cardiovascular Flashcards
define atherosclerosis
an arteriosclerosis characterized by atheromatous deposits in and fibrosis of the inner layer of the arteries
Plaques – go into bv = occlusion
Rupture = sudden occlusion
formation of an atheroma
Arise on lesion in bv where smooth endothelium is damaged
Fatty streak – precurser lesion
plts stick to damaged tissue
proliferation of endothelium
fibrous cap forms on top of endothelium
deposition of cholesterol in core - fatty core
necrotic debris
block lumen = stenosis
Rupture = thrombosis and occlusuion
RF for atherosclerosis
Age
Sex
Genetics
Hyperlipidaemia
Hypertension
Smoking
Diabetes Mellitus
have multiplicative effect
age as a RF for MI
Clinically silent until reach threshold in middle age
Risk increases 5x form 40-60 yr
And risk increases with each decade
sex as a RF for CVD
Premenopausal women protected (HRT no protection)
Postmenopausal risk increases (older ages greater than men)
After 65 oestrogen can increase risk of CVS
genetics as a RF fro cvd
FH most sig independent RF
Some mendelian disorders (eg Familial Hypercholesterolaemia)
Most multifactorial (genetic polymorphisms -> clustered risk factors HT, DM)
hyperlipidaemia as a RF for cvd
LDL – cholesterol to peripheral tissue
HDL – take from plaque to liver and excrete in bile
Exercise can increase HDL
diet rich in LDL = bad
statins - inhibit HMG-CoA reductase rate limiting enzyme in liver cholesterol synth
HTN as a rf for cvd
increases risk of IHD by 60%
HTN – risk of LV hypertrophy = myocardial ischemia
smoking as a rf for cvd
double death rate by IHD
stopping reduces the risk sig
dm as a rf for cvd
Induces hypercholestrolaemia
Increases risk of atherosclerosis
doubles IHD risk
other rf for cvd
Inflammation - associated with atherosclerosis, CRP
Metabolic syndrome - central obesity, insulin resistance, htn, dyslipidaemia – proinflammatory state, triggered by cytokines from adipocytes.
Lipoprotein (a) - correlate risk with coronary and cerebrovascuilar disease independent other RF
Haemostasis (procoagulation)
Lack of exercise
Stress
Obesity
endothelial dysfunction - more likely to get plaques
pathogenesis of atherosclerosis
response to injury hypothesis:
Endothelial disruption – interrupt flow – LDL deposit
-> inflammatory response
?
chronic inflammation and healing response -> endothelial injury
interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with endothelial cells and smooth muscle cells -> lesion progression
monocytes adhere to endothelium #
-> migrate into intima
-> macrophages and foam cells
plt adhesion
Factor release from activated platelets, macrophages, -> smooth muscle cell recruitment.
Smooth muscle cell proliferation, extracellular matric production, and recruitment of T cells.
Lipid accumulation -> extra & intracellular, macrophages & smooth muscle cells
-> thickening of wall
White – cholesterol clefts
what are fatty streaks
Earliest lesion in bv – doesn’t cause dysfunction - No flow disturbance
Lipid filled foamy macrophages
In virtually all children >10yrs
Relationship to plaques uncertain
Same sites as plaques
what is an atherosclerotic plaque
Patchy – local flow disturbances
Only involve portion of wall
Rarely circumferential
Appear eccentric
Composed of – cells, lipid, matrix
* Cells – sm, macrophages, T cells
* Matrix – collagen, elastic, proteoglycans
* Lipids – intra and extracellular lipids
what are the consequences of atheroma
stenosis
acute plaque change
summarise stenosis
critical stenosis is where demand is more thanm supply
sx at ~70% occlusion (or diameter <1mm)
Causes “stable” angina
Can lead to Chronic Ischaemic Heart Disease
Acute plaque rupture can occur
diff between a stable and a vulnerable plaque
Get inflammatory response
Stable plaque – lipid core thin and cap is thick
Vulnerable – large lipid core, and thin cap – likely to thrombosis
pathology 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 (neutrophils) then macrophages (clear up debris)
5-10 days removal of debris
1-2 weeks granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
Weeks-months strengthening, decellularising scar
MI pathology at 1-3 days
Coagulation necrosis,
loss nuclei & striations,
neutrophils +++ (polymorphs because acute inflammatory reaction)
myocytes lose nuclei - because starved of oxygen
MI pathology at 10-14 days
granulation tissue
foamy macrophages
MI pathology at >2mo
A lot of fibrosis and scar formation
angioplasty
complications of MI
- Contractile dysfunction – 40% infarct-> cardiogenic shock with 70% mortality rate
- Arrhythmia due to myocardial irritability & conduction disturbance – bradycardia, supraventricular tachycardia etc.
-
Myocardial rupture - left ventricular free wall most common, septum less common, papillary muscle least common.
(At mean 4-5days, range 1-10 days) - recurrence
- dressler syndrome - pericarditis on 2nd or 3rd day
- RV infarction
- infarct extension - new necrosis next to old
- infarct expansion - necrotic muscle stretches, press on ventricles and reduce output -> mural thrombosis
- mural thrombus
- Ventricular aneurysm, late -> thrombus, heart failure, arrhythmia, do not rupture
- Papillary muscle rupture
- Chronic Ischaemic Heart Disease (Chronic IHD) = progressive late heart failure
ventricular aneurysm
papillary muscle rupture
MI complication time frame
