Atherosclerosis and MI Flashcards
What is cardiogenic shock?
Loss of perfusion due to malfunction of the heart
What is ischaemic heart disease?
All heart diseases resulting from reduced O2 supply to heart muscle
List three forms of acute coronary syndrome (ACS)
- Angina
- Acute coronary occlusion
- Myocardial infarction
Describe how an atheroma is formed
There is a tear in an artery wall; fatty material is deposited in the wall and the narrowed artery becomes blocked by a blood clot
What are statins?
Drugs that reduce/prevent cholesterol build-up in vessels
What two things may occur when fatty acids are present via diet/liver synthesis?
Oxidised for fuel, or converted to triglycerides and stored in adipose tissue
Free fatty acids travel through blood bound to which protein?
Albumin
Triglycerides (TAGs) and cholesterol are transported between organs in ____.
Lipoproteins
What are lipoproteins?
Lipid droplets assembled around protein particles called apo-lipoproteins
Apo-lipoproteins drive the metabolism of particles by…
Binding to receptors on cell membranes
What is the relevance of LDL to cardiovascular disease?
LDL is small enough to enter the arterial wall and deposit lipids between endothelium and smooth muscle
Macrophages in blood vessels cannot regulate cholesterol uptake and so become what kind of cells?
Foam cells
What are foam cells?
Lipid-loaded macrophages that secrete pro-inflammatory cytokines
What is the major function of HDL?
To remove cholesterol from peripheral tissues and return it to the liver to be degraded to bile acids and excreted; this is why they are associated with CVD prevention
Describe Tangier’s disease
- Rare genetic disease
- Mutation in a cholesterol transporter required to move cholesterol out of cells
- Almost complete lack of HDL
- Hypertriglyceridaemia (high TAG levels)
- Early onset atherosclerosis
Describe the development of atherosclerosis
- LDL deposits lipids between endothelium and smooth muscle
- Accumulation of LDL in sub-endothelial space triggers endothelial cells to secrete chemokines
- Chemokines induce monocyte infiltration
- Monocytes differentiate into macrophages
- Macrophages phagocytose LDL
- Sustained LDL uptake induces foam cell formation
- Foam cells cannot leave the lesion, and recruit other inflammatory cells
Give three examples of how atherosclerotic lesions can become unstable
- Necrosis/apoptosis of foam cells
- Increased inflammation
- Breakdown of the fibrous cap
What can trigger the core necrosis in an atherosclerotic lesion?
Necrosis of the foam cells can occur as a consequence of:
- Growth factor deprivation
- Hypoxia
- Toxic cytokines
- ER stress due to excess cholesterol accumulation in the ER membrane
Activated mast cells promote which conversion process?
Macrophages into foam cells
How do mast cells become activated and what do they release to trigger conversion?
Mast cells bind to molecules and become ‘activated’, and release secretory granules which contain enzymes (proteases), heparin and histamine
What is the effect of mast cells in relation to macrophage function?
Mast cells make LDL more accessible to macrophages, promoting foam cell conversion, while removing HDL from the region
How do ACE inhibitors contribute to hypertension rx?
Inhibit activation of angiotensin, an enzyme that increases BP
How do diuretics contribute to hypertension rx?
Reduce blood volume, therefore BP
How do calcium channel blockers contribute to hypertension rx?
Reduce muscle tone in artery walls
How do beta blockers (particularly B1 blockers) contribute to hypertension rx?
Counteract sympathetic NS-mediated vasoconstriction
In general terms, explain how smoking causes atherosclerosis
- Releases toxins into bloodstream
- Toxins cause inflammatory effect
- Inflammation causes cellular damage
- Cell damage increases incidence of thrombotic events
Give two ways smoking effects endothelial cells
- Damages endothelial cells leading to unstable vessel walls
- Decreases NO availability, causing vasoconstriction
What is the effect of smoking on platelets?
Increases platelet aggregation
What is the effect of smoking on the clotting cascade?
Smoking has a pro-coagulant effect through:
- Decreased tPA
- Increased fibrinogen
- Increased tissue factor
What is the effect of smoking with regard to inflammation?
Reactive oxygen species generation and other effects of these molecules create a strong pro-inflammatory environment (which promotes atherosclerosis)
What is the effect of smoking on blood lipids?
Decreases HDL, increases LDL
Where does an arterial thrombosis occur?
Directly at the site of the atheroma
What is an embolism?
An object that travels in the bloodstream and does not dissolve
What is a thromboembolism?
A clot that travels
True or false: GTN dilates coronary vessels
What is ischaemic heart disease?
Progressive constriction of coronary arteries
What triggers stable angina pectoris?
Exercise
What is acute coronary occlusion?
A sudden change in atherosclerotic plaque in which platelets start to adhere to the plaque, creating a small clot
Acute coronary occlusion often precedes what event?
Myocardial infarction
What is myocardial infarction?
Death of cardiac muscle cells due to ischaemia
What are the two main types of myocardial infarction?
Transmural and subendocardial
Differentiate between transmural and subendocardial myocardial infarctions
- Transmural MI - transverses entire portion of heart wall
- Subendocardial MI - impact is partially through the heart wall
Describe the electrophysiology and relevant ECG characteristics of a non-transmural myocardial infarction
- Injured area: depolarised
- Depolarising current travels toward the positive electrode
- Baseline voltage prior to QRS will be elevated (depolarised)
- ST segment appears lower in comparison (ST depression)
- Isoelectric point has shifted up, so when it actually depolarises and reaches the level of the ST segment, the segment looks lower
Describe the electrophysiology and relevant ECG characteristics of a transmural myocardial infarction
- Injured area: depolarised
- Depolarising currents are travelling away from the positive electrode
- Baseline voltage prior to QRS will be lowered (hyperpolarised; more negative)
- ST segment appears higher in comparision (STEMI)
What is the function of tenecteplase?
Converts plasminogen to plasmin which then breaks down the fibrin around the clot
What is the function of clopidogrel/aspirin?
Inhibits receptors on the surface of platelets to inhibit platelet aggregation
What is the function of enoxaparin?
Irreversibly inactivates clotting factor Xa, preventing formation of new clots
What is tested in hospital to determine MI?
Cardiac enzymes, namely troponin levels
