Mechanism of atheroma and infarction Flashcards
Atheroma
Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, leading to restriction of the circulation and a risk of thrombosis.
-weakened wall so risk of it rupturing
Infarction
Obstruction of the blood supply to an organ or a region of a tissue, typically by a thrombus (blood clot) or embolus causing local death of the tissue
so, what is a myocardial infarction?
infarction in the myocardium, local death of the tissue
aneurysm
excessive localised swelling of the wall of an artery
what can cause an infarction?
an aneurysm
what the difference between arteries in the heart and other organs and the consequence of this?
cardiac arteries, are functional end arteries
with most tissues, if one artery gets blocked there’s another route - but not in the heart
if there is a thrombus or embolus in heart, the tissue can be starved of oxygen
what is atherosclerosis?
A complex inflammatory process
- mediated by LDL and angiotensin II. An ongoing systemic inflammatory disease makes it all worse (eg. rheumatoid arthritis)
- LDL in blood get deposited in arteries but made a lot worse by ongoing inflammatory processes
common sites for atherosclerosis
- Carotid Arteries - aorta to brain. if blocked, starving big areas of the brain of oxygen. circle of willis is a network of arteries underneath the brain which supply diff parts of the brain with blood - a clot here means you can have a stroke and where the clot is determines which part of the brain is starved and what your symptoms are.
- Coronary arteries - functional end arteries, so a clot or an atherosclerotic plaque in the coronary artery starves part of the heart because there is no other arterial route to get there
- Iliac arteries - in pelvis about to go legs
- Aorta
initiation of atherosclerosis (1)
Low levels of inflammation, necrotic cell debris and free radicals in the endothelium cause oxidation of LDL’s
Endothelial cells start to become a little bit inflamed and activated and express cytokines and adhesion molecules as part of a normal inflammatory response.
Causes circulating monocytes, which are looking for infected cells, to bind to the activated endothelium. They do this by expressing adhesion molecules, undergo diapedesis move through the tissue into the intima layer.
Once monocytes are in the tissue they differentiate into tissue macrophages which release their own inflammatory mediators which attract more macrophages (appropriate immune response IF there was a virus)
plaque formation (2)
macrophages begin to absorb LDL’s from the circulation and become foam cells
these activated foam cells release growth factors which affect the medial muscle layer: they cause smooth muscle cells to cross the internal elastic lamina into the intima
the activated smooth muscle cells once in the intimate release growth factors, collagen and elastin - not secreting collagen and elastin in the right place
plaque maturation (3)
smooth muscle cells accumulate LDL and become smooth muscle foam cells. they continue to make extracellular matrix of elastin and collagen, which forms a fibrous plaque - this can weaken the wall of the vessel and can get bigger and bigger, narrowing the lumen
this plaque is underneath the endothelium and it means that foam and muscle cells in this region become hypoxic because of the poor oxygen supply.
the cells begin to undergo apoptosis and release their fat that accumulates in the intimacy underneath the fibrous cap - called the lipid core.
the dying cells also release matrix metalloproteases (and other enzymes) which can break down the fibrous matrix towards the edge of the fibrous plaque - may be vulnerable to enzymatic digestion
calcification and instability (4)
calcium deposits may form around the atheroma - visible on a CT scan. affect arterial compliance and they make the vessel stiff and stop the vessel stretching - can be dangerous when the vessel can’t stretch a higher pressures
could be an advantage?
why might a few calcium deposits around the plaque be advantageous?
prevents the fibrous plaque from breaking off, so it can’t expose the underlying collagen - would lead to a thrombus event and the formation of a blood clot
when does atheroma begin?
when we are young
- macrophage foam cells develop between birth and 10 yrs old
- 65% of people have smooth muscle foam cells by puberty
- maturation of fibrous cap at 30-40 yrs
plaque rupture (5)
plaque can rupture in 2 situations:
1) if the central core becomes too large
2) the dying cells succeed in releasing enzymes that digest the fibrous plaque
this results in the sub-endothelium being exposed (the endothelium is normally an anticoagulant surface) - collagen is exposed.
collagen forms very good bases for clotting, and this means there is a pro-coagulant surface in an artery - thrombus could form which may occlude the artery.
