Mechanism of Atheroma & Infarction

Question 1

What is Atheroma?

Answer 1

The degeneration of artery walls caused by the accumulation of fatty deposits and scar tissue leading tot he restriction of circulation and a risk of thrombosis

Question 2

What is infarction?

Answer 2

An obstruction of blood supply to an organ/tissue region, typically a thrombus or embolus causing necrosis

Question 3

What is a thrombus?

Answer 3

A blood clot formed in a vessel and remains there

Question 4

What is an embolus?

Answer 4

A blood clot that travels from it’s site of formation to another location in the body

Question 5

What is the role of lipoproteins?

Answer 5

Transfer fats around the body - make fats available to be taken up via receptor mediated endocytosis

Question 6

Which lipids are carried via LDLs?

Answer 6

Cholesterol
phospholipids
Triglycerides

Question 7

What is atherosclerosis?

Answer 7

A disease in which plaque builds up inside your arteries

Question 8

What causes the inflammation during atherosclerosis?

Answer 8

Complex inflammatory response mediated by LDLs and angiotensin II

Question 9

What can cause atherosclerosis & inflammation to worsen?

Answer 9

An ongoing systemic inflammatory disease makes it all worse

e.g. rheumatoid arthritis

Question 10

What are the common sites of atherosclerosis?

Answer 10

Carotid arteries & Circle of Willis
Coronary Arteries
Iliac Arteries
Aorta

Question 11

Describe how the inflammatory response is initiated in atehrosclerosis

Answer 11

1. Endothelial cells activated by inflammatory triggers
   
   • LDL particle oxidation mainly stimulated by necrotic
     cell debris + free radicals in endothelium
2. Endothelial cells activated and express cytokines and
   adhesion molecules
3. Circulating myocytes bind to activated endothelium.
   -> start expressing adhesion molecules, move through
   tissue residing in intimal layer
4. Monocytes differentiate -> tissue macrophages
   
   • release own inflammatory mediators

Question 12

What is the issue with the inflammatory response initiation during atherosclerosis?

Answer 12

It’s the appropriate immunological response to inflammation but, it’s in the incorrect place

Question 13

Describe how plaques form within vessels

Answer 13

1. Macrophages accumulate LDL from circulation
   
   • > become foam cells
2. Activated foam cells release growth factors, causing
   smooth muscle to leave medial layer and cross internal
   elastic lamina entering intima
3. Activated smooth muscle cells also release growth
   factors
   
   • may begin collagen + elastin synthesis in intima layer

Question 14

Outline the process of plaque maturation

Answer 14

1. Smooth muscle cells accumulate LDL forming a 2nd
   type of foam cell
   
   • continue to produce extracellular matrix of elastin +
     collagen => fibrous plaque
2. Cells under plaque = oxygen starved => apoptosis and
   release their fat to form globules which accumulate in
   intima => lipid core
3. Dying cells release matrix metalloproteinases +
   enzymes -> breakdown fibrous matrix towards plaque
   edge
4. Large lipid core covered in fibrous plaque - may be
   vulnerable to enzymatic digestion

Question 15

What is calcification?

Answer 15

Hardening of tissue due to deposition / conversion into calcium carbonate or other insoluble calcium compounds

Question 16

What role does calcification play in atheroma?

Answer 16

Later on in life calcium deposits may form around the atheroma (seen via CT)
- role of calcium is unknown

Question 17

Explain why calcium may be hazardous in vessels?

Answer 17

Reduces arterial stretch and compliance

Question 18

Why may calcium deposits be beneficial to vessels?

Answer 18

A lot of calcium deposits (compared to a few) could prevent lipid core breaking off, exposing intima full of collagen -> potential to form thrombus

Question 19

When does atheroma formation occur during our lifetime?

Answer 19

Macrophage foam cells develop between 0 - 10 yrs
Smooth muscle foam cells develop by puberty
Lipids accumulate
<40 yrs maturation of fibrous cap

Question 20

How does thrombosis occur?

Answer 20

If central core becomes too large, plaque rupture can occur and subendothelium is exposed.
The endothelium is normally an anticoagulant surface

Question 21

What causes arteries to become pro-coagulant during thrombosis?

Answer 21

Collagen forms a very good base for clotting along with other proteins and factors in the intima -> provides pro-coagulant surface in arteries

Question 22

What is the consequence of a thrombus forming?

Answer 22

May occlude the artery

Question 23

What are the consequences of occlusive thrombosis?

Answer 23

• MI (heart attack)
• Occurs when blood flow decreases / stops to a part of
  the heart -> causes damage to myocardium

Question 24

What are the consequences of atheroma due to thromboembolism?

Answer 24

• Ischaemic Stroke
• Obstruction due to embolus from elsewhere in the
  body (usually carotid artery) blocking blood supply to
  part of the brain
• Other types of ischaemic stroke occur

Question 25

Describe the pathology of an aneurysm due to wall thickness

Answer 25

- e.g. Aortic aneurysm - causes weakness in aortic wall - increasing risk of aortic rupture - Rupture causes internal bleeding -> can cause shock and death if not treated immediately

Question 26

Give examples of how systemic inflammation promotes atheroma

Answer 26

``` e.g. rheumatoid arthritis Parasite infections lead to chronic inflammation Genetic & environmental influences - everyone has atheroma - genes cause vulnerability - environment causes manifestations ```

Question 27

Where does arterial occlusion usually occur?

Answer 27

Mainly in carotid and cardiac coronary arteries

Question 28

What is the consequence of arterial occlusion?

Answer 28

Anything downstream from an arterial occlusion become starved of oxygen e.g. Ischaemia - The reduced blood flow leads to symptoms such as angina on exercise

Question 29

What are the consequences of a detached arterial thrombus?

Answer 29

A thrombus becoming detached can: - Block cardiac arteries (MI) - block cerebral (stroke) > can cause serious damage or death

Question 30

Where does venous occlusions occur?

Answer 30

In lungs or legs

Question 31

What are the effects of venous occlusions?

Answer 31

In legs don't cut off oxygen supply Causes pain and swelling Hydraulic pressure causes oedema

Question 32

What is the consequence of a detached venous thrombus?

Answer 32

Could return to right side of heart and enter pulmonary circulation causing pulmonary embolism

Question 33

What causes a stable cardiac angina?

Answer 33

Due to permanent flow limitation | Not necessarily infarction

Question 34

What can cause unstable cardiac angina?

Answer 34

Due to transient thrombosis | Not necessarily infarction

Question 35

What is the cause of myocardial infarction?

Answer 35

Due to complete occlusion

Question 36

Describe the changes you'd see in ECG for a patient with MI

Answer 36

- STEMI (elevated ST level due to MI) damaged heart tissue doesn't depolarise properly sp ST elevated above baseline

Question 37

What is the survival rates of MI

Answer 37

50% survive their first MI | 1/2 won't live past the month

Question 38

Outline the complications presented with MI

Answer 38

- Acute cardiac failure - Conduction issues; arrhythmia - Papillary damage; valve dysfunction - Mural thrombosis; stroke - Wall rupture - Chronic heart failure; myocardial scarring

Question 39

Describe the features of a thromboembolic stroke

Answer 39

Occurs when thrombus at carotid plaque rupture travels to smaller cerebral vessels 85% from carotid atheroma rupture 15% from stasis in LA due to arrhythmia

Question 40

Outline features of a non-thromboembolic stroke

Answer 40

Due to hypo-perfusion, loss of BP e. g. - heart failure - haemorrhage - shock - aneurysm rupture - bleeding in brain