Mechanism of Vascular Disease: Atheroma Flashcards
Causes of myocardial infarction?
Muscle cell death (left ventricle - rarely in right as muscle is thinner)
Loss of blood supply
Occlusion of anterior descending branch of left coronary
Coronary artery thrombosis
What does infarction mean?
Necrosis due to loss of blood supply
Blood test for myocardial infarction?
Elevated troponin and cardiac enzymes - released when cells undergo death by necrosis (contents released can leak into blood)
What is an atheroma?
Disease process of elastic ARTERY walls, in response to injury mechanism; complications are common and serious and there is a degree of preventability to the disease
Accumulation of degenerative material in the tunica intima (inner walls) - narrows lumen
Referred to as FIBRO-FATTY PLAQUE
Formation of an atheroma?
Deposition of fat and fibrosis (scar tissue) - myofibroblasts produce collagen and fibrinite (scar tissue that has no elasticity, instead of smooth muscle)
Deposition of needle-shaped cholesterol crystal, scar tissue and lipid and platelet accumulation
Structure of a coronary artery?
Endothelium Tunica intima Internal elastic lamina Tunica media External elastic lamina Tunica adventitia
Risk factors for atheroma?
Family history - unchangeable Male Smoking Hypertension Diabetes Plasma lipids Obesity Age Geography
Reducing atheroma risk?
Family history cannot be changed Cannot change gender but pre-menopausal females have reduced risk Non-smoker BP control Diabetes control/prevention Diet Exercise Moderate alcohol Low lipids Geography often cannot be changed
Pathogenesis of atheroma?
Fatty streak
Fibrofatty plaque
Proliferative atheroma
Complicated atheroma
Different blood vessels can display different stages
Aetiology of atheroma?
Endothelial injury:
Response to injury (inflammatory)
Macrophages, platelets - exit circulation between injured cells leading to:
Lipid accumulation
Smooth muscle proliferation - instead of being contractile, scar tissue is laid down
Causes of endothelial injury?
Lipids
Pressure
Toxins
Sheer stress
Describe endothelial injury
Neutrophils activate their integrins, which bind to endothelial ICAMS
Leukocyte attachment via expression of selectins, then VCAMs and ICAMs (for firmer adhesion) on endothelium
Due to certain chemicals, expression is increased
Transepithelial migration may be guided by further adhesive interactions, involving molecules such as PECAM1, which endothelial cells express at intercellular junctions
Accumulation of macrophages, containing uptaken lipid
wbcs release substances that activate other cells, like IL-1 and MCP-1 (MCP-1 is for chemotaxis so other cells accumulate)
All forms a fatty streak -early stage of atheroma
Leucocyte surface adhesion is increased by?
Complement component C5a
Leukotriene B4
Tumour Necrosis Factor (TNF)
What chemicals increase expression of ICAM-1 and ELAM-1 (Endothelial Leucocyte Adhesion Molecule)?
IL-1
Endotoxins
Tumour Necrosis Factor
Where do atheroma tend to form?
Tend to develop earliest and most severely around vascular bifurcation sites
Histology of fatty streak?
Will see intimal lipid
When removing parafin wax, lipids removed so macrophages containing lipids can be seen
Plaque formation?
Platelets accumulate and release PDGF (Platelet Derived Growth Factor) - drives proliferation and migration of smooth muscle towards higher conc. of it, so media is broken down
More cells accumulate - adventitia prevents spread outwards so lumen is narrowed instead
Myofibroblasts produce collagen and fibrinite (scar tissue that has no elasticity)
Fibrofatty plaque formation, due to cholesterol crystals, scar tissue and lipid and platelet accumulation
What is complicated atheroma?
Triggers coagulation cascade leading to a thrombus
Plaque rupture and intramural haemorrhage also leads to thrombus
Complications of atheroma?
Thrombosis Aneurysm Dissection Embolism Ischaemia
Describe aneurysm
Marked dilatation of atheromatous vessel and are common in aorta
Thus, lose elasticity, so no recoil, and so tearing and rupture/thrombus formation
Describe dissection
Blood tears layers of vessel walls apart and pours into wall
Life-threatening
What is atherosclerosis?
Similar process affecting arterioles
May cause functional target organ damage, like retinopathy (blindness), renal failure, vascular dementia, foot ischaemia and poor healing
Infarction is rare
Risk factors for atherosclerosis?
Hypertension
Diabetes
Vasculitis
