atheroma + infarction Flashcards
Key components of atheromatous plaques (5)
what does fibrous cap do? what does it sit on top of? what happens to smooth muscle cells? what is the necrotic core? what infiltrates into the plaque? what else infiltrates at base of plaque?
1) Fibrous cap -> sits on top of necrotic core + cellular layer hence smooth muscle/collagen/elastin therefore fibrous layer encases the lesion
2) smooth muscle cells will have migrated from the intima
3) necrotic core -> build up of lipid + cholesterol
4) infliltration of immune cells (migrated into plaque)
5) neovascularization at base of plaque hence new blood vessels infiltrate into the plaque region
Development of atheromatous plaques
what does it start off as? and lead to an accumulation of?
what develops over this?
what could eventually happen and what does it activate?
start off as fatty streaks leading to an increased accumulation of lipids which develop into an atheroma
fibrous cap develops over the lesion
plaque ruptures + activates thrombosis and can occlude the vessel
Most common sites of plaque build up
5
Circle of Willis Carotid arteries Coronary arteries Aorta Iliac arteries
Major risk factors for atherosclerosis
Age Male sex (premenopausal women protected) Genetics Hyperlipidaemia Smoking Hypertension Diabetes mellitus Obesity Metabolic syndrome Alcohol Drugs Systemic inflammation promotes atheroma Rheumatoid arthritis Parasitic infections
The modern view of atherosclerosis: A complex inflammatory process
what are 2 inflammatory mediators which are ‘healthy’?
example of ongoing systemuc inflammatory disease? what does it do?
Angiotensin II is an inflammatory mediator
Low density lipoprotein is an inflammatory mediator
An ongoing systemic inflammatory disease accelerates atherosclerosis
e.g. rheumatoid arthritis
Atheroma - initiation
what gets actcivated? by what? what effect does this have?
what bind to this acitvated cell and what happens to them? what effect do these cells have and where?
❶ Circulating inflammatory mediators activate endothelial cells which become dysregulated and express cytokines and adhesion molecules (e.g. vascular cell adhesion molecule (VCAM-1)
❷. Circulating monocytes bind to the activated endothelium (rolling hypothesis) and migrate between endothelial cells in the intimal tissue
❸. Monocytes differentiate into tissue macrophages and release inflammatory cytokines into the intima ❹.
atheroma - plaque formation
what do macrophages upregulate? what does this allow?
what does further release for prinflammatory mediators do?
what do vascular smooth muscle cells release? what does this stimulate (2)? what is known as and why?
❶ Macrophages upregulate scavenging receptors which allows the uptake of LDL and conversion of macrophages into lipid-laden foam cells.
❷ Further release of proinflammatory mediators stimulates vascular smooth muscle cells to migrate from the media into the intimal space
❸. Vascular smooth muscle cells release growth factors that stimulate cell division and proliferation as well as synthesizing collagen and elastin. This is known as the ‘synthetic phenotype’ as VSMCs loose their contractile properties ❹.
atheroma - plaque formation
foam cells
what develops into foam cells? why? what causes them to become foamy?
what is further released and what does this stimulate + activate? what happens to these cells and what will they secrete?
tissue macrophages develop into foam cells due to macropages upregulating scavenger receptors -> this will mediate the uptake of LDL into the cell therefore will become foamy
Further release of cytokines which stimulate + activate the smooth muscle cells -> normally contractile muscle cells that regulate vascular tones will begin to move + migrate out of the media and into the intima
These muscle cells will secrete other type of proteins in resposne to cytokines + growth factors (e.g elastin + collagen)
The growth factors will also act on smooth muscle cells to stimulate cell division + proliferation
Why are smooth muscle cells called synthetic?
Not contractile
hence they become synthetic as they secrete collagen + elastin (lose contractile properties)
Maturation of Plaque
what also become foam cells? how?
what happen to both types of foam cells? what does this lead to and what do we call this?
what forms about this? why?what do we call this?
❶ Smooth muscle cells also start to accumulate LDL becoming smooth muscle foam cells.
❷ Both types of foam cell eventually undergo apoptotic cell death releasing pools of lipid that accumulate forming an expanding lipid core within the intimal layer called an atheroma.
❸ A fibrous plaque of extracellular matrix components elastin and collagen forms a layer above the atheroma resulting in a fibroatheroma ❹.
Calcification of the plaque
why does this occur?
what is deposited and effect of this?
what is this used as?
Calcification occurs as foam cells in regional environment will release CA2+
Ca2+ will deposit in fibrous layer and region hence hardening the atheroma
Can be used clinically as a marker of athersclerosis therefore a biomarker of a lesion to identify the degree of Ca2+ within atheroma
Plaque rupture
what can happen to the lipid core? and if this happens, what process does it activate and why?
❶ The lipid core can become necrotic and start to fracture and fragment creating fissures within the core. It can rupture through the endothelial layer causing trauma and exposing subendothelial collagen and tissue factor to the blood. This initiates the clotting cascade forming a thrombus.
Consequences of atheroma (2) + examples
Occlusive Thrombosis
e.g. myocardial infarction
Thromboembolism
e.g. ischaemic stroke
Consequences of atheroma (2) + examples
Peripheral vascular disease
e.g. critical limb ischaemia
Hence will reduce o2 supply in limb which will reduce healing and increase ulcerfication
Aneurysm due to wall weakness
e.g. aortic aneurysm
Some causes of chest pain
Broken rib Collapsed lung Nerve infection (shingles) “Pulled” muscle Infection Heart burn (hernia) Pericarditis Blood clot in the lungs (PE) Angina - (chest pain upon exertion hence more work of the heart and less o2 supply leads to pain) Myocardial infarction
