CVS Pathology Flashcards
Describe the pathogenesis of an aortic dissection
- Medial weakness (commonly from HTN), medial hypertrophy vasa vasorum, intimal tear, blood flow dissects the media -> medial haematoma.
- Cystic medial degeneration (HTN)
- Risk factors – HTN, CT disease (e.g. Marfan’s, Ehlers-Danlos), iatrogenic (e.g. arterial cannulation), pregnancy, trauma
How are aortic dissections classified?
By site of involvement:
Stanford
Proximal (A) and distal (B)
DeBakey
I – ascending and descending
II – ascending only
III – descending only (better prognosis)
What are the potential consequences of aortic dissection?
- Rupture back into intima or out through adventitia
- Most common cause of death is rupture into pericardial, pleural or peritoneal cavities
- Other outcomes include cardiac tamponade, aortic insufficiency, MI, extension into any of the branches of the aorta causing obstruction +/- ischaemia, transverse myelitis
What are the causes of Aortic valve stenosis?
- Post-inflammatory scarring (Rheumatic fever)
- Senile calcific Ao Stenosis
- Calcification of congenitally deformed valve
What is calcific aortic stenosis?
- Ao Stenosis most common valvular abnormality (2%)
- Wear and tear => calcification on normal or cong bicuspid valves (1%). Newer evidence implicates chronic injury from HTN, hyperlipdaemia & inflammation.
- Clinically significant in 6-7th decade in bicuspid valves, 8-9th decade in prev. normal valves
- Heaped up calcified masses within cusps=> protrude through to outflow tracts. Functional valve area decreased.
What are the consequences of calcific aortic stenosis?
- LV outflow obstruction=> increased pressure gradient over valve. (Severe when valve area 0.5-1 cm2)
- CO maintained by concentric LVH. Hypertrophied myocardium ischaemic.
- Impaired systolic and diastolic function.
- Decompensation => angina, CCF, syncope
What are the causes of acute pericarditis?
- Infectious; viral, pyogenic bacteria
- Immune mediated (presumed); Rheumatic fever, SLE, Scleroderma, post cardiotomy. Post MI (Dressler’s), Drug hypersensitivity reaction.
- Other; AMI, uraemia, post cardiac surgery, neoplastic, trauma, radiation
What types of pericardial fluid exudate occur?
- Serous; usually non-infectious inflammation, RF, SLE, uraemia, tumours
- Fibrinous/serofibrinous; (most common) post MI, Dressler’s, trauma, post surgery but also as in 1.
- Purulent/suppurative; almost always bacterial invasion from local infection, lymphatic or blood seeding, or at operation
- Haemorrhagic
- Caseous
Describe the clinical features of pericarditis
- Pericardial rub (may be absent if large effusion).
- Pain, fever (chills and rigors if suppurative)
- Signs of cardiac failure
Outline the steps involved in the pathogenesis of atherosclerosis
Response to injury hypothesis:
- Endothelial injury and dysfunction
- Lipoprotein (mainly LDL) accumulation and oxidation in vessel wall
- Monocyte adhesion and migration into intima and transformation into foam cells and macrophages
- Platelet adhesion
- Smooth muscle cell migration from media into intima
- Subsequent smooth muscle cell proliferation in intima
- Enhanced lipid accumulation within intimal cells (macrophages and smooth muscle cells)
List the potential causes of endothelial injury?
- Hyperlipidaemia,
- Hypertension,
- Smoking
- Haemodynamic factors (disturbed flow patterns)
- Homocysteine
- Toxins
- Viruses
- Immune reactions
List the major risk factors for aortic dissection?
- Hypertension
- Connective tissue diseases eg. Marfan Syndrome,
- Iatrogenic: coronary artery catheterisation, coronary artery by pass.
- Pregnancy
- Trauma
Describe the morphological features of aortic dissection
- Most frequent pre-existing = medial degeneration of elastic tissue
- Intimal tear aorta extends into the media.
- Haematoma spread between the middle and outer thirds along the laminar planes of the media and formed a blood filled channel.
- Disrupts outward causing massive haemorrhage or re-rupture into the lumen of the aorta producing a false lumen.
What are the consequences of aortic dissection?
- Dissects proximally towards the aortic valve and vessels of the neck and causes disruption of the aortic valve, cardiac tamponade, myocardial infarction, cerebral vascular accident.
- Dissects distally into the renal, mesenteric, iliac & femoral arteries causing ischaemia.
- Compression of the spinal vessels causing transverse myelitis.
Describe the pathological changes in myocardium following occlusion of a coronary artery
- Loss of contractility (<2mins); loss of ATP (50% at 10min, 10% at 40min); irreversible cell injury (20-40min); microvascular injury (>1hour); coagulative necrosis.
- Minutes: myofibrillar relaxation, glycogen depletion, mitochondrial and cell swelling.
- 40minutes: sarcolemmal disruption, mitochondrial amorphous densities.
- Necrosis first in subendocardium, endocardium is spared. 4-12hour coag necrosis, edema, haemorrhage
What are the potential consequences of reperfusion?
- Early: no damage.
- Late: reperfusion hemorrhage; acceleration of disintegration of damaged myocytes; exaggerated contraction of myofibrils; some new injury from oxygen free radicals.
- ‘Prolonged post-ischaemic ventricular dysfunction’
What are the different types of cardiomyopathy?
- Dilated cariomyopathy
- Hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
What are the causes of acquired cardiomyopathy?
- Infections (viral, bacterial, fungal)
- Toxic (alcohol, cobalt, chemotherapy)
- Metabolic (hyperthyroidism, nutritional deficiency)
- Genetic (storage disorders, muscular dystrophies)
- Infiltrative (sarcoid, carcinoma, radiation)
- Immunologic (autoimmune, rejection)
How dilated and hypertrophic cardiomyopathy differ?
- Dilated CM: gradual 4-chamber hypertrophy and dilation, systolic dysfunction with hypocontraction, poor LV EF (<40%), usually indolent progressive CHF
- Hypertrophic CM: heavy, muscular (myocardial hypertrophy), hypercontractile (normal or high LV EF), poorly compliant hearts with poor diastolic relaxation, 1/3 have ventricular outflow obstruction
What are the complication of hypertrophic cardiomyopathy?
- Sudden cardiac death (VT, VF)
- AF with mural thrombus and embolisation
- Infective endocarditis
- CHF
In acute myocardial infarction, what sequence of events leads to acute coronary artery occlusion?
- Sudden change in atheromatous plaque - haemorrhage, erosion, ulceration, rupture, fissure
- Platelet adherence, activation & aggregation leading to microthrombi
- Vasospasm from platelet released mediators
- Activation of coagulation pathway (intrinsic) causing thrombus
- Vessel occlusion
Describe the time course of myocardial injury after acute coronary artery occlusion
Reversible:
- Cessation of aerobic metabolism, decreased ATP production, lactic acid production (secs)
- Loss of contractility, acute heart failure (2 mins)
- ATP reduction (10-40 mins)
Irreversible:
- Irreversible cell injury (20-40 mins)
- Myonecrosis (begins after 30 mins)
- Microvascular injury (1 hour)
- Coagulation necrosis after 2-4 hrs ischaemia - blood flow >10%
What systemic factors affect infarct healing?
- Nutritional: protein, vitamin C
- Metabolic: diabetes
- Circulatory: arterial or venous
- Hormonal: glucocorticoids
Which arteries are most affected by atherosclerosis?
Large elastic arteries - lower abdo aorta
Coronary arteries
Popliteal arteries
Internal carotid arteries
Circle of Willis
What are the pathological consequences of atherosclerosis?
- Atherosclerotic stenosis - restricting bloodflow to downstream tissues
- Acute plaque change - erosion, rupture or haemorrhage further increasing luminal stenosis and iscahemia
- Thrombosis - over disrupted plaque or embolization and downstream osbtruction
- Vasoconstriction - due to endothelial dysfunction or products released by aggregated plts or infl cells
Describe the pathogenesis of an abdominal aortic anuersym
Structure or function of the vascular wall connective tissue is compromised:
- Poor intrinsic quality of the vascular wall connective tissue, e.g. Marfan’s syndrome, Ehlers-Danlos sy
- Collagen degradation vs synthesis by local inflammation (proteolytic enzymes), e.g. atherosclerotic plaque, vasculitis
- Loss of vascular smooth muscle cells or the inappropriate synthesis of non-collagenous or non-elastic ECM (cystic medial degeneration)
What are the clinical consequences of a AAA?
- Rupture into the preitoneal cavity orretroperitoneal tissues with massive, potentially fatal haemorrhage
- Obstruction of a branch vessel resulting in ischaemic injury, e.g. iliac, renal, mesenteric, or vertebral arteries
- Embolism from atheroma or mural thrombus
- Impingement on an adjacent structure, e.g. ureter, vertebrae
- Nothing (if < 4cm)
What is the risk of rupture of a AAA?
Related to size:
≤ 4cm nil
4-5cm 1% per year
5-6cm 11% per year
> 6cm 25% per year
