Pathology- Thrombosis, Embolism, Infarction Flashcards
what is ischaemia?
insufficient blood supply
what is infarction?
death of tissue as a result of ischaemia
what is thrombosis
the formation of a blood clot inside a blood vessel, obstructing the flow of blood
what is embolism
the blockage of an artery by an embolus (foreign body e.g. blood clot (mass of coagulant), air bubble etc)
what is atheroma also known as
atherosclerosis, hardening of the arteries, coronary heart disease, ischaemic heart disease
atheroma is the principle cause of death and disability in the western world true or false
true
what are the aetiology of atheroma
smoking, hypertension, hyperlipidemia, diabetes, age (older), sex (males), genetics
what causes primary endothelial injury
smoking, hypertension, hyperlipidemia, immune factors, toxins, viruses, turbulent blood flow
what does increased LDL and reduced HDL - or - increased V-CAM, IL-1 or TNF expression lead to
accumulation of lipids and macrophages
what causes the migration of smooth muscle cells
PDGF (platelet derived growth factor), FGF (fibroblast growth factor), TGF beta (transforming growth factor)
what are foam cells
dead macrophages containing consumed LDL
what surrounds the fatty streak
fibrous cap (collagen fibres) and damaged endothelium
what happens to atheromatous plaques over time
progress and become complicated
fatty streak- fibrofatty plaque- complicated plaque (with overlying thrombus)
further loss of luminal potency and arterial wall weakness
under what circumstances (3) is atheromatous narrowing of an artery likely to produce critical disease
it is the only artery supply a tissue/organ
small artery diameter
overall blood flow is reduced
what are the complications of atheroma
stenosis, thrombosis, aneurysm, dissection, embolism
what is stenosis and what does it lead to
narrowing of the arterial lumen,
reduced elasticity,
reduced flow in systole,
tissue ischaemia
what are the clinical effects of cardiac ischaemia
reduced exercise tolerance
angina
unstable angina
myocardial infarction
cardiac failure
describe cardiac fibrosis and what it causes
loss of cardiac myocytes- replacement by fibrous tissue
loss of contractility, reduced elasticity and filling
can arterial stenosis affect any artery
yes
what can arterial stenosis in carotid arteries cause
TIA, stroke and vascular dementia (reduction in cognitive skills due to reduction in blood flow to brain)
what can arterial stenosis cause when in the renal arteries
hypertension and renal failure
what can arterial stenosis cause when in the peripheral arteries
claudication (cramping in lower leg due to insufficient blood supply) and foot/leg ischaemia
what does superadded
to add in a way that compounds the effect
what are the clinical effects of thrombosis
infarctions; myocardial cerebral renal intestinal
what is an aneurysm
Abnormal and persistent dilatation of an artery due to a weakness in its wall
what are the types of aneurysm
mycotic (fungus) atherosclerotic dissecting congenital arteriovenous traumatic syphillitic
where is the most common site for an aneurysm
abdominal aorta
what are the complications of an aneurysm
rupture, thrombosis, embolism, pressure erosion of adjacent structures, infection
what is an arterial dissection
splitting within the media by flowing blood
what are the risk factors for arterial dissection
middle age +/- atheroma
what is a false lumen
filling of blood inbetween tunica intima and media
what can artial dissection cause
sudden collapse, high mortality
what conditions are associated with aortic dissection
atheroma, hypertension, trauma, coarctation, marfan’s, pregnancy
what are the usual consequences caused by embolis
cerebral infarct
renal infarct and renal failure
lower limb infarction
describe the structure of athero-embolism
cholesterol clefts within embolic material
where sites are preferred for thrombosis formation
VIRCHOWS TRIAS
sited of endothelial injury
turbulent blood flow
hypercoaguable blood
how is a thrombus formed
intravascular coagulation which requires;
- platelet activation
- fibrin production via coagulation cascade
is the formation of t thrombus an active or passive process
active
what is the difference between activated and inactivation platelets
activated platelets (more sticky) attract and aggregate with other platelets.
also aggregate with fibrin
what is the start and end point of the coagulation cascade
start platelets
end fibrin
what happens to collagen when the endothelium is lost
exposed and binds to glycoprotein Ia/IIb and von Willebrands factor (vWF) (surface receptors) on platelets activating them
what event during platelet activation allows them to bind
increase in intergrins (transmembrane receptors that facilitate cell-extracellular matrix (ECM) adhesion)
what binds fibrinogen on platelets
glycoprotein IIb/IIIa
what do activated platelets release
granules to attract other platelets (vWF, platelet activating factors (PAF), thromboxane A2 (TXA2), ADP
why is it called the coagulation cascade
One factor activates another and so on like a domino effect
what does the domino affect of the coagulation cascade allow
Sequences provide lots of opportunities for checks and balances – areas to inhibit or stimulate
what is the common pathway both the intrinsic and extrinsic pathways of the coagulation pathways
converting fibrinogen to fibrin to cross linked fibren
what is the coagulation cascade dependant on
calcium dependant
what initiates the extrinsic coagulation pathway
tissue injury
what does the intrinsic pathway start with
hageman factor (FXII) and kalikrien
what is Prothrombin Time (PT)
blood test measuring how long it takes blood to clot (intrinsic pathway)
what joins together yo make the common pathway of the extrinsic coagulation pathway
tissue factor (TF) binds with factor VII
what is the blood test used to characterise blood coagulation in the extrinsic pathway
Activated Partial Thromboplastin Time (APTT)
what factors activate fibrinogen and turn it into fibrin
II and XIII
what is required to make factors II, VII, IX and X
vitamin K
what is vitamin K
fat soluble vitamin, stored in the liver
what factors are missing in liver disease
II, VII, IX and X
what does warfarin stop the production of
factors II, VII, IX and X
describe hypercoagulable blood
extra thick
in a normal arterial system why is there not coagulation
as high flow system so pro-coagulant materials washed along before being able to do anything
what is needed for thrombosis to occur in arterial systems
underlying atherosclerosis
what is atherosclerosis
formation of plaques etc. at sites of endothelial damage
why is there increased endothelial damage at branched arteries
as turbulent flow where arteries branch
what are common resulting conditions of atherosclerosis
cerebral infarction, carotid atheroma-emboli (TIA or cerebral infarcts), myocardial infarction (cardiac failure), aortic aneurysm, peripheral vascular disease, gangreen
what are complications of atherosclerosis
thrombosis, exercised induced angina, stable angina, plaque rupture
what is unstable angina
when coronary arteries have been occluded due to thrombus
what is primary vasculitis
autoimmune disease characterised by inflammation directed at vessel walls (immune system attacks own vessels)
name 4 branching arteries
coronary arteries, above bifurcation of aorta, origin and division of carotid arteries, renal arteries, superior mesenteric artery
why do branching vessels pose such a risk- give 2 examples
as vessels distal to branches are susceptible to embolism and infarction
stroke, small bowel infarction
what does turbulence cause
endothelial cell injury
stasis
what is margination
increased contact of platelets etc with vessel walls
what is stasis
when blood flow slows down
where does blood flow slow down (stasis)
deep venous system, faulty valves, venous insufficiency
what causes hypercoaguability
dehydration, polycythemia (number of cells), leukaemias (increase white blood cells)
what degrades clots
plasmin
what are three anti clotting proteins
protein C, protein S and antithrombin III
what factors do proteins C and S degrade
factor V and VIII
what factors do antithrombin III degrade
II, IX and X
what is factor V leiden
a variant (mutated form) of human factor V which causes an increase in blood clotting (hypercoagulability) (inherited disorder)
what other deficiencies can lead to hypercoaguability
protein C deficiency, protein S deficiency, antithrombin III deficiency
what are components involved in anti thrombotic mechanisms
plasmin, protein C and S, antithrombin III
also heparin
what is heparin
anticoagulant drug
what are secondary causes of hypercoagulability
Prolonged immobility Significant tissue injury – burns, RTA Antiphospholipid syndrome – autoimmune Myocardial infarction Atrial fibrillation (irregular cardiac rhythm) cancer therapt marantic endocarditis
how does cancer cause hypercoagulability
Activate coagulation cascade through tumour produced TF, mucin, inflammatory cytokines
how does therapy cause hypercoagulability
many chemotherapeutic agents injure endothelium and increase risk of thrombosis
what are more low risk secondary causes of hypercoagulability
the pill, smoking, renal disease, cardiomyopathy
what is an embolism
Dislodge thrombus – travels around the vascular system until it gets stuck
what can cause an embolism (the thrombus)
clot, air, septic, amniotic fluid, tumour, fat
how do cells die from hypoxia
lack of ATP, increase calcium,leads to breakdown of membranes, cytoskeleton and DNA plus releases pro death factors
