Atherosclerosis Flashcards
What is atherosclerosis
Buildup of fatty plaques on arterial walls
Modifiable risk factors of atherosclerosis - 4
- Smoking
- Hypertension
- Hyperlipidemia
- Diabetes
Hyperlipidemia as a risk factor of atherosclerosis
Hypercholesterolaemia
High density lipoprotein = good
Low density lipoprotein = bad
Diabetes as a risk factor of atherosclerosis
Makes blood vessels more rigid - Advanced glycoprotein end products (AGE)
Abnormal cross linking traps LDL
Non-modifiable risk factors - 3
- Genetics
- variation in cholesterol metabolism, inflammatory response, control of BP
- Male
- likely due to oestrogen
- Age
- 40s to 60s
6 stages of formation of atherosclerotic plaque
- Primary endothelial injury
- Uptake of LDL from blood into intima of artery where it is oxidised to become OXLDL
- Macrophages migrate across the endothelium into intima where they take up OXLDL to become foam cells + form fatty streak
- Activated macrophages release cytokines and growth factors particularly Platelet derived growth factor (PDGF) resulting in proliferation of smooth muscle layer and deposition of collagen forming a scab
- As plaque enlarges Blood flow is compromised
- Unstable angina / MI result when large enough plaque ruptures activating clotting cascade and thrombus formed occludes artery
Causes of primary endothelial injury
Smoking
Hypertension
Bifurcations are more susceptible
Complications of atheroma - 3
Aneurysm
Stenosis
Dissection
What is stenosis + what can it cause
Narrowing and reduced elasticity of the arterial lumen
:. Reduced flow in systole
Can cause ischaemia in some tissues
Arterial stenosis can affect any artery
What is an Aneurysm
Abnormal and persistent dilation of an artery due to a weakness in its wall
Most common in abdominal aorta
Complications of aneurysm - 5
- Rupture
- Thrombosis
- Embolism
- Pressure erosion of adjacent structures
- Infection
What is Dissection
Splitting within the media by flowing blood
Splits into lanes through vessel walls
What is haemostasis
The arrest of bleeding and the maintenance of vascular patency
Requirements of haemostasis - 4
Permanent state of readiness
Prompt response
Localised response
Protection against unwanted thrombosis
What is primary haemostasis
Formation of platelet plug
What is secondary haemostasis
Formation of fibrin clot
What is Fibrinolysis
Breakdown of fibrin clot
Components of haemostatic system - 4
Primary haemostasis
Secondary haemostasis
Fibrinolysis
Anticoagulant defences
Platelets - what + lifespan
Small anucleate discs
Mean lifespan of 7-10 days
How and where are platelets formed
In the marrow by budding from megakaryocytes
What is Von Willebrand factor (VWF) and how does it affect platelets
Released when endothelium is damaged
Platelets have receptors for it so stick to site of injury
Platelets secrete various chemicals which leads to platelet aggregation of platelets
Causes of failure of platelet plug formation - 3
- Vascular
- Platelets
- VWF deficiency
Vascular causes of failure of platelet plug formation
Can be hereditary e.g. Marfans
Can be aquired - age related, vitamin C deficiency, vasculitis
What is thrombocytopenia and reasons
Reduced number of platelets
Marrow problem - reduced production
Increased destruction - coagulopathy - autoimmune conditions
What causes reduced function of platelets
Drugs
- Aspirin
- NSAIDS
Renal failure
Von Willebrand factor deficiency
Can be aquired but mostly hereditary
Consequences of failure of platelet plug formation - 4
Spontaneous bruising and purpura
Mucosal bleeding
- epistaxis
- gastrointestinal
- conjunctival
- menorrhagic
Intercranial haemorrhage
Retinal haemorrhage
Screening test for primary haemostasis
Platelet count
3 pathways in formation of fibrin clot
Intrinsic pathway
Extrinsic pathway
Final common pathway
What activates the intrinsic pathway of fibrin clot formation
What clotting factors are involved
Activated by contact with a damaged surface
Factor XII -> XI -> IX -> common pathway
What activates the extrinsic pathway of fibrin clot formation
What clotting factors are involved
Pathway activated by release of tissue factors
Factor VII -> common pathway
What actives the final common pathway and what molecules are involved
Proceeds the intrinsic or extrinsic pathways
Factor X causes prothrombin (factor II) to be converted to thrombin (factor IIa)
Thrombin converts Fibrinogen (factor I) to Fibrin (factor II)
Also converts factor XIII to XIIIa (fibrin mesh)
What are the causes of failure of fibrin clot formation (3)
Single clotting factor deficiency - hereditary
Multiple clotting factor deficiencies - aquired
Increased Fibrinolysis
What are two reasons for multiple clotting factor deficiency
Liver failure - all coagulation factors are synthesised in the liver
Vitamin K deficiency - require to synthesise factors 2,7,9,10
What are the tests for fibrin clot formation deficiency
- Prothrombin time
- extrinsic pathway
- Activate partial thromboplastin time
- intrinsic pathway
What is the difference between an arterial and venous thrombus
Arterial
- white thrombus
- embolis lodges in artery in brain
- treated with anti platelets
Venous
- red thrombus
- embolis lodges in lung
- treated with anti-coagulants
