Pathology of Atheroma Flashcards
Define Atheroma/Atherosclerosis
The formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries
What happens as a result of atheromatous plaque in coronary arteries?
Myocardial Ischaemia -> Angina
What is a common complication of atheroma?
Thromboembolism
Remember Arteriosclerosis is not the same as atherosclerosis!!! wat is it dogh?
Arteriosclerosis is an age-related change in muscular arteries.
Smooth muscle hypertrophys, apparent reduplication of IEL with intimal fibrosis. All leads to a decreased vessel diameter.
What CV conditions does arteriosclerosis contribute to?
Cardiac, Cerebral, colonic and renal ischaemia.
Obviously in the elderly given its an age related condition.
When is arteriosclerosis likely to become apparent to a clinician?
When the CVS is further stressed by haemorrhage, surgery, infection or shock.
What are the phases of atheroma?
- > Fatty Streak
- > Early Atheromatous Plaque
- > Fully developed atheromatous plaque
A fatty streak is the earliest phase of an atheroma, what does it look like and what comprises it?
A yellow linear elevation within the intimal lining of the artery.
Its made of masses of lipid laden macrophages.
What is the significance of a fatty streak?
It has no clinical significance as it causes no effects and it may well disappear on its own,
However these patients are considered ‘at risk’ of developing atheromatous plaques.
In what age is it common to see fatty streaks in arteries?
Young children
An early atheromatous plaque is the first non-reversible stage of atheroma development, what does it look like and what is it made of?
Early atheromatous plaque looks like smooth yellow patches in the T. Intima.
Its made of lipid laden macrophages much like a fatty streak
In what age do we commonly see an early atheromatous plaque?
Young adults and up.
What makes up a fully established atheromatous plaque?
A central lipid core covered by a fibrous tissue cap all within the intimal lining.
What fibrous tissue provides structural strength to the atheromatous plaque, and what produces it?
Collagen in the fibrous cap provides structural strength to a plaque.
The collagen is made in smooth muscle cells
What cell types are found within the fibrous tissue cap?
Inflammatory cells such as macrophages, T lymphocytes and mast cells.
Other than the obvious lipids, what is found in the central lipid core of a fully developed atheromatous plaque?
Cellular debris derived from macrophages that died in the plaque.
What gives many atheromatous plaques a ‘foamy’ rim?
Macrophages that have partially broken down lipoproteins to give the foamy appearance.
What feature of a fully developed atheromatous plaque is a useful marker in angiograms/CT?
The extensive dystrophic calcification
Where do atheromas most often form?
At points of turbulent flow.
Such as the branchin points of arteries.
What do we call a late stage plaque that covers a large area?
Confluent
What are the features of a complicated atheroma?
The same as a fully developed atheromatous plaque (lipid core + fibrous capsule) Plus: - Haemorrhage into the plaque - Plaque rupture or fissuring - Thrombosis
Atheroma can be caused by one major risk factor alone, what is this?
Hypercholesterolaemia (hyperlipidaemia)
How do genetics cause hypercholesterolaemia?
The présence/function of LDL receptors is determined genetically.
1/500 are heterozygous for mutations resulting in reduced function and therefore increased blood LDL.
1/1million are homozygous and usually die of coronary atheroma before adulthood.
What are the signs of major hyperlipidaemia?
LDL, HDL, total cholesterol and triglyceride levels.
Corneal arcus (cholesterol deposit around iris) Xanthelesmata (cholesterol deposit in periorbital region) Tendon Xanthomata (On the tendons of knuckles or achilles usually)
A family history of MI or atheroma
What are the types of hyperlipidaemia?
Primary or Familial
Acquired or Secondary
Idiopathic
What other strong risk factors accelerate the process of plaque formation?
Smoking Hypertension Diabetes Mellitus Being Male Being Elderly
What other risk factors contribute in some way to atheroma but not hugely?
- Obesity
- Sedentary lifestyle
- Low birthweight
- Low socio-economic status
What are the 2 major steps in formation of atheromatous plaques?
- Injury to the endothelial lining
- Chronic inflammatory and healing response of vascular wall
What is the more detailed process of development of the lipid core of an atheroma?
Essentially. circulating lipid along with smooth msucle and inflammatory cells form a large mass within the endothelium that drives continued inflammation adding to itself.
- Endothelial injury & dysfunction
- LDL accumulates in the exposed vessel wall
- Monocytes adhere to the endothelium, migrate into the intima and convert macrophages
- Platelets adhere to the injury.
- Activated platelets & macrophages release growth factors that drives smooth muscle cell recruitment
- Smooth muscle proliferates, ECM is produced and T cells are recruited
- Lipids accumulate, both extracellular and within foamy macrophages.
What are the 2 most important ways the endothelium becomes injured?
By haemodynamic disturbances (turbulent flow) By hypercholesterolaemia (lipoproteins are partially degraded when stuck to the wall by inflammatory cells releasing toxic growth factors and cytokine that directly damage the wall.)
How is the function of injured endothelial cells different?
+ The injured cells have a high permeability for LDL hence why it accumulates so much.
+ Increased Thrombogeneicity
+ Incread expression of cell adhesion molecules which help form the messy sticky atheroma.
How does the fibrous cap form on an atheroma?
Chronic inflammation leads to tissue repair.
Growth factors like PDGF are released leading to synthesis of collagen, elastin and mucopolysaccharide much like a scar along with smooth muscle proliferation.
The growth factors are released by platelets, the endothelium, macrophages and smooth muscle cells.
How does an established plaque spread?
Patches of endothelium covering are destroyed by organisation (smooth muscle invades and collagen is deposited). This also forms microthrombi (blood clots) on the surface/
How serious is atheromatous disease?
Can be benign all the way to life threatening.
Complications of atheroma can also be life threatening
What are the common consequences of atheroma?
- Progressive narrowing of lumen (stenosis)
- Acute atherotrhombotic occulusion
- Embolisation to a distal arterial bed
- Ruptured atheromatous aortic aneurysm
What happens if stenosis of the vessel lumen gets to 50-75%?
Thers a critical reduction of blood flow in the distal arterial bed and reversible tissue ischaemia occurs.
Give an example of reversible tissue ischaemia due to atheromatous stenosis?
A stenosed atheromatous coronary artery can lead to stable angina
What do we mean when we say reversible tissue ischaemia?
It is triggered by something and can be relieved.
E.g. myocardial ischemia occurs on exertion and is relieved by rest.
What happens if the stenosis is very severe (i.e. >75% of the lumen)?
Ischaemic pain occurs at rest.
e.g. unstable angina in a stenosed atheromatous coronary artery
What do we call stenosis of the peripheral arteries (ilieal/femoral/popliteal etc)
Peripheral Arterial Disease
Most often due to atheroma.
What is the major symptom of peripheral arterial disease?
Intermittent Claudication (on exertion usually so its clearly reversible tissue ischemia)
What happens to the tissue if theres longstanding tissue ischemia?
The affected organ atrophys.
E.g. longstanding severe atherosclerotic renal artery stenosis leads to renal atrophy
How does an acute atherothrombotic occlusion occur?
- The plaque ruptures
- Exposes highly thrombogenic plaque contents
- Activates coagulation cascade
- Very quick thrombotic occlusion
What happens if a thrombotic occlusion is total?
- > Total occlusion
- > Irreversible ISchaemia
- > Necrosis (infarction) of tissue
How does an embolisation to a distal arterial bed occur?
Small thrombus fragments detach from the atheroma.
They travel to distal vessels and get stuck, occluding the vessels of the capillary bed.
This gives you small local infarcts
What happens if small emboli occlude heart vessels?
Dangerous small foci of necrosis within the myocardium leading to life threatening arrhythmias
What happens if emboli detach from an atheroma in the carotid artery?
Either a cerebral infarct causing full blown stroke
Or Transient Ischaemic Attack (mini-stroke, TIA)
How does a ruptured atheromatous abdominal aortic aneurysm occur?
Inflammatory activity due to the lipid plaque causes the T. Media underneath to erode.
The vessel gradually dilatates until it suddenly ruptures.
Result: massive retroperitoneal haemorrhage and often death.
What else can occur due to an aneurysm in the abdominal aorta?
Prior to rupturing the atheromatous plaque can form a mural thrombus which gives off emboli to the legs.
What is mural thrombus?
A thrombus in the wall of a heart chamber of large artery (provided it doesnt totally occlude it)
What is a vulnerable atheroma?
One at high risk of becoming complicated. i.e. rupturing and forming a thrombosis.
How do we recognise vulnerable atheroma?
Thin fibrous tissue cap
Large lipid core
Prominent Inflammation
What preventative measures can be taken to lower risk of atheromatous disease?
- Smoking cessation
- BP control
- Weight loss
- Regular exercise
- Improve Diet
What preventative measures can we take to control the impact of existing atheromatous plaques?
Cholesterol lowering drugs.
Aspirin (inhibits platelets thus decresing risk of thrombosis
Surgery
