Week 3 - Cardiovascular Flashcards
What is atherosclerosis?
The narrowing of arteries.
Causes and worsens other conditions.
What is dyslipidaemia/hyperlipidaemia?
Dyslipidaemia = imbalance between HDL/LDL.
Hyperlipidaemia = High cholesterol.
What is visceral adiposity?
BMI mainly around the waistline rather than generally high BMI.
What is the inflammatory response for atherosclerosis?
Phase 1.
1. Damage to the endothelial layer of the arterial wall attracts white blood cells and other immune cells - monocytes, T-lymphocytes.
2. Triggers expression of adhesion molecules on the endothelium.
3. LDL infiltrates and is oxidised.
4. Monocytes enter intimal layer and become macrophages.
5. Macrophages engulf LDL and become foam cells.
Phase 2.
1. Foam cells multiply.
2. A fatty streak develops
3. smooth muscle cells (SMCs) migrate from the tunica media and proliferate providing a collagen matrix.
4. inflammatory cytokines released
5. Calcified plaque forms and eventually ruptures.
Outline the process of cholesterol development.
Cholesterol is produced by the liver.
HMG-CoA converts into melavonate which is converted into cholesterol.
Statins block the converter enzyme (HMG-CoA reductase).
Cholesterol is transported through the blood with LDL –> LDL-C.
HDL-C transports cholesterol away from peripheral tissues back to the liver for disposal - reverse cholesterol transport and so is cardioprotective.
Pathophysiology of hypercholesterolemia
Genetic mutations.
LDL receptor on the liver - reduced number of functional receptors. - Increases amount of LDL in bloodstream.
Apo-B –> LDL cannot bind to receptor as effectively so increases circulating LDL as less is brought into the liver cell.
Enhances PCSK9 = enzyme that degrades the LDL receptors.
How to identify a statin?
Give examples of statins
Ends in statin.
Atorvastatin, simvastatin.
What do statins do? Mechanism of action.
Block the action of HMG-CoA reductase. This enzyme is required to make cholesterol.
Improves cholesterol profiling - higher HDL, lower LDL/TG.
Increase LDL receptors.
Main side effects of statins
Muscle pain in lower limbs. Dull ache.
Related to increasing risk of T2D.
What is hypertension?
Sustained elevation of systemic arterial blood pressure.
What are the different stages of hypertension?
Stage 1 = >140/90
stage 2 = >160/100
Stage 3 = >180/110
What is resistant hypertension?
low responsiveness to treatment despite 3 anti-hypertensives or controlled with 4 anti-hypertensives.
How is blood pressure regulated normally?
how is it different in hypertensives?
Renin is released and converts angiotensin into angiotensin 1.
ACE (angiotensin converting enzyme) converts angiotensin 1 into angiotensin 2.
Angiotensin 2 increases sympathetic activity.
In hypertension the negative feedback loop that decreases renin does not happen.
What is the normal function of the SNS?
Consequences of excessive SNS activity.
Release of nor-adrenaline which binds to B1 and B2 receptors (B1 is key - on the heart).
Activates growth stimulatory protein and adenylcyclase.
Increased cAMP and therefore protein kinase A. which phosphorylates calcium channels increasing likelihood of opening (influx) = force of contraction.
Increased force of contraction and HR.
Reduced efficiency - increased afterload = EDV.
Cardiac hypertrophy.
Disrupted RAS mechanism of BP regulation
Increased renin secretion triggered by SNS activity.
Increased water reabsorption, increasing blood volume (angiotensin 2 and aldostserone) and water retention.
Increased vasoconstriction.
Impact of atherosclerosis on shear stress, mechanism for high BP.
Sheer stress is the force on the endothelial surface. It is athero-protective - forces arteries wider.
Endothelial damage and altered arterial geometry leads to non-laminar blood flow (reduced sheer stress).
Reduced nitric oxide also causes less vasodilation.
Arterial walls are stiffer so less compliant to BP.
Which drug is chosen for high blood pressure?
3 categories
Diabetic, age, ethnicity.
Those who are less than 55, not African or Caribbean, diabetic need to take ACE inhibitors or ARBs.
If older than 55, black African or African Caribbean and no diabetes then take CCBs.
What do ACE inhibitors end in?
IL e.g. ramipril, captopril.
What do ACE inhibitors do?
block ACE that converts angiotensin 1 into angiotensin 2.
This causes reduced aldosterone release, reduced vasoconstriction, promotes vasodilation.
What are the main side effects of ACE inhibitors.
Dry cough, metallic taste, skin rash.
Profound drop in BP on first dose –> leads to dizziness with exercise or postural changes.
What do beta blockers end in?
OL e.g. Atenolol, bisoprolol.
What do beta blockers do? Mechanism of action.
Block the B1 adrenergic receptors of the heart. This stops the nor adrenaline binding to the receptors as much, reducing calcium uptake for contraction so decreasing force and velocity of contractions.
What are the side effects of betablockers?
Reduced chronotropic and ionotropic response - reduced ability to reach maximum HR and restrict exercise capacity/duration.
Dizziness/hypotension post exercise.
Cold fingers and toes.
Must be a gradual reduction in dose as if not can lead to rebound in angina and MI.
What is angina?
An uncomfortable sensation in the chest (chest pain) and neighbouring anatomy produced by myocardial ischemia - reduction in blood supply.
Usually occurs with activity/stress and disappears on rest.
Difference between stable and unstable angina.
Stable - predictable.
Chronic pattern of transient (temporary) chest pain.
Occurs when exerted i.e. physical activity/exercise.
Unstable angina - absolute contraindication to exercise
Pattern of increased frequency and duration of chest pain.
Produced by less exertion or even at rest (no pattern).
High likelihood of MI if left untreated.
Pathophysiology of angina
Atherosclerosis leads to progressive obstruction.
Arterial spasm leads to sudden reversible obstruction.
Build up of plaque ruptures forming a thrombus which blocks the artery.
All three lead to ischemia (reduced blood flow) and hypoxia (reduced oxygen).
GTN spray for angina
It is a form of nitric oxide so acts as an effective vasodilator, relaxing arteries and reducing pain associated with ischemia.
What is a side effect of using a GTN spray?
Dizziness post exercise (don’t take before).
