Atheroma, Thrombosis & Embolism Flashcards
What is the definition of an atheroma?
an intimal lesion that protrudes into a vessel wall
it consists of a raised lesion with a soft core of lipid and is covered by a fibrous cap
What is meant by an “intimal lesion”?
intimal means that the atheroma is present in the innermost layer of the blood vessel wall
What does the lipid core of an atheroma mostly consist of?
cholesterol and cholesterol esters
cell debris
foam cells
calcium
How does the fibrous cap of an atheroma occur?
Macrophages and smooth muscle cells produce collagen and elastin
These are extracellular matrix proteins that will form over the top of the lesion
What cells are present within an atherosclerotic plaque?
smooth muscle cells
macrophages
foam cells
lymphocytes
collagen
elastin
On which layer of the blood vessel does an atheroma occur?
The intima (innermost layer)
What are foam cells?
macrophages or smooth muscle cells that migrate from the media and have engulfed lipid
What makes vessels more prone to developing an atheroma?
If they are sites of turbulent flow
This is typically where there is a bifurcation of an artery
What are examples of vessels that are commonly affected by atheroma?
- abdominal aorta
- coronary arteries
- popliteal arteries
- carotid vessels
- circle of willis in the brain
What are the 2 categories of risk factors for atheroma?
non modifiable and modifiable
What are examples of non-modifiable risk factors for atheroma?
- increasing age
- male gender
- family history
- genetic abnormalities
What are examples of modifiable risk factors for atheroma?
- hyperlipidaemia (LDL:HDL)
- cigarette smoking
- diabetes
- c-reactive protein
What is the difference in function of HDL and LDL?
HDL removes cholesterol from lesions
LDL brings cholesterol into the atherosclerotic lesions
What starts the process of atherosclerosis?
Damage or injury to the endothelium of an artery
What 4 categories tend to cause endothelial damage that leads to atherosclerosis?
- high blood pressure
- high cholesterol
- an irritant, such as nicotine
- certain diseases, such as diabetes
Why is C-reactive protein a risk factor for atherosclerosis?
It is a sign of inflammation
Atherosclerosis develops as a chronic inflammatory response of the arterial wall to endothelial injury
What causes an atherosclerotic lesion to progress after it has initially developed?
it progresses through interactions of modified lipoproteins, macrophages, T-cells and the normal cellular constituent of the arterial wall
What are the first 3 stages in the development of atherosclerosis?
- endothelial injury leads to increased permeability
- leukocytes adhere to the endothelium and emigrate through to the intima
- cytokines and chemokines cause smooth muscles cells to emigrate to the intima from the media
What are the stages involved in the development of atherosclerosis, leading up to fibrous plaque formation?
- chemokines and cytokines activate macrophages
- macrophages and smooth muscle cells engulf the lipid
- smooth muscle cells proliferate and produce ECM proteins that form the fibrous plaque
What are the stages involved in development of atherosclerosis after fibrous plaque formation?
- cells start to die and a necrotic core forms in this region
- neovascularisation occurs - small vessels form at the edges of the lesions
What is the earliest lesion in atherosclerosis?
When does it develop?
a fatty streak
they begin to form in adolescence
What do fatty streaks look like when they first develop?
they begin as multiple small flat yellow spots
these eventually coalesce into streaks that are >/= 1 cm
How do fatty streaks affect blood flow?
The initial lesions are not significantly raised
They do not cause flow disturbance
Do all fatty streaks develop into atherosclerotic plaques?
Not all fatty streaks are destined to progress to an atheromatous plaque
What colour does an atherosclerotic plaque appear?
It appears white yellow
The superimposed thrombus on the plaque appears red
What does an initial atherosclerotic plaque consist of?
intimal thickening and lipid accumulation
What are ostia and how do they relate to fatty streak formation?
They are holes where branching arteries come off of the aorta
Fatty streaks form around the ostia
What are the 6 stages in atherosclerotic lesion development?
- initial lesion
- fatty streak
- intermediate lesion
- atheroma
- fibroatheroma
- complicated lesion
What are the 4 sequelae of atherosclerosis?
- rupture, ulceration or erosion
- haemorrhage into plaque
- atheroembolism
- aneurysm formation
What happens during the rupture, ulceration and erosion of an atherosclerotic plaque?
rupture, ulceration and erosion of the intimal surface exposes the blood to highly thrombogenic substances
this induces thrombosis which leads to lumen occlusion
What can thrombus generation and lumen occlusion lead to?
the blood can no longer flow to downstream tissues
this leads to ischemia and possible infarction
Why may haemorrhage into an atherosclerotic plaque occur?
New vessels may form at the edge of the lesion and bleed into it
This causes the lesion to enlarge and lead to haemorrhage
What is the definition of a thrombus?
a solid mass of blood constituents formed within the vascular system in vivo
What are the 2 types of thrombus?
Arterial thrombosis
Venous thrombosis
What are arterial and venous thrombosis most commonly due to?
Arterial thrombosis is most commonly superimposed on atheroma
Venous thrombosis is most commonly due to stasis
What are the 3 components of Virchow’s Triad?
- endothelial injury
- abnormal blood flow
- hypercoagulability
What is the mechanism for arterial thrombosis?
typically from rupture of an atherosclerotic plaque
What is the mechanism for venous thrombosis?
typically from a combination of factors from Virchows triad
What locations are mostly affected by arterial thrombosis?
Left heart chambers and arteries
Often occurs in atrial fibrillation when there is pooling and stasis of the blood
What locations are mostly affected by venous thrombosis?
Venous sinusoids of muscle and valves of veins
It tends to affect more dilated wide veins
What diseases can result from arterial thrombosis?
- acute coronary syndrome
- ischaemic stroke
- claudication in peripheral vascular disease
What diseases can result from venous thrombosis?
- deep vein thrombosis
2. pulmonary embolism
What are the compositions of arterial and venous thromboses like?
Arterial is mainly platelets
Venous is mainly fibrin
What are the treatments for arterial and venous thromboses?
Arterial - anti-platelet agents
Venous - anticoagulants
What are examples of anti-platelet agents?
clopidogrel
What are examples of anticoagulants?
heparin, warfarin
Why does peripheral vascular disease cause pain on walking?
the arterial supply to the legs is reduced due to thrombosis
What kind of things cause endothelial damage?
smoking and hypertension cause endothelial dysfunction
surgery, trauma and catheterisation cause endothelial damage
What are the 2 categories of ‘hypercoaguability’?
hereditary and acquired
What are examples of hereditary hypercoagulability conditions?
- factor v leiden
- prothrombin G20210A
- protein c and s deficiency
What are examples of acquired hypercoaguability conditions?
- cancer
- chemotherapy
- oral contraceptives, hormone replacement therapy
- pregnancy
- obesity
- HIT
What are examples of things that cause stasis?
- immobility
- polycythemia
These can cause endothelial injury
What is the role of Factor V?
How does Factor V Leiden affect this?
Factor V is a component of the coagulation cascade
It is inactivated by protein C and S acting together
Mutation of factor V leads to an increased risk of thrombosis as Factor V is resistant to inactivation by protein C and S
What is the prothrombin G20210A mutation?
a mutation in the prothrombin gene that leads to increased thrombosis as there is more activated prothrombin
What tends to be a sign that there may be a hereditary hypercoagulability condition?
if a patient tends to develop multiple DVTs and develops DVTs at a young age with no other predisposing risk factors
How does stasis affect the flow of platelets in a blood vessel?
Platelets usually flow in the centre of the blood vessel
In stasis, the platelets move to the side of the vessel where they are in contact with the endothelium
In what other way can stasis lead to thrombosis?
stagnant blood flow means there is no removal of pro-thrombotic factors
What is polycythemia?
having more red blood cells in the blood than normal
What is the difference between a clot and a thrombus when it comes to platelets?
Platelets are not involved in a clot
Platelets and fibrin are involved in a thrombus and form lines of Zahn
What is the difference in appearance between a clot and a thrombus?
a clot is red and gelatinous
a thrombus is firm
a venous thrombosis is red
an arterial thrombus is pale
How do clots and thromboses attach to the vessel wall?
Clots do not attach to the vessel wall
a thrombus is attached to the vessel wall
Do clots and thromboses form inside or outside of blood vessels?
a clot can occur inside or outside a vessel
a thrombus only occurs inside the vessel
What are the 5 sequelae of thrombosis?
- occlusion of vessel
- dissolution
- incorporation into vessel wall
- recanalisation
- embolisation
What happens in occlusion of a vessel due to thrombosis?
there will be no blood flow to downstream tissues
this leads to ischemia and infarction
What is dissolution of a thrombus?
the thrombus is broken down and dissolved
What is recanalisation of a thrombus?
macrophages/smooth cells grow into a thrombus, leading to new blood vessel formation
small capillaries grow into the thrombus, which join up and form channels
What is embolisation?
part of the thrombus breaks off and travels somewhere else in the body
What is the definition of an embolus?
a mass of material in the vascular system able to become lodged in a vessel and block its lumen
What is the most common embolus?
pulmonary embolus derived from a deep vein thrombosis
What are most emboli derived from?
thrombi
What are the different types of emboli?
- atheromatous plaque materia
- vegetation on heart valves
- fragments of tumour
- amniotic fluid
- gas
- fat
Why does the size of the embolus affect the effects it has?
the pulmonary arteries branch and become smaller and smaller
the size of the embolus determines where it lodges in the arteries
What is a saddle embolus?
a large embolus that blocks all of the blood going from the heart into the lungs
blockage of the circulation leads to acute respiratory and cardiac problems and sudden death
Where do systemic emboli tend to originate from?
the heart or an atheromatous plaque
What can a systemic emboli cause?
- cerebrovascular accident
- transient ischaemic attack
- gangrene
- bowel necrosis
