Vascular and cardiac pathology Flashcards
coronary heart disease, cvd and strokes are responsible in total for what proportion of deaths?
1/3
what is atherosclerosis?
atheromatous deposits in the innre layer of the artery followed by fibrosis of the same
what is the pathophysiology of atherosclerosis?
endothelium of vessel damaged
Endothelial injury
Lipoprotein accumulation (LDL) (deposition off cholesteerol in core - “fatty core”)
Monocyte adhesion to endothelium
Monocyte migration into intima -> macrophages & foam cells
Platelet adhesion - stick to damaged tissue
Factor release
Smooth muscle cell recruitment
fibrous caps form on top of endothelium
endothelium proliferates
this is the formation of the plaque
-> Response to Injury Hypothesis
what are the Constitutional Risk Factors (impossible/hard to control) in atherosclerosis
Age
Gender - Postmenopausal risk increases
Genetics - most significant independent risk factor
- mendelian or multifactorial inheritance
what is the MOA of statins?
Statins inhibit HMG-CoA reductase rate limiting enzyme in liver cholesterol synthesis
which factors perrpetuate atheroma formation?
Early atheroma arises in intact endothelium
Endothelial dysfunction important – increase permeability, gene expression & adhesion
Haemodynamic disturbance -> dysfunction
Hypercholesterolaemia -> dysfunction
Inflammation -> vicious circle
what is the Earliest lesion in atherosclerosis ?
fatty streak
lsit some Consequences of Atheroma?
Stenosis
- stable angina : at approx 70% occlusion
Acute/Sudden Plaque Change
- Rupture - Erosion - Haemorrhage into plaque – increase size
Majority of plaques that show acute change have _____ luminal stenosis prior to acute change. they are named as ____ victims
only mild to moderate
“asymptomatic potential victims”
what are the characteristics of a Vulnerable Plaque?
Lots foam cells or extracellular lipid
Thin fibrous cap
Few smooth muscle cells
Clusters inflammatory cells
why does emotional stress increases risk of sudden death ?
Adrenalin increases blood pressure & causes vasoconstriction
Increases physical stress on ‘vulnerable plaques’
plaque rupture can lead to which things?
Vessel occlusion
Thrombosis
mechanism for plaque growth
what are the different preesentations of IHD?
Angina pectoris
Myocardial infarction
Chronic IHD with heart failure
Sudden cardiac death.
ruptures, haemorrhage and erosions of plaques lead to?
prothrombotic factor activation
leads to superimposed thrombus which increases occlusion
small plaque
vs large plaque in patient who has been suffering from angina
which is moree likely to rupture?
small one
just by figures - so not everyone has a stepwise progression
__% stenosis can lead to pain at rest
90%
which vessels tend to be affected most in IHD?
epicardial vessels:
Plaques mainly form in first few cm of LAD or LCX
Entire length RCA
list the types of angina and their cause?
Stable, Prinzmetal,Unstable
- Stable comes on with exertion, relieved by rest, no plaque disruption
- Prinzmetal Uncommon, due to artery spasm
3. Unstable angina: Disruption of plaque Superimposed thrombus Possible embolisation or vasospasm Warning of impending infarction
what is the pathogenesis of an MI?
Sudden change to plaque Platelet aggregation Vasospasm Coagulation Thrombus evolves
what is the prognosis of MI?
Potentially reversible
Irreversible after 20-30 minutes
which arteries are most implicated in MI?
LAD – 50%, ant wall LV, ant septum, apex
RCA - 40%, post wall LV, post septum, post RV
LCx - 20%, lat LV not apex
after an MI what does cellular response look like?
After 1 day - Neutrrophils (+ loss of nuclei & striations)
After 3 days - macrophage
7days+ (1 wk+) - fibroblasts n collagen
- will still see granulation tissue, macrophages
which factors are associated with worse prognosis in MI?
Age, female, DM, previous MI
characterise a typical reperfusion injury
Arrhythmias common
reversible cardiac failure lasting several days - “stunned myocardium”
List some complications of MI?
Contractile dysfunction – 40% infarct-> cardiogenic shock with 70% mortality rate
Arrhythmia due to myocardial irritability & conduction disturbance
Myocardial rupture - free wall most common, septum less common, papillary muscle least common.
(At mean 4-5days, range 1-10 days)
Pericarditis (Dressler syndrome) 2nd or 3rd day !!
RV infarction
Infarct extension – new necrosis adjacent to old
Infarct expansion
Mural thrombus
Chronic Ischaemic Heart Disease
Papillary muscle rupture
and more
what is the aetiology of Sudden Cardiac Death?
Felt to be acute ischaemia induced electrical instability!!
Others:
Marked atherosclerosis (>75% stenosis) in one or more vessels
10% non atherosclerotic cause (long QT etc)
½ have plaque rupture
Genetic
how does heart failure present?
Congestive Heart Failure (L&R)
Left sided (-> SOB, pulmonary oedema)
Right sided (-> peripheral oedema)
list some causes of heart failure?
Ischaemic heart disease Valve disease Hypertension Myocarditis Cardiomyopathy
list some complications of heart failure?
Sudden Death
Arrhythmias
Systemic emboli
Pulmonary oedema with superimposed infection
fibrosis and replacement of ventricular myocardium is sen on microscopy in which condition?
heart failure
list the types of cadiomyopahty?
dilated, hypertrophic, restrictive
too thin, too thick, too stiff
what is the aetiology of restrictive cardiomyopathy?
Idiopathic or secondary to myocardial disease eg amyloid, sarcoidosis
Normal size heart – big atria
which cardiomyopathy has a signifficant familial component?
Hypertrophic (HCM):
Left ventricular hypertrophy
Familial in 50% (autosomal dominant, variable penetrance)
Beta-myosin heavy chain
Thickening of septum narrows left ventricular outflow tract
what is the order of valve involvement in CHRONIC RHEUMATIC VALVULAR DISEASE?
Mitral > Aortic > Tricuspid > Pulmonic
Mitral alone 48%, Mitral + aortic 42%
a lot of thickening and fusion occurs
what is the Commonest cause aortic stenosis?
Calcific aortic stenosis
Calcium deposits outflow side cusp
list some causes of AORTIC REGURGITATION
rheumatic disease -causes rigidity
microbial endocarditis - causes destruction
Disease of aortic valve ring : Marfan's Syndrome Dissecting aneurysm Syphilitic aortitis Ankylosing spondylitis
what are true/false aneurysms?
True - all layers wall
False – extravascular haematoma
list somecauses of aneurysms?
Weak wall
Congenital eg Marfans
Atherosclerosis
Hypertension
