Week 3 - Cardiovascular

Question 1

What is atherosclerosis?

Answer 1

The narrowing of arteries.
Causes and worsens other conditions.

Question 2

What is dyslipidaemia/hyperlipidaemia?

Answer 2

Dyslipidaemia = imbalance between HDL/LDL.
Hyperlipidaemia = High cholesterol.

Question 3

What is visceral adiposity?

Answer 3

BMI mainly around the waistline rather than generally high BMI.

Question 4

What is the inflammatory response for atherosclerosis?

Answer 4

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.

Question 5

Outline the process of cholesterol development.

Answer 5

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.

Question 6

Pathophysiology of hypercholesterolemia

Answer 6

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.

Question 7

How to identify a statin?
Give examples of statins

Answer 7

Ends in statin.
Atorvastatin, simvastatin.

Question 8

What do statins do? Mechanism of action.

Answer 8

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.

Question 9

Main side effects of statins

Answer 9

Muscle pain in lower limbs. Dull ache.
Related to increasing risk of T2D.

Question 10

What is hypertension?

Answer 10

Sustained elevation of systemic arterial blood pressure.

Question 11

What are the different stages of hypertension?

Answer 11

Stage 1 = >140/90
stage 2 = >160/100
Stage 3 = >180/110

Question 12

What is resistant hypertension?

Answer 12

low responsiveness to treatment despite 3 anti-hypertensives or controlled with 4 anti-hypertensives.

Question 13

How is blood pressure regulated normally?
how is it different in hypertensives?

Answer 13

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.

Question 14

What is the normal function of the SNS?
Consequences of excessive SNS activity.

Answer 14

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.

Question 15

Disrupted RAS mechanism of BP regulation

Answer 15

Increased renin secretion triggered by SNS activity.
Increased water reabsorption, increasing blood volume (angiotensin 2 and aldostserone) and water retention.
Increased vasoconstriction.

Question 16

Impact of atherosclerosis on shear stress, mechanism for high BP.

Answer 16

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.

Question 17

Which drug is chosen for high blood pressure?

Answer 17

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.

Question 18

What do ACE inhibitors end in?

Answer 18

IL e.g. ramipril, captopril.

Question 19

What do ACE inhibitors do?

Answer 19

block ACE that converts angiotensin 1 into angiotensin 2.
This causes reduced aldosterone release, reduced vasoconstriction, promotes vasodilation.

Question 20

What are the main side effects of ACE inhibitors.

Answer 20

Dry cough, metallic taste, skin rash.
Profound drop in BP on first dose –> leads to dizziness with exercise or postural changes.

Question 21

What do beta blockers end in?

Answer 21

OL e.g. Atenolol, bisoprolol.

Question 22

What do beta blockers do? Mechanism of action.

Answer 22

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.

Question 23

What are the side effects of betablockers?

Answer 23

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.

Question 24

What is angina?

Answer 24

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.

Question 25

Difference between stable and unstable angina.

Answer 25

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.

Question 26

Pathophysiology of angina

Answer 26

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).

Question 27

GTN spray for angina

Answer 27

It is a form of nitric oxide so acts as an effective vasodilator, relaxing arteries and reducing pain associated with ischemia.

Question 28

What is a side effect of using a GTN spray?

Answer 28

Dizziness post exercise (don’t take before).