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Cardiovascular System > Pathophysiology of Atheroma > Flashcards

Pathophysiology of Atheroma Flashcards

1
Q

What is an atheroma also known as?

A

atherosclerosis

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2
Q

What is an atheroma?

A

Formation of plaques in the intima of large and medium-sized arteries.

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3
Q

What does atheroma lead to when the lumen of arteries is narrowed?

A

ischaemia

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4
Q

What is a serious consequence from myocardial ischaemia due to atheroma?

A

angina

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5
Q

What is myocardial ischaemia complicated by?

A

thromboembolism

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6
Q

What is arteriosclerosis? (3)

What is it not? (1)

A

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.

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7
Q

What sorts of ischaemia can be caused by arteriosclerosis?

4

A
  • cardiac
  • cerebral
  • colonic
  • renal
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8
Q

When does arteriosclerosis become clinically apparent?

4

A

When CVS is further stressed by:

  • haemorrhage
  • major surgery
  • infection
  • shock
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9
Q

What is the earliest lesion present in atheroma?

2

A
  • a fatty streak

- yellow linear elevation of lipid-laden macrophages

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10
Q

In what group of patients are fatty streaks found (earliest significant lesion of atheroma)?

Are they clinically significant?

A

young children

No - they may go away.

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11
Q

What is the stage of atheroma prior to fully developed atheromatous plaque i.e. following initial fatty streak development?

(1)

A
  • Early atheromatous plaque
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12
Q

In what group of patients are early atheromatous plaques found?

A

young adults

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13
Q

What are the characteristics of an early atheromatous plaque?

(2)

A
  • smooth yellow patches in intima

- lipid-laden macrophages

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14
Q

Describe the composition of a fully developed artheromatous plaque.

(3)

A
  • Central lipid core
  • fibrous tissue cap
  • covered by arterial endothelium
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15
Q

What does collagen in the fibrous cap of an atheromatous cap do?

What produces the collagen?

A
  • provides structural strength to the structure

- smooth muscle

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16
Q

Which inflammatory cells reside in the fibrous cap of a fully developed atheromatous plaque?

(3)

A

macrophages
T-lymphocytes
mast cells

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17
Q

What is the core of an atheromatous plaque made from?

2

A
  • cellular lipids

- debris from macrophages (died in plaque)

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18
Q

What is often found around the rim of the atheromatous plaque?

A

foamy macrophages, due to uptake of lipoproteins by scavenger receptors

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19
Q

What often forms in late development of artheromatous plaques?

A

dystrophic calcification

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20
Q

Where are atheromatous plaques most likely to form?

What is specific about these places?

A
  • at arterial branching points/bifurcations

- turbulent blood flow

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21
Q

What are some features of complicated atheroma?

3

A
  • haemorrhage into plaque = calcification

- plaque rupture/fissuring - thrombosis

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22
Q

What is the most important risk factor form atheroma?

A

hypercholesterolaemia

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23
Q

What is the congenital abnormality that can cause primary lipidaemia?

A
  • lack of cell membrane receptors for LDL
  • carriers affected (heterozygous)
  • homozygous individuals affected more severely.
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24
Q

What happens to patients homozygous for this type mutation?

3

A
  • much less functional membrane receptors for LDL.
  • very high cholesterol levels in the blood
  • coronary artery atheroma in infancy/teens
  • death
25
Q

What is the familial form of hyperlipidaemia called?

A

primary hyperlipidaemia

26
Q

What is the acquired form of hyperlipidaemia called?

A

secondary (idiopathic)

27
Q

What are some signs of major hyperlipidaemia?

4

A
  • premature corneal arcus
  • tendon xanthomata
  • xanthelasmata
  • FH of MI/atheroma
28
Q

What is corneal arcus?

A

an opaque ring forms around the margin of the cornea (common in elderly).

29
Q

What is tendon xanthomata?

Where is it usually found?

A
  • deposits of fat/foamy macrophages in the tendons

- usually of the knuckles and achilles

30
Q

What is xanthelasmata?

Where is it usually found?

A
  • cholesterol deposits under the skin

- usually around eyelids

31
Q

What are the main risk factors for atheroma i.e. for same cholesterol levels?

(6)

A 
Smoking
Hypertension
Diabetes mellitus
Male
Elderly

or of course increased cholesterol/lipid levels.

32
Q

What are less strong risk factors for atheroma?

5

A
  • obesity
  • sedentary lifestyle
  • low socioeconomic background
  • low birthweight
  • role of microorganisms
33
Q

What are the two main steps in the development of atheromatous plaques?`

A
  1. injury to endothelial lining
  2. chronic inflammation and healing response of vascular wall to agent causing injury

This process repeated leads to atheromatous plaque development.

34
Q

Describe in detail the development of atheromatous plaques?

8

A
  1. Endothelial injury
  2. LDL accumulates to vessel wall
  3. Monocyte adhesion to endothelium → foamy macrophages in intima
  4. Platelet adhesion
  5. Platelet factor release
  6. smooth muscle cell recruitment and proliferation
  7. extracellular matrix production and T-cell recruitment
  8. Lipid accumulation (extracellular and in foamy macrophages)
35
Q

What are some common causes of endothelial disturbance that can cause atheroma?

A
  • haemodynamic disturbances (turbulent blood flow)

- hypercholesterolaemia

36
Q

How does hypercholesterolaemia cause endothelial damage?

A

increases local production of reactive oxygen species

37
Q

How does hypercholesterolaemia cause atheromatous plaques?

4

A
  1. lipoproteins (LDL) aggregate in intima
  2. LDL modified by freeradicals produced by inflammatory cells
  3. modified LDL taken up by macrophages = foamy macrophages
  4. these are toxic to endothelial cells plus release growth factors (cytokines).
38
Q

How are injured endothelial cells functionally altered to bring about atheroma?

(3)

A
  • increased cell adhesion molecules (e.g. ICAM-1)
  • increased permeability for LDL
  • increased thrombogenicity
39
Q

___________ cells + ______ in the _______ layer = ________

A

inflammatory
lipids
intima
plaques

40
Q

Describe the formation of an advanced atheromatous plaque.

3

A
  1. lipid-laden macrophages die through apoptosis = debris in lipid core.
  2. inflammatory response.
  3. smooth muscle proliferation, synthesis of collage, elastin and mucopolysaccharide = fibrous cap around lipid core.
41
Q

What is PDGF?

A

a group of molecules/ growth factors released from platelets.

42
Q

How do established plaques grow in volume?

2

A
  1. endothelial loss
  2. microthrombi formed at denuded areas of plaque surface (smooth muscle proliferation and collagen deposition).
  3. cycle repeats
43
Q

What is the main symptom of ileal, femoral or popilteal artery stenosis?

A

intermittent claudication

44
Q

What causes stable angina?

A

stenosed atheromatous coronary artery, small obstruction

45
Q

What is unstable angina?

What causes unstable angina?

A

Ischaemic pain at rest.

very severe stenosed atheromatous coronary artery

46
Q

What does long standing tissue ischaemia cause?

A

atrophy of the affected organ

47
Q

What are the major complications of atheroma?

2

A

Acute atherothrombotic occlusion

  • rupture of plaque
  • total occlusion of artery
48
Q

What occurs when a plaque ruptures?

2

A
  • highly thrombotic contents released into blood

- activation of coagulation cascade and thrombotic occlusion in very short time.

49
Q

What happens when there is a total occlusion of an artery?

A
  • irreversible ischaemia

- necrosis of tissue (infarct)

50
Q

The total occlusion of a coronary artery leads to what?

A

MI

51
Q

What causes a stroke?

A

total occlusion of the carotid or cerebral artery

52
Q

Total occlusion of ileal, femoral or popliteal arteries lead to what?

A

lower limb gangrene

53
Q

What can be a cause of small infarcts in organs distal to an atheromatous plaque?

A

small thrombus fragments can emolise and block smaller arteries when the large original plaque ruptures

54
Q

What can small emboli from atheromatous plaques cause if the block a coronary artery branch?

A

small foci of necrosis which can cause life-threatening arrhythmias

55
Q

What can debris from a carotid artery atheromatous plaque cause?

A

stroke, TIA, cerebral infarct

56
Q

What can happen when an atheromatous plaque slowly extends in to the media of the aorta and weakens it?

A

an aneurysm

or sudden rupture causing retroperitoneal haemorrhage.

57
Q

What are the features of atheromatous plaques that give them a high risk of having thrombotic complications?

(3)

A
  • thin fibrous cap
  • large lipid core
  • prominent inflammation
58
Q

What are the approaches to prevent atheromatous plaques from forming?

(5)

A 
smoking cessation
blood pressure control
weight loss
regular exercise
dietary modifications
59
Q

What are the some general drugs used to prevent atheromatous plaques?

(2)

A
  1. Cholesterol lowering drugs

2. Aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)

Cardiovascular System (37 decks)

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