Pathophysiology of Atheroma Flashcards
What is an atheroma also known as?
atherosclerosis
What is an atheroma?
Formation of plaques in the intima of large and medium-sized arteries.
What does atheroma lead to when the lumen of arteries is narrowed?
ischaemia
What is a serious consequence from myocardial ischaemia due to atheroma?
angina
What is myocardial ischaemia complicated by?
thromboembolism
What is arteriosclerosis? (3)
What is it not? (1)
It is not the same as an atheroma.
It is an aged related change in muscular arteries. It presents with:
- smooth muscle hypertrophy
- reduplication of internal elastic laminae
- intimal fibrosis
These all lead to a decrease in diameter size.
What sorts of ischaemia can be caused by arteriosclerosis?
4
- cardiac
- cerebral
- colonic
- renal
When does arteriosclerosis become clinically apparent?
4
When CVS is further stressed by:
- haemorrhage
- major surgery
- infection
- shock
What is the earliest lesion present in atheroma?
2
- a fatty streak
- yellow linear elevation of lipid-laden macrophages
In what group of patients are fatty streaks found (earliest significant lesion of atheroma)?
Are they clinically significant?
young children
No - they may go away.
What is the stage of atheroma prior to fully developed atheromatous plaque i.e. following initial fatty streak development?
(1)
- Early atheromatous plaque
In what group of patients are early atheromatous plaques found?
young adults
What are the characteristics of an early atheromatous plaque?
(2)
- smooth yellow patches in intima
- lipid-laden macrophages
Describe the composition of a fully developed artheromatous plaque.
(3)
- Central lipid core
- fibrous tissue cap
- covered by arterial endothelium
What does collagen in the fibrous cap of an atheromatous cap do?
What produces the collagen?
- provides structural strength to the structure
- smooth muscle
Which inflammatory cells reside in the fibrous cap of a fully developed atheromatous plaque?
(3)
macrophages
T-lymphocytes
mast cells
What is the core of an atheromatous plaque made from?
2
- cellular lipids
- debris from macrophages (died in plaque)
What is often found around the rim of the atheromatous plaque?
foamy macrophages, due to uptake of lipoproteins by scavenger receptors
What often forms in late development of artheromatous plaques?
dystrophic calcification
Where are atheromatous plaques most likely to form?
What is specific about these places?
- at arterial branching points/bifurcations
- turbulent blood flow
What are some features of complicated atheroma?
3
- haemorrhage into plaque = calcification
- plaque rupture/fissuring - thrombosis
What is the most important risk factor form atheroma?
hypercholesterolaemia
What is the congenital abnormality that can cause primary lipidaemia?
- lack of cell membrane receptors for LDL
- carriers affected (heterozygous)
- homozygous individuals affected more severely.
What happens to patients homozygous for this type mutation?
3
- much less functional membrane receptors for LDL.
- very high cholesterol levels in the blood
- coronary artery atheroma in infancy/teens
- death
What is the familial form of hyperlipidaemia called?
primary hyperlipidaemia
What is the acquired form of hyperlipidaemia called?
secondary (idiopathic)
What are some signs of major hyperlipidaemia?
4
- premature corneal arcus
- tendon xanthomata
- xanthelasmata
- FH of MI/atheroma
What is corneal arcus?
an opaque ring forms around the margin of the cornea (common in elderly).
What is tendon xanthomata?
Where is it usually found?
- deposits of fat/foamy macrophages in the tendons
- usually of the knuckles and achilles
What is xanthelasmata?
Where is it usually found?
- cholesterol deposits under the skin
- usually around eyelids
What are the main risk factors for atheroma i.e. for same cholesterol levels?
(6)
Smoking Hypertension Diabetes mellitus Male Elderly
or of course increased cholesterol/lipid levels.
What are less strong risk factors for atheroma?
5
- obesity
- sedentary lifestyle
- low socioeconomic background
- low birthweight
- role of microorganisms
What are the two main steps in the development of atheromatous plaques?`
- injury to endothelial lining
- chronic inflammation and healing response of vascular wall to agent causing injury
This process repeated leads to atheromatous plaque development.
Describe in detail the development of atheromatous plaques?
8
- Endothelial injury
- LDL accumulates to vessel wall
- Monocyte adhesion to endothelium → foamy macrophages in intima
- Platelet adhesion
- Platelet factor release
- smooth muscle cell recruitment and proliferation
- extracellular matrix production and T-cell recruitment
- Lipid accumulation (extracellular and in foamy macrophages)
What are some common causes of endothelial disturbance that can cause atheroma?
- haemodynamic disturbances (turbulent blood flow)
- hypercholesterolaemia
How does hypercholesterolaemia cause endothelial damage?
increases local production of reactive oxygen species
How does hypercholesterolaemia cause atheromatous plaques?
4
- lipoproteins (LDL) aggregate in intima
- LDL modified by freeradicals produced by inflammatory cells
- modified LDL taken up by macrophages = foamy macrophages
- these are toxic to endothelial cells plus release growth factors (cytokines).
How are injured endothelial cells functionally altered to bring about atheroma?
(3)
- increased cell adhesion molecules (e.g. ICAM-1)
- increased permeability for LDL
- increased thrombogenicity
___________ cells + ______ in the _______ layer = ________
inflammatory
lipids
intima
plaques
Describe the formation of an advanced atheromatous plaque.
3
- lipid-laden macrophages die through apoptosis = debris in lipid core.
- inflammatory response.
- smooth muscle proliferation, synthesis of collage, elastin and mucopolysaccharide = fibrous cap around lipid core.
What is PDGF?
a group of molecules/ growth factors released from platelets.
How do established plaques grow in volume?
2
- endothelial loss
- microthrombi formed at denuded areas of plaque surface (smooth muscle proliferation and collagen deposition).
- cycle repeats
What is the main symptom of ileal, femoral or popilteal artery stenosis?
intermittent claudication
What causes stable angina?
stenosed atheromatous coronary artery, small obstruction
What is unstable angina?
What causes unstable angina?
Ischaemic pain at rest.
very severe stenosed atheromatous coronary artery
What does long standing tissue ischaemia cause?
atrophy of the affected organ
What are the major complications of atheroma?
2
Acute atherothrombotic occlusion
- rupture of plaque
- total occlusion of artery
What occurs when a plaque ruptures?
2
- highly thrombotic contents released into blood
- activation of coagulation cascade and thrombotic occlusion in very short time.
What happens when there is a total occlusion of an artery?
- irreversible ischaemia
- necrosis of tissue (infarct)
The total occlusion of a coronary artery leads to what?
MI
What causes a stroke?
total occlusion of the carotid or cerebral artery
Total occlusion of ileal, femoral or popliteal arteries lead to what?
lower limb gangrene
What can be a cause of small infarcts in organs distal to an atheromatous plaque?
small thrombus fragments can emolise and block smaller arteries when the large original plaque ruptures
What can small emboli from atheromatous plaques cause if the block a coronary artery branch?
small foci of necrosis which can cause life-threatening arrhythmias
What can debris from a carotid artery atheromatous plaque cause?
stroke, TIA, cerebral infarct
What can happen when an atheromatous plaque slowly extends in to the media of the aorta and weakens it?
an aneurysm
or sudden rupture causing retroperitoneal haemorrhage.
What are the features of atheromatous plaques that give them a high risk of having thrombotic complications?
(3)
- thin fibrous cap
- large lipid core
- prominent inflammation
What are the approaches to prevent atheromatous plaques from forming?
(5)
smoking cessation blood pressure control weight loss regular exercise dietary modifications
What are the some general drugs used to prevent atheromatous plaques?
(2)
- Cholesterol lowering drugs
2. Aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)
