W3: atherosclerosis Flashcards
Which main cardiac veins are anterior and which ones are posterior?
Anterior:
anterior cardiac vein
great cardiac vein
small cardiac vein
Posterior:
posterior cardiac vein
Middle cardiac vein
(Small loops around skins on both sides?)
What vessel do most of the coronary veins drain into?
Coronary sulcus
Which vein does not drain into the coronary sulcus? Where does it drain into?
Anterior cardiac vein - drains directly into the right atrium
What type of adrenergic receptors are found in the heart and which one is most prevalent?
Beta 1 and Beta 2. the most predominant one is BETA 1
Describe the cardiovascular changes that occur during exercise
Increased: Force of contractility Heart Rate Stroke Volume Cardiac Output MAP Blood flow
Decreased:
Total peripheral resistance
Explain the role that the ANS plays in in the increases in heart rate and blood pressure during exercise
Increases sympathetic activity release Noradrenaline which binds to the Beta receptors on the heart. This increases rate of conduction, contraction and heart rate.
This increase in force of contraction of the heart increases cardiac output and blood pressure.
Decrease in sympathetic activity also contributes to increased HR.
Sympathetic activity also induces vasoconstriction in skeletal muscle arterioles and increase blood flow here. (Adrenaline binds to alpha receptors)
Define atherosclerosis
Atherosclerosis is chronic inflammatory disease of the arterial wall resulting in the hardening and narrowing of (medium and large) arteries due to plaque formation.
describe the pathophysiology of atherosclerosis
Damage to endothelium occurs due to cigarette smoke, toxins, viruses, hyperlipidaemia, diabetes, hypertension, high LDL levels.
This damages stimulates an inflammatory response and endothelial cells generate inflammatory mediators and cytokines to increase adhesion of WBCs. This generates oxidant stress.
The endothelium increases its permeability to lipids and this causes LDLs to deposit in the tunica Intima.
LDLs become oxidised and there is transmigration of WBCs, including monocytes. Monocytes move in and become macrophages. Macrophages engulf the oxidised LDLs and become lipid-laden foam cells.
These foam cells aggregate on the blood vessel to form a fatty streak. They also release chemokines attract more monocytes.
Foam cells release cytokines to trigger migration of SMCs from tunica media to tunica Intima and growth factors to induce their proliferation.
SMC proliferation and formation of a dense ECM results in superficial fibrous cap covering the fatty streak. Foams cells become so full with lipid that they burst/die and release their lipid contents. This lipid debris contributes to the necrotic, lipid core below the fibrous cap.
Presence of MMPs and oxidant stress thin the fibrous cap making the plaque unstable. If the plaque ruptures, there is thrombus formation and vessel occlusion resulting in myocardial ischemia.
what makes a plaque vulnerable?
Large lipid core
Thin fibrous cap
Abundance of inflammatory cells
Smaller number of SMCs so fibrous cap is less thick
Risk factors of Coronary artery disease?
Age
Gender (male)
Genetic factors
Obesity Diabetes Hypertension High LDL levels Infection Lack of exercise High saturated fat diet Excessive alcohol Stress
Describe how coronary artery stenosis results in myocardial ischaemia
CA stenosis is narrowing of the artery either due to atherosclerosis or a blood clot. This reduces the blood flow to the heart and causes myocardial ischaemia where there is an insufficient oxygen supply to the heart.
Explain the production, character and distribution of cardiac chest pain
Myocardial schema results in angina pectoris. this occurs when myocardial oxygen demand is higher than the supply.
The chest pain is produced by a build up of metabolites (adenosine, K, Co2, lactate) which activate sensory neurons.
Character of chest pain: tight, pressurised. It occurs centrally and can radiate to the left arm/shoulder and jaw.
What are associated symptoms of angina pectoris?
Breathlessness Sweating Pallor Nausea Vomiting
Describe the difference between stable and unstable angina and their origins?
Stable:
Chest pain is predictable.
Occurs due to physical exertion, exercise, cold weather, strong emotion.
Lasts up to 15 minutes
Origin: atherosclerosis plays a role as oxygen demand is not met
Unstable:
Unpredictable chest pain
Occurs randomly, even when at rest
Pain is more severe and lasts for 30 minutes or longer.
Origin: temporary coronary artery occlusion - Small plaque rupture and platelet aggregation which temporarily occludes the coronary arteries. Clot is then washed away.
Indicative of a future bigger heart attack.
What is variant angina caused by and is it common and predictable?
Caused by vasospasm of coronary artery.
Uncommon
Unpredictable
Describe what occurs during thrombus formation? When does it lead to myocardial infarction
when a plaque ruptures, there is thrombus formation to stop the lipid contents spilling into the lumen.
This involves platelet aggregation, migration of inflammatory cells, vasoconstriction and clot formation.
If the vessel is completely occluded then myocardial infarction occurs and there is death of cardiac myocytes.
Describe the investigations of angina pectoris
Laboratory tests: to check for presence of high troponin levels (troponin leaks into blood after angina attack)
ECG: check for heart abnormalities
Chest Xray to rule out other causes of chest pain.
Stress echo: Echocardiogram taken before and after exercise. Patient performs a physical activity usually on a treadmill. Speed and resistance increases with time. Checks for abnormalities in wall motion of heart.
Exercise stress test (ECG): same as above but ECG is recorded.
Nuclear stress test: radioactive substance is injected into patient and their coronary blood flow is measured before and after stress.
CT coronary angiogram: contrast dye is injected into vein and special Xray images are taken to view coronary blood flow.
Invasive coronary angiogram: contrast dye is injected, catheter is inserted into artery and passed up into coronary artery. X ray images are used to check for narrowing.
Describe the coronary steal phenomenon
Downstream of an occlusion, the arteries are maximally vasodilated. This is because the narrowing causes a reduction in the blood and oxygen supply. There is active hyperaemia and the blood vessel compensates by vasodilating to its maximal dilation.
So vasodilators have no effect on these occluded areas as they cannot dilate them further. Instead, they vasodilate already well-perfused areas and blood is stolen from occluded areas.
Explain why reducing preload with venous dilators or afterload with arterial dilators brings benefit in all forms of angina
Venous dilators: Reduction in preload = the amount of blood that fill the ventricles during diastole Reduction in venous return Decreased stretch of ventricle Reduced strength of contraction Decreased myocardial oxygen demand
Arterial dilators:
Reduction in after load = pressure that the heart must overcome to open the aortic valve and eject blood. (amount of work hard needs to do)
reduces myocardial work
decreases myocardial oxygen demand
List the main drugs used to treat angina
Nitrovasodilators L-type Calcium Channel Blockers Beta adrenoreceptor blockers Ivabradine Antihypertensive, lipid lowering, anti platelet (aspirin) ACE inhibitors
Describe the mechanism of Nitrovasodilators, giving 2 examples and their side effects
Nitrovasodilators are pro drugs. They are very lipophilic and readily enter Smooth Muscle Cells. They are reduced to NO and activate Soluble Guanylate Cyclase. SGC converts CTP to cGMP.
e.g. GTN (glyceryl trinitrate): a sublingual spray to prevent being detoxified and broken down in the liver, so that its active form may enter the blood plasma. It acts rapidly, then prophylactically or after attack.
e.g. isosorbide mononitrate and dinitrate
Slower in onset but has a longer duration.
side effects:
Decreased sensitivity if SOME of them are taken continuously. Need nitrate-free periods.
Headaches
Describe the mechanism of L-type Calcium channel blockers, giving 2 examples and their side effects
These block calcium entry into vascular smooth muscle or cardiac muscle.
Work in one of 2 ways:
Open channel block (cork in a bottle): directly goes into channel and blocks.
Allosteric modulation: binds to another site on the channel and reduces channel opening.
e.g. nifedipine, verapamil, diltiazem
Effects: dilates arteries more than veins reduces After load reduces HR and Force of contraction decreases myocardial oxygen demand
Side effects: Constipation Headache Coronary steal Cardiac Dysrhythmias Cardiac failure (if overdose)
Describe the mechanism of Beat adrenoreceptor blockers, giving 2 examples and their side effects
Beta Blockers reduce HR, SV and CO. This decreases myocardial oxygen demand
e.g. propranolol and atenolol (beta 1 only)
Side effects: Hypoglycaemia Intolerance to exercise Vivid dreams Exacerbates asthma
Describe the mechanism of Ivabradine
Ivabradine blocks Sodium channels so decreases rate of impulse firing and HR (but NOT FORCE). This reduces myocardial work and oxygen demand.
what are surgical treatments for angina?
Angioplasty/Percutaneous Coronary Intervention: insertion of a catheter into the artery and passing it up into a coronary artery. A balloon is inflated to widen the artery and stent may be placed too to keep it open.
Coronary Artery Bypass Graft surgery: healthy arteries are taken from part of the body and used to bypass the blocked arteries.
If you have a stent placed, what drug do you need to take for the rest of your life?
Aspirin
what lifestyle changes can be made to treat angina?
Increase exercise Healthy eating Quit smoking Lose weight treat disease e.g. diabetes, hypertension, high cholesterol Avoid large meals Limit alcohol consumption Reduce stress
What are the risk factors for atherosclerosis?
Non-modifiable:
Age
Gender
Family History
Modifiable: Obesity Smoking High saturated fat diet High LDL levels Hypertension Diabetes Infection
How is cholesterol transported and why is this the case?
Cholesterol is transported by lipoproteins was it is very insoluble.
What are lipoproteins composed of?
Apoproteins
Lipids
What do chylomicrons do?
They transport triglycerides which have been absorbed by the intestines to the liver or adipose tissue or muscle
What do VLDLs do?
They carry newly synthesised triglycerides from the liver to adipose tissue
What is IDL?
Idl is the intermediate between VLDL and LDL
WHAT is LDL and what does it do?
LDL is a major carrier of cholesterol. It carries cholesterol from the liver to tissues.
What is HDL and what does it do?
Good cholesterol.
It absorbs cholesterol released by dying cells. Also acts as reverse transport to take cholesterol to the liver.
Transports cholesterol from tissues to liver
What is the exogenous pathway of cholesterol transport?
Following digestion and absorption of dietary fat, Triglycerides and cholesterol are taken from the intestine and packaged in chylomicrons.
Chylomicrons circulate in the blood and the enzyme, Lipoprotein lipase, causes them to release Fatty acids. These are stored in adipose tissue or muscle cells.
This leaves behind chylomicron remnants which are taken up the liver via ApoE binding to the chylomicron remnant receptors.
Free fatty acids and cholesterol are stored in the liver.
What is the endogenous pathway of cholesterol transport?
Liver synthesis cholesterol ester and TG and packages them into VLDL particles.
The VLDL circulate and are attacked by the lipoprotein lipase enzyme which causes release of free fatty acids into adipose tissue/muscle cells.
This leaves behind IDL which can either be taken up directly by the liver via LDL receptors.
OR
Is converted into LDL which circulates. its eh plasma and is taken up by peripheral tissues that need cholesterol.
Any left over LDL is removed by the liver via the LDL receptor.
What do statins do, how do they work and give two examples?
Statin lower cholesterol levels. They are competitive inhibitors of rate-limiting step in cholesterol biosynthesis.
By blocking a rate-limiting enzyme they reduce cholesterol synthesis and more LDL is taken up by the liver from circulation.
E.g. Simvastatin and pravastatin
What are the advantages and disadvantages of an exercise stress test?
Adv:
Low risk
Low cost/resource
Dis:
Not always accurate
Many patients unsuitable due to bad hips/knees etc
what are the requirements for a CT coronary angiogram?
need to be on a beta blocker to slow down the heart (not all patients can be on them)
Need good renal function
What are the disadvantages of invasive coronary angiogram?
Low risk BUT the highest risk
High resource
Risk fo harming the arteries or inducing MI
Give two examples of anti-platelet drugs?
Aspirin
Clopidogrel
Give two examples of anti-coagulant drugs?
Heparin
Warfarin
Which lipoprotein contains the most triglycerides?
chylomicrons
list the main lipoproteins in plasma?
Chylomicrons, LDL, HDL, VLDL
What are the functions of apoproteins?
Transport of lipid
Gives structural integrity to particle
Identifies type of lipid in lipoprotein
Regulating uptake and metabolism of lipid into cells
What happens to the risk of CHD as triacylglycerol increases?
As TAG increases, CHD risk increases
