary cardiomyopathies have myocardial involvement as a component of a systemic or multisystem disorder
*needed to pass
What are the types of cardiomyopathy? Give a cause of each
Hypertrophic *: 75% genetic cause, autosomal dominant HCM
Dilated *: alcohol, myocarditis, idiopathic, peripartum, genetic
Restrictive *: infiltrative (amyloidosis, sarcoidosis), non-infiltrative (idiopathic, scleroderma)
*needed to pass + one example of each
What type of cardiomyopathy is alcoholic cardiomyopathy?
Dilated
What are the clinical consequences of an aneurysm?
- Painful/painless mass
- Rupture* (risk increases with diameter >5cm, modest increase >4cm; retroperitoneal or intraperitoneal with rapid fatal haemorrhage)
- Obstruction: branch obstruction (e.g. mesenteric, vertebral, renal)
- Embolism: plaque or thrombus
- Impingement/compression of adjacent structures (e.g. ureter)
- Infection (mycotic aneurysm)
*needed to pass + 2 others
Describe the pathogenesis of an aortic dissection
- HTN*: aorta of hypertensive patients have medial hypertrophy of vaso vasorum and degenerative changes in the media
- Connective tissue disease (inherited or acquired)
- Both of the above cause weakness in the media*
- An aortic dissection starts with an intimal tear* and the blood dissects into the media along laminar planes either distally or proximally leading to the formation of a medial haematoma which may then rupture outwards
- Can subsequently develop cystic medial degeneration
*needed to pass
How are aortic dissections classified?
By site of involvement (either classification to pass):
1. Stanford:
- Type A: proximal to L subclavian
- Type B: distal to L subclavian
2. Debakey:
- Type I: ascending and descending aorta
- Type II: ascending only
- Type III: descending only
What are the potential consequences of aortic dissection?
3 to pass:
- Rupture back into intima or through adventitia
- Rupture out or into pericardial, pleural or peritoneal cavities
- Cardiac tamponade, aortic insufficiency, MI, distal ischaemia, spinal cord ischaemia
- Death
What are the risk factors for aortic dissection?
- Male
- Age 40-60
- HTN*
- Connective tissue disorders (e.g. Marfans, Ehlers-Danlos)
- Complication of arterial cannulation (iatrogenic)
- Trauma
- Pregnancy
*needed to pass + 1 other
What are the pathological consequences of aortic stenosis?
- Concentric LV hypertrophy*
- LV outflow obstruction
- Myocardial ischaemia (coronary artery disease need not be present)
- Syncope
- Aortic dissection
- Heart failure (diastolic or systolic)
- Endocarditis (uncommon)
*needed to pass + 3 others
What are the most common causes of aortic stenosis?
2 to pass:
- Calcific/degenerative
- Bicuspid valve
- Rheumatic heart disease
What clinical signs may differentiate calcific aortic stenosis from rheumatic aortic stenosis?
- Rheumatic disease involves more than one valve (i.e. aortic and mitral)
- Absence of features of MS/MR
- Absence of features of AR
What are the predisposing factors for calcific aortic stenosis?
- Age*: normal valve 70-90yrs, bicuspid 50-70yrs
- Bicuspid valve or other congenital abnormality
- Wear and tear, chronic injury
- Hyperlipidaemia
- HTN
- Inflammation
- Other factors associated with atherosclerosis
*needed to pass + 1 other
What are the potential complications of a congenital bicuspid aortic valve?
- Calcification*
- Stenosis*
- Regurgitation
- Infective endocarditis
- Aortic dilation
- Dissection
*needed to pass + 2 others
What are the systemic and local factors that lead to atherosclerosis?
- HTN*
- Hyperlipidaemia*
- Toxins from cigarette smoke*
- Homocysteine
- Infectious agents
- Inflammatory cytokines (e.g. TNF) can also stimulate pro-atherogenic patterns of endothelial cell gene expression
Two most important causes of endothelial dysfunction are haemodynamic disturbances and hyperlipidaemia*
Local flow disturbances (e.g. turbulence at branch points)* leads to increased susceptibility of certain portions of a vessel wall to plaque formation
*needed to pass
Which arteries are most often affected by atherosclerosis?
3/5 to pass:
- Lower abdominal aorta
- Coronary arteries
- Popliteal arteries
- Internal carotid arteries
- Vessels of the circle of Willis
How does an atherosclerotic plaque suddenly cause symptoms?
2/5 to pass:
1. Rupture, ulceration or erosion:
- Of the intimal surface of atheromatous plaques exposes the blood to highly thrombogenic substances and induces thrombosis
- Such thrombosis can partially or completely occlude the lumen and lead to downstream ischaemia
2. Haemorrhage into a plaque:
- Rupture of the overlying fibrous cap, or of the thin-walled vessels in the area of neovascularisation, can cause intra-plaque haemorrhage
3. Atheroembolism:
- Plaque rupture can discharge atherosclerotic debris into the bloodstream, producing microemboli
4. Aneurysm formation:
- Atherosclerosis-induced pressure or ischaemic atrophy of the underlying media, with loss of elastic tissue, causes weakness resulting in aneurysmal dilation and potential vessel rupture
5. Occlusion:
- Small vessels can occlude, compromising distal perfusion
Describe the differences between stable and vulnerable atherosclerotic plaque
- Stable:
- Dense collagenous and thickened fibrous caps * with minimal inflammation * and small underlying atheromatous * core - Vulnerable:
- Thin fibrous cap *, large lipid core * and increased inflammation *
- Prone to rupture
*2/3 for each
Name some causes of dilated cardiomyopathy
2/4 to pass:
- Myocarditis (mostly viral)
- Toxins (alcohol, chemotherapeutics, cobalt)
- Congenital
- Pregnancy
What are potential pathological consequences of dilated cardiomyopathy?
2/5 to pass:
- Valve dysfunction (incompetent mitral/tricuspid)
- Mural thrombi and embolisation
- Lethal arrhythmia
- Atrial fibrillation
- Death from progressive failure
What are the causes of acquired cardiomyopathy?
- Infections*: viral, bacterial, fungal, protozoal
- Metabolic*: hyperthyroidism, nutritional
- Infiltrative*: sarcoid, carcinoma
- Immunological*: autoimmune myocarditis
- Drugs/toxins*: alcohol, chemotherapy
- Ischaemic
- Hypertensive
- Valvular
3/5 needed to pass + examples
How do dilated and hypertrophic cardiomyopathy differ?
Dilated:
- Cardiac dilatation
- Poor LVEF (<40%)*
- Impaired contractility (systolic dysfunction)*
Hypertrophic:
- Myocardial hypertrophy
- Normal or high LVEF*
- Impaired compliance (diastolic dysfunction)*
*needed to pass
What is cor pulmonale?
R-sided heart failure that is not secondary to L-sided heart failure (pure RHF)*
- Can be acute (e.g. massive PE) or chronic (e.g. chronic lung disease)
*needed to pass
What are the common causes of cor pulmonale?
Common feature is pulmonary HTN*:
- Diseases of pulmonary parenchyma (e.g. COPD, fibrosis, bronchiectasis)
- Diseases of pulmonary vessels (e.g. primary pulmonary HTN, recurrent PE, extensive pulmonary arteritis e.g. Wegener’s granulomatosis)
- Disorders affecting chest movement (e.g. marked obesity, kyphoscoliosis, neuromuscular)
- Disorders causing pulmonary arterial constriction (e.g. hypoxaemia, metabolic acidosis, chronic sleep apnoea, altitude sickness)
*needed to pass + 3 others
What are the major morphological features of cor pulmonale?
Pulmonary congestion is minimal whereas engorgement of the systemic and portal venous systems may be pronounced (3 to pass):
- Heart: RV hypertrophy and dilatation, leftward bulging of septum
- Liver / portal system: congestive hepatomegaly, centrilobular necrosis, congestive splenomegaly
- Pleural, pericardial and peritoneal spaces: effusions, ascites
- Subcutaneous tissues: oedema (dependent and peripheral portions of body, anasarca)
What factors predispose to infective endocarditis?
Cardiac factors*:
- Myxomatous mitral valve
- Calcific aortic stenosis
- Bicuspid aortic valve
- Prosthetic valves
- Rheumatic heart disease
Host factors*:
- Neutropaenia
- Immunodeficiency
- Malignancy
- Therapeutic immunosuppression
- Diabetes
- Alcohol
- IVDU
- Bacteraemia
*2 examples from each to pass
Which organisms commonly cause infective endocarditis?
- Streptococcus viridans*
- Staphylococcus aureus*
- Staphylococcus epidermidis
- Enterococci
- HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
- Fungi
*needed to pass + 1 other
What are the complications of infective endocarditis?
Local*:
- Erosion/destruction of underlying cardiac tissue (valve, myocardium)
- Abscess formation
Systemic*:
- Systemic emboli and infarcts (e.g. of brain, kidneys, lung, subcutaneous tissues i.e. Janeway lesions, retina)
- Glomerulonephritis (immunologically mediated)
*1 of each needed to pass
What is heart failure?
When cardiac function is impaired* and/or the heart is unable to maintain a CO* sufficient for the body’s metabolic needs
*needed to pass
Classify the types of heart failure
- Systolic dysfunction (contractile dysfunction):
- E.g. myocardial contractile dysfunction secondary to ischaemia, AMI, pressure or volume overload, dilated cardiomyopathy - Diastolic dysfunction (inadequate filling):
- E.g. LV hypertrophy, myocardial fibrosis, amyloidosis, pericarditis - Others:
- E.g. arrhythmias, regurgitant flow (MR), outflow obstruction (AS), HOCM - Left heart failure:
- E.g. IHD, HTN, valvular diseases (AS), rheumatic heart disease, myocardial disease - Right heart failure:
- E.g. secondary to left heart failure, PE, pulmonary HTN
What are the clinical features of heart failure?
3/5 to pass:
1. Cardiovascular:
- 3rd heart sound, gallop
- Murmurs
- Displaced apex beat
- JVP elevation
- AF
2. Respiratory:
- Dyspnoea
- Orthopnoea
- PND
- APO
- Pleural effusions
3. Renal:
- Renin-angiotensin-aldosterone system activation
- Fluid retention
- Pedal oedema
- AKI
4. Neurological:
- Confusion secondary to hypoxia
5. Hepatic:
- Engorgement/congestion
- Ascites
- Cirrhosis (late)
What are the major causes of heart failure?
- Ischaemic heart disease*
- Valvular heart disease*
- HTN*
- Cardiomyopathy
- Fluid overload
*2/3 to pass + 1 other
What pathological processes can occur in the myocardium in heart failure?
2 to pass:
- Infarction
- Ischaemia of myocardium
- Calcification
- Hypertrophy of cardiac myocytes
- Interstitial fibrosis
What are the pathological changes in the liver caused by heart failure?
- Nutmeg liver (congestion/oedema)
- Centrilobular necrosis* (results from central hypoxia)
- Centrilobular fibrosis* -> cardiac sclerosis (due to longstanding right heart failure)
- Cardiac cirrhosis in extreme cases
*needed to pass
How is hypertension classified?
Primary (essential)
Secondary
What are the causes of secondary hypertension?
6 examples from 3 different systems:
1. Renal:
- Acute glomerulonephritis
- Chronic renal disease
- Polycystic disease
- Renal artery stenosis
- Renal vasculitis
- Renin-producing tumours
2. Endocrine:
- Adrenocortical dysfunction (e.g. Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia, licorice ingestion)
- Exogenous hormones (e.g. glucocorticoids, oestrogen including pregnancy-induced and OCP, sympathomimetics and tyramine-containing foods, MAOIs)
- Phaeochromocytoma
- Acromegaly
- Hypothyroidism
- Hyperthyroidism
- Pregnancy-induced
3. Cardiovascular:
- Coarctation of aorta
- Polyarteritis nodosa
- Increased intravascular volume
- Increased CO
- Rigidity of the aorta
4. Neurological:
- Raised ICP
- Sleep apnoea
5. Psychogenic:
- Acute stress (including surgery)
- Pain
What is an acute coronary syndrome?
ACS is a clinical manifestation of ischaemic heart disease, and can present as unstable angina, acute MI (either STEMI or NSTEMI) or sudden cardiac death
What are the pathological processes that underlie acute coronary syndrome?
- Typically initiated by an unpredictable and abrupt conversion of a stable atherosclerotic plaque to an unstable and potentially life-threatening atherothrombotic lesion through rupture, superficial erosion, ulceration, fissuring, or deep haemorrhage
- In most instances, plaque changes (typically associated with intra-lesional inflammation) precipitate the formation of a superimposed thrombus that partially or completely occludes the artery
Following acute myocardial infarction, what complications might a patient have?
3 to pass:
1. Contractile dysfunction causing hypotension (cardiogenic shock in 10-15%)
2. Arrhythmias (e.g. sinus bradycardia, AF, HB, tachycardia, VT, VF)
3. Myocardial rupture (ventricular free wall rupture 2-7 days post MI, septum rupture, papillary muscle rupture)
4. Ventricular aneurysm
5. Pericarditis (2-3 days post MI) / Dressler’s syndrome / pericardial effusion / tamponade
6. Infarct expansion
7. Papillary muscle dysfunction
8. Progressive heart failure
9. Mural thrombus
Describe the pathogenesis of myocardial infarction due to atherosclerosis
- Acute plaque change*:
- Rupture/fissuring
- Erosion/ulceration
- Haemorrhage into atheroma - Thrombosis*:
- Platelet adhesion, aggregation and micro-thrombi formation
- Platelet release of mediators causing vasospasm
- Activation of coagulation pathway leading to thrombus - Vasoconstriction* stimulated by:
- Circulating adrenergic agonists
- Locally released platelet contents
- Endothelial cell dysfunction causing decreased NO
- Perivascular inflammatory cell mediators - Vessel occlusion* leading to:
- Decreased myocardial blood flow
- Myocyte necrosis
*3/4 needed to pass + understanding
What are the main cardiac rupture syndromes?
1/3 to pass:
- Free wall -> tamponade (most common; occurs at 1-10 days)
- Septum (causes VSD and L-to-R shunt)
- Papillary muscle dysfunction (causes severe MR)
What changes occur in ventricular remodeling?
Hypertrophy and dilation * -> increased O2 demand -> ischaemia and depressed cardiac function * -> scar formation * -> stiffening * and hypertrophy
*3 to pass
What systemic factors affect infarct healing?
3/4 to pass:
- Nutritional: protein, vitamin C
- Metabolic: diabetes
- Circulatory: arterial, venous
- Hormonal: glucocorticoids
Describe the time course of myocardial injury after acute coronary artery occlusion
Reversible injury:
- Cessation of aerobic metabolism within seconds
- Decreased ATP production and increased lactic acid production (noxious metabolites)
- Loss of contractility within 1 min
- Ultrastructural changes (myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling) within a few mins
- ATP depletion up to 40 mins
Irreversible injury:
- Myocyte injury (defects in sarcolemmal membrane and cell leakage) within 20-40 mins
- Initially subendocardial then transmural myocyte death
- Microvascular injury within 1hr
- Coagulation necrosis after >2hrs (more protracted if collaterals)
What are the causes of pericarditis?
- Infectious:
- Viral*
- Pyogenic bacteria
- TB
- Fungal - Immune-mediated:
- Rheumatic fever
- SLE
- Scleroderma
- Post cardiotomy
- Post MI (Dressler’s)
- Drug hypersensitivity reaction
- AMI
- Uraemia
- Post cardiac surgery
- Neoplastic
- Trauma
- Radiation
*needed to pass + 1 immune-mediated + 1 other
What types of pericardial fluid exudates occur?
2/5 to pass:
1. Serous:
- Usually non-infectious inflammation (e.g. RF, SLE) but also viral, uraemia, tumours
2. Fibrinous/serofibrinous:
- Most common
- Post MI, Dressler’s, trauma, post-surgery
- Also as in 1
3. Purulent/suppurative:
- Almost always bacterial
- May be due to invasion from local infection, lymphatic or blood seeding, or from surgery
4. Haemorrhagic
5. Caseous (TB)
Describe the characteristic clinical features of pericarditis
- Chest pain* (dull or sharp, pleuritic, positional)
- Pericardial friction rub* (may be absent if large effusion)*
- Fever* (chills and rigors if suppurative)
- Signs of cardiac failure
- In constrictive pericarditis: distant or muffled heart sounds, elevated JVP, peripheral oedema
*needed to pass
