S2: Atheroma and Infarction Flashcards
Compare the old and modern view of atherosclerosis
Old view: When young people are healthy and will have unobstructed blood vessels. During age, people get fat stored in your artery walls, eventually this fat explodes and causes thrombosis.
Modern View: Atherosclerosis is that it is a complex inflammatory process. We now agree that low density lipoprotein is an inflammatory mediator (it “annoys the endothelium as well as activating various inflammatory cells). Angiotensin II (a vasoconstrictor) is also an inflammatory mediator, endothelial cells do not like large amounts of it.
Risk factors for athersclerosis
- Age
- Male sex (premenopausal women protected)
- Genetics
- Hyperlipidaemia
- Smoking
- Hypertension
- Diabetes mellitus
- Obesity
- Metabolic syndrome
- Alcohol
- Drugs
- LDL and Ang II
- Ongoing systemic inflammatory disease e.g. rheumatoid arthritis
- Parasitic infections
What are the 3 components of atheromatous plaques?
- Fibrous cap:
Smooth muscle and collagen in dynamic equilibrium - Cellular layer:
Smooth muscle, macrophages, lymphocytes, less connective tissue - Necrotic core:
Lipid, cholesterol clefts, firin, foam cells, cell debris
What are the most common sites of plaque build up?
The arteries that tend to be affected are branch points in larger arteries like:
- Carotid arteries (cause stroke if break off)
- Circle of willis
- Coronary arteries
- Iliac arteries
- Aorta
What are the stages of atheroma development?
- Initiation
- Plaque Formation - development of foam cells
- Maturation of the plaque - accumulation of more lipids and maturation of fibrous cap
- Calcification and Instability
Describe initiation of atheroma development
- Substances like oxidised LDLs, angiotension as well as inflammation will irritate the endothelium.
- The endothelium becomes activated and releases cytokines (which are inflammatory mediators that tell nearby cells to be inflamed) and adhesion molecules (molecules endothelial cells express that allow other cells e.g. immune to stick to endothelial cells)
The result of activated endothelium is that circulating WBCs such as monocytes will stick to these endothelial cells by the adhesion molecules and enter the artery wall (diapedesis) and become a tissue macrophage.
Monocytes do this all around the body, in skin, lung etc. but they DO NOT belong in the intima of arteries and this is the start of an atheroma.
Describe the plaque formation of atheroma development
The tissue macrophage starts to take up circulating fat (LDL) and become a foam cell. At the same time it releases lots of inflammatory mediators and growth factors which encourages nearby smooth muscle cells in media to migrate to intima (where they don’t belong).
In the process of moving into the intima and division, the smooth muscle cells start to synthesise and release collagen and elastin which are structural proteins.
Describe maturation of the plaque of atheroma development
The smooth muscle cells eventually start taking up circulating fat become smooth muscle foam cells (2 types of foam cells)
Some of these cells are now so far from blood supply so they start to die and there is now a lipid core (called necrotic core as it contains dead cells). So there is piling of dead cells and fat into a big ‘blob’. This is being maintained by the secretion of elastin and collagen forming the fibrous cap.
Describe calcification and instability of atheroma development
As the plaque really starts to mature, calcification occurs due to the foam cells getting confused by all the growth cells and they start to develop a bone like profile releasing calcium deposits.
It seems like they provide structural support and stop the plaque rupturing.
It may be that little calcium creates more instability but once there is lots present it is like ‘solid motor’ which stops rupturing.
Explain the atheroma rupture
Eventually the endothelium breaks and once this happens you have the von Williebrand factor exposed to activate platelets and the tissue factor to activate the coagulation cascade –> THROMBOSIS
A clot could occur in the middle of a coronary artery that would occlude downstream and lead to an MI
What are the consequences of atheroma?
- Occlusive thrombosis (occludes an artery) e.g. MI
- Thromboembolism (thrombus forms somewhere and moves somewhere else) e.g. Ischaemic stroke where plaque in carotid artery erupts causing a thrombus to move up into the brain
- Aneurysm due to wall weakness (process of making neointima weakens wall) e.g. aortic aneurysm
- Peripheral vascular disease e.g. critical limb ischaemia
Why is the heart and brain very vulnerable to drop in perfusion?
Brain = cannot anaerobically respire Heart = very demanding of O2
What evidence is there saying that atherosclerosis is inevitable?
- We know from mummified remains that atheroma is as old as modern man and even seen in hunter-gatherer societies.
- Even vegan cultures ended up with atherosclerosis, the reason is because of chronic infections/inflammation.
- Parasitic inflammation also causes systemic inflammation (which hunter gatherers and mummies had)
Our vulnerability to forming atheroma’s is genetic, it is in our genes. It is then the environmental influences that determine if that vulnerability becomes manifest in our lives.
List some causes of chest pain
- Broken rip
- Collapsed lung
- Nerve infection (shingles)
- ‘Pulled’ muscle
- Infection
- Heart burn (hernia)
- Pericarditis
- Blood clot in the lungs (PE)
- Angina
- MI
What is an infarction?
Dead tissue
