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
Describe the development of an atheroma throughout life
- Development of macrophage foam cells occurs between birth and 10 years
- Development of smooth muscle foam cells occurs by puberty (for 65% of people)
- Accumulation of more lipids carries on throughout life
- Maturation of fibrous cap occurs between 30 and 40 years
- > 40 years: risk avoidance
What is the use of collagen during plaque rupture?
Collagen forms very good bases for clotting along with other proteins and factors in the intima, which gives us a pro-coagulant surface in an artery
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
Consequences of atheroma: THROMBOEMBOLISM
- e.g. Ischaemic stroke
- Obstruction due to an embolus from elsewhere in the body (usually carotid artery)
- Blocks the blood supply to the brain
- Other types of Ischaemic strokes can occur
Consequences of atheroma: ANEURYSM DUE TO WALL WEAKNESS
- e.g. aortic aneurysm
- Cause weakness in the wall of aorta
- Increases risk of aortic rupture
- When the rupture occurs, massive internal bleeding results
- Unless treated immediately, shock and death can occur
How does the examination of ancient mummies suggest that atherosclerosis may be inevitable?
- MRI scans on Egyptians mummies
- Used to remove all organs but leave the heart
- MRIs shows calcium deposits, indicating atherosclerosis
- Suggests that atheroma is as old as the modern man, because it is found in hunter-gatherer societies
- Vegan/paleo-diet cultures are ending up with atherosclerosis suggesting it cant just be down to lifestyle choices
- One possibility could be chronic infection/inflammation
What are five possible explanations for atheroma formation?
- Systemic inflammation promotes atheroma formation, e.g. rheumatoid arthritis
- Wood fire smoke, giving low inflammatory response (ancestors spent a lot of time in caves burning fires)
- Parasite infections lead to chronic inflammation
- Genetic vulnerability
- Environmental influences, eg. lifestyle, diet etc.
Describe the consequences of an arterial occlusion
- likely to occur in the cardiac and carotid arteries
- anything downstream from arterial occlusion becomes starved of oxygen i.e. ischaemia
- reduced blood flow can lead to symptoms e.g. angina on exercise
- Thrombus becoming detached can block the cardiac arteries (MI) or cerebral arteries (stroke) and cause death/serious damage very quickly
Describe the consequences of a venous occlusion
- an occlusion in the legs doesn’t cut off the oxygen supply
- it will cause pain and swelling as hydraulic pressure causes odaema
- a Thrombus may detach and return to the right side of the heart
- It could then enter the pulmonary circulation, causing a pulmonary embolism
Describe what can be examined on the post-mortem of a patient with myocardial infarction
- Dilated left ventricle, indicating long term heart failure
- Old white MI (years/months before death
- Viable muscle
- Extensive yellow necrotic myocardium, 7-10 days post-infarction
- Hemorrhagic myocardium 4-7 days post-infarction plus mural thrombus
What causes stable cardiac angina?
- occurs due to permanent flow limitation
- not necessarily infection
What causes myocardial infarction?
Complete occlusion
What causes unstable cardiac angina?
- transient thrombosis
- not necessarily infarction
What are ECG changes that can be observed to diagnose patients with MI?
- The ST wave is elevated in MI: STEMI
- This is because damaged heart tissue doesn’t depolarize properly, so this section is elevated above the baseline
Prognosis of Myocardial Infarction
- 50% of the population survive their first MI
- The other 50% wont survive the first month
List some complications of Myocardial Infarction
- Acute cardiac failure
- Conduction problems: arrhythmia
- Papillary damage: valve dysfunction
- Mural thrombosis: stroke
- Wall rupture
- Chronic heart failure: myocardial scarring
Ischaemic strokes
- clot causing embolic stroke
- plaque causing thrombotic stroke
Haemorrhagic strokes
- burst aneurysm causing subarachnoid hemorrhage
- torn artery causing intracerebral hemorrhage
Difference between ischaemic and haemorrhagic strokes
Ischaemic: block blood supply due to plaque or thrombus
Haemorrhagic: blood supply reduced due to internal bleeding
Stroke due to thromboembolism
- Thrombus at the carotid plaque rupture travels into smaller cerebral vessels
- 85% from the carotid atheroma rupture
- 15% from stasis in the left atrium due to arrythmia
Non-thromboembolic stroke
Due to:
- hypo-perfusion
- loss of blood pressure (e.g. heart failure, haemorrhage, shock)
- aneurysm rupture
- bleeding in the brain