Mechanism of atheroma and infraction Flashcards
What is an atheroma?
- Process that occurs in the walls of the arteries
- Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to the restriction of the circulation and a risk of thrombosis
- Can weaken the wall of the vessels, eventually rupturing it
What is meant by Infarction?
- Obstruction of the blood supply to an organ/region of a tissue
- Typically by a thrombus or embolus, causing local death of the tissue
- Could happen anywhere (we’re particularly interested in myocardial infarction)
Describe the historical view of the formation of atheroma
- When young, the blood vessel is clear and unclogged
- As you get older, fat is laid down in the artery wall: clogging up the arteries
- ‘Infarct’ occurs when the fat stores detach and cause thrombosis
What is the historical view for the treatment of atheroma?
Improve diet and exercise more regularly
Role of lipoproteins in the formation of atheroma
- Lipoproteins transfer fats around the body so they are available to be taken up by the cells (via receptor mediated endocytosis)
- Lipids carried by LDLs include: cholesterol, phospholipids and triglycerides
Describe how atherosclerosis is a complex inflammatory process
- It is mediated by low density lipoproteins (LDL) & angiotensin II
- An ongoing systemic inflammatory diseases makes it all worse (e.g. rheumatoid arthritis)
What are common sites for atherosclerosis and inflammation?
The common sites are larger arteries:
- Carotid arteries & circle of Willis
- Coronary arteries
- Iliac arteries
- Aorta
Describe the process of Initiation
- Inflammatory triggers active arterial endothelial cells. Oxidation of LDL particles, mainly stimulated by the 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 then 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.
Summarise the process of Initiation
- Oxidized LDL: Inflammation, Angiotensin
- Activated endothelium
- Adhesion/ Diapedesis
- Tissue macrophages
Describe the process of plaque formation
- Macrophages then 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 may also begin synthesizing collagen and elastin in the intima layer
Describe the process of maturation of the plaque
- Smooth muscle cells accumulate LDL becoming a second type of foam cell but they continue to make an extracellular matrix of elastin and collagen which forms a fibrous plaque
- 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.
- The dying cells release matrix 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
What is calcification?
Later on in life, calcium deposits can form around the atheroma (these will be visible on a CT scan)
What is the argument based on the role of calcium deposits?
- The role remains uncertain
- Calcification may actually stabilize the plaque
- A lot of calcium deposits rather than a few could be an advantage
What occurs if the central core becomes too large?
A large plaque can occur and the sub-endothelium is exposed
What is the endothelium?
An anti-coagulant surface
