Heart Failure

Question 1

Describe the pressure profiles in the left atrium, left ventricle and the aorta for a single cardiac cycle.

Answer 1

atrial systole - rise in atrial pressure, AV valves open and the atria empty blood into the ventricles.

isovolumetric ventricular contraction -increase in ventricular pressure closing the AV valves. The ventricular pressure is less than the aortic pressure, so the aortic valve closes. Pressure is generated but no blood is ejected.

ventricular ejection - ventricular pressure is greater than the aortic pressure and the aortic valve opens and blood is ejected.

isovolumic ventricular relaxation -ventricular pressure is less than aortic pressure and the aortic valve closes. Ventricular pressure is greater than atrial pressure and the AV valve remains shut. The pressure falls but there is no filling.

ventricular filling - ventricular pressure is less than atrial pressure, the AV valve opens and blood enters the ventricle.

Question 2

Explain the origin of the 1st and 2nd heart sounds

Answer 2

The first heart sound is a low pitched ‘lub’ associated with AV valve closure. The second sound is a brief, high pitched ‘dup’ associated with aortic/pulmonary valve closure.

Question 3

Describe the origins of the jugular venous pulse

Answer 3

Pulsations in the internal jugular vein reflect right atrial pressure changes (no valves).

Question 4

Define the terms cardiac output, heart rate and stroke volume and give approximate (+/-10%) values for these in a healthy adult at rest.

Answer 4

Cardiac output in litres per minute is equal to stroke volume (litres per beat) multiplied by the heart rate (beats per minute).

Question 5

State the influence of venous return on cardiac output.

Answer 5

increasing venous return will increase cardiac output

Question 6

Define the terms preload, afterload and contractility and describe how a change in each of these will affect cardiac performance.

Answer 6

preload - initial stretching of cardiac myocytes prior to contraction, ventricular filling.

afterload - the force or load against which the heart has to contract to eject blood.

Question 7

Define Starlings law of the heart (the Frank/Starling relationship), relating left ventricular end diastolic volume to stroke volume.

Answer 7

the stroke volume of left ventricle will increase as the left ventricular volume increases due to the myocyte stretch causing a more forceful systolic contraction.

Question 8

Describe the mechanisms that control the release of renin

Describe the components of the renin-angiotensin-aldosterone system

Answer 8

Stimuli for renin release is decreased renal perfusion pressure (detected by granular cells), decrease in NaCl concentration (detected at the macula densa) and increase sympathetic nerve activity (via activation of beta-1 adrenoceptors.

Renin acts on angiotensinogen, a plasma protein produced by the liver. Angiotensin converting enzyme breaks down angiotensin I to angiotensin II.

Question 9

Describe the biological actions of angiotensin II, vasopressin and aldosterone

Answer 9

Angiotensin II - a potent vasoconstrictor, enhances sympathetic nerve function, increases the release of aldosterone, promotes thirst, releases vasopressin (an antidiuretic hormone) from the posterior pituitary gland, has trophic effects in the heart and blood vessel and increases oxidative stress.

Vasopressin - It has an effect of direct vasoconstriction. It also increased the number of aquaporin-2 channels in the distal tubules and collecting duct of the kidney, which increased fluid retention. Because of this, vasopressin is known as the antidiuretic hormone (ADH).

Aldosterone - This increases the expression of sodium channels and activates the sodium potassium pump. This results in retention of sodium and water in the body. The net effect of aldosterone is that we reclaim 3Na+ for exchanging 2K+ ions into the kidney tubule. When the renin-angiotensin system is activated, we lose potassium ions.

Question 10

Understand the pathological causes that can increase renin-angiotensin system activity

Answer 10

Decreases in blood flow to the kidney is an important stimulus for renin release. It can occur physiologically with normal variations in fluid intake but can also result from pathological causes such as a decrease in cardiac output due to heart failure. Renal stenosis or aortic stenosis (narrowing of the renal artery or aorta), produces renin-induced hypertension.

Question 11

Define the term hypotensive shock and causes of this condition

Answer 11

Hypotension is low blood pressure. Hypotensive shock is a condition in which blood pressure is below the autoregulatory range for maintenance of cerebral and renal perfusion, such that consciousness is lost and vital organ perfusion critically impaired.

Question 12

Define chronic heart failure in one sentence

Answer 12

Heart failure is the failure of the heart to act as a pump to meet the circulatory needs.

Question 13

Distinguish between acute and chronic heart failure

Answer 13

Heart failure can be chronic or acute (which is after a myocardial infarction).

Question 14

Identify the main causes of chronic heart failure

Answer 14

Hypertension, ischaemia, lung disease

Question 15

State the main humoral factors involved in neurohormonal adaptation

Answer 15

To compensate for circulatory failure, there is activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system, antidiuretic hormone, and atrial natriuretic peptide. Only atrial natriuretic peptide has a positive effect.

Question 16

Distinguish between left and right ventricular failure and biventricular failure

Answer 16

left ventricular failure is often due to secondary hypertension. The left ventricle is imparied and has poor output, leading to an increase in left atrial and pulmonary venous pressure with pulmonary oedema.

is when the right ventricle output fails. This is often due to lung disease or pulmonary valvular stenosis. Signs and symptoms of right ventricular failure are a raised venous pressure, increased jugular venous pulse, an enlarged liver, and oedema.

Question 17

State the key symptoms of left and right ventricular failure and biventricular failure

Answer 17

left - pulmonary oedema, dyspnea, a cough, orthopnoea, and inspiratory crepitations.

biventricular failure - fatigue, listlessness, poor exercise tolerance (which determines the grade of heart failure), cold peripheries, low blood pressure, reduced urine flow and weight loss.

Question 18

State how a diagnosis of chronic heart failure may be made

Answer 18

Diagnosis of heart failure is by its symptoms, an examination, an echocardiogram (an ejection fraction of less than 45% indicates heart failure), BNP levels and a chest x-ray.

Question 19

Define atrial fibrillation

Answer 19

no obvious p waves on an ECG, Atrial fibrillation is where left ventricle valve failure leads to increased pressure in the left atria, causing distension, which leads to atrial fibrillation.

Question 20

Identify the goals of treatment for chronic heart failure

Answer 20

The goals of treatment is to identify and treat any cause, reduce cardiac workload, increase cardiac output, counteract maladaptation, relieve symptoms, and prolong the quality of life.

Question 21

Describe the mechanism of action of angiotensin converting enzyme (ACE) inhibitor (e.g. ramipril)

Answer 21

Ramipril is an ACEI. These reduce arterial and venous vasoconstriction, reducing after and preload. They reduce salt and water retention and reduce circulating volume. These drugs are also used in hypertension.

Question 22

Describe the mechanism of action of an angiotensin AT1 receptor antagonist (e.g. losartan)

Answer 22

AT1 receptor antagonists block the action of AII. They are far less likely to give rise to a cough and are an alternative to ACE inhibitors.

Question 23

Describe the role of loop (e.g. furosemide) and thiazide diuretics in the management of chronic heart failure

Answer 23

Diuretics reduce circulating volume, reduce the preload on the heart and relieve pulmonary an peripheral oedema. Loop diuretics may cause hypokalemia.

Question 24

Describe the mechanism of action and role of beta-blockers (e.g. bisoprolol) in the management of stable chronic heart failure

Answer 24

They reduce disease progression, symptoms and mortality. hey reduce sympathetic stimulation, heart rate and O2 consumption. They oppose the neurohormonal activation, which leads to myocytes dysfunction and are especially useful in failure associated with ischaemia. They are antiarrhythmic and will control heart rate in atrial fibrillation.

Question 25

Describe the mechanism of action and role of an aldosterone receptor antagonist (spironolactone) in the management of chronic heart failure

Answer 25

This is a mineralocorticoid (aldosterone) receptor antagonist (MRA) that is now being used as an effective agent which reverses the LVH.

Question 26

Describe the mechanism of action and role of digoxin in the management of chronic heart failure and with concurrent atrial fibrillation

Answer 26

Digoxin is a positive inotropic and inhibits Na+/K+ ATPase. Sodium accumulates in the myocytes and is exchanged with Ca2+, leading to increased contractility. The sodium gradient is reduced and this reduces the efflux of Ca2+.Digoxin impairs AV conduction and increases vagal activity via the CNS. digoxin toxicity is a major problem as it has a narrow therapeutic window. The heart rate should be no lower than 60bpm.

Question 27

Distinguish between stable and unstable angina

Answer 27

Stable angina - limits the heart’s ability to respond to increase demand, symptoms of exertion relieved by rest.

unstable angina - plaque rupture and the formation of non-occlusive thromboembolism or vasospasm leads to symptoms at rest.

Question 28

Describe the mechanism of action and role of nitrates (e.g. glyceryl trinitrate) in the management of ischaemic heart disease

Answer 28

Pharmacological management is by using nitrates or venodilation, which leads to a decrease in preload and a reduction in cardiac work.

Question 29

Describe the mechanism of action and role of beta-blockers (e.g. atenolol) in the management of ischaemic heart disease

Answer 29

• block beta adrenoceptors and are negatively inotropic and chronotropic.
• reduce cardiac work and prevent symptoms. Coronary flow only occurs during diastole, so by slowing the heart the diastolic period will be increased, as well as the time for coronary blood flow. Antiarrhythmic effects will reduce the risk of myocardial infarction.

Question 30

Describe the mechanism of action and role of calcium channel blockers (e.g. both rate limiting and dihydropyridine agents) in the management of ischaemic heart disease

Answer 30

These have a vasodilative effect and improve coronary blood flow, preventing symptoms. Rate limiting agents have myocardial depressant and bradycardic actions, reducing cardiac work. Verapamil exerts class IV antiarrhythmic activity.

Question 31

Describe the role of antiplatelet drugs (e.g. low dose aspirin and clopidogrel) in the management of ischaemic heart disease

Answer 31

These are used to prevent thromboembolism and include low dose aspirin.

Question 32

Describe the mechanism of action and role of statins (e.g. simvastatin) in the management of cardiovascular disease

Answer 32

Statins are HMG-CoA reductase inhibitors, stopping the catalyzation of the formation of cholesterol. Statins reduce plasma cholesterol, and the reduction of hepatic cholesterol synthesis leads to an upregulation of hepatic LDL receptors. They are used to manage high cholesterol and /or reduce cardiovascular risk.

Question 33

Give an outline of the approach to pharmacological management of ischaemic heart disease

Answer 33

After an MI, a beta blocker, ACE inhibitor, stain and antiplatelet drug may be used. You can only use a beta blocker with a dihydropyridine calcium blocker, not a rate-limiting calcium blocker as it does not affect the heart.

Question 34

Define atheroma

Answer 34

a build-up of fatty deposits on the walls of the arteries around the heart

Question 35

Describe the processes involved in atheroma development and the associated risk factors

Answer 35

There are four recognisable stages, the fatty streak, lipid plaque, fibrolipid plaque, and complicated atheroma.

Fatty Streak - Blood lipids enter the intima through damaged endothelium. There is an accumulation of oxidized LDL in macrophages. Lipids are then phagocytosed by macrophages in the intima to make a raised fatty streak.

Lipid Plaque - Some lipids are released by macrophages, creating lipid plaque. Macrophages secrete cytokines which stimulate myofibroblasts to secrete collagen. There is early damage to the elastic lamina and media. Collagen then covers the plaque surface, forming white-yellow fibrolipid plaque. The media thins, with replacement of muscle fibres by collagen.

The ulceration of the endothelium exposes collagen with fibrin-platelet thrombus formation.

Question 36

Describe the potential consequences and complications of atheroma

Answer 36

The expansion of the intima reduces the size of the lumen, reducing blood flow and the oxygenation of the tissue. Ulceration of the athermous intima gives a predisposition to thrombus formation and vessel occlusion. Plaque fissure and haemorrhage can occur.

Question 37

Define what an aneurysm is, and their underlying pathology

Answer 37

An aneurysm is an anormal permanent focal dilation of an artery. The most common type of aneurysm is secondary to atherosclerosis. Other types occur, which are syphilitic, developmental in cerebral vessels, dissecting aneurysm of the thoracic aorta, and mycotic aneurysms.