Vascular pathology Flashcards
Define thrombosis
The formation of a blood clot in a blood vessel (artery or vein)
What is Virchow’s triad?
The three factors which predispose to thrombi (blood clots in vessels)
1) Endothelial injury/dysfunction
2) Hypercoagulability
3) Haemodynamic changes (stasis/turbulence)
What is endothelial injury/dysfunction?
Physical endothelial damage or endothelial cell dysfunction
What are the causes of endothelial injury/dysfunction?
- Hypertension
- Toxins from tobacco smoke
- Hyperlipidaemia, chronic hyperglycaemia
- Bacterial endotoxins
- Medical devices
What does endothelial injury/dysfunction result in?
- loss of protective layer that discourages attachement of cells and clotting proteins
- change in the gene expression pattern to a phenotype that is proinflammatory and prothrombotic
- Main cause of arterial or intracardiac (within the heart) thrombi
- These thrombi are rich in platelets and so are treated with antiplatelet drugs, e.g. aspirin
Describe some characteristics of relative stasis
- Slow flowing blood in veins, e.g. prolonged immobility, long operations
- Loss of laminar flow
- Contributes to endothelial dysfunction
- Decreased washout of coag factors, increased cell contact with epithelium
Describe some characteristics of turbulent blood flow
- Chaotic flow with focal stasis and loss of laminar flow
- Contributes to endothelial injury (shear stress) and/or dysfunction
- Occurs in arterial vessels (e.g. narrowed arteries (stenosed), branch points)
Name some causes of hypercoagulability
Inherited disorders of coagulation factors e.g.:
Factor V Leiden mutation – this mutation makes factor V resistant to inhibition, goes into overdrive
Antithrombin III deficiency
Protein C or S deficiency
Acquired disorders, e.g.: Dehydration Tobacco smoke, obesity Pregnancy, hormonal contraceptive use Disseminated cancer Postoperative Heparin-induced thrombocytopenia. Develop antibodies to the heparin Antiphospholipid syndrome. Autoimmune disease.
What is Budd-Chiari syndrome?
hepatic vein thrombosis; abdo pain / ascites / hepatomegaly
Give some examples of superficial venous thrombosis
e.g. anterior chest wall (Mondor’s disease) or varicose vein thrombosis, with painful thrombophlebitis; usually of little clinical significance
What is Paget-Schroetter disease?
thrombosis of axillary or subclavian vein (arm vein)
What is deep vein thrombosis and what are the signs and symptoms?
venous thrombus forming in the deep veins of the leg or pelvis (iliac veins)
swelling, pain, tenderness, erythema, increased temperature
What things can increase the risk of deep vein thrombosis?
1) Bed rest and immobilisation – reduced muscle action and slow venous return -> stasis
2) Pregnancy – stasis due to enlarging uterus and hypercoagulability
3) Post-surgical – stasis due to immobilisation, vascular injury and release of procoagulant factors
What is the clinical consequence of thrombi?
Cause obstruction to blood flow or embolisation (later)
What can happen if there’s a thrombus in an artery?
ischaemia and infarction of tissues
Ischaemia → restriction in blood supply resulting in oxygen insufficiency for cellular metabolism
Infarction → tissue death (necrosis) due to inadequate blood supply (ischaemia)
Limb artery thrombosis → limb ischaemia
Coronary artery thrombosis → myocardial infarction
Cerebrovascular artery thrombosis → stroke
What is propagation of a thrombus?
- Enlargement and growth along the vessel due to further platelet and fibrin deposition
- Can lead to vascular occlusion and/or embolism
What is embolisation?
- Embolus → A detached intravascular solid, liquid or gas that is carried by the blood to a site distant from its point of origin
- Detachment of part or all of thrombus from site of origin to lodge at a distant site (thromboembolism)
- Can cause occlusion and infarction
What is resolution/dissolution of a thrombus?
- Fibrinolysis and autolytic degeneration of cellular components of thrombus
- Restoration of blood flow
What is organisation of a thrombus?
Ingrowth of granulation tissue and fibrous repair
What is recanalisation of a thrombus?
new channel forms in organising thrombus
What are the different types of embolism?
- Thromboembolism – dislodged thrombus; most common
- Fat embolism – droplets of fat from e.g. fractures, orthopaedic procedures, massive soft tissue injury, liposuction
- Air (gas) embolism – e.g. decompression sickness, medical procedures
- Amniotic fluid embolism – triggers serious allergic reaction if it goes into mother’s circulation
Unless otherwise specified it is thrombus embolising
What are some common sites of arterial thromboembolism?
Heart – most commonly left ventricle or left atrium
- Ventricular thrombus secondary to myocardial infarction
- Atrial fibrillation
- Infected heart valve – endocarditis (→ septic embolism, with distal infection)
Arterial vessels
- Atheromatous plaque
- Aortic aneurysms – abnormal dilatation of a blood vessel
Describe the cause and effects of pulmonary thromboembolism
Due to embolism from DVT
Route of embolism:
DVT → IVC → right side of heart → pulmonary circulation
Effect depends on size:
Tiny vessel occlusion → asymptomatic
Multiple tiny emboli over a prolonged period → pulmonary hypertension
Small / medium vessels occlusion → symptomatic +/- infarction
Signs and symptoms: shortness of breath, pleuritic chest pain (pain on inspiration), cough and haemoptysis, tachycardia, tachypnoea, hypoxia
Major pulmonary arteries (e.g. saddle embolus) → sudden death
Name the 3 types of arteries
1) Elastic arteries
2) Muscular arteries
3) Small arteries and arterioles
Describe elastic arteries
(large arteries, generally >10mm)
- Pulmonary arteries, aorta and main it’s main branches…
- Brachiocephalic trunk, common carotid, subclavian, common iliacs
- Need to be elastic as relatively thin compared to diameter, so can stretch/recoil with systole/diastole
- Media is thick; mainly layers of elastin/collagen, very little smooth muscle
- Adventitia has vasa vasorum – small blood vessels
Describe muscular arteries
(medium arteries, 0.1mm to 10mm)
- Generally, the other “named” arteries
- Media is between thin internal/external elastic layers, and primarily made of smooth muscle (but gradual transition from elastic arteries)
- Less elastic but capacity for vasoconstriction
Describe small arteries and arterioles
(<0.1mm)
- Have an internal elastic layer only
- Small arteries have up to 8 smooth muscle layers in media
- Arterioles have one or two layers (<30 mm)
- Deliver blood to capillaries; can control flow by dilating/contracting
- Origin of most peripheral vascular resistance, so useful in regulating BP
Describe the structure of veins
- Same three layers as arteries (intima/media/adventitia)
- Intima and media are thinner than arteries
- Adventitia tends to be the most developed layer
- Overall, thinner wall compared to lumen
Large veins have vasa vasorum – blood supply
Small veins known as venules (10-50mm diameter)
Define arteriosclerosis
- “hardening of the arteries”
- Generic terms for arterial wall thickening and loss of elasticity
- Three specific types
What are the three types of arteriosclerosis?
1) Arteriolosclerosis
2) Mönckeberg medial sclerosis
3) Atherosclerosis (most common)
What is arteriolosclerosis?
- Affects small arteries/arterioles, may result in distal ischaemia
- Usually seen with hypertension or diabetes
What is Mönckeberg medial sclerosis?
- Calcific deposits in muscular arteries, usually in over-50s
- Lesions do not restrict lumen – not clinically significant
What is atherosclerosis?
- Progressive arteriosclerosis of medium/large arteries due to atheromatous plaque
What are the 4 stages of atherogenesis?
1) Chronic endothelial injury
2) Endothelial dysfunction
3) Fatty streak development
4) Atheroma development
What happens in stage 1 (Chronic endothelial injury) of atherogenesis?
- Lesions develop in tunica intima of large/medium arteries following endothelial injury
- Predisposing factors include: LDL hyperlipidaemia, diabetes, hypertension, smoking, some viral/bacterial infections (e.g. HIV, HCV, CMV, H. pylori)
What happens in stage 2 (endothelial dysfunction) of atherogenesis?
- Increased permeability to LDL cholesterol
- Increased adherence of WBCs to endothelium
- Reactive oxygen species from endothelial injury oxidise LDL in intima
- Monocytes enter tunica intima → macrophages
What happens in stage 3 (fatty streak development) of atherogenesis?
- Macrophages phagocytose oxidised LDL → foam cells (spongy cytoplasm appearance due to being loaded with lipid-containing vesicles)
- Foam cells + infiltrated T-lymphocytes form fatty streak (initial atherosclerotic lesion)
What happens in stage 4 (atheroma development) of atherogenesis?
- Smooth muscle cells migrate from media and proliferate to surround deposits
- Fibroblasts form a protective layer around the lesion (fibrous cap)
- The final atheromatous plaque contains a combination of:
- Smooth muscle cells, macrophages, T-cells, foam cells, cholesterol deposits and cellular debris
- Progression: accumulation of lipids and loss of integrity of endothelium
- Advanced lesions: thin tunica media, calcification of lipid deposits, necrosis
What do fatty streaks look like macroscopically and microscopically?
Macroscopic:Begin as minute yellow, flat areas that coalesce into elongated lesions, 1 cm or more in length.
Microscopic: Composed of lipid-filled foamy macrophages but are only minimally raised and do not cause any significant flow disturbance
What does an atherosclerotic plaque look like macroscopically and microscopically?
Macroscopic:intimal thickening and lipid accumulation; whitish-yellow raised lesions up to 1.5cm diameter (can coalesce)
Thrombus overlying ruptured plaques look red-brown
Microscopic:three key components
- Cells: smooth muscle cells, macrophages, T cells
- Extracellular matrix: collagen, elastic fibres, proteoglycans
- Intra/extracellular lipids
Lumen, fibrous cap, central core (mainly lipid)
What are the clinical consequences of atheroma formation?
1) Thrombosis due to ulceration and rupture of atheroma plaque
Occludes blood supply → ischaemic necrosis (infarction)
2) Distal embolisation of atheromatous debris post-rupture (e.g. trash foot)
3) Intermittent ischaemia from stenosis (narrowing)
E.g. angina, intermittent claudication, mesenteric ischaemia
4) Destruction of underlying vessel → aneurysm formation
Secondary rupture/thrombosis
What are some other causes of infarction other than thrombus/atheroma?
1) Vasospasm eg. cerebral vasospasm after subarachnoid haemorrhage
2) Dissecting aortic aneurysm - rip in the intima
3) Extrinsic compression eg. by tumour, or oedema (compartment syndrome)
4) Twisting eg. testicular torsion
