Thrombosis and Infarction Flashcards
what two factors prevent blood clotting unnecessarily?
- laminar flow - cells travel in centre of arterial vessels, and don’t touch the sides
- endothelial cells which line vessels are not ‘sticky’ when healthy
describe basic clot formation
coagulation cascade results in formation of a fibrin meshwork that entraps the cells into a solid but elastic clot
commonly form after death
what is a thrombus?
a solid mass of blood constituents formed within an intact vessel in life
what 3 things make up Virchow’s triad?
abnormalities of vessel wall; abnormalities of blood flow; abnormalities of blood constituents
why do we need clot-forming cells and proteins in the blood?
to stop massive haemorrhage if we cut/scratch our selves
what is the first stage of thrombosis?
platelet aggregation
describe the process of platelet aggregation
upon coming into contact with collagen, platelets release chemicals (e.g. ADP) from dense granules that cause the aggregation of other platelets, and set off the clotting cascade.
chemicals released from alpha granules cause platelet adhesion to damaged vessel walls.
after platelet aggregation, what is next in the process of thrombosis?
platelet aggregation sets off clotting cascade, so a fibrin mesh begins to form - traps red blood cells
what tends to initiate arterial thrombosis?
atheromatous plaque protrudes into lumen, causing turbulent blood flow.
turbulence leads to loss of intimal cells.
denuded plaque surface exposed to blood flow - platelets will settle on exposed collagen.
thrombus forms.
give an example of what may cause damage to endothelial wall?
cigarette smoking causing endothelial cell injury - change in vessel wall and change in blood flow over injured cells
describe the layers seen in an arterial thrombus
first layer = platelet layer - due to platelet aggregation on damaged wall
second layer = fibrin mesh and trapped red blood cells
these alternating layers = lines of Zahn
what typically initiates venous thrombosis?
most form at valves - they naturally cause a degree of turbulence - may be damaged by trauma, stasis and occlusion
what predisposes someone to venous thrombosis?
fall in blood pressure, causing slowing of blood flow over turbulent areas - eg during surgery, or following MI.
immobility is a big risk for venous thrombosis in calf - stasis, as no contraction of surrounding muscles.
define embolism
the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel
list the possible causes of embolus
FATBAT Fat Air Thrombus Bacteria (endocarditis vegetation) Amniotic fluid Tumour
describe the path of an embolus in the venous system
vena cava»_space; through R side of heart»_space; lodge somewhere in pulmonary arteries.
will not pass through lungs as blood vessels split down to capillary level.
describe the path of an embolus in the arterial system
can travel anywhere downstream of its entry point
what is the most common cause of a pulmonary embolism?
deep vein thrombosis of the leg becomes dislodged, makes way to pulmonary arterial system and occludes
define ischaemia
a reduction in blood flow to a tissue without any other implications
define infarction
reduction in blood flow to a tissue to such an extent that it can no longer support maintenance of cells and they die.
“ischaemic death of tissue in living body”
what is the most common cause of infarction?
thrombosis of an artery to the extent it occludes it
what makes an organ more susceptible to damage by infarction?
end arterial supply - if this supply is interrupted they have no other way of getting nutrients/O2
name organs which have a dual arterial supply
liver - portal venous and hepatic artery
lungs - pulmonary venous and bronchial artery
brain - around circle of Willis
list some causes infarction/ischaemia
Obstruction: THROMBOSIS arterial embolism atherosclerotic plaques Compression: tumour/volvulus/hernia Vasoconstriction: e.g. cocaine vasoconstriction --> MI Rupture of artery due to trauma
what are the risk factors for atherosclerosis?
increasing age male gender hypertension smoking diabetes hypercholesterolaemia - high LDL, low HDL
what is a fatty streak? what is it composed of?
first stage of atheroma formation - yellow elevation of intima.
masses of lipid-laden macrophages.
describe the structure of fully developed atherosclerotic plaque
central lipid core
cap of fibrous tissue covered by the arterial endothelium
cap contains macrophages, T lymphocytes and mast cells
what provides the structural strength of an atherosclerotic plaque?
connective tissues in the fibrous cap (collagens) - produced by SMCs
describe atheromatous lesions
rich in cellular lipids and cellular debris.
soft, semi-fluid, highly thrombogenic lesions.
bordered by a rim of foam cells
what are foam cells?
macrophages that have phagocytosed oxidised lipoproteins via a membrane-bound scavenger receptor.
large amounts of cytoplasm, with foamy appearance.
what are the two basic steps in the development of an atheromatous lesion?
- injury to the endothelium of the arterial wall
2. tissue response of vascular wall to injury
what arteries are commonly affected by atheroma?
aorta (esp abdo aorta)
coronary arteries
cerebral arteries
common iliac/femoral arteries
what are the key stages in development of atherosclerosis?
- chronic endothelial injury
- plasma proteins (inc. LDL) diffuse into intima
- monocytes bind receptors expressed (due to step 1), differentiate into macrophages
- macrophages take up LDL to form foam cells - on death, release contents to form extracellular lipid pools
- platelet adhesion
- release of cytokines and growth factors by platelets/activated macrophages - migration of SMCs to site
- these are repair SMCs, producing collagen in attempt to stabilize the lesion
what is the function of SMCs in the development of atherosclerosis?
act as repair SMCs, producing collagen to try and stabilize the legion
what causes the formation of extracellular lipid pools in atherosclerotic plaques?
death of foam cells - spill out their lipid-rich contents
describe what happens in acute atherothrombotic occlusion
plaque rupture exposes thrombogenic plaque contents (collagen, lipid, debris).
activation of coag cascade and rapid thrombotic occlusion of vessel occurs.
describe what happens in a ruptured abdominal atherosclerotic aneurysm
rupture of a weakened dilated atheromatous abdominal aneurysm - retroperitoneal haemorrhage and death
