Atheroma, Thrombosis & Embolism Flashcards
Define atherosclerosis
- Degeneration of arterial walls characterised by fibrosis, lipid deposition, inflammation limiting blood circulation & predisposes to thrombosis
- Primary pathological abnormality of arterial thrombosis
Which blood vessels are commonly affected by atherosclerosis?
- Bifurcations (turbulent flow)
- Abdominal aorta
- Coronary arteries
- Popliteal arteries
- Carotid vessels
- Circle of Willis
What are risk factors for atherosclerosis?
Non-modifiable= Age, male, FH, genetic Modifiable= Smoking, diabetes, hypertension, hyperlipidaemia/cholestrolaemia, CRP, physical inactivity
What are the causes and the first step in atherosclerosis?
- Haemodynamic injury, chemicals, irradiation, immune complex deposition
- First step= endothelial injury
What is the pathophysiology of atherosclerosis?
- Due to chronic injury & repair of endothelium
- Prescence of hyperlipidaemia lipid will accumulate in inner vessel (intima)
- Monocytes migrate into intima & ingest lipid = foam cells
- Stage known as fatty streak
- Foam cells secrete chemokines attracting more monocytes, lymphocytes & s.muscle cells
- S.muscle proliferate & secrete connective tissue
- Atherosclerotic plaque formed from fat, extracellular material, leukocytes & S.muscle
What are the components of an atheromatous plaque?
-Fibrous cap (S.muscle, marophages, foam cells, lymphocytes, collagen, elastin)
-Necrotic centre (Cell debris, cholesterol crystals, Ca & foam cells)
Adhered to media
What sequences can follow atherosclerosis?
- Occlusion
- Weakening of vessel walls (aneurysm formation)
- Erosion (thrombosis formation)
What is thrombosis and how is this different to a clot?
- Solidification of blood contents formed in the vessel during life
- Different in pathogenesis & morphology
How is a clot different from a thrombus?
C= Stagnant blood, enzymatic process, elastic, adopts shape of vessel
T=Within body during life, firm, dependant on platelets
What are platelets?
-Fragments of megakaryocytes in bone marrow
-Circulate in bloodstream
Bind to collagen exposed by endothelial damage & activate
-Secrete: a granules (PDGF, fibronectin,fibrinogen) dense granules (chemotactic chemicals)
What are the components of Virchow’s triad?
- For platelet adhesion & thrombus formation
- Change in intimal surface of the vessel (damage)
- Blood constituents (hypercoagulability)
- Pattern of blood flow (stasis)
Describe cardiac thrombi
- Known as mural thrombi
- Occur over areas of endomyocardial injury (MI, myocarditis)
- Can occur with arrhythmias & cardiomyopathy
What are possible consequences of thrombosis?
- Occlusion of vessel
- Resolution
- Incorporation into vessel wall
- Recanalisation
- Embolisation
What is an embolus?
A mass of material in the vascular system able to lodge in a vessel and block it
- may be endo/exogenous
- May be solid/liquid/gas
What is the most common type of emboli?
Pulmonary emboli
common cause of hospital morbidity& mortality
Risk factors=genetic & acquired
What are risk factors for an embolism?
- Acquired= Immobility, malignancy, heart failure, obesity, pregnancy, oestrogens, renal disease, smokers
- Genetic= thrombotic disorders (protein S deficiency, FV leiden)
What are the clinical effects of a pulmonary (or central) emboli?
- Small= asymptomatic multiple may result in pulmonary hypertension
- Medium= Acute respiratory & cardiac failure (V/Q mismatch, RV strain)
- Large= Death ‘saddle emboli’
What are causes of a systemic emboli?
- Arise within the heart- MI/AF
- Arise within arterial circulation-atheroma
What is an infective emboli?
- Usually from vegetations on infected heart valves
- Effects compunded by infective nature
- May lead to mycotic aneurysm formation
What is a tumour emboli?
- Bits break off as tumour penetrates vessel
- Not usually cause of immediate physical problems
- Major route of dissemination
What is a gas emboli?
- Air (obstetric procedures/ chest wall injury) >100ml to cause clinical effects
- Nitrogen (decompression sickness, divers, tunnel workers), nitrogen bubbles enter bones, joints, lungs
What is an amniotic fluid emboli?
- Inc uterine pressure during labour may force amniotic fluid into maternal uterine veins
- Lodge in lungs causing respiratory distress
- Can shed skin cells histologically
What is a fat embolism?
- Microscopic fat emboli in 80% patients with significant trauma at post mortem
- Sudden onset of respiratory distress
- Fatal in 15%
What is a foreign body emboli?
- Particles injected intravenously
- Leads to a granulomatous reaction
What is the pathogenesis of a venous thrombus?
- Venous stasis
- Hypercoagulable states
- Thrombi predominantly composed of fibrin lesser role of platelet accumulation & aggregation
What are risk factorsfor VTE?
-Active cancer or cancer treatment
-Over 60
-Critical care
-Dehydration
-Major trauma
-Surgery
-Immobility
-Obesity
-Varicose veins with phlebitis
-Contraceptive pill
Hormone replacement therapy
-Personal/1st degree family history of VTE
What is thrombophilia?
-Familial or acquired disorders of the haemostatic mechanism which predispose to thrombosis
OR
-Patients who develop VTE spontaeously, at an early age, recurrently, disproportionate severity
Name some heritable thrombophilias
-Antithrombin deficiency
-Protein C & S deficiencies
-Activated protein C resistance/FV leiden
Prothrombin 20210A
-Dysfibrinogenaemia
Name an acquired thrombophilia
-Antiphospholipid syndrome= antiphospholipid antibodies on at least 2 occassions 8 weeks apart with VT/AT/recurrent fetal loss
What are the clinical features of thrombophilia?
- DVT/PE
- Superficial thrombophlebitis
- Arterial thrombosis
- Obstetric complications
- Coumarin induced skin necrosis
- Thrombosis of cerebral, axillary, portal, mesenteric veins
What is factor V leiden?
-FV resistant to cleavage by APC
-Single mutation in factor V gene
-Most common familial thrombophilia
-
Describe prothrombin 20210A
- Point mutation in 3’ untranslated region of prothrombin gene
- Increased prothrombin levels
