Vascular Pathology 1 - Atherosclerosis, Aneurism, Dissection Flashcards
What is ischaemia?
Deficiency of blood in a tissue causing a shortage of oxygen and impaired aerobic respiration
What is ischaemia due to?
increased demand for oxygen that is not met, local vascular narrowing or occlusion, systemic reduction in tissue perfusion
What is hypoxia?
A deficiency of oxygen in tissues
What is hypoxia due to?
Ischaemia, impaired respiratory function, decrease in oxygen carrying capacity of the blood
What is an infarct?
An area of necrosis caused by acute ischaemia
What is a thrombus?
A clotted mass of blood that forms within the cardiovascular system during life
What is an embolus?
An intravascular solid, liquid or gaseous mass carried in the blood stream to a site remote from its origin
What is atherosclerosis?
An accumulation of lipid and fibrous connective tissue in the intima of medium and large arteries
What is the first step in the pathogenesis of atherosclerosis?
Chronic endothelial injury due to hyperlipidaemia, hypertension, smoking, hemodynamic factors, toxins, viruses, immune reactions
What is the response to the chronic endothelial injury?
Endothelial dysfunction
What happens in endothelial dysfunction?
Increased vascular permeability, platelet adhesion (by exposure of the subendothelial ECM), monocyte adhesion (by expression of selectins, VCAM-1 and ICAM-1), release of PDGF, decreased releasing factors to inhibit clotting, production of ROS, altered release of vasoactive substances
What is the result of endothelial dysfunction?
LDLs can gain entry to the intima
What happens to LDLs once they enter the intima?
They are oxidised by ROS
What causes the recruitment of monocytes to the intima?
the leukocyte adhesion molecules on the endothelium (selectins, VCAM-1, ICAM-1) and the chemoattractant signals (IL-8, MCP-1)
How are foam cells formed?
By the phagocytosis of LDL by macrophages
Why do smooth muscle cells migrate from the media into the intima?
In response to the PDGF released from the endothelium and macrophages as well as FGF and TGF
What do smooth muscle cells in the intima do?
Secrete ECM (mostly collagen) to wall off the lipid core of the plaque
How is the lipid rich necrotic core of the plaque formed?
The break down of foam cells by apoptosis and the breakdown of collagen by matrix metalloproteinases
What are the results of atherosclerosis?
vessel stenosis, impaired vasodilation, plaques vulnerable to rupture, local prothrombotic environment
What are the risk factors for atherosclerosis?
- age
- gender
- family history
- hypertension
- diabetes mellitus
- smoking
- hypercholesterolaemia
- obesity
- physical inactivity
- proteinuria
- type A personality
- infections
Why is diabetes a risk factor for atherosclerosis?
Because hyperglycaemia causes oxidative stress and damages endothelium and patients have smaller denser LDL which is more atherogenic
At what stage of atherosclerosis do you see fatty streaks?
When there are foamy macrophages present but before migration of smooth muscle cells
What other features are seen histologically in atherosclerosis?
cholesterol clefts, calcification, lymphocytes
What are the complications of atherosclerosis?
ischaemia (narrowing), infarction (athero-embolism or thrombo-embolism), aneurysm
