Annette Battersby

Question 1

Describe the mechanisms of SOB

Answer 1

• Dyspnoea caused by interaction of peripheral chemoreceptors, central chemoreceptors, mechanoreceptors and the respiratory center.
• Respiratory center divided into 3 groups, ventral/dorsal medullary, pontine group. The dorsal medulla controls inhalation, ventral medulla controls exhalation and pontine controls the frequency and intensity of medullary signals.
• Mechanoreceptors in the trachea, lungs, and pulmonary vessels detect volume and irritant changes, and signal via the vagus nerve to respiratory center to increase ventilation (rate/depth), and to stimulate coughing.
• Peripheral chemoreceptors include aortic and carotid bodies, they respond to hypoxia and hypercapnia + acidosis causes them to increase sensitivity. They signal to the NTS via glossopharyngeal nerve.
• Central chemoreceptors mainly in the ventral medulla and retrotrapezoid nucleus respond to CO2, because of BBB
• Heart failure –> pulmonary edema –> dyspnea

Question 2

Describe the cascade of events that lead to cold and clammy hands?

Answer 2

• Primarily due to hypovolaemic or cardiogenic shock.
• When heart failure occurs, heart cannot pump as much blood. Therefore, there is a reduced stroke volume and a reduced cardiac output.
• There is then a decrease in arterial pressure, and hence the sympathetic pathway of the heart is activated to increase the HR.
• The sympathetic nervous system causes the secretion of adrenaline and noradrenaline, all which cause vasoconstriction of blood vessels which causes increased resistance and increased HR, to try and increase Cardiac output and blood pressure.
• This means there is reduced blood flow to hands and feet due to vasoconstriction
• Additionally, body is circulating most of the available blood to the brain and other vital organs to compensate for the failing heart’s inability to pump blood to entire body. Therefore, extremities such as hands get less blood to warm them, and hence will be cold.

Question 3

what is pulse pressure?

Answer 3

pulse pressure= systolic pressure- diastolic pressure

the maximal change in the aortic pressure during systole

Question 4

what is the major determinant of pulse pressure?

Answer 4

• The major determinant of pulse pressure is aortic compliance and stroke volume. As compliance increases the smaller the pulse pressure.

Question 5

what can cause low pulse pressure?

Answer 5

decreased cardiac output

Question 6

what can cause high pulse pressure?

Answer 6

hypertension or atherosclerosis, iron deficiency anaemia and hyperthyroidism

Question 7

what can cause a pan-systolic murmur

Answer 7

Mitral/tricuspid regurgitation and ventricular septal defects

Question 8

what is the third heart sound?

Answer 8

S3 is the third heart sound, aka ventricular gallop, occurs just after S2 in early diastole just after the opening of the mitral valve. Results from increased atrial pressure leading to increased flow rates, as seen in congestive heart failure, which is the most common cause of a S3. Dilated ventricles also contribute to the sound because they are a result of overly compliant myocardium. Normally the LV is not overly compliant so the S3 sound is not loud enough to be heard on auscultation. An S3 sound can be a normal finding in children, pregnant women and well-trained athletes.

S3 is a low-pitched sound; this is helpful in distinguishing a S3 from a split S2, which is high pitched. A S3 heart sound should disappear when the diaphragm of the stethoscope is used and should be present while using the bell; the opposite is true for a split S2.

Question 9

Describe the pathophysiology of oedema?

Answer 9

Edema results from increased movement of fluid from the intravascular to the interstitial space or decreased movement of water from the interstitium into the capillaries or lymphatic vessels. The mechanism involves one or more of the following: Increased capillary hydrostatic pressure. Decreased plasma oncotic pressure

SEE NOTES FOR FLOWCHART

Question 10

why do you get oedema in cardiac failure?

Answer 10

pulmonary oedema and pitting oedema are a result of poor cardiac output due to heart failure, causing a back up of fluid and poor circulation - hence an increased pressure in the pulmonary arteries and pooling of blood in the legs due to gravity, respectively causing fluid to move from capillaries to the interstium. This is further made worse due to poor venous drainage (again because of the poor circulation) as lymphatic drainage is hindered.

Question 11

describe the effect of thyroid hormone on the heart

Answer 11

• Hyperthyroidism:
o Palpitations, may even provoke arrhythmias e.g. atrial fibrillation.
o Can also cause tachycardia.
o Excess thyroid hormone also causes the heart to beat harder and faster and may trigger abnormal heart rhythms. One is atrial fibrillation, a disorganized rhythm in the heart’s upper chambers. A related symptom is palpitations, a sudden awareness of your heartbeat. People with hyperthyroidism may also have high blood pressure. In a person with clogged, stiff heart arteries, the combination of a forceful heartbeat and elevated blood pressure may lead to chest pain or angina.

• Hypothyroidism:
o Bradycardia.
o Hypothyroidism can affect the heart and circulatory system in a number of ways. Insufficient thyroid hormone slows your heart rate. Because it also makes the arteries less elastic, blood pressure rises in order to circulate blood around the body. Elevated cholesterol levels, which contribute to narrowed, hardened arteries, are another possible consequence of low thyroid levels.

Question 12

consequences of cardiomegaly

Answer 12

• Blood clots due to stasis of blood
• Heart failure- weaker heart muscle, as myocardium dilates, less overlap between actin and myosin so harder for them to shorten the sarcomere
• Murmurs- ventricles dilate so valves can’t close properly
• Cardiac arrest and sudden death

Question 13

MICA of GTN

Answer 13

• MOA: classes as a nitrate. Converted by mitochondrial aldehyde dehydrogenase to nitric oxide, which then activates guanylate cyclase. This leads to synthesis of cGMP (cyclic guanosine 3,5 monophosphate), activating the signalling cascade that leads to the dephosphorylation of myosin light chain of smooth muscles, causing relaxation and increased blood flow in the blood vessel and cardiac tissue. GTN results in decreased work of the heart, decreased BP, relief of anginal symptoms and increased blood flow to the myocardium. Decreases preload.
• Indications: prophylaxis of angina, treatment of angina, control of hypertension and myocardial ischaemia during and after cardiac surgery, induction of controlled hypotension during surgery, congestive heart failure, unstable angina, anal fissures
• Contraindications: aortic stenosis, cardiac tamponade, constrictive pericarditis, hypertrophic cardiomyopathy, hypotensive conditions, hypovolemia, mitral stenosis, raised ICP due to cerebral haemorrhage or head trauma, toxic pulmonary oedema.
• Adverse effects: arrhythmias, cerebral ischaemia, dizziness, drowsiness, flushing, headache, hypotension, nausea, vomiting, cyanosis.

Question 14

MICA metoprolol

Answer 14

• MOA: beta blocker- beta-1 adrenergic receptor inhibitor specific to cardiac cells.
• Indications: hypertension, angina, arrhythmias, migraine prophylaxis, hyperthyroidism, early intervention within 12h of infarction.
• Contraindications: asthma, cardiogenic shock, hypotension, marked bradycardia, metabolic acidosis, phaeochromocytoma, second degree AV block, uncontrolled heart failure.
• Adverse effects: abdominal discomfort, bradycardia, confusion, depression, dizziness, dry eyes, dyspnoea, fatigue, heart failure, constipation, palpitations, postural disorders, chest pain, drowsiness

Question 15

MICA LMWH

Answer 15

• MOA: anticoagulant. Binds reversibly to antithrombin 3, which in normal circumstances inactivates thrombin. Heparin binding to antithrombin 3 leads to instant inactivation of factors 2a and 5a. It is not a thrombolytic or fibrinolytic drug but rather prevents existing clots developing further.
• Indications: tx of PE, unstable angina, acute peripheral arterial occlusion, DVT, thromboprophylaxis, haemodialysis, maintenance of patency in catheters and cannulas.
• Contraindications: acute bacterial endocarditis, major trauma, neonates, epidural anaesthesia, haemophilia or haemorrhagic disorders, peptic ulcer, recent cerebral haemorrhage, recent eye surgery, recent nervous system surgery, thrombocytopenia
• Adverse effects: haemorrhage, heparin-induced thrombocytopenia, skin reactions, thrombocytopenia, thrombocytosis, CNS haemorrhage, alopecia, hyperK, osteoporosis

Question 16

MICA digoxin

Answer 16

• MOA: cardiac glycoside, which reversibly inhibits sodium potassium pump, thus increasing intracellular sodium and calcium levels in the myocyte, which increases the contractile force of the heart and increases left ventricular ejection fraction. It also stimulates the parasympathetic nervous system via the vagus nerve, affecting the SAN and AVN decreasing heart rate.
• Indications: AF or atrial flutter, heart failure
• Contraindications: constrictive pericarditis, hypertrophic cardiomyopathy, intermittent complete heart block, myocarditis, second degree AV block, ventricular tachycardia or fibrillation
• Adverse effects: arrhythmias, cardiac conduction disorders, dizziness, diarrhoea, eosinophilia, nausea, skin reactions, vomiting, depression, anorexia, gynaecomastia, headache.

Question 17

MICA rivaroxaban

Answer 17

• MOA: competitive inhibitor of free and clot bound factor 5a, which is needed to activate prothrombin to thrombin, which is needed for the conversion of fibrinogen to fibrin, the final stage in the clotting cascade. Irreversible action.
• Indications: prophylaxis of VTE, tx of DVT and PE
• Contraindications: active bleeding, antiphospholipid syndrome, malignant neoplasms at high risk of bleeding, oesophageal varices, recent brain surgery, recent GI ulcer, recent spinal surgery, vascular aneurysm.
• Adverse effects: anaemia, constipation, diarrhoea, fever, GI discomfort, haemorrhage headache, hypotension, menorrhagia, nausea, oedema, pain in extremities, renal impairment, avoid in pregnancy and breast feeding.

Question 18

definition of CHF

Answer 18

the heart is unable to pump enough blood to meet the metabolic needs of the body due to pathological changes in the myocardium.

Question 19

RFs for CHF

Answer 19

obesity, smoking, COPD, drugs (recreational and prescribed e.g. NSAIDs), alcohol, HT, coronary artery disease, diabetes, sleep apnoea (low oxygen sats), congenital heart defects, valvular heart disease, arrhythmias

Question 20

DDx for CHF

Answer 20

AKI, acute respiratory distress syndrome, pneumonia, COPD, cirrhosis, emphysema, MI, nephrotic syndrome, pneumothorax, PE

Question 21

Aetiology of CHF

Answer 21

coronary artery disease, MI, HT, valvular heart disease DM, renal disease, infiltrative diseases, dilated cardiomyopathy, cardiac arrhythmias, myocarditis

Question 22

Clinical features of CHF

Answer 22

nocturia, fatigue, tachycardia, various arrhythmias, S3/S4 gallop on auscultation, cachexia (extreme weight loss and muscle wasting), SOB, oedema, tachycardia, ascites, anorexia, nausea, coughing up pink foamy mucus.

Question 23

Pathophysiology of CHF

Answer 23

decrease in muscle contractility, increased preload resulting in pulmonary congestion and dyspnoea, increase in systemic vascular resistance (afterload) which further reduces CO, increased HR to compensate with associated increase in sympathetic tone and circulating catecholamines to increase contractility and HR to maintain CO. Also get cardiac muscle hypertrophy.

Question 24

Ix for CHF

Answer 24

full hx, blood tests-routine bloods, cardiac enzymes, BNP, ECG, CXR, echocardiogram, cardiac stress test, angiography

Question 25

Mx of CHF

Answer 25

lifestyle changes, loop diuretics e.g. furosemide, thiazide diuretic e.g. chlorothiazide, thiazide like diuretic e.g. metolazone, ACEi e.g. ramipril, beta-blockers e.g. metoprolol, angiotensin 2 receptor antagonists e.g. valsartan, renin inhibitors e.g. enalapril, anticoagulants e.g. warfarin, cardiac glycoside e.g. digoxin

Question 26

Prognosis for CHF

Answer 26

50% have an average life expectance of less than 5 years, nearly 90% die within one year of diagnosis.

Question 27

What is Starling’s law of the heart

Answer 27

• Starling’s law states that the more the heart fills the harder it will contract therefore the bigger the stroke volume (up to a point). This is based on the principle that the force developed in a muscle fibre depends on the degree to which the fibre is stretched. Therefore a rise in central venous pressure will result in an increased stroke volume automatically.
• The Starling curve relates stroke volume to venous pressure and the slope defines the contractility of the ventricles.
• The preload of the heart is the volume of venous blood that stretches the resting cardiac muscle. The filling of the left ventricle during ventricular diastole results in the end-diastolic volume.

Question 28

What is Laplace’s law

Answer 28

• Afterload - Laplace’s Law
• = is determined by Wall Stress directed through the heart wall. More energy of contraction is needed to overcome this Wall Stress to produce ejection – heart doesn’t function as efficiently
• We want to reduce afterload ultimately, as it opposes the ejection of blood from the heart
• Laplace’s law describes parameters that determine Afterload:
• Wall Tension (T), Pressure (P), and Radius (r) in a chamber (ventricle)
• Opposes Starling’s Law at rest
• ↑arterial blood pressure => ↑wall stress, ↑afterload, ↓ejection

– heart compensates
• Increased Wall Thickness (w) leads to hypertrophy (greater myocyte size)
• Decreased Afterload – Increased SV/CO
• Same Wall Stress but now over greater area (more sarcomeres)
• Less Wall stress per sarcomere
• Less opposition to contraction of sarcomeres
• But - this requires more energy (as more sarcomeres used)
• Greater O2 use, ultimately decreases contractility - heart failure
• Vicious circle of heart failure

Question 29

describe hormonal regulation of vasculature?

Answer 29

• Renin, also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body’s renin–angiotensin–aldosterone system —also known as the renin–angiotensin–aldosterone axis—that mediates the volume of extracellular fluid and arterial vasoconstriction.
• Ventricular natriuretic peptide or brain natriuretic peptide, also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume.
• Brain natriuretic peptide (BNP) is a peptide hormone that is released in response to volume expansion and the increased wall stress of cardiac myocytes. BNP helps to promote diuresis, natriuresis, vasodilation of the systemic and pulmonary vasculature, and reduction of circulating levels of endothelin and aldosterone.

Question 30

Main principles in management of heart failure

Answer 30

• The most important medications for a person with heart failure are an ACE Inhibitor and Beta blocker, these are used for ALL patients:
• ACE Inhibitor therapy – Inhibit the production of Ang II, a potent vasoconstrictor. By doing this it causes peripheral vasodilatation, decreasing afterload on the heart (as the central venous pressure decreases). It also reduces aldosterone release, which decreases salt/water retention from kidneys reducing heart preload. They have been shown to improve symptoms and improve survival. If intolerant to ACE inhibitor give Ang II receptor antagonist.

• Beta Blocker – Improve symptoms and reduce cardiovascular mortality in patients with chronic stable heart failure. This is through blocking the effect of the chronically activatedsympathetic system.

• Diuretics – Used in patients with fluid overload. They promote renal sodium excreting and water follows, reducing circulating volume and the stress on the heart from hypertension. It also reduces the pulmonary and systemic congestion. In this way it is more symptomatic relief.
• Loop diuretics e.g. furosemide are potent diuretics used in moderate/severe HF
• Thiazide diuretics e.g. bendroflumethiazide are mild diuretics that work in the DCT
• Aldosterone antagonists e.g. spironolactone are relatively weak diuretics
• Digoxin – Used as a third line treatment in LV failure, used earlier if patient also has AF.
• Ivabradine – Certain patients.
• Inotropes – Occasionally used.

Question 31

MICA spironolactone

Answer 31

M: K sparing diuretic. Spironolactone competitively inhibits mineralocorticoid (aka aldosterone) receptors in the distal convoluted tubule
· By inhibiting the receptor, it inhibits aldosterone dependant sodium potassium exchange channels
· This leads to increased sodium and water excretion and more potassium retention

I: 	Heart failure, hypertension, hyperaldosteronism, adrenal hyperplasia, nephrotic syndrome
·   	For heart failure, specifically *NYHA class III-IV heart failure
·   	Also management of oedemea in cirrhotic adults not responsive to fluid and sodium restrictions
·   	For nephrotic syndrome, when treatment with other diuretics and sodium and fluid restriction is inadequate
·   	Also used for its antiandrogenic effects in transgender female patients

C: o Addison’s disease. Aka primary adrenal insufficiency
o Acute renal insufficiency, significant renal compromise, anuria.
o Hyperkalaemia.

A: ·   	Acute kidney Injury
·   	Confusion/dizziness
·   	Electrolyte imbalance
·   	Hyperkalaemia
·   	Metabolic Acidosis
·   	Gynaecomastia
·   	Nausea/vomiting

Question 32

MICA atorvastatin

Answer 32

M: statin. Competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which usually catalyses the conversion of HMG-CoA to mevalonate.
· This is an early rate limiting step in lipid metabolism and synthesis, including cholesterol, LDL (bad cholesterol) and VLDL

I: dyslipidaemia, prophylaxis of CV events e.g. MI

C: · Statins should be used with caution in patients at increased risk of muscle toxicity, including those with a PH/FH of muscular disorders such as myopathy or rhabdomyolsis, previous history of muscular toxicity, a high alcohol intake, renal impairment or hypothyroidism. In patients with increased risk of muscle effects, a statin should not be started if their baseline creatine kinase concentration is more than 5 times the upper limit of normal
· It is also contraindicated in pregnancy

A: · Common adverse effects for patients taking atorvastatin include arthralgia (joint pain), indegestion, diarrhea, nausea, nasopharyngitis (cold), insomnia, urinary tract infection, and pain in extremities.
· muscle aches, muscle tenderness, or muscle weakness
· Patients with impaired renal function may be at increased risk of developing rhabdomyolysis (breakdown of muscle tissue that leads to the release of muscle fibre contents into the blood)

Question 33

MICA bisoprolol

Answer 33

M: cardio selective B1 adrenergic R blocker. Selectively blocking B1 adrenoceptors, which are located mainly in the heart
· B1 receptors Gs coupled so increase adenyl cyclase activity resulting in increased cAMP which increased intracellular Ca2+ concentration.
· When B1 receptors are normally activated by noradrenaline, they lead to a positive ionotropic and chronotropic effect leading to an increase in blood pressure and greated cardiovascular work, increasing the demand for oxygen.
· Bisoprolol reduces cardiac workload by having a negative ionotropic and chronotropic effect, thus reducing the oxygen demand of the heart
· B1 receptors are also present in the juxtaglomerular cells of the kidney, and blocking these b1 receptors leads to the reduction of renin release, therefore reducing the effects that the RAAS system normally has on blood pressure, leading to a reduction in BP.

I: Mild to moderate hypertension
· Can also be used to treat heart failure, atrial fibrillation and angina pectoris (chest pain due to coronary heart disease)

C: Severe bradycardia, hypotension
· advanced AV block unless a functioning pacemaker is present because beta blockers depress conduction through the AV node.
· Should be avoided in patients with acute pulmonary oedema
· Contraindicated in patients with cardiogenic shock or acute uncontrolled heart failure due to systolic ventricular dysfunction
· Should be used cautiously with heart failure, starting initially with a low dose, and then increased gradually.

A: Bradycardia, depression, confusion, dizziness, AV block, constipation, muscle craps, muscle weakness, postural hypotension