Pbl 15 It S Just Indigestion

PBL 15 – IT’S JUST INDIGESTION

1998 Paper 1, Part A: Q1-12, 14-18

A 52 year old man wakes in the night suffering excruciating central chest pain, sweats, nausea, vomiting, and severe shortness of breath. He has a recent history of episodes of chest pain during moderate exertion that radiated into the left arm, and was relieved by glyceryl trinitrate.

Question 1. List the key information concerning this man’s problem. (2 marks)

 52yo male  wakes in middle of night with o excruciating central chest pain o sweats o nausea o vomiting o severe shortness of breath  recent history of episodes of chest pain during moderate exertion that radiated to his left arm o Relieved by glyceryl trinitrate

Question 2. List the structures from which central chest pain can arise. (4 marks)

 Heart  Oesophagus  Sternum  Lungs  Pectoralis major???

Question 3. What are the most likely pathological processes that could explain the key information that you listed in Question 1? (2 marks)

The central chest pain radiating to the left arm is indicative of cardiac damage. The possibilities include:  Ischaemic heart disease (caused by the occlusion of a blood vessel supplying myocardium) o Myocardial infarction o Angina pectoris o Unstable angina  Acute pericarditis  Mitral valve stenosis  Pulmonary valve disease Question 4. Describe the basic nervous mechanisms and peripheral pathways that are involved in cardiac pain. (3 marks)

 Cardiac nociceptors enter the spinal cord via the T1-T4/5 (sympathetic) spinal nerves, mainly in the middle to inferior cardiac nerves but some pass directly to the spinal nerves  It is said that the superior cardiac nerves carry no general afferents  Peripherally the cardiac fibres pass through the cardiac plexus and run with the cardiac arteries  Myocardial anoxia may provoke symptoms of angina pectoris – namely presternal pain, mainly to the left chest, shoulder, arm and neck. In other words the dermatomes supplied by the T1-T4/5 spinal nerves  Cardiac afferents running in the vagal branch (parasympathetic) are mainly responsible for reflexes which depress cardiac function

Question 5. Explain why cardiac pain is usually felt centrally in the chest and is commonly referred to the arm. (3 marks)

This is to do with the mechanism known as referred pain. In a lot of cases afferent sensory fibres from cutaneous and visceral regions come together and travel up the same spinal nerve to the brain. The brain cannot tell the diferrence between these two signals and refers the pain received from the visceral nociceptor to the superficial structure (skin). The area of skin supplied by a particular spinal nerve is known as a dermatome. Therefore in this case cardiac nociceptors sending pain impulses would come together with the nociceptors of the dermatomes supplied by T1-4/5. The brain not being able to tell these two apart would refer the pain to the skin, hence the central chest pain radiating to the left arm as those are the dermatomes supplied by T1-T4/5

Question 6. Select the single correct response: (3 marks)

(a) Glyceryl trinitrate

A is optimally effective following oral administration (sublingual administration) B preferentially dilates peripheral veins C dilates coronary arteries to relieve anginal pain D is resistant to metabolism in the liver E unlike other organic nitrates, does not need to be stored in airtight containers

(b) Glyceryl trinitrate

A induces lupus-like symptoms in at least 20% of patient B is the preferred nitrate because of the low incidence of associated headache C induces tolerance within four days of continuous administration D unlike erythrityl tetranitrate, rarely causes palpitations E decreases afterload more than preload, thus lowering blood pressure (c) Glyceryl trinitrate

A opens ATP-sensitive potassium channels on endothelial cells B increases cAMP production in vascular smooth muscle cells by adenylate cyclase C blocks voltage-operated calcium channels on both endothelial and vascular smooth muscle cells D increases NO production and release from endothelial cells E activates guanylate cyclase to produce cGMP in vascular smooth muscle cells

He is rushed to hospital by a coronary care ambulance, his pulse weak and rapid, blood pressure low, and respiration noisy and gasping. He is coughing up pink frothy material. He is admitted to hospital where myocardial infarction is confirmed by ECG.

Question 7. Define what is meant by myocardial infarction. (1 mark)

An infarction is a focused area of necrotic ischaemic tissue. In the case of a myocardial infarction the tissue involed is myocardium or heart muscle.

Question 8. What is the likely reason for his noisy and gasping breathing and the pink frothy material being coughed up? (1½ marks)

In the event that the infarction damaged the left side of the heart, namely the left ventricle the following features could be seen:  An accumulation of blood in the pulmonary vasculature due to the inefficiency of the left heart to move it on to the systemic circulation would result in an increase in hydrostatic pressure. This would lead to pulmonary oedema as fluid leaks from the blood into the alveolar spaces. (frothy)  Microhaemorrhages due to the increased pressure would release RBC into the alveolar spaces (pink)  This fluid build-up in the alveolar spaces would decrease the area for successful ventilation (gasping)

Question 9. List the signs you might expect the ECG to show in the first 48 hours after a major myocardial infarct. (1 mark)

 ST elevation  Abnormal Q waves  Inversion of T waves at site of injury

Question 10. (a) Report the ventricular rate and rhythm. (2 marks)

Each small square = 0.04sec. Each large square = 5 small squares = 0.2 sec. 5 large squares = 1sec Rate is either regular or irregular, are there P waves present, what is the relationship between P and QRS, is QRS wide? Question 11. On the above diagram indicate which three leads will be most affected by an injury potential involving the inferior (diaphragmatic) wall of the left ventricle. (1 mark)

AvF, II, III

Question 12. Above is a record of the aortic pressure during a cardiac cycle. On the diagram indicate the time at which the flow through the left coronary artery is maximal. (1 mark)

This occurs opposed to normal vasculature during diastole. It would be at the start of diastole.

In spite of treatment by specialists in the coronary care unit the patient dies two hours after admission. Autopsy reveals atherosclerosis and thrombosis of the left circumflex artery.

Question 14. Explain what is meant by thrombus, indicating its structural components. (2 marks)

A thrombus is a formation in the vascular lumen which is an aggregation of coagulated blood containing platelets, fibrin and entrapped cellular elements. A thrombus by definition s adherent to the vascular epithelium and is different from a simple blood clot (which is just the activation of the coagulation cascade and can form in vitro or in situ in the post mortem state. The most common cause is atherosclerosis.

Question 15. Select the single correct response: (2 marks)

Likely treatment of this patient on arrival at hospital would have included:

(a) Aspirin

A to prevent platelet aggregation B to relieve central chest pain C to assist in opening coronary arteries D to inhibit the coagulation cascade E to activate fibrinolysis

(b) the use of thrombolytic therapy

A to prevent conversion of thrombin to prothrombin B to activate breakdown of fibrin-containing thrombi C to decrease the adhesiveness of platelets D to inhibit cyclooxygenase and phospholipase E prevents production of clotting factors II, VIII, IX and X Question 16. From where do the coronary arteries originate? (1 mark)

The right and left coronary arteries originate from the aortic sinus. The circumflex and left anterior descending originate, left marginal and in most cases the posterior interventricular artery from the Left coronary and the right marginal and SA nodal artery originates from the right coronary

Question 17. To what extent is the following statement true? The right coronary artery supplies the right heart and the left coronary artery supplies the left heart. (3 marks)

In the very general sense this is mostly true however exceptions exist. Left coronary artery supplies:  Most of the left ventricle  Part of the right ventricle  Anterior 2/3 of interventricular septum  Most of the left atrium Right coronary artery:  Most of the right ventricle  Variable part of left ventricle (diaphragmatic aspect)  Posterior-inferior part of interventricular septum  Right atrium  Part of the left atrium  Conducting system till the crura

Question 18. What is meant by the term 'end artery' and to what extent does it apply to the coronary arteries? (2 marks)

An end artery is one which undergoes progressive branching without the development of channels connecting with other arteries. The coronary arteries display this feature as they branch over the whole heart yet are only originating from the right and left coronary arteries. 1998 Paper 3, Part E: Q5

Question 5. (5 marks) OPTIONS ______Heart Rate CVP Blood Pressure ______A 160 1 70/40 B 40 3 140/60 C 80 4 160/100 D 120 20 80/50 E 100 3 130/80 F 72 4 120/70 G 90 9 100/70 H 140 6 180/100 I 80 4 190/60 J 60 4 90/60 ______

Which of the cardiovascular profiles listed in the options above is most likely to be associated with the following scenarios? 1. An anxious 21 year old male university student about to do a university exam. - C 2. A 19 year old male following a MVA which caused a ruptured spleen. - A 3. A 65 year old male collapses with severe retrosternal chest pain and shortness of breath. - H 4. A 35 year old female tourist presents with headaches 2 days after running out of her ACE inhibitor. - H 5. A 16 year old female who faints after getting out of bed. - J 6. A 21 year old male marathon runner at rest. – B

1999 Paper 3, Part A: Q2-5, 7-13

The following year Bill returns to your surgery complaining of occasional chest pain over the preceding 4 months.

Question 2. State three (3) organs or systems from which the pain might originate. For each organ /system indicate an underlying pathological process which can cause chest pain. (3 marks)

1) Cardiovascular System- blockage of a coronary artery leads to ischemia of the heart tissue that it supplied. While the heart is insensitive to touch, cutting or temperature, pain is felt when the afferent nerve endings are stimulated by chemicals such as those released by cells during ischemia. These afferent nerves follow the sympathetic nerves and are derived from T1-T4/5 segments. Alternatively the parietal pericardium is also sensitive to pain (via the afferent component of the phrenic nerve C3-C5). Thus conditions irritating the parietal pericardium such as pericarditis can also result in chest pain. 2) Respiratory System – Inflammation of the pleura may cause rubbing of the visceral and parietal layers causing chest pain derived from phrenic and intercostals nerves innervating the parietal pleura. Pleurisy can be caused by neoplasm, inflammation, pulmonary infarction etc. 3) Esophagus- Gastro-oesophageal Reflux. The oesophagus receives sensory innervation from most notably the vagus nerve thus pain is detected by vagal afferent fibers.

Question 3. For each of the three (3) causes you have proposed, give two (2) features you would elicit in your history that would support the diagnosis. Explain the mechanism of each. (6 marks)

1) Angina: Ask if the pain is brought on by activity (heart becomes deprived of O2 because diastole is shortened during times of increased activity. This will lead to ischemia and cause the angina pain. Ask where the pain is felt. For instance if it radiates to the left arm and jaw it is likely to be pain from the visceral heart. Ask patient if they have previously had ischemic heart disease as this is the most important risk factor for further ischemia.

2) Pleurisy Ask the patient if the pain increases upon a deep breathing. In pleurisy the pain will increase upon a deep breath or coughing due to the fact this action will cause rubbing of the pleura. Ask the patient if he/she has recently been sickrecently. Pleurisy is often associated with upper respiratory tract infections and pneumonia. 3) Ulceration Ask the patient if the pain is relieved by antacids. Ask the patient if they have ever noticed any acid or a bitter taste in their throat.

Question 4. For two (2) of the three (3) causes you have proposed, give three (3) features you would elicit in your examination that would support the diagnosis. Explain the mechanism of each.

Ischaemic Heart Disease (IHD): - auscultate the heart listening for – S3, S4, decreased intensity of heart sounds, valvular insufficiency (partilucalry, late systolic mumur usually caused by papillary muscle dysfunction due to ischaema). -Respiratory rate: tachypnoea common in left ventricle failure due to raised pulmonary pressures etc. - ECG changes

Pleurisy: - Auscultate the lungs listening for a pleural friction rub, which is a grating sound occuring when thickened, roughened pleural surfaces rub together as the lungs expand and contract. - Have the patient take a deep breath and make note of any signs of pain (whincing etc). Try to have the patient localize the pain. - Obtain an X-ray. While pleurisy is unlikely to be seen on x-ray conditions causing pleurisy such as neoplasm may show up. It is also useful in ruling out some of the other causes of chest pain. - Ask patient to sit up and lean forward. Ask if this helps to relieve the pain (characteristic of pleurisy). Question 5. What basic nervous stimuli and afferent pathways are involved in cardiac pain? (5 marks)

Chemosensitive and mechanosensitive receptors in the heart are stimulated by metabolic products of ischemia. Of particular note are mediators such as adenosine and bradykinin are released and this stimulates receptors of the sympathetic and vagal afferent pathways.

Question 7. (5 marks) Respond to the following statements as TRUE (T), FALSE (F), DON’T KNOW (D) CIRCLE YOUR CHOICE

1. The first heart sound occurs at the opening of the aortic and pulmonary valves T F D 2. The first heart sound occurs at the closing of the atrioventricular valves T F D 3. The second heart sound occurs at the closing of the aortic and pulmonary valves T F D 4. The second heart sound occurs at the opening of the atrioventricular valves T F D 5. Valves never make an audible sound when opening T F D 6. Normal valves usually open silently T F D 7. Turbulent blood flow generates sounds T F D

After taking a detailed history and performing a physical examination, the GP considers that ischaemic heart disease is the most likely cause of Bill’s chest pain. He is advised to take glyceryl trinitrate sublingually at the onset of pain.

Question 8. (5 marks) Respond to the following statements as TRUE (T), FALSE (F), DON’T KNOW (D) Regarding Glyceryl Trinitrate CIRCLE YOUR CHOICE

1. dilates coronary arteries during myocardial ischaemia T F D 2. dilates arterioles to decrease afterload T F D 3. dilates veins to decrease preload T F D 4. relaxes precapillary sphincters to reduce blood pressure T F D 5. it is destroyed by the acidity of the stomach T F D 6. it is rapidly metabolised during a single passage through the liver T F D 7. gastro-intestinal absorption is grossly delayed by food T F D

Question 9. Explain the alterations in cardiac muscle electro-physiology resulting from ischaemia. (4 marks)

The cardiomyocytes normally function as a single unit (functional synctium). Intercalated discs (desmosomes of cardiomyocytes) keep cells together during a contraction and gap junctions allow ions to pass for cell to cell. Ischemia will cause damage to the tissue and ions will be released from dead cells. These extracellular ions will disrupt the conduction pathway by partially depolarizing surrounding cells and depolarization and repolarization events will be hampered. Question 10. Explain the dependence of cardiac ventricular contraction on a supply of oxygen and nutrients.

Cardiac muscle is unlike skeletal muscle in that it relies almost entirely on aerobic respiration. This means that it needs an almost constant supply of O2. Cardiomyocytes are flexible in their fuel source, but preferentially utilize fatty acids (between meals). A lack of O2 is thus of greater potential harm because the heart can utilize multiple different fuel sources.

Question 11. The GP orders a test to measure cardiac enzymes.

(i) Which two (2) enzymes would be measured? (2 marks)

CK-MB isoenzyme and cardiac troponin I subunit

(ii) Why might the serum concentrations change in ischaemic heart disease?

The ischemia causes cell death with consequent release of cellular contents into the blood

(iii) How can you know the enzymes are of cardiac origin? (3 marks)

Both enzymes are very cardiac specific and are not found at any significant level in other cell types. Thus if they are elevated in the blood they are most likely to have come from cardiac muscle cells.The MB isoform of creatine kinase is heart specific and is differentiated from isoforms of creatine kinase that predominate in the skeletal muscle and the brain. The isoform of troponin that is tested is distinct from that found in skeletal. muscle.

Question 12. How does elevated serum cholesterol lead to atherosclerosis? (7 marks)

If total cholesterol levels are elevated, it is likely that there are also elevated levels of LDL. LDL is very susceptible to oxidization (ox-LDL) by free radicals of both endogenous (metabolism) and exogenous (pollution , smoking etc). ox-LDL is pro-atherogenic and the main factor leading to progression of fatty streaks (which everyone has) by damaging the endothelium, stimulating monocyte extravasion and differentiation into tissue macrophages, and promotes smooth muscle cells to assume the synthetic phenotype. Normally LDL is taken up by macrophages, via LDL receptors, and the LDL is broken into amino acids and cholesterol. As cholesterol is cytotoxic its uptake is regulated such that as cholesterol levels build up in the cytosol, LDLR expression is reduced. Ox-LDL however is selectively taken up by scavenger receptors present on both macrophages and synthetic smooth muscle cells. Scavenger receptors are not negatively regulated as LDLR are and thus as much cholesterol accumulates as LDL can be oxidized. Cholesterol is esterified in the cytosol by ACAT which give the macrophages a foam cell appearance. As cholesterol is cytotoxic the macrophages undergo cell death and release their contents into the surrounding area. This leads to the formation of and increase in size of an atheromatous core. Clearly, the limiting factor is LDL thus high levels of serum cholesterol result in increased LDL formation and a higher absolute amount of ox-LDL. Question 13. What dietary factors predispose to elevated serum cholesterol? (3 marks)

Generally, high cholesterol diets result in high levels of LDL (people of differing gene polymorphisms may be affected to a greater or lesser extent). Particular foods which are high in cholesterol are those containing animal fats and saturated fats such as butter. Interstingly, plants are unable to synthesise cholesterol so they are great foods for people on a low cholesterol diet.

2000 Paper 2, Part C: Q2

Joanne presents at her local health clinic complaining of chest pain.

Question 2. (5 marks) List five (5) structures from which chest pain may originate in any patient. For each structure, indicate a pathological process that could cause chest pain.

Heart – IHD Lungs – PE, infection Oesophagus – reflux Ribs - costochondritis Muscles – strain/ tear

2001 Paper 1, Part B: Q1-6, 8-18

Michael C, a 52 year old man, wakes in the night suffering severe central chest pain, sweating, nausea, vomiting, and severe shortness of breath. He has a recent history of episodes of chest pain during moderate exertion that radiated into the left arm, and were relieved by sublingual glyceryl trinitrate.

Question 1. (4 marks) List the eight (8) anatomical structures from which central chest pain can arise, that are most relevant to this case.

Pleural membrane, parietal pericardium, intercostals muscles, esophagus, costochondral joints, ribs, stern costal joints, aorta

Question 2. (1 mark) What is the most likely pathological process to explain the patient’s presentation?

Ischemia of the myocardium

Question 3. (3 marks) Describe the basic nervous mechanisms and peripheral pathways that are involved in cardiac pain. Occlusion in coronary artery→release adenosine and bradykinin→stimulation of noicoceptors in parietal pericardium and increased firing of action potential→signal carried through cardiac plexus→enters spinal cord at T1-T6 by dorsal root ganglion→travels up spinothalamic tract and perceived as pain by the thalamus.

Question 4. (3 marks) Explain why cardiac pain is usually felt centrally in the chest and is commonly referred to the arm.

Pain is felt centrally in the chest because other central chest structures have somatic fibers which enter the dorsal root ganglion at the same point as does the arm. Therefore brain perceives the pain as being located in the arm and central chest.

Question 5. (3 marks) List six (6) major cardiovascular disease risk factors. For each risk factor, indicate whether it is fixed or potentially modifiable.

Family history of CVD-fixed, smoking-potentially modifiable, being male-fixed, high blood pressure-potentially modifiable, high blood cholesterol-potentially modifiable, diet high in fatty foods and cholesterol (potentially modifiable).

Question 6. (4 marks) Glyceryl trinitrate donates nitric oxide. Explain its effects in patients with cardiac pain.

Nitric oxide is a vasodilator. Its primary effect in cardiac pain is toe dilate the veins. This causes accumulation of blood in the venous circulation and thus a reduced preload. Because of the reduced pre-load the cardiac output is decreased and as the heart is doing less work it requires less work. Decreased oxygen demand means less main due to ischemia of the myocardium.

Question 8. (5 marks) Indicate which of the following statements are true or false with respect to infarction: Respond to the following statements as TRUE (T), FALSE (F) OR DON’T KNOW (D) CIRCLE YOUR CHOICE

1) Is a reversible type of tissue injury T F D 2) refers to a type of tissue injury caused by a deficient supply of oxygenated blood T F D 3) is associated with extensive haemorrhage when occurring in the heart T F D 4) in some organs, may be caused by venous occlusion T F D 5) myocardial infarction leads to caseous necrosis T F D 6) removal of infarcted tissue occurs by a process termed “organisation” T F D 7) granulation tissue is produced at the site of infarction T F D

Question 9. (1.5 marks) List three (3) changes you might expect the ECG to show in the first 48 hours after a major myocardial infarct.

Elevated ST, T inversion, large Q wave Question 10 (5 marks)

(a) Report the ventricular rate and rhythm (2 marks)

Regular rhythm of approximately 60 beats per minute.

(b) Specify the approximate mean QRS axis (vector) for this patient. (1 mark)

(d) On the ECG above circle and label any Q waves (1 mark)

Question 11. (1 mark) Which three (3) leads will be most affected by an injury potential involving the inferior (diaphragmatic) wall of the left ventricle?

AvF, II, III

Question 12. (1 mark) Below is a record of the aortic pressure during a cardiac cycle. On the diagram indicate the time at which the flow through the left coronary artery is maximal. 0.5 seconds In spite of treatment by specialists in the coronary care unit the patient dies two hours after admission. Autopsy reveals atherosclerosis and thrombosis of the left circumflex artery.

Question 13. (5 marks) Components of a thrombus visible with a light microscope, may include: Respond to the following statements as TRUE (T), FALSE (F) OR DON’T KNOW (D) CIRCLE YOUR CHOICE

1. Fibrin T F D 2. Plasmin T F D 3. Platelets T F D 4. Megakaryocytes T F D 5. Red blood cells T F D 6. White blood cells T F D 7. Collagen T F D

Question 14. (8 marks) What blood plasma analytes would be most useful for you to measure, as a means of estimating the presence and severity of any myocardial damage? For each analyte that you choose, indicate the limitations to its use.

Creatine kinase- not specific for cardiac could come from skeletal. Cardiac specific troponins-Very specific last for up to 7 days Lactate d/h- not very specific Myoglobin- levels drop off rapidly

Question 15. (4 marks) Aspirin is used for prophylaxis against coronary vessel thrombosis. Explain its mechanism of action in relation to thrombosis.

Blocks COX which is required for the formation of thromboxane. Thromboxane is a pro-thrombin mediator. Therefore decreased thromboxane means decreased formation of thrombi. Since platelets don’t have a nucleus they can’t synthesize more COX there has a lasting effect for life time of platelet (20 days).

Question 16. (1 mark) From where do the coronary arteries originate?

Ascending aorta. Question 17. (2 marks) What is meant by the term 'end artery' and to what extent does it apply to the coronary arteries?

An end artery doesn’t end with another vessel the coronary artery is an example of this.

Question 18. (2 marks) Discuss the mechanism of action, and predict unwanted effects, for TPA used in an attempt to achieve reperfusion of the ischaemic zone.

Tissue plasminogen activator→activates plasminogen→plasminogen cleaves fibrin→breaks up the clot.

2001 Paper 3, Part C: Q6-9

Question 6 (3 marks) A clinician has identified a patient who does not produce any functional apolipoprotein (apo) . This patient has elevated fasting triglycerides.

(a) What triglyceride-containing particles would be found in this patient's blood when fasting? (1.5 marks)

Chylomicrons, VLDL

(b) Why are the triglycerides elevated to abnormal normal levels? Explain your reasoning.

Apolipoproteins are needed in order for the chylomicrons to be recognised by peripheral tissues, such as liver and adipose, hence their absence increases the blood concentration of chylomicrons

Question 7 (6 marks) Describe the process whereby cholesterol-rich plasma lipoproteins are taken up from the circulation into cells.

LDLS are manufactured in the liver and are lipoproteins with a high cholesterol, low protein content. On their surface are apolipoproteins specific for tissues eg. APO-B100 . Circulating LDLs attach to peripheral tissues that require cholesterol and their contents are expelled into the cell . Remnants are taken up by the liver and recycled to form more LDLs

Question 8 (5 marks) Use a flow diagram or list the steps involved in the development of an atherosclerotic plaque.

Circulating LDLS pass through damaged endothelium (tunica media) of blood vessels  oxidised by macrophages  bond to scavenger receptors on macrophages  process not able to be regulated  accumulation of LDLs  formation of foam cells  cell necrosis and release of growth/inflammatory factors  fibroblasts secrete collagen and there is overgrowth of smooth muscle  development of atherosclerotic plaque

Mrs C has a blood pressure of 165/105 and is admitted to hospital.

It is decided to reduce the risk of further strokes by reducing her blood pressure and an Angiotensin Converting Enzyme (ACE) inhibitor is prescribed.

Question 9 (5 marks) Briefly outline three (3) mechanisms of action of this class of anti-hypertensive agents

Mechanism of action of ACE inhibitors: . Cause a decrease in angiotensin II which is a potent vasoconstrictor resulting in a decrease in blood pressure . Angiotensin II also has a direct effect on Na+ reabsorption in the proximal convoluted tubule so less sodium is reabsorbed and there is an increased fluid loss resulting in a decreased blood pressure . Angiotensin II also stimulates aldosterone release causing increased Na+ exchange for K+ in the collecting duct. This increases the Na+ in plasma. When this is inhibited there is a decrease in aldosterone levels and a decrease in Na+ reabsorption

2001 Paper 3, Part E: Q6

Question 6. (3 marks) Describe the mechanism of action of the anticoagulant heparin.

Heparin bind to antithrombin III and increases its activity. ATIII inactivates thrombin as well as factors IX, X, XI, XII. This prevents thrombin from forming fibrin.

2002 Paper 2, Part A: Q1-3, 5, 6

Mr Allan B. 70 years old complains of three (3) weeks of ankle oedema and shortness of breath on exertion. He is known to have had a myocardial infarction four (4) years ago and he has since been taking aspirin 100mg daily and a β blocker (atenolol, 50mg daily). On examination, he has a pulse rate of 78/min and the rhythm is irregularly irregular. The blood pressure varies around 130/80 mm Hg. The apex beat is in the anterior axillary line in the 6th intercostal space. He has pitting ankle oedema, the Jugular Venous pressure is at 7cm (45O angle) and his liver is 15cm in span by percussion. He has scattered crackles in both lung bases. You establish that his current rhythm of atrial fibrillation is new and that he was in sinus rhythm one (1) month ago. Question 1. (5 marks) a) Complete the following table by stating whether the following features of Mr B’s presentation are normal or abnormal, and the significance of each. (4 marks)

Feature Normal / abnormal Significance Apex beat Abnormal Cardiac hypertrophy Oedema Abnormal Congestive heart failure JVP Abnormal Congestive right heart failure Crackles Abnormal Pulmonary Oedema b) What single hypothesis could explain all these features? (1 mark)

Congestive heart failure

Question 2. (5 marks) a) In the accompanying diagram (Figure 1), mark the position of the sino-atrial node.

b) What is the usual arterial blood supply to the sino-atrial node? (1 mark)

A branch from the right coronary artery c) State the ranges of pressures (in mm Hg) normally encountered in the four (4) cardiac chambers shown in Figure 1 during diastole and systole. [values may be shown directly on Fig 1] (3 marks)

RA = 2-8 RV = 20-30/2-8 LA = 2-8 LV = 120/5

Question 3. (8 marks) a) What electro-physiological events are represented by the PR interval on the electrocardiogram? The P wave indicates depolarisation of the atria It then takes time for the atrial contraction and the electrical stimulation to reach the atrioventricular node. Conduction down the purkinje fibers is the only way for conduction to go from the atria to the ventricle. The speed of conduction through the AV node dictates the length of the PR interval. The R wave is the depolarisation of the ventricle after the subsequent period of time

b) In the frontal plane, the ECG appearances of the standard leads, recorded from electrodes attached to the limbs are normally as shown in Figure 2. On the diagram, label leads I, II, III, aVR, aVL and aVF on the diagram. (3 marks)

AvL AvR

III AvF II

Question 5. (9 marks) a) Describe three (3) actions of noradrenaline on the cardiovascular system and the receptors which mediate those responses (3 marks)

An increase in the sympathetic control of the heart rate It increases the contractility of the heart Works to increase systemic venous pressure to bring more blood back to the heart b) Prazosin is a selective antagonist at alpha1-adrenoceptors. What effects would you expect on systolic blood pressure, blood glucose concentrations and circulating lipids and why? (3 marks)

There will be a decrease in blood pressure because the blood vessels relax and vasodilate. Alpha1-adrenoceptors have been shown to increase the levels of HDL and decrease total circulating lipids. There will be a decrease in blood glucose uptake by the cells because the uptake may depend upon the alpha1-adrenoceptor. c) Describe the major expected cardiac response/s following activation of the vagus nerve. (1 mark)

The vagus nerve will act on the heart to decrease heart rate by manipulating the SA node. d) What major cardiovascular response would you expect following intravenous infusion of acetylcholine? Why is this response different from vagal nerve activation?

You would expect a decrease in cardiac conduction all over the heart. This is different because the heart muscles individually will just contract more slowly whereas slowing the node only changes the speed of the node depolarisation.

Question 6. (3 marks) Figure 3 represents the normal jugular venous pulse waves a, c and v.

a) On the diagram, mark where the first (1st) and second (2nd) heart sounds will occur (S1, S2). (1 mark) b) What is the relationship between the clinically observed height of the jugular venous pressure and right atrial pressure? (1 mark)

The higher the JVP, the higher the right atrial pressure. c) In Mr A.B., what will be the effect of atrial fibrillation on his jugular venous pulse waves? (1 mark)

The atria will remain fuller from A until the V wave when the tricuspid reopens

2002 Paper 2, Part D: Q6-9

Question 6. (6 marks) She has been taking a cholesterol lowering agent for 5 years. Describe the process whereby cholesterol-rich plasma lipoproteins are taken up from the circulation into cells.

Cholesteral rich lipoproteins in LDL are derived from vldls and have B-100 surface proteins that are recognized by receptors on the cell surface most are taken up into the liver, while some goes into other cells. Once inside the cells they are broken down into building blocks for other molecules.

Question 7. (5 marks) Use a flow diagram or list the steps involved in the development of an atherosclerotic plaque. circulating LDL and an endothothelial injury - LDLs enter the tunica introma of the blood vessel - Oxidized LDL - Scavenged by macrophages that form into foam cells - Release growth factors become big cells and start to bule into artery - Causes turbulence and collagen depostion and forms plaque with fibrous cap

Mrs C has a blood pressure of 165/105 and is admitted to hospital.

Question 8. (3 marks) Henrietta was given alteplase (tissue plasminogen activator) by intravenous infusion within minutes of arrival at the hospital. What is the expected therapeutic benefit of this procedure and its mechanism?

This will activate plasminogen to plasmin that is bound in the thrombus and will break down the fibrin so that the thromus blockage will break down, this allows blood flow in again

About a week after the initial stroke, it was decided to decrease the risk of further strokes by reducing her blood pressure using a slow-release formulation of the calcium entry blocker, felodipine, in combination with hydrochlorothiazide.

Question 9. (6 marks) a) Felodipine is described as vascular-selective. What other actions within the cardiovascular system would you expect from a non-selective calcium entry blocker such as verapamil? (2 marks)

By blocking the entry of calcium, calcium channel blocker (CCBs) decrease the contraction of the heart and dilate (widen) the arteries. By dilating the arteries, CCBs reduce the pressure in the arteries. This makes it easier for the heart to pump blood, and, as a result, the heart needs less oxygen. By reducing the heart's need for oxygen, CCBs prevent or relieve angina. CCBs also are used for treating high blood pressure because of their blood pressure-lowering effects. CCBs also slow the rate at which the heart beats and are therefore used for treating certain abnormal heart rhythms such as atrial fibrillation. b) Name one (1) major adverse effect that you would expect from calcium entry blockers such as felodipine? (1 mark)

Periferal oedema / nausea / comstipation c) Describe the mechanism of action of hydrochlorothiazide in the control of blood pressure.

By blocking the action of the sympathetic nervous system on the heart, these agents relieve stress on the heart. They slow the heart beat, lessen the force with which the heart muscle contracts and reduce blood vessel contraction in the heart, brain, and throughout the body. This one is also a diuretic and works by inhibiting Na+ uptake in the distal tubule which results in a decrease in fluid levels. 2002 Paper 3, Part A: Q3, 5, 6b

Question 3. (6 marks) A clinician has identified a patient who does not produce any functional apolipoprotein E(apoE). This patient has elevated fasting triglycerides.

(a) What triglyceride-containing particles would be found in this patient's blood when fasting? (1 mark)

VLDL

(b) Why are the triglycerides elevated to abnormal levels? Explain your reasoning.

Because of the lack of apoprotein, tissues that need the triglycerides are not able to bind to the VLDLs Because of this, they are not able to extract the triglycerides and cholesterol that they need Subsequently, as the triglycerides are not going into the tissues then they are remaining in circulation, leading to elevated abnormal levels.

Question 5. (5 marks) a) Explain the mechanism by which warfarin acts as an anticoagulant. (4 marks)

It blocks the actions of Vitamin K Vitamin K is essential for activating clotting factors 2, 7, 9 and 10. If these factors cannot activate, then the clotting cascade is inhibited and coagulation will be diminished.

(b) What investigation would you request to assess the degree of anti-coagulation with warfarin? (1 mark)

A prothrombin time test.

Question 6. (12 marks) b) Beta-adrenoceptor antagonists are widely used in cardiovascular medicine. Give four cardiovascular diseases or symptoms that may be treated with an orally active betaadrenoceptor antagonist and a brief description of a possible mechanism of action which is relevant to each disease or symptom. (4 marks) Angina – reduces HR and cardiac output, increased time in diastole, thus better perfusion of coronary arteries. Arrhythmia – reduces sympathetic stimulation on SA Node, thus slows HR. Also increases refractory period between beats thus reduces arrhythmia. Headache – Prevents vascular caliber changes, some headaches caused by vasodilation or vasoconstriction of vessels in brain, beta-blockers prevent this. Hypertension – mechanism not fully understood.

2003 Paper 1: Q5

Question 5. (4 marks) Describe the Frank-Starling Law of the heart.

2003 Paper 3, Part D1

Question 1. (8 marks) List eight (8) anatomical structures of the chest from which pain may arise. (Do not list pathological processes or abnormal structures.)

Gall bladder, Liver, Heart, Great vessels, Lungs, Pleura, Diaphragm, Peritoneum, Chest wall etc., Oesophagus, Nerves, Stomach.

Question 2. (6 marks) Develop three (3) hypotheses, each involving a different organ system, which might explain Stephen’s chest pain. Specific diagnoses are not required.

Heart, Ischaemic pain due to blockage of coronary arteries. Gall bladder, pain due to cholecystitis. Pleurisy, inflammation of the lung pleura.

Question 3. (10 marks) List five (5) questions about the nature of Stephen’s pain you would ask as part of the history that would assist you in refining your hypotheses as to its cause.

When did the pain begin (onset)? What brings on the pain (provocation)? Describe the pain for me (quality)? Does the pain radiate to anywhere else (radiation)? Grade the severity of the pain on a 1 - 10 scale for me (severity). How long does the pain last (Time)? Is the pain relieved by anything (intervention)?

2003 Paper 3, Part D2

Stephen describes the pain as being behind his sternum and “gripping” in nature. This is the third time it has happened over the last few weeks. The first couple of times it occurred when he was walking the dog after dinner. On both those occasions, the pain was severe enough for him to stop walking but disappeared after he had rested for a few minutes. However, the last episode which occurred while he was playing golf the previous day was both more severe and prolonged. It also extended down his left arm and up into his jaw. Stephen does not smoke and regularly has 2-3 standard drinks per day. He works as a bus driver and is moderately overweight (BMI 28). A check-up 12 months ago revealed a BP of 140/90 and a total cholesterol of 6.6 (RR < 5.5mM), and his HDLcholesterol of 1.1 (RR 0.9 – 2.2 mM). Since then he has tried to increase his weekly exercise but he usually only manages a walk a couple of times per week and a game of golf every few weeks. There is no family history of cardiovascular disease. However, his older brother has recently been diagnosed with NIDDM.

Question 1. (10 marks) Describe the pathway by which pain arising from the heart travels to the brain and how it is referred to other parts of the body. (Name specific structures or spinal segments where appropriate).

Pain is referred to the brain via visceral afferent nerve fibres from the heart. These are sensitised by damaged tissue releasing cellular components. These afferents run with the sympathetic nervous innervation of the heart back to the dorsal root of the spinal cord. It attaches to the spinal cord levels T1 - T5. These spinal levels also receive information from the left arm and the central praecordium. The brain has a poor visceral map and, therefore, gets confused and refer's the pain to the arm and the centre of the chest. Fibres will run up to the brain from the spinal cord, enter the thalamus, and then be relayed to parts of the cerebrum.

Question 2. (10 marks) Hypertension and hypercholesterolaemia are two features identified in Stephen’s history as risk factors for cardiovascular disease. a) Provide a detailed description of the mechanism by which hypertension increases the risk of cardiovascular disease. (5 marks)

Hypertension increases the pressure on the endothelial walls. These walls will be damaged. The damaged endothelium then may be covered over by either a platelet aggregation or may uptake cholesterol and begin to form an atherosclerotic plaque. b) Provide a detailed description of the mechanism by which hypercholesterolaemia increases the risk of cardiovascular disease. (5 marks)

Increased levels of LDLs in the blood lead to increased uptake of LDLs into the tunica media of the endothelium. The LDLs are then oxidised and stored in foam cells. These foam cells form the basis of atherosclerosis formation.

Question 3. (12 marks) a) Use the attached “New Zealand Cardiovascular Risk Calculator” (at the end of this booklet) to estimate Stephen’s risk of having a cardiovascular event in the next five (5) years. Be as precise as you can be, remembering his age is 55 years. Be sure to document the steps of your calculations as you proceed. (6 marks)

Stephen is a 55 year old male, who does not smoke, has a total cholesterol : HDL cholesterol ratio of 6 : 1, and has a blood pressure of 140/90. By using these values and comparing them to the appropriate values on the Cardiovascular Risk Calculator, it can be determined that Stephen is in the 'green' risk category. This color category gives Stephen a 5 - 10% risk factor of a cardiovascular event in the next five years. b) Calculate the NNT (number needed to treat) if you were to introduce an intervention which was able to reduce Stephen’s 5 year risk by 30%. Explain (in laymans’ terms) what your result means. (6 marks)

7.5% x 0.7 = 5.25% 5 year risk ARR = 7.5 - 5.25 = 2.25 % 1/ 0.0225 = 45 patients This means that if I treated 45 patients for 5 years, I would prevent 1 MI.

On examination you find that Stephen has no visible jugular venous pulsation while lying supine at 45 degrees, he has a resting pulse rate of 100bpm, his femoral, popliteal and dorsalis pulses are palpable. Both feet are cold. There is no ankle oedema. The apex beat is in the 5th left intercostal space and mid clavicular line. He has two heart sounds and no murmurs. Breath sounds are normal. His blood pressure is 150/100.

Question 4. (10 marks) a) This is an earlier normal ECG trace for Stephen. Briefly describe the main features you would look for when interpreting this trace. (6 marks)

1. A sinus rhythm 2. A good rate 3. A clear base line 4. The QRS interval that it is <0.12 5. PR interval is <0.2 secs 6. QT interval <0.45 b) In this ECG trace, list two (2) abnormal features which would be consistent with an acute myocardial infarction. (2 marks)

T wave inversion, ST elevation, Q wave in lead 3 c) Which ECG Limb leads might you examine when you view: the inferior aspect of the heart (3 leads). the left lateral aspect of the heart (2 leads).

Inferior - II, III, AvF Left lateral - I, AvL

Stephen is diagnosed with angina pectoris and advised on lifestyle changes. He is also prescribed a beta-blocker (metoprolol; 50 mg three times a day) and glyceryl trinitrate (anginine) as required, as a transdermal patch applied once daily.

Question 5. (8 marks) How does metoprolol lead to both an increase in oxygen supply and a decrease in oxygen demand of the myocardium?

- A beta blocker works on beta receptors in the sinoatrial node & slow down heart contraction. - A slower heart allows greater time for blood to be pumped through the coronary arteries (which close when the heart is in systole). - This leads to increased oxygen supply to the myocardium. - Beta blockers slow the heart rate and therefore the work rate of the contraction of the myocardium

2003 Paper 3, Part E: Q6 Question 6. (4 marks) Describe the mechanism of action of the anticoagulant heparin.

The anticoagulant heparin acts by up regulating anti-thrombin 3. This enzyme then binds to thrombin, inactivating it. It also will bind factor Xa which will prevent prothrombin being converted to thrombin. With no thrombin, fibrinogen will not be cleaved into the insoluble fibrin and so, no clot! It is not an antifibrinolytic.

2004 Paper 1: Q7, 8

Question 7. (4 marks) One of your patients has severe mitral valve stenosis. a) What is the effect on preload and how does this affect cardiac output in this patient?

b) What are the consequences, if any, to the pulmonary circulation? (1 mark)

c) Would you usually hear this heart murmur during ventricular systole or ventricular diastole? (1 mark)

Question 8. (4 marks) One of your patients has severe aortic valve stenosis. a) What effect might this have, if any, on the left ventricle? Briefly explain your answer.

b) Why might he feel dizzy? (1 mark)

c) Would you usually hear this heart murmur during ventricular systole or ventricular diastole?

2004 Paper 3, Part F: Q6

Question 6. (18 marks) Because of Stephen’s right sided chest pain and shortness of breath, it is decided to perform an ECG: a) Name the events in the cardiac cycle that the P wave, QRS complex and T wave represent on an ECG tracing. (3 marks) P Wave – Atrial Depol QRS Complex – Atrial Repol and Ventricle Depol T Wave – Ventricle Repol b) List the components of an ECG recording that need to be considered when determining if the trace is normal. (10 marks)

1. A sinus rhythm 2. A good rate 3. A clear base line 4. The QRS interval that it is <0.12 5. PR interval is <0.2 secs 6. QT interval <0.45

2005 Paper 1, Part C: Q2-7

Question 2. (5 marks) a) In the accompanying diagram (Figure 1), mark the position of the sino-atrial node.(1 mark)

b) In the left ventricle, the pressure range (mm Hg) during systole and diastole for a normal subject is approximately : i) 120/6 ii) 160/80 iii) 120/80 iv) 25/2 v) 40/10 c) In the right ventricle, the pressure range (mm Hg) during systole and diastole for a normal subject is approximately : i) 120/6 ii) 160/80 iii) 120/80 iv) 25/2 v) 40/10

Question 3. (16 marks) a) What electro-physiological events are represented by the PR interval on the electrocardiogram? (4 marks)

The P wave indicates depolarisation of the atria It then takes time for the atrial contraction and the electrical stimulation to reach the atrioventricular node. Conduction down the purkinje fibers is the only way for conduction to go from the atria to the ventricle. The speed of conduction through the AV node dictates the length of the PR interval. The R wave is the depolarisation of the ventricle after the subsequent period of time b) In the frontal plane, the ECG appearances of the standard leads, recorded from electrodes attached to the limbs are normally as shown in Figure 2. Label the diagram, indicating which are representative of leads I, II, III, aVR, aVL and aVF on the diagram. (6 marks) AvL AvR

III AvF II c) Assuming that you have already checked the ECG calibration and patient identity, name four (4) of the main features that you would determine in the examination of an ECG.

1. A sinus rhythm 2. A good rate 3. A clear base line 4. The QRS interval that it is <0.12 5. PR interval is <0.2 secs 6. QT interval <0.45

Question 4. (8 marks) List and define the four (4) major determinants of cardiac output.

Heart Rate, After-load, preload, Ionotropic State

Question 5. (9 marks) Mr Best has been taking aspirin since he suffered a myocardial infarction four years ago. Other drugs which are also used to treat myocardial infarction are glyceryl trinitrate and tissue plasminogen activator (tPA).

For each of these three (3) drugs, describe their mechanism of action and one (1) key adverse effect.

Question 6. (6 marks) Figure 3 represents the normal jugular venous pulse waves a, c and v.

The higher the JVP, the higher the right atrial pressure. c) In Mr A.B., what will be the effect of atrial fibrillation on his jugular venous pulse waves? (1 mark)

The atria will remain fuller from A until the V wave when the tricuspid reopens

Question 7. (6 marks) a) Name four (4) risk factors for Myocardial Infarction. (4 marks)

Hypertension, Familial Hx, Hyperlipidaemia, Male

b) Other than cardiac arrhythmia and cardiac failure, name two complications of myocardial infarction.

Congestive Heart Failure, Fatigue

2005 Paper 3, Part C1

Julia, a 40 year old woman presents to your general practice complaining of chest pain over the last two days. She is new to your practice which is situated in a small town in far Western Queensland. You are the only doctor in the town and also hold a position as the medical superintendent of the local four bed hospital. The nearest major centre is 400 kilometres away by road.

Question 1. (10 marks) List five (5) pathological processes/mechanisms which could be responsible for Julia’s pain. Give one (1) clinical example of each process.

Heart – Angina Stomach – Ulcer Lung – Pneumonia Rib – Broken Muscle – Tear

Question 2. (6 marks) List six (6) characteristics of the pain you would ask Julia about.

Where it is, How bad it is, When it comes on, Relieving, Aggravating, What it feels like

Question 3. (6 marks) An ECG, performed by the practice nurse when Julia first arrived, appears below.

a) Briefly describe the main positive and negative findings on this trace. (5 marks)

Good baseline, Good rhthym, bad could be elevated ST, T inversion

b) Do these findings indicate a normal or abnormal ECG?

Normal

2005 Paper 3, Part C2

Julia describes the pain as intermittent and sharp in a band around the posterior and lateral part of left lower chest. It is triggered by movements of her upper body, particularly twisting and sidebending. With these movements it radiates into the interscapular region. It is not related to breathing or coughing. She has no associated fever, cough sputum or haemoptysis. She is otherwise well. The pain began while she was helping her husband to repair some fences on their cattle property. She had no past history of this pain. She had no history of recent trauma and no recent prolonged travel or immobilisation. Her general appearance is normal at rest but she winces with pain on moving around. She is afebrile and examination of her cardiovascular and respiratory systems is completely normal. Likewise examination of her skin, abdomen and breasts is normal. Her spinal posture is normal but she has pain and restriction with rotation and sidebending of her thoracic spine. She has marked tenderness of the midthoracic spinous processes, the left midthoracic spinal joints and muscles and along the posterior part of the left 7th rib. Palpation in these areas reproduces her pain. Xrays of her chest, ribs and thoracic spine are normal.

Question 1. (3 marks) Given the clinical information above, what is the most likely diagnosis of her pain?

Rib dislocation.

2006 Paper 1, Part B1

Stephen F, 55 years old, presents to your general practice complaining of recurrent episodes of chest pain. He is a new patient to your practice which is situated in a small town in far Western Queensland. You are the only doctor and also hold a position as the medical superintendent of the local four bed hospital. The nearest major centre is 400 kilometres away by road. Question 1. (8 marks) List eight (8) anatomical structures of the chest from which pain may arise. (Do not list pathological processes or abnormal structures.)

Gall bladder, Liver, Heart, Great vessels, Lungs, Pleura, Diaphragm, Peritoneum, Chest wall etc., Oesophagus, Nerves, Stomach.

Question 2. (6 marks) Develop three (3) hypotheses, each involving a different organ system, which might explain Stephen’s chest pain. Specific diagnoses are not required.

Heart, Ischaemic pain due to blockage of coronary arteries. Gall bladder, pain due to cholecystitis. Pleurisy, inflammation of the lung pleura. Question 3. (10 marks) List five (5) questions about the nature of Stephen’s pain you would ask as part of the history that would assist you in refining your hypotheses as to its cause.

2006 Paper 1, Part B2

Stephen describes the pain as being behind his sternum and “gripping” in nature. This is the third time it has happened over the last few weeks. The first couple of times it occurred when he was walking the dog after dinner. On both those occasions, the pain was severe enough for him to stop walking but disappeared after he had rested for a few minutes. However, the last episode which occurred while he was playing golf the previous day was both more severe and prolonged. It also extended down his left arm and up into his jaw. Stephen does not smoke and regularly has 2-3 standard drinks (beer) per day. He works as a bus driver and is moderately overweight (BMI 28). A check-up 12 months ago revealed a BP of 145/95 and a total cholesterol of 6.6 (RR < 5.5mM), and his HDL cholesterol of 1.1 (RR 0.9 – 2.2 mM). Since then he has tried to increase his weekly exercise but he usually only manages a walk a couple of times per week and a game of golf every few weeks. There is no family history of cardiovascular disease. However, his older brother has recently been diagnosed with NIDDM.

Question 1. (10 marks) Hypertension and hypercholesterolaemia are two (2) features in Stephen’s history that are known risk factors for ischaemic heart disease. a) List four (4) risk factors other than hypertension and hypercholesterolemia that Stephen has. (4 marks)

Male, Old, Sedentary, Overweight b) List four (4) possible risk factors about which there is no information in the history.

Diabetes, Atherosclerosis, Eating Pattern, Previous events c) List two (2) risk factors that the history indicates Stephen does not have. (2 marks)

Smoker, Family Hx

Question 2. (5 marks) Provide a detailed description of the mechanism by which hypertension increases the risk of cardiovascular disease, starting with its effect on afterload.

Question 3. (9 marks) a) This is an earlier recorded normal ECG trace for Stephen. Briefly describe the main features you would examine when interpreting this trace. (5 marks)

1. A sinus rhythm 2. A good rate 3. A clear base line 4. The QRS interval that it is <0.12 5. PR interval is <0.2 secs 6. QT interval <0.45 b) In this abnormal ECG trace, list two (2) features which would be consistent with an acute myocardial infarction. (2 marks)

Elevated ST, T inversion, large Q wave c) Which ECG Limb leads might you examine when you view (2 marks) 1) the inferior aspect of the heart (3 leads).

II, AvF, III

2) the left lateral aspect of the heart (2 leads).

AvL, I, V6, V5

After examination and investigations, Stephen is diagnosed with angina pectoris and advised on lifestyle changes. He is also prescribed a beta-blocker (metoprolol; 50 mg three times a day) glyceryl trinitrate, as a transdermal patch applied once daily and sublingual glyceryl trinitrate (anginine) to be used for pain if required.

Question 4. (4 marks) Explain the mechanism of action of beta-blockers like metoprolol. Consider their role in both increasing supply of oxygen to the myocardium and decreasing oxygen demand of the myocardium.