Atheroma and thrombosis Flashcards
What is atherosclerosis?
Degeneration of arterial walls characterised by fibrosis, lipid deposition and inflammation which limits blood circulation and predisposes to thrombosis.
What are the common risk factors for atherosclerosis?
Male sex
Post-menopausal women
Hyperlipidaemia (m)
Hypertension (m)
Diabetes (m)
Smoking (m)
Genetic
Other: CRP, increased homocystiene (m)
Describe the pathophysiology underlying atherosclerosis.
- Arises due to chronic injury and repair of the endothelium
- First step: endothelial injury
- Causes: haemodynamic injury, chemicals, immune complex deposition, irradiatio
- In the presence of hyperlipidaemia lipid will accumulate in the inner most part of the vessel (the “intima”)
- Monocytes will migrate into the intima (due to lipid and endothelial injury (VCAM1)) and ingest the lipid becoming foam cells
- This stage is a FATTY STREAK
- The “foam cells” are secrete chemokines attracting more monocytes/macrophages, lymphocytes and smooth muscle cells
- Smooth cells proliferate and secrete connective tissue
- This mixture of fat, extracellular material and leukocytes and smooth muscle form the atherosclerotic plaque
What are the potential sequelae of atherosclerosis?
- Occlusion
- Weakening of the vessel walls - aneurysm formation
- Erosion
- Haemmorhage
- Embolus
What is an embolus?
- A mass of material in the vascular system able to lodge in a vessel and block it
- May be endo- or exogenous
- May be solid, liquid or gas
What is a thrombosis?
•Solidification of blood contents formed in the vessel during life
Different from a clot in both pathogenesis and morphology. Clot elastic, soft and conforms to vessel body wall. Thrombus firm.
What is the role of platelets in thrombosis?
•Bind to collagen exposed by endothelial damage and become activated
•Secrete
–Alpha granules: fibrinogen, fibronectin, PDGF
–Dense granules: chemotactic chemicals
What is Virchow’s triad?
- Platelet adhesion and subsequent thrombus formation requires changes in……
- The intimal surface of the vessel
- The pattern of blood flow
- Blood constituents
What are the features of venous thrombosis?
Intimal change - valves
Change in blood flow - immobile
Change in blood constituents - eostrogen, toxins from smoking
What is a paradoxical embolus?
Embolus formed on left side of heart and crosses defect in septum to right??
What are the acquired risk factors for thrombosis?
Immobility
Malignancy
Previous VTE
Heart failure
Eostrogens
Obesity
Pregnancy
Where do systemic thrombi usually arise?
The heart
What is the most common site of origin for pulmonary emboli?
Deep leg veins
What is the gold standard diagnostic test from PE?
CTPA
What are infective emboli?
Usually from the vegetations on infected heart valves
Effects compounded by the infective nature – may lead to mycotic aneurysm formation
Common in IVDU and those with artificial heart valves.
What is a tumour embolus?
- Bits may break off as tumours penetrate vessels
- Do not usually cause immediate physical problems
- Major route of dissemination
What are gas emboli?
•Air (vessel opened into the air)
–Obstetric procedures / chest wall injury
–>100ml to cause clinical effects
•Nitrogen
–Decompression sickness (“the bends”)
–Divers, tunnel workers
–Nitrogen bubbles enter bones, joints and lungs
What are the features of the amniotic fluid emboli?
- Increased uterine pressure during labour may force AF into maternal uterine veins (1:50,000 deliveries)
- Lodge in lungs à respiratory distress
- Can see shed skin cells histologically
What are the features of fat emboli?
- Microscopic fat emboli found in 90% patients with significant trauma
- Sudden onset of respiratory distress
- Fatal in 10%
What are the features of foreign body emboli?
- Particles injected intravenously
- E.g. talc in IVDU’s
- Leads to a granulomatous reaction
