Vascular pathology

Question 1

Define thrombosis

Answer 1

The formation of a blood clot in a blood vessel (artery or vein)

Question 2

What is Virchow’s triad?

Answer 2

The three factors which predispose to thrombi (blood clots in vessels)

1) Endothelial injury/dysfunction
2) Hypercoagulability
3) Haemodynamic changes (stasis/turbulence)

Question 3

What is endothelial injury/dysfunction?

Answer 3

Physical endothelial damage or endothelial cell dysfunction

Question 4

What are the causes of endothelial injury/dysfunction?

Answer 4

• Hypertension
• Toxins from tobacco smoke
• Hyperlipidaemia, chronic hyperglycaemia
• Bacterial endotoxins
• Medical devices

Question 5

What does endothelial injury/dysfunction result in?

Answer 5

• 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

Question 6

Describe some characteristics of relative stasis

Answer 6

• 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

Question 7

Describe some characteristics of turbulent blood flow

Answer 7

• 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)

Question 8

Name some causes of hypercoagulability

Answer 8

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.

Question 9

What is Budd-Chiari syndrome?

Answer 9

hepatic vein thrombosis; abdo pain / ascites / hepatomegaly

Question 10

Give some examples of superficial venous thrombosis

Answer 10

e.g. anterior chest wall (Mondor’s disease) or varicose vein thrombosis, with painful thrombophlebitis; usually of little clinical significance

Question 11

What is Paget-Schroetter disease?

Answer 11

thrombosis of axillary or subclavian vein (arm vein)

Question 12

What is deep vein thrombosis and what are the signs and symptoms?

Answer 12

venous thrombus forming in the deep veins of the leg or pelvis (iliac veins)

swelling, pain, tenderness, erythema, increased temperature

Question 13

What things can increase the risk of deep vein thrombosis?

Answer 13

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

Question 14

What is the clinical consequence of thrombi?

Answer 14

Cause obstruction to blood flow or embolisation (later)

Question 15

What can happen if there’s a thrombus in an artery?

Answer 15

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

Question 16

What is propagation of a thrombus?

Answer 16

• Enlargement and growth along the vessel due to further platelet and fibrin deposition
• Can lead to vascular occlusion and/or embolism

Question 17

What is embolisation?

Answer 17

• 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

Question 18

What is resolution/dissolution of a thrombus?

Answer 18

• Fibrinolysis and autolytic degeneration of cellular components of thrombus
• Restoration of blood flow

Question 19

What is organisation of a thrombus?

Answer 19

Ingrowth of granulation tissue and fibrous repair

Question 20

What is recanalisation of a thrombus?

Answer 20

new channel forms in organising thrombus

Question 21

What are the different types of embolism?

Answer 21

• 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

Question 22

What are some common sites of arterial thromboembolism?

Answer 22

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

Question 23

Describe the cause and effects of pulmonary thromboembolism

Answer 23

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

Question 24

Name the 3 types of arteries

Answer 24

1) Elastic arteries
2) Muscular arteries
3) Small arteries and arterioles

Question 25

Describe elastic arteries

Answer 25

(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

Question 26

Describe muscular arteries

Answer 26

(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

Question 27

Describe small arteries and arterioles

Answer 27

(<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

Question 28

Describe the structure of veins

Answer 28

• 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)

Question 29

Define arteriosclerosis

Answer 29

• “hardening of the arteries”
• Generic terms for arterial wall thickening and loss of elasticity
• Three specific types

Question 30

What are the three types of arteriosclerosis?

Answer 30

1) Arteriolosclerosis
2) Mönckeberg medial sclerosis
3) Atherosclerosis (most common)

Question 31

What is arteriolosclerosis?

Answer 31

• Affects small arteries/arterioles, may result in distal ischaemia
• Usually seen with hypertension or diabetes

Question 32

What is Mönckeberg medial sclerosis?

Answer 32

• Calcific deposits in muscular arteries, usually in over-50s
• Lesions do not restrict lumen – not clinically significant

Question 33

What is atherosclerosis?

Answer 33

• Progressive arteriosclerosis of medium/large arteries due to atheromatous plaque

Question 34

What are the 4 stages of atherogenesis?

Answer 34

1) Chronic endothelial injury
2) Endothelial dysfunction
3) Fatty streak development
4) Atheroma development

Question 35

What happens in stage 1 (Chronic endothelial injury) of atherogenesis?

Answer 35

• 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)

Question 36

What happens in stage 2 (endothelial dysfunction) of atherogenesis?

Answer 36

• 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

Question 37

What happens in stage 3 (fatty streak development) of atherogenesis?

Answer 37

• 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)

Question 38

What happens in stage 4 (atheroma development) of atherogenesis?

Answer 38

• 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

Question 39

What do fatty streaks look like macroscopically and microscopically?

Answer 39

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

Question 40

What does an atherosclerotic plaque look like macroscopically and microscopically?

Answer 40

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)

Question 41

What are the clinical consequences of atheroma formation?

Answer 41

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

Question 42

What are some other causes of infarction other than thrombus/atheroma?

Answer 42

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