L20. Pathology of Arterial Diseases Flashcards
What is arteriosclerosis?
The hardening of the arteries as a result of ageing and the ‘wear and tear’ associated with it.
Arteries lose their elasticity and as a result become narrowed
What conditions accelerate or predispose to arteriosclerosis?
Diabetes
Hypertension
What is the pathogenesis of arteriosclerosis?
Damage to the intima of the endothelium (normal in ageing) leads to the healing response:
- recruitment of smooth muscle cells which synthesis collage
- more collagen = less elastin content (Arteries cannot relax)
What is hyaline arteriosclerosis?
thickening of the walls of arterioles by the deposition of homogeneous pink glassy appearance (amorphous) hyaline material
- proteins from the blood leaking into the subendothelium
What are the consequences of arteriosclerosis?
Impairment of the arteries control of blood pressure
May result in poor blood supply (due to narrowing) - ischaemia
Possibility of stretching out the vessel = microaneurysm and haemorrhage.
(cerebral haemorrhage, benign nephrosclerosis, hypertensive retinopathy)
What is atherosclerosis?
A build up of inflammatory, fibrotic, necrotic and fatty material in the arteries leading to a slow narrowing with potential rupture
What are the 2 main components of the atheroma (plaque)?
Fibrous cap + Necrotic Core
What are the stages of pathogenesis of atherosclerosis?
- Fatty streak formation: collection of foam cells in the intima
- Damage: inflammation and accumulation of cholesterol, inflammatory infiltrate and fibrosis
- Stable atherosclerotic plaque
- Unstable atherosclerotic plaque (rupture)
What are the features of the atherosclerotic plaque? [10]
- Thickened Intima
- Thinned media
- Narrowed Lumen
- Necrotic Core
- Fibrous Cap
- Inflammatory Cells
- Calcification
- Cholesterol Clefts
- Foam Cells
- Neovascularisation
What are the two types of pathologic calcification?
- DYSTROPHIC: formation of calcium deposits in cell degeneration (Eg. atherosclerosis, TB, cancer)
- METASTATIC: serum calcium and phosphate levels are too high reaching precipitation thresholds in vessels, kidneys and other tissue
Compare and contrast a stable vs. vulnerable plaque
Stable: Complete and thick fibrous cap Small core Less inflammatory cells Likely asymptomatic
Unstable: Prone to rupture (Acute plaque events) Thin fibrosis cap or ulcerations Large lipid filled and NECROTIC core More inflammatory cells <50% stenosis is likely asymptomatic
What is an acute plaque event?
Plaque rupture
Haemorrhage into the plaque: thickening = narrowing
from the neovascularisation or shoulder weakness
Erosion of the endothelium
What are the consequences of an acute plaque event?
- Thombosis
- Thromboembolism
- Atheroembolism
(Less common) - Chronic ischeamia = stable angina
- Aneurysm due to weakened media- high likelihood of rupture/haemorrhage
What defines chronic ischaemia (in terms of stenosis?) - what are the results?
> 70% stenosis of the lumen
= Stable angina and claudication
What are the non-modifiable risk factors of atherosclerosis?
Age (old), Male gender, family history, certain genes, history of atherosclerosis
What are the modifiable risk factors of atherosclerosis?
Hypertension, smoking, diabetes, cholesterol, sedentary lifestyle
What is the role of the endothelium in atherosclerosis?
Damaged endothelium becomes activated
= increased permeability
= expression of adhesion molecules, cytokines and growth factors
= inflammatory infiltrate and LDL infiltrate
= Accumulation of oxLDLs + foam cells
= change from anti- to pro-coagulant
What is the role of cholesterol (LDL levels) in atherosclerosis?
Accumulation of low density lipoproteins (LDLs) in Intima
- become oxidised and then taken up by macrophages (foam cells)
- oxLDL is toxic to endothelial and other cells
- able to stimulate inflammatory cytokines
- production of free radicals increases inflammation (cycle)
What is the role of inflammation in atherosclerosis?
They perpetuate the endothelial dysfunction
Attract more inflammatory cells
Macrophages: foam cells, ROS production, cytokines, MMP production
What is the role of smooth muscle cells in atherosclerosis?
Migrate from the media into the intima and change phenotype
= Proliferative
= synthetic (collagen)
In attempt to make a thick and stable fibrous cap
What is an aneurysm and what is it caused by?
An abnormal dilation of the blood vessels (or heart)
- due to a weakness in the media (Eg. inflammation due to atherosclerosis, infection or due to a congenital abnormality)
What are some consequences of aneurysms?
Risk of rupture and haemorrhage
Eg. Intracranial haemorrhage or aortic haemorrage
What is the difference between a saccular and fusiform true aneurysm? And the differences between a false aneurysm and a dissection?
Saccular: bulging out of the vessel on one side
Fusiform: bulging out of the vessels on both sides
False: Extravasation of blood into the wall leading to aneurysm/bulging out of one part of the wall
Dissection: extravasation of blood into the wall that spreads (doesn’t bulge as much)
What is an abdominal aortic aneurysm (AAA)?
A fusiform aneurysm
Often the aneurysm contains a thrombus which can embolise
LINES OF ZAHN
Why is AAA associated with atherosclerosis?
Because the inflammatory environment weakens the ECM and the intimal thickening interferes with the wall perfusion
How is the risk of rupture of an AAA defined?
> 5cm diameter
What is a berry aneurysm?
Mainly occurs in the cerebral circulation
Due to weakening of the vessel
And is a major cause of subarachnoid haemorrhage
What is a dissection?
When blood is present in the media
What is dissection strongly associated with and why?
Hypertension
Because the high arterial pressure forces blood into the media
What are the types of dissection?
Type A: (1) dissection and extravasation of blood through the media the whole length of the artery on both sides
(2) extravasation of blood in a localised area of the artery on both sides
Type B: Extravasation of blood through the media of the length of the artery on only one side
What artery does dissection commonly occur in and what are the consequences?
The aorta (especially the ascending)
- compresses or block important arteries
- rupture into the pericardium (cardiac tamponade)
- rupture into the thorax (esanguination)
