Block A - Atherscelorosis Flashcards
what does hypertension feed into ?
Hypertension feeds into atherosclerosis, stroke and heart failure. It is a huge risk factor.
Individuals with hypertension can go on to develop atherosclerosis, which will ultimately lead to coronary heart disease which can lead to a heart attack ( myocardial infarction) , if left untreated this will result in heart failure.
are there symptoms of hypertension ?
Some patients will develop angina, chest pain, and treatment is important foe hypertension which can be managed to prevent these situations occurring.
structure difference of arteries and veins ?
Arteries have a thicker muscle layer than veins. Both vessels have the endothelial layer and luminal layer side of the vessel which releases chemical mediators. The lumen must remain as wide as possible so that blood flow is not restricted.
endothelial cells ?
Single layer of cells lining lumen of blood vessels
Act as physical barrier to blood cells such as inflammatory cells. Without this barrier, blood cells would be activated and clot called thrombus.
The endothelial cells release bioactive substances to prevent inadvertent thrombus formation, which could occlude blood flow
Release mediators that inhibit platelet activation , as this would form a clot and would block blood flow.
Causes relaxation/contraction of underlying smooth muscle.
endothelial derived relaxant factors ( EDRF’s)
Endothelial derived relaxant factors ( EDRF’s) are important in smooth muscle relaxation which keeps the blood vessel diameter dilated to decrease resistance to blood flow.
endothelial derived contraction factors ( EDCF’s)
Endothelial derived contraction factors ( EDCF’s) that promote vasoconstriction coming from the endothelial cells.
atherscleorisis development , wat causes it and what did it used to be believed ?
Previously thought to be a disease of lipid/cholesterol storage due to a build up in the blood vessels .
Now considered an inflammatory condition.
Major risk factor is hypertension
Earliest stage is the development of a fatty streak in the blood vessel.
stage one of development ?
Insult or stress to vascular endothelium by smoking, high shear stress, infection will lead to an increased adhesion and migration of leukocytes. This increases permeability to lipids and to LDL’s – bad cholesterol. Which enables a build up of fatty streak in the lumen and focus of inflammation.
The monocyte migrates through to the lumen and allows the migration of LDL’s which are oxidised by the macrophages , the oxidisation of LDL’s allows the macrophages to transform into foam cells , which becomes a focus on inflammation in the lumen of the blood vessel
LDL uptake and monocyte migration ?
LDL uptake occurs via transcytosis, this is the rate limiting factor for the plasma cholesterol concentration. The monocytes migrate in response to high LDL and they mature into macrophages. The LDL is oxidised by the release of superoxide from macrophages and the OxLDL are taken up by macrophages to form lipid-laden foam cells.
Stage II ?
That focused sited of inflammation then allows platelet adhesion of platelets circulating in the blood , the activated platelets then release platelet derived growth factor (PDGF) which leads to migration of smooth muscle cells form the blood vessels to form a fibrous cap over the foam cell layer
Stage III ?
These lesions then become stiff, bulky and calcified , these plaques become very brittle and this increases the risk they will rupture. Plaque rupture exposes underlying tissue & leads to thrombus formation. If the thrombus is large enough this can cut off blood supply in coronary artery (M.I.) Occlusion of the blood vessel in the coronary artery can lead to myocardial infarction.
is this proccess rapid ?
This process takes time to develop so there is a time window when intervention can occur to prevent atherosclerosis developing into the advanced stage which has greater problems.
coparison of healthy and disease coronary artery ?
There are severe stenosis, calcification , recent Thrombosis and cholesterol Crystals , this can lead to conditions such as stroke , MI and heart failure.
effects of disease , blood flow ?
It reduces vessel lumen diameter resulting in a decreased blood flow at rest
impaired relaxant function of SM ?
Impaired relaxant function of smooth muscle, an inability to increase flow in response to demand because of this atherosclerotic disease. This inability to increase flow to supply oxygen can lead to angina – chest pain.
Impaired antithrombotic function ?
Impaired antithrombotic function of endothelium there is an increased likely hood in developing thrombosis, and this increases the risk of myocardial infarction.
RIsk factors for plaque formation ?
Hypertension – is the biggest factor here
High plasma cholesterol-LDL with low HDL
Smoking
Underlying Disease
Lifestyle factors ( smoking and alcohol)
Underlying Infections possibly linked
angina ?
This is a condition that many patients with atherosclerosis will suffer from. The term is derived from Greek and Latin and can be translated as ‘a strangling feeling in the chest’. It occurs due to ischaemia, lack of oxygen supply and underlying coronary artery disease (atherosclerosis.
Patients can have worsening angina attacks which are a sudden onset at rest and attacks lasting more than 15 min are symptoms of unstable angina. These may imply an M.I. and require urgent medical attention. There is often a link between angina and exercise as this increases the demand for oxygen, this supply via the blood is dramatically reduced and chest pain is felt.
why does ischaemia occur ?
Ischaemic area occurs as there is an occlusion in the coronary circulation , leading to impaired blood flow to this region , lack of oxygen resulting in ischaemia and chest pain.I n some cases this can progress to a heart attack.
types of angina - angina of effort ?
Angina of effort (Stable angina)
- Predictable in nature chest pain brought on by exercise
- caused by permanent narrowing of coronary by atheroma
- attacks usually short-lived (2-3 min)
- Can be treated effectively by relaxing the vasculature in the area.
variant ( prinzmetal’s angina ) ?
Variant (Prinzmetal’s) angina
- Uncommon form of angina
- occurs at rest, cyclical in character
- caused by coronary artery spasm leading to chest pain
unstable angina ?
Unstable angina
- normally a progression of stable angina, however, can occur in patients not previously suffering from angina. - Sudden alteration in pattern of angina pain - may imply impending acute coronary occlusion - dangerous with high mortality
symptoms of angina ?
pain
breathlessness due to lack of oxygen
elevated left ventricular end-diastolic pressure
reduced coronary blood flow
metabolic changes
Changes in Electrocardiogram (ECG)
These can be picked up by cardiovascular monitoring to determine if a patient is suffering from angina.
what angina a result of ?
Angina is a result of an imbalance in oxygen supply and demand.
Oxygen supply is coming from
Cardiac output (ability of heart to pump oxygenated blood to the issue , including the heart itself.
Hemoglobin levels containing iron to carry oxygen around the body
Respiratory function
Fitness of heart muscle and muscle throughout the body.
Oxygen demand placed on the body from the heart
Work of the heart
Contractility
HR
hypertrophy of heart ?
Hypertrophy of the heart , increase in size to try and work more efficiently , only happen up to a certain point before cardiovascular dysfunction occurs.
myocardial ischemia ?
A heart attack which happen very shortly after the heart becomes ischaemic or deprived from oxygen. Myocardium becomes ischemic within 10 seconds of a coronary occlusion.
Working cells around the ischaemia will remain viable for up to 20 minutes as anaerobic mechanisms kick in such as Lactic acid. Free radical damage will occur, especially after reperfusion which is when the tissue is damaged when blood supply returns to tissue after a period of ischemia.
aute coronary syndrome ?
Acute coronary syndrome develops from an unstable plaque, transient ischemia occurs which is a short-term loss of oxygen to the heart and short term chest pain by unstable angina which can happen at rest. This can lead to an indicator of myocardial infarction, which occurs due to sustained ischemia. Sustained ischaemia, however, can also occur without any previous unstable angina. This leads to necrosis and damage to the heart where the ischemia has occurred.
stable plaque ?
A stable plaque forms in the coronary vasculature and can lead to stable angina. There’s no immediate risk of this plaque rupturing and leading to thromboses and occlusion of a blood vessel.
treatment for stable angina - drug nitrates ?
Drug
Nitrates used as they mimic the action of nitric oxide which act as a relaxant factor to the underlying smooth muscle, leading to vasodilation and an increase in the oxygen supply.
However, tolerance can occur in patients , this can be managed by using lower doses less frequently.
beta blockers ?
Beta blockers improve cardiac output , reduce the demand on the heart and therefore help to relieve the symptoms of angina
calcium channel blockers ?
Calcium Channel Blockers improve cardiac output , reduce the demand on the heart and therefore help to relieve the symptoms of angina
surgery ?
Surgery in severe cases
Bypass
PCI – percutaneous intervention such as a stent coated in drugs to be eluted from the stent to promote the vessels staying open to improve blood supply. (PTCA, Stent)
nitroglycerine ?
Vasodilating actions which are quick
Primarily acts on veins and large arteries
Uptake by Vascular Smooth Muscle cells and converted to active form: Nitric oxide.
Therapeutic uses: Stable Angina
Decreases preload = decreases contraction = decreases oxygen demand
lipid lowering drugs - statins ?
Statins (e.g. simvastatin) – reduce plasma LDL and are used in patients with risk factors like atherosclerosis for prevention of arterial disease (and possible MI).
fibrates ?
Fibrates (e.g. ciprofibrate) – reduce circulating LDL (modest effect). Complex mechanism of action.
inhibtors of cholesterol absorption ?
Inhibitors of cholesterol absorption (e.g. ezetimibe) – works by blocking a transport protein of cholesterol. Considered as an addition to a statin where response is weak or instead of a statin.
fish oil derivitives ?
Fish oil derivatives (omega 3) – evidence for improvements in patients with atherosclerotic disease but mechanism of action still not fully understood.
