Vascular disease Flashcards
What are the stages in atherosclerotic plaque formation?
- Endothelial injury and dysfunction , causing (among other things) increased vascular permeability, leukocyte adhesion, and thrombosis 2. Accumulation of lipoproteins (mainly LDL and its oxidized forms) in the vessel wall 3. Monocyte adhesion to the endothelium , followed by migration into the intima and transformation into macrophages and foam cells 4. Platelet adhesion 5. Factor release from activated platelets, macrophages, and vascular wall cells, inducing smooth muscle cell recruitment, either from the media or from circulating precursors 6. Smooth muscle cell proliferation, extracellular matrix production , and recruitment of T cells. 7. Lipid accumulation both extracellularly and within cells (macrophages and smooth muscle cell)
what is the difference between a stable and unstable plaque?
Stable atherosclerotic plaque: - Thicker fibrous cap - less inflammatory cells Unstable atherosclerotic plaque: - thinner fibrous cap (or even ulceration) - larger necrotic core - more inflammatory cells - Prone to rupture, leading to “Acute Plaque Events” Acute plaque events: – plaque rupture – haemorrhage into plaque – erosion of endothelium - Leading to: – thrombosis – thromboembolism – atheroembolism
What is an aneurysm?
Abnormal localised dilation of blood vessel (or heart) - Due to a weakness in the media – e.g. inflammation, infection, congenital - Risk is of rupture and haemorrhage – e.g. intracranial, or from aorta
What is Dissection?
An arterial dissection arises when blood enters a defect in the arterial wall and tunnels between its layers. Dissections are often but not always aneurysmal • Blood in the media under arterial pressure – between inner 2/3rds and outer 3rd
What is Ischemia and Infarction?
Ischemia: Deficiency, real or relative, of oxygenated blood in a tissue causing a shortage of oxygen and impaired aerobic respiration Due to: – local vascular narrowing or occlusion – increased demand for oxygen that is not met – systemic reduction in tissue perfusion May be acute or chronic Infarction: Death (necrosis) of tissue due to ischaemia – most commonly arterial occlusion
What is the difference between Acute and Chronic ischemia?
Acute Ischemia acute decrease in supply or increase in demand for blood in an organ, e.g: – coronary thrombosis, causing myocardial infarction – thromboembolus from LA to brain, causing ischaemic stroke or transient ischaemic attack (TIA) – walking up a steep hill with atherosclerotic arteries, causing attacks of angina (and claudication) – torsion or volvulus blocking a vein – shock, reducing blood supply to everything Chronic Ischemia long-term situation where blood supply is inadequate for the needs of the organ, e.g: – atherosclerotic disease causing atrophy of lower limbs – renal artery stenosis causing renal atrophy – hyaline arteriolosclerosis causing benign nephrosclerosis
What factors influence the size of an infarct?
Some tissues are more sensitive than others • e.g. neurons die after 3-4min without oxygen Some organs have different blood supplies • e.g. lung has pulmonary and bronchial arteries
What is the difference between a red and a pale infarct?
“Red infarction”: where there is haemorrhage into the infarcted tissue, due to: – dual blood supply (e.g. lungs, liver) – collateral blood supply (e.g. intestine) – venous infarction (e.g. testicular torsion) – reperfusion (common with emboli to the brain) “Pale infarction”: where there is no haemorrhage – due to a blocked “end artery” – most organs: heart, kidney, spleen…
What is the difference between a haematoma and a thrombus?
Haematoma: A localized swelling that is filled with blood caused by a break in the wall of a blood vessel
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Thrombus: An abnormal clotted mass of blood within the unruptured CV system<!--EndFragment-->
What are the differences between arterial and venous thrombi and which drugs are more effective for each?
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- Arterial thrombi contain a higher proportion of platelets (and fibrin) because platelets can adhere even with faster arterial blood flow
– “white” thrombus
– associated with endothelial dysfunction/damage
– aspirin more useful for preventing arterial thrombosis
- Venous thrombi contain a higher proportion of blood cells (and fibrin)
– “red thrombus”
– associated with blood stasis and hypercoagulability
– warfarin more useful for preventing venous thrombosis
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What is Virchow’s triad which predisposes thrombus formation?
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- Abnormal endothelium
- Loss of endothelium exposes collagen, vWF, TF
- Endothelial activation or dysfunction
– may be caused by inflammatory cytokines, toxins, hypertension, cholesterol, smoking, etc.
- Reduces anti-coagulant activity
- Increases pro-coagulant activity
- Induces thrombosis in the absence of “injury”
- Abnormal blood flow
- Turbulence
- Stasis
- Loss of laminar flow (brings cells/platelets into contact with vessel wall and possibly being activated)
- Allows any activated clotting factors to accumulate (and continue their cascade)
- Abnormal blood coagulability
• Genetic (“primary”)
Factor V Leiden, others
• Not genetic (“secondary”)
- Oestrogen: Contraceptive pill; pregnancy
- Cancer
- Smoking, obesity, age etc.
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What are the fates of a thrombus?
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- Dissolution
– Fibrinolysis: tPA, Protein C and S, etc., but less likely the older the thrombus gets
- Organisation and recanalisation
(“organisation” = granulation tissue = capillaries)
- Propagation – Can grow longer (and crumblier…)
- Embolisation
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What is an embolus?
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Intravascular mass carried in the blood stream
- solid, liquid or gaseous
- carried to some site remote from its origin or point of entrance into the blood stream
- Blocks the vessel it lodges in
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What are the different types of embolism?
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Pulmonary embolus
- usually from DVT (legs)
- Can be asymptomatic, cause transient hypoxia or sudden death
Arterial thromboembolism
- usually from atheroma or heart (atria, valves, ventricle)
- usually involves turbulence and/or platelets adhering to a dysfunctional blood vessel surface
- will block an artery downstream and cause ischaemia and infarction
Venous thrombosis and embolism
- significant thromboemboli usually arise in the deep veins of the legs/pelvis
- usually travels through the right side of the heart and lodges in the pulmonary arteries
- other venous emboli (e.g. air emboli or embolism from IV drug use) will follow the same path
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What is the body’s response to infarction and healing of infarction?
Infarction: Coagulative necrosis
• “Ghost outlines” of dead cells
Infarction: Acute inflammation Images:
• Cellular contents leak – “DAMP receptors”
– stimulates inflammation
Infarction: Healing
• Granulation tissue … > … scar
