Cardiac pathology Flashcards
Definition and pathophysiology of atherosclerosis
Chronic inflammation in intima of large arteries characterized by intimal thickening and lipid
accumulation
Steps of atherogenesis:
1. Endothelial injury
2. LDL enters intima and is trapped in sub-intimal space
3. LDL is converted into modified and oxidized LDL causing inflammation
4. Macrophages take up ox/modLDL via scavenger receptors and become foam cells
5. Apoptosis of foam cells causes inflammation and cholesterol core of plaque
6. Increase in adhesion molecules on endothelium results in more macrophages and T cells
entering the plaque
7. Vascular smooth muscle cells form the fibrous cap
Components of atherosclerotic plaques
Atherosclerotic plaques have 3 principal components:
- Cells - including SMC, macrophages and other leukocytes;
- ECM including collagen;
- Intracellular and extracellular lipid
Risk factors for atherosclerosis
Risk Factors:
Modifiable: Type 2 Diabetes Mellitus, Hypertension, Hypercholesterolaemia, Smoking
Non-modifiable: Gender (Males>Females), increasing age, Family History
Abdominal aorta affected more than thoracic aorta.
More prominent around origins (ostia) of major branches; turbulent blood flow has
low/oscillatory shear stress, which is atherogenic. High laminar flow is protective.
Pathogenesis of MI
a dynamic interaction between coronary atherosclerosis, plaque rupture,
superimposed platelet activation, thrombosis and vasospasm -> occlusive intracoronary thrombus
overlying a disrupted plaque. This results in myocardial necrosis secondary to ischaemia. Severe
ischaemia lasting >20-40mins results in irreversible injury and myocyte death.
Types of complications following MI
Mechanical
Arrhythmias
Pericardial
Mural thrombus
Mechanical complications of MI (5)
Contractile dysfunction due to loss of muscle -> cardiogenic shock
Congestive cardiac failure – due to ventricular dysfunction (and arrhythmias)
LV infarct – papillary muscle dysfunction/necrosis/rupture -> mitral regurgitation
Cardiac rupture of; ventricular wall (haemopericardium), septum (left to right shunt,
VSD), papillary muscle (MR)
Ventricular aneurysm – usually develops >4 weeks post-MI (causes persistent ST elevation)
Histological evolution of MI
● Under 6 hours - normal by histology (CK-MB also normal)
● 6–24 hrs - loss of nuclei, homogenous cytoplasm, necrotic cell death
● 1-4 days - infiltration of polymorphs then macrophages (clear up debris)
● 5-10 days - removal of debris
● 1-2 wks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
● Weeks-months - strengthening, decellularising scar tissue.
Common causes of heart failure (6)
● Ischaemic heart disease ● Valve disease ● Myocarditis ● Hypertension ● Dilated cardiomyopathy ● Arrhythmias
Complications of heart failure
● Sudden Death
● Systemic emboli
● Arrhythmias
● Deep vein thrombosis and pulmonary embolism
Pathology of different types of heart failure
Left: Pooling of blood within pulmonary circulation due to high pressures in left side of heart
→ dyspnoea, orthopnoea, PND, wheeze, fatigue. Eventually leading to decreased peripheral
blood pressure and flow.
Right: Often secondary to LVF but can be primarily caused by chronic severe pulmonary
hypertension. There is minimal pulmonary congestion but engorgement of systemic and portal
venous systems, clinically seen as peripheral oedema, ascites, facial engorgement. NUTMEG LIVER
Congestive: Left and right
Types of cardiomyopathy
Dilated
Hypertrophic (hypertrophic obstructive)
Restrictive
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Where in the body does rheumatic fever effect?
Age: 5-15
● Heart: pancarditis i.e. endocarditis, myocarditis, pericarditis;
● Joints: arthritis and synovitis;
● Skin: Erythema marginatum, subcutaneous nodules
● CNS: Encephalopathy, Sydenham’s chorea
Clinical features of rheumatic fever
2-4 weeks after strep infection
Diagnosis with Sterp A infection + 2 major criteria or 1 major + 2 minor criteria
Commonly affects mitral valve only (70%) but can affect both mitral and aortic (25%)
Histology: Beady fibrous vegetations (verrucae), Aschoff bodies (small giant-cell granulomas)
and Anitschkov myocytes (regenerating myocytes).
Treatment: Benzylpenicillin
Major criteria for rheumatic fever
Jones' major criteria: C - Carditis A - Arthritis S - Sydenham's chorea E - Erythema marginatum S - Subcutaneous nodules
Minor criteria for rheumatic fever
○ fever ○ raised ESR or CRP ○ migratory arthralgia ○ prolonged PR interval ○ previous rheumatic fever ○ malaise ○ tachycardia