Mechanism of Atheroma and Infarction Flashcards
Describe atheroma
Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue and leading to a restriction of the circulation and a risk of thrombosis
Describe infarction
Obstruction of the blood supply to an organ or region of tissue usually by a thrombus or embolus causing local tissue death
What is atherosclerosis and what makes it worse?
- A complex inflammatory process mediated by low density lipoprotein (LDL), angiotensin II and various inflammatory substances
- An ongoing systemic inflammatory disease makes it worse (eg. rheumatoid arthritis)
Where is atheroma formation common?
- Carotid arteries and circle of willis
- Coronary arteries
- Iliac arteries
- Aorta
Describe the inititation stage of atheroma formation
- Inflammatory triggers activate arterial endothelial cells. Oxidation of LDL particles, chiefly stimulated by presence of necrotic cell debris and free radicals in the endothelium
- LDL and inflammation, endothelial cells start to become activated and express cytokines and adhesion molecules
- 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
- 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
Describe the plaque formation stage of atheroma formation
- Macrophages begin to accumulate LDL from the circulation and become foam cells
- 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
- The activated smooth muscle cells also release growth factors and begin synthesising collagen and elastin in the intima layer
Describe the plaque maturation stage of atheroma formation
- Smooth muscle cells accumulate LDL becoming a second type of foam cell but they continue to make extracellular matrix of elastin and collagen which forms a fibrous plaque
- Cells underneath this plaque become oxygen starved then start to undergo apoptosis and release their fat which forms a globule of fat accumulating in the intima known as the lipid core
- The dying cells release matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque leaving a larger lipid core covered by a fibrous plaque that can be vulnerable to enzymatic digestion
Describe calcification and instability
- Later on in life 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
Describe when atheroma begins to form and when development of it occurs (hint: age)
- Development of macrophage foam cells occurs between birth and 10 years old
- Approximately 65% of people have smooth muscle foam cells by puberty
- There is then accumulation of more lipids which allows maturation of a fibrous cap between 30 and 40 years old
Describe what happens in a plaque rupture
- 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 a very good bases for clotting along with other proteins and factors in the intima. This gives us a pro-coaguant surface in an artery
- A thrombus now forms which may occlude the artery
What are the consequences of atheroma
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
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
Compare arterial and venous occlusion
Arterial occlusion -
- Particularly cardiac and carotid arteries
- Anything downstream from the arterial occlusion becomes starved of oxygen
- The reduced blood flow can lead to symptoms such as angina on exercise
Thrombus can become detached and block the cardiac arteries or cerebral arteries and cause death or serious damage very quickly
Venous occlusion -
- We tend to think of as happening in the legs but here an occlusion does not cut off the oxygen supply
- It will cause pain and swelling as hydraulic pressure causes oedema
- Thrombus may detach and return to the right side of the heart and could enter the pulmonary circulation causing a pulmonary embolism
What is an MI and compare MI and angina
Myocardial infarction -
Caused by a plaque moving and occluding the coronary arteries completely
Angina and MI -
- Stable cardiac angina - due to permanent flow limitation - not necessarily infarction
- Myocardial infarction - due to complete occlusion
- Unstable cardiac angina - due to transient thrombosis - not necessarily infarction
State some complications of MI
- Acute cardiac failure
- Conduction problems - arrhythmia
- Papillary damage - valve dysfunction
- Mural thrombosis - stroke
- Wall rupture
- Chronic heart failure - myocardial scarring
Describe the two main causes of strokes
Stroke due to thromboembolism -
- Ischemic
- Thrombus at carotid plaque rupture travels into smaller cerebral vessels
Non thromboembolic stroke -
- Haemorrhagic
- Due to hypoperfusion, loss of blood pressure (e.g. from heart failure, haemorrhage, shock) or aneurysm rupture and bleeding in the brain
