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Cardiovascular System > Pathophysiology of atheroma > Flashcards

Pathophysiology of atheroma Flashcards

1
Q

What is atheroma/atherosclerosis?

A

Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries

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2
Q

What can atheromas cause?

A

Serious consequences: angina due to myocardial ischaemia

- Complicated by thromboembolism

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3
Q

What is arteriosclerosis?

A
  • It is not atheromatous.
  • Age-related change in muscular arteries
  • Age-related change in muscular arteries
  • Smooth muscle hypertrophy, apparent reduplicationof internal elastic laminae, intimal fibrosis causes a decrease in vessel diameter
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4
Q

How does arteriosclerosis affect the body?

A

Contributes to high frequency of cardiac, cerebral, colonic and renal ischaemia in elderly.

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5
Q

When are clinical features of arteriosclerosis most apparent?

A

They are most apparent when CVS further stressed by haemorrage, major surgery, infection, shock.

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6
Q

Is it possible to have arteriosclerosis and atheromatous together?

A

YES

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7
Q

What is a Fatty streak in atherosclerosis?

A
  • It is the earliest visible lesion of atherosclerosis

- It is due to an accumulation of lipid-laden foam cells in the intimal layer of the artery.

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8
Q

What is the main hallmark of established atherosclerosis?

A

Over time , the fatty streak evolves into a fibrous plaque, the hallmark of established atherosclerosis.
- Patients are at risk when there are atheromatous plaques

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9
Q

Features of a Fatty streak

A
  • Earliest significant lesion
  • Seen in young children
  • Yellow linear elevation of intimal lining
  • Comprises masses of lipid-laden macrophages
  • No clinical significance
  • May disappear
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10
Q

Features of early atheromatous plaque

A
  • Seen in young adults onwards
  • Smooth yellow patches in intima
  • Lipid-laden macrophages
  • Progress to established plaques
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11
Q

What does a fully developed atheromatous plaque contain?

A
  • Central lipid core with fibrous tissue cap, covered by arterial endothelium
  • Collagens (produced by smooth muscle cells) in cap provide structural strength
  • Inflammatory cells (macrophages, T-lymphocytes, mast cells) reside in fibrous cap: recruited from arterial endothelium.
  • Central lipid core rich in cellular lipids/debris derived from macrophages (died in plaque)
  • Soft, highly thrombogenic, often rim of “foamy” macrophages
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12
Q

Features of complicated atheroma

A
  • It has the same features of established atheromatous plaque (lipid-rich core, fibrous cap) plus:
  • Haemorrhage into plaque (calcification)
  • Plaque rupture/fissuring
  • Thrombosis
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13
Q

What is calcified atheroma?

A

Aortic valve calcification is a condition in which calcium deposits form on the aortic valve in the heart.
- These deposits can cause narrowing at the opening of the aortic valve. This narrowing can become severe enough to reduce blood flow through the aortic valve — a condition called aortic valve stenosis.

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14
Q

Aetiology of atheroma

A
  • Hypercholesterolaemia is the most important risk factor.
  • Causes plaque formation and growth in absence of other known risk factors
  • Importance of LDL cholesterol: studies of patients/animals with genetically determined lack of cell membrane receptors for LDL.
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15
Q

What is hypercholesterolaemia?

A

Hypercholesterolemia (high cholesterol), is the presence of high levels of cholesterol in the blood.
- It is a form of hyperlipidemia, high blood lipids, and hyperlipoproteinemia (elevated levels of lipoproteins in the blood).

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16
Q

What is the LDL cholesterol problem in 1/500 caucasians?

A
  • Decreased functional receptors on cell surfaces.

- Elevated plasma LDL cholesterol levels.

17
Q

What are signs of major hyperlipidaemia?

A
  • Familial/primary vs acquired/secondary
  • Biochemical evidence: LDL, HDL, total cholesterol, triglycerides
  • Corneal arcus (premature)
  • Tendon xanthomata (knuckles, achilles)
  • Xanthelasmata
  • Risk/premature/family history MI/atheroma
18
Q

Risk factors for atheroma

A
  • Smoking
  • Hypertension
  • Diabetes mellitus
  • Being male
  • Being old
    These accelerate process of plaque formation driven by lipids.

Other risk factors: huge variation in disease severity among patients with same cholesterol levels.

19
Q

Less strong risk factors for atheroma

A
  • Obesity
  • Sedentary lifestyle
  • Low socio-economic status
  • Low birthweight
  • ?role of micro-organisms?
20
Q

Two step process in the development of atheromatous plaques

A
  1. Injury to endothelial lining of artery
  2. Chronic inflammatory and healing response of vascular wall to agent causing injury

Chronic/episodic exposure of arterial wall to these processes causes formation of atheromatous plaques.

21
Q

Order of events in the pathogenesis of atherosclerosis

A
  • Endothelial injury and dysfunction
  • Accumulation of lipoproteins (LDL) in vessel wall
  • Monocyte adhesion to endothelium > migration into intima and transformation to foamy macrophages.
  • Platelet adhesion
  • Factor release from activated platelets, macrophages > smooth muscle cell recruitment
  • Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment.
  • Lipid accumulation (extracellular and in foamy macrophages).
22
Q

What are the most important causes of endothelial injury?

A
  • Haemodynamic disturbances (turbulent flow)
  • Hypercholesterolaemia (chronic hypercholesterolaemia can directly impair endothelial cell function by increasing local production of reactive oxygen species)
23
Q

In hypercholesterolaemia, how do lipoproteins aggregate?

A
  • lipoproteins aggregate in intima and are modified by free radicals produced by inflammatory cells → modified LDL accumulated by macrophages but not completely degraded → foamy macrophages → toxic to endothelial cells plus release of growth factors, cytokines
24
Q

How are injured endothelial cells functionally altered?

A
  • Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
  • High permeability for LDL
  • Increased thrombogenecity

Inflammatory cells, lipids → intimal layer → plaques

25
Q

How does advanced plaque formation occur?

A
  • Large numbers macrophages, T-lymphocytes
  • Lipid-laden macrophages die through apoptosis > lipid into lipid core
  • Response to injury = chronic inflammatory process: 1. Inflammatory reaction 2. Process of tissue repair
  • Growth factors (PDGF) → proliferation intimal smooth muscle cells, subsequent synthesis collagen, elastin, mucopolysaccharide
  • Fibrous cap encloses lipid rich core
  • Growth factors secreted by platelets, injured endothelium, macrophages and smooth muscle cells.
26
Q

What forms at denuded areas of plaque surface in development of atheromatous plaques?

A

Microthrombi
- Microthrombi formed at denuded areas of plaque surface → organised by same repair process (smooth muscle cell invasion and collagen deposition

  • Repeated cycles gradually increase plaque volume.
27
Q

What are consequences of atheroma: clinical manifestations?

A
  • Many plaques form over lifetime, many clinically unnoticed
  • Clinical disease: relatively benign to life-threatening/fatal.
  • Acute changes in plaques (complicated atheroma) → serious consequences
28
Q

What occurs due to high grade plaque stenosis

A

This causes progressive lumen narrowing

29
Q

What does acute atherthrombotic occlusion cause?

A
  • Major complications: rupture of plaque → acute event
  • rupture exposes highly thrombogenic plaque contents (collagen, lipid, debris) to blood stream → activation of coagulation cascade and thrombotic occlusion in a very short time.
30
Q

What can a total occlusion cause?

A

Total occlusion → irreversible ischaemia → necrosis (infarction) of tissues

e.g. myocardial infarct (coronary artery), stroke (carotid, cerebral artery), lower limb gangrene (ileal, femoral, popliteal artery).

31
Q

Who is at heightened risk for arterial embolisation?

A

Surgical and intensive care patients are at a heightened risk for arterial embolisation due to pre-existing conditions such as age, hypercoagulability, cardiac abnormalities and atherosclerotic disease.

32
Q

Where do most arterial emboli originate and travel?

A

-Most are clots that originate in the heart and travel to distant vascular beds where they cause arterial occlusion, ischaemia, and potentially infarction.

33
Q

How does ambolisation of the distal arterial bed occur?

A
  • Detachment of small thrombus fragments from thrombosed atheromatous arteries → embolise distal to ruptured plaque.
  • Embolic occlusion of small vessels → small infarcts in organs.
34
Q

How does ruptured atheromatous abdominal aortic aneurysm occur?

A
  • Media beneath atheromatous plaques gradually weakened (lipid-related inflammatory activity in plaque)
    → gradual dilatation of vessel
  • Sudden rupture → massive retroperitoneal haemorrhage (high mortality)
  • Aneurysms >5cm diameter are at high risk of rupture
  • Mural thrombus → emboli to legs
35
Q

What are vulnerable atheromatous plaques?

A
  • Atheromatous plaques that rupture with subsequent thrombosis: distinct morphological features.
  • Typically thin fibrous cap, large lipid core, prominent inflammation.
36
Q

What causes an increase in risk of plaque rupture?

A

Pronounced infammatory activity → degradation, weakening of plaque → increased risk of plaque rupture

  • Secretion of proteolytic enzymes, cytokines and reactive oxygen species by plaque inflammatory cells.
  • Highly stenotic plaques often large fibrocalcific component, little inflammation
37
Q

What are preventative and therapeutic approaches for atherosclerosis?

A
  • Stop smoking
  • Control blood pressure
  • Weight loss
  • Regular exercise
  • Dietary modifications
38
Q

Secondary prevention methods for atherosclerosis?

A

Cholesterol lowering drugs, aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)

  • OR surgical options

Cardiovascular System (36 decks)

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