Mechanisms of Atheroma and Infarction

Question 1

What is the difference between atheroma and an infarction?

Answer 1

Atheroma:
Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis
Infarction:
Obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue

Question 2

What fats are involved with atheroma?

Answer 2

Lipoproteins transfer fats around the body so they are available to be taken up by the cells via receptor mediated endocytosis
The lipids carried by LDLs include cholesterol, phospholipids and triglycerides

Question 3

How is the inflammation process involved with atherosclerosis?

Answer 3

A complex inflammatory process:
Mediated by low density lipoprotein (LDL), angiotensin II and various inflammatory substances
An ongoing systemic inflammatory diseases makes it all worse (e.g. rheumatoid arthritis)
Common sites are the larger arteries such as:
Carotid arteries and circle of Willis
Coronary arteries
Iliac arteries
Aorta

Question 4

Recall the initiation stage of atheroma

Answer 4

1. Inflammatory triggers active arterial endothelial cells
   Oxidation of LDL particles, chiefly stimulated by the presence of necrotic cell debris and free radicals in the endothelium.
   
   2. LDL and inflammation, endothelial cells start to become activated and express cytokines and adhesion molecules
   3. Circulating monocytes bind to the activated endothelium
      They start expressing adhesion molecules and begin to move through the tissue and reside in the intimal layer
   4. Monocytes differentiate into tissue macrophages which release their own inflammatory mediators
      It is an appropriate immunological response to inflammation but in the wrong place here

Question 5

Recall the plaque formation stage of atheroma

Answer 5

1. Macrophages then begin to accumulate LDL from the circulation and become foam cells
   
   2. Activated foam cells release other growth factors which cause smooth muscle cells to leave the medial layer and cross the internal elastic lamina entering the intima
   3. The activated smooth muscle cells also release growth factors and may also begin synthesising collagen and elastin in the intima layer

Question 6

Recall the plaque maturation stage of atheroma

Answer 6

1. Smooth muscle cells accumulate LDL becoming a second type of foam cell but they continue to make extracellular matric of elastin and collagen which forms a fibrous plaque
   
   2. Cells underneath this plaque become oxygen starved they begin to undergo apoptosis and release their fat which forms a globule of fat that is now accumulating in the intima, known as the lipid core
   3. The dying cells release matric metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque leaving a large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion

Question 7

Recall the calcification and instability of the lipid core in atheroma

Answer 7

Later on in life, if it doesn’t burst straight away, calcium deposits may form around the atheroma and these are visible on a CT scan
The role of calcium deposits remains uncertain, there have been arguments that calcification may actually stabilise the plaque
Calcium may be a bad thing, but paradoxically a lot of calcium deposits rather than a few could be a sight advantage

Question 8

When does atheroma begin?

Answer 8

Atheroma begins when we are young

Question 9

How does the plaque rupture?

Answer 9

If the central core becomes too large plaque rupture can occur and the sub-endothelium is exposed
The endothelium is normally an anticoagulant surface
Collagen forms very good bases for clotting along with other proteins and factors in the intima
This gives us a pro-coagulant surface in an artery
A thrombus now forms which may occlude the artery

Question 10

What are the consequences of atheroma?

Answer 10

Occlusive thrombosis:
E.g. myocardial infarction
Commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle
Thromboembolism
E.g. ischaemic stroke
In this case obstruction due to an embolus from elsewhere in the body (usually carotid artery) blocking blood supply to part of the brain
Other types of ischaemic strokes occur
Aneurysm due to wall weakness:
E.g. aortic aneurysm
Cause weakness in the wall of the aorta and increase the risk of aortic rupture
When rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur

Question 11

What is the difference between arterial and venous occlusion?

Answer 11

Arterial occlusion:
Particularly cardiac and carotid arteries
Anything downstream from arterial occlusion becomes starved of oxygen i.e. ischaemia
The reduced blood flow can lead to symptoms such as angina on exercise
A thrombus becoming detached can block the cardiac arteries (MI) or cerebral arteries (stroke) and cause death or serious damage very quickly
Venous occlusion:
We tend to think of as happening in the legs, but here an occlusion doesn’t cut off the oxygen supply
It will cause pain and swelling as hydraulic pressure causes oedema
However a thrombus may detach and return to the right side of the heart and could enter the pulmonary circulation causing a pulmonary embolism

Question 12

How can we tell someone who has passed away has had a myocardial infarction?

Answer 12

The left ventricle here is very dilated indicating long term heart failure
He had a MI moths or years before death
He has had a haemorrhagic event and mural thrombus some days after his last MI which is probably what killed him eventually
Notice the necrotic myocardium post infarction

Question 13

What is the difference between angina and an MI?

Answer 13

Stable cardiac angina:
Atherosclerosis in the artery but not completely blocking
Due to permanent flow limitation, ok at rest but pain on exercising
Not necessarily infarction
Myocardial infarction:
Due to complete occlusion, tissue downstream is ischaemic
Unstable cardiac angina:
Due to transient thrombus, so suddenly get pain without exercise, palpitation, sweating etc.
Not necessarily infarction

Question 14

What are some complications of MI?

Answer 14

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

Question 15

How do strokes happen?

Answer 15

Stroke due to thromboembolism:
Thrombus at carotid plaque rupture travels into smaller cerebral vessels
85% from carotid atheroma rupture
15% from stasis in left atrium due to arrhythmia
Non-thromboembolic stroke:
Due to hypo-perfusion, loss of blood pressure (e.g. heart failure, haemorrhage, shock) or aneurism rupture and bleeding in the brain