L9 - Atheroma, thrombosis and embolism Flashcards
what is an atheroma?
Intimal lesion that protrudes into the vessel wall
- raised lesion
- soft core of lipid
- fibrous cap
what cells would you find in the fibrous cap of an atheroma?
- SMC
- macrophages
- foam cells
- lymphocytes
- collagen and elastin
- proteoglycans
- neovascular
what cells would you find in the necrotic centre of an atheroma?
- cell debris
- cholesterol crystals
- foam cells
- calcium,
which vessels are commonly affected by atheroma?
bifications (sites of tubulent flow)
- abdominal aorta
- coronary arteries
- popliteal arteries
- carotid vessels
- circle of willis
which is the most common site of atheroma?
abdominal aorta
what are some non-modifiable risk factors for atheroma?
- increasing age
- male gender
- family history
- genetic abnormalities
are women more or less likely to get atheroma than men?
less likely up until menopause
- then after menopause the risk is equal between men and women
what are some modifiable risk factors for atheroma/atherosclerosis?
- hyperlipidemia
- hypertension
- smoking
- diabetes
- CRP
why is the CRP protein a risk factor in atherosclerosis?
- usually seen in inflammatory conditions
- can cause damamge to vessel walls = atherogenesis
what is atherogenesis?
the formation of fatty deposits in the arteries.
what is atherosclerosis caused by?
- high blood pressure
- high cholesterol
- an irritant, such as nicotine (can release free radicals)
- disease such as diabetes
what is atherosclerosis?
Atherosclerosis is a disease in which plaque builds up inside your arteries.
what is atheroma?
Intimal lesion that protrudes into the vessel wall
why does atherosclerosis develop?
due to chronic inflammatory response of the. arterial wall to endothelial injury
what are the steps of response-to-injury hypothesis?
- Chronic endothelial injury
- Accumulation of lipoproteins
- Monocyte adhesion to the endothelium
- SMC proliferations and ECM production
- factor release
- platelet adhesion
in the response-to-injury hypothesis, what occurs due to chronic endothelial injury?
- increased permeability
- leukocyte adhesion
- thrombosis
in the response-to-injury hypothesis, what occurs due to the accumulation of lipoproteins?
Low-density lipoprotein molecules (LDL) becoming oxidized (LDL-ox) by free
radicals, particularly oxygen free (ROS).
- When oxidized LDL comes in contact with an artery wall, a series of reactions occur
to repair the damage to the artery wall caused by oxidized LDL. - cholesterol can move in the bloodstream, transported by lipoproteins
in the response-to-injury hypothesis, what occurs due to factor release?
Induces SMC recruitment
NB: factors released from activated platelet, macrophages and vascular wall cells
in the response-to-injury hypothesis, what occurs due to SMC proliferations and ECM production?
- artery becomes inflamed
- cholesterol plaque covers affected area causing:
narrowing of artery
what happens as a result of a narrowed artery?
reduced blood flow
increases blood pressure
in the response-to-injury hypothesis, what occurs due to lipid accumulation?
gives rise to fatty streaks
evolves into a fibre fatty atheroma
what is a a fibrofatty atheroma
contains proliferated SMC and has a ECM formed
what is a fatty streak?
The earliest lesion in atherosclerosis
what is a fatty streak composed of?
lipid filled foamy macrophages
fatty streaks cause flow disturbance, true or false?
false
These lesions are not significantly raised and do not cause flow disturbance
all fatty streaks progress to atheromatous plaque, true or false
false
Not all fatty streak are destined to progress to atheromatous plaque
what are the stages of atherosclerosis?
- initial lesion
- fatty streak
- intermediate lesion
- atheroma
- fibroatheroma
- complicated lesion
describe an initial lesion?
- histologically “normal”
- macrophage infiltration
- isolated foam cells
describe a fatty streak?
mainly intracellular lipid accumulation
describe a Intermediate lesion?
intracellular lipid accumulation; small extracellular lipid pools
what is the Sequelae of atherosclerosis?
- Rupture, ulceration or erosion of the intimal surface
- Haemorrhage into plaque
- Atheroembolism
- Aneurysm formation
what is a Hemostatic plug?
a scab formed at the site of vascular injury
what is Thrombosis?
formation of a blood clot inside a intact blood vessel
what is Hemostasis?
a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage)
- maintains blood in fluid state in vessels
- allows for rapid formation of a homeostatic clot at the site of injury
what would inhibit thrombosis?
inactivation of Xa and IXa
what would promote thrombosis?
platelet adhesions
coagulation sequence
what is the difference in mechanism behind a arterial thrombosis and a venous thrombosis (VTE)?
arterial:
typically from a rupture of a atheromatous plaque
venous:
combination of factors from Virchow triad
what is the difference in location between a arterial thrombosis and a venous thrombosis (VTE)?
arterial:
left heart chambers, arteries
VTE:
venous sinusoids of muscle and valves of veins
what is the different diseases are caused by a arterial thrombosis and a venous thrombosis (VTE)?
arterial:
- acute coronary syndrome
- ischaemic stroke
- claudication
VTE:
- DVT
- pulmonary embolism
what is the difference in composition between a arterial thrombosis and a venous thrombosis (VTE)?
arterial:
mainly platelets
VTE:
mainly fibrin
what is the difference in treatment between a arterial thrombosis and a venous thrombosis (VTE)?
arterial:
anti-platelet agents (clopidogrel)
VTE:
anticoagulants (heparin, warfarin)
what type of thrombus would you treat with anticoagulants (heparin, warfarin)?
venous thrombosis (VTE)
what type of thrombus would you treat with anti-platelet agents (clopidogrel)?
arterial thrombosis
a thrombosis made up of mainly fibrin would likely be what type of thrombus?
venous thrombosis (VTE)
a thrombosis made up of mainly platelets would likely be what type of thrombus?
arterial thrombosis
what are the 3 components of Virchow’s triad?
endothelial injury
abnormal blood flow/stasis
hypercoagulability
with reference to Virchow’s triad, what factors contribute to abnormal blood flow/stasis?
immobility
polycythemia
with reference to Virchow’s triad, what factors contribute to hypercoagulability?
hereditary:
- factor V leiden
- prothrombin G20210A
- Protein C and S deficiency
Acquired:
- cancer
- chemotherapy
- OCR/HRT
- pregnancy
- obesity
- HIT
with reference to Virchow’s triad, what factors contribute to endothelial damage?
- smoking
- hypertension
- surgery
- catheter
- PICC lines
- Trauma
what is the difference between a clot and a thrombus?
clot:
- platelets not involved
- occurs outside vessel (hematoma) or inside
- red
- gelatinous
- not attached to a vessel wall
Thrombus:
- platelets involved
- only occurs inside a vessel
- red (venous), pale (arterial)
- firm
- attached to vessel wall
what is the Sequelae of thrombosis?
- occlusion of vessel
- dissolution
- incorporation into vessel wall
- recanalisation
- embolism
what is an embolus?
A mass of material in the vascular system able to lodge in a vessel and block it
NB:
- May be endo- or exogenous
- May be solid, liquid or gas
