Block 2 - Cardiovascular Flashcards

Question

**Discuss the Basic Mechanism, Comments and Examples of each of the classes of Anti-Arrhythmic Agents (Vaughan Williams Classification).** * What do Class Ia agents do to the cardiac AP? * What do Class Ib agents do to the cardiac AP? * What do Class Ic agents do to the cardiac AP? * Where do Class II predominately act? * What do Class III agents do to the cardiac AP? * Where do Class IV predominately act?

Answer 1

**Atrial Fibrillation:** 1. NO discrete P WAVES!! 2. Chaotic rhythm 3. Irregular QRS 4. Narrow QRS 5. Irregularly Irregular

Answer 2

**Atrial Flutter:** 1. Look in V1 for regular waves 2. Regularly Irregular 3. Saw-tooth "F" waves 4. Narrow QRS 5. Pattern can be 2:1 or 4.1

Answer 3

**Right Bundle Branch Block on ECG** 1. QRS duration \> 0.12 seconds (3 x small squares) 2. RSR’("M") in V1 and V2 with R’ \> R 3. Slurred S wave in lead I, aVL, V5, and V6 4. Drop of Q

Answer 4

**Left Bundle Branch Block on ECG** 1. QRS duration \> 0.12 seconds (3 x small squares) 2. Broad RSR’("M") in I, aVL, V5, and V6 3. Broad, dominant, monomorphic S wave in V1 and V2 **Treat as MI until proven otherwise!**

Answer 5

**Wolff-Parkinson White Syndrome on ECG** 1. Characterised by attacks of rapid heart rate (pre-excitation syndrome) 2. ECG may not always show tachycardia 3. Short PR interval 4. A delta wave (slurring of the upstroke of the QRS complex)

Answer 6

**Supraventricular Tachycardia on ECG** 1. Narrow complex (regular) 2. No visible P waves (buried in QRS)

Answer 7

**Ventricular Tachycardia on ECG** 1. Bizarre morphology 2. Regular, wide, rapid complex tachycardia = Emergency! 3. Monomorphic (QRS complex symmetrical) or polymorphic (QRS complex not symmetrical such as with Torsades)

Answer 8

**Atrial Ectopic / Premature Atrial Contraction on ECG** 1. Extra (premature) heart beat 2. An abnormal (non-sinus) P wave is followed by a QRS complex 3. P wave typically has a different morphology and axis to the sinus P waves 4. The abnormal P wave may be hidden in the preceding T wave, producing a “peaked” or “camel hump” appearance **Frequent Ectopy Patterns:** 1. Bigeminy (normal, ectopic, normal, ectopic) 2. Trigeminy (normal, normal, ectopic) 3. Couplets (two ectopics in a row) 4. Triplets (three in a row)

Answer 9

**Ventricular Ectopic beats on ECG** 1. Extra (premature) heart beat 2. Broad QRS complex (≥ 120 ms) with abnormal morphology 3. Premature beat that occurs earlier than would be expected for the next sinus impulse 4. Usually followed by a full compensatory pause 5. Discordant ST segment and T wave changes

Answer 10

**Torsades de Pointes on ECG** 1. Characteristic “twisting” morphology 2. Like a party streamer 3. Regularly irregular * In patients with known long QT syndrome* * Emergency!*

Answer 11

**Left Ventricular Hypertrophy on ECG** 1. Larger complexes (thicker muscle) Left axis deviation 2. Deep S in V2, R in V5 3. ST depression laterally

Answer 12

**Myocardial Ischaemia on ECG** 1. ST depression (at rest ECG normalises) 2. T wave inversion

Answer 13

**Myocardial Infarction on ECG** * ST elevation (starts at J point) * ECG can be normal at start until tissue death * **STEMI:** 1. Persistent elevation \>1mm in 2 limb leads 2. Persistent elevation \> 2mm in 2 contiguous chest leads 3. New LBBB * **NSTEMI** 1. ST depression \> 0.5mm 2. T wave inversion \> 2mm * **Old Infarct (Death of Muscle)** 1. Q waves where there is no contraction (persist long term) 2. T wave inversion

Answer 14

**Pericarditis on ECG** 1. Diffuse ST elevation (diffuse pericardial inflammation) 2. Will change over days not minutes (unlike STEMI)

Answer 15

**Pacemakers on ECG** 1. Spike then LBBB pattern (RV pacing)

Answer 16

**_Anxiety Presentation:_** * **Emotional:** Excessive and persistent worry, nervousness, fatigue and restless * **Cardiac:** Palpitations, increased heart rate, dizziness, chest pain or discomfort * **Respiratory:** Shortness of breath, difficulty breathing, choking sensation, hyperventilation * **Gastrointestinal:** Abdominal churning, nausea, diarrhoea * **Temperature:** Chills, hot flushes, sweating * **Somatic:** Tremor, tension, shaking, numbness & tingling * **General:** Sense of impending doom, hyperarousal, ANS hyperactivity, weak, having t rouble concentrating and sleeping, and having the urge to avoid things (avoidance behaviour) that trigger anxiety **Relationship to Cardiac Presentation:** 1. Threat is perceived by amygdala 2. Threat is processed by hypothalamus which activates SNS 3. SNS is activated and releases adrenaline and noradrenaline which will have systemic effects

Answer 17

**Development of Atherosclerosis (RECAP):** ***Fatty Streak → Atheroma → Fibrous Plaque → Occlusion/Rupture*** 1. Endothelial injury due to irritants such as LDL, chemicals from smoking or hypertension. 2. Endothelial dysfunction resulting in increased permeability, leukocyte adhesion, monocyte adhesion and emigration. 3. LDL bind to receptor on endothelial cells surface and are internalised to under the tunica intima. 4. Monocytes follow the LDL into the endothelium and break them down via oxidation (inflammation). 5. If monocytes ingest too many LDL and cholesterol, they will die and become foam cells that remain deposited under the endothelium. 6. Monocytes secrete pro-inflammatory cytokines for the recruitment of more monocytes, which ingest more LDL and become foam cells, forming a fatty streak. 7. The fatty streak is thrombogenic, and platelets can bind to the damaged endothelium secreting platelet derived growth factor (PDGF). 8. PDGF encourages recruitment, proliferation and growth of smooth muscle cells to the tunica intima. 9. Smooth muscle cells secrete collagen, proteoglycans, elastin fibrous cells that form a fibrous cap around the fatty streak (fatty streak and fibrous cap are referred to as plaque). 10. Calcium is also deposited in the fatty streak as the fibrous cap prevents its removal by HDL. 11. Calcium crystalises and stiffens blood vessels walls. 12. Consequently, the fibrous cap can rupture and expose underlying foam cells to blood giving rise to a thrombus (blood clot). Thrombosis can lead to aneurysm, occlusion, ischemia and infarction whilst progressive plaque growth can lead to stenosis.

Answer 18

**Gross Anatomy of the Coronary Arteries:** Aorta → Aortic Sinuses → Coronary Ostio (Openings in Aorta) → Left and Right Coronary Arteries * **Right Coronary Artery:** Supplies SA node, right atrium and ventricle * **Right Posterior Descending Artery:** Supplies AV node, interventricular septum and right and left ventricles * **Right Marginal Artery:** Supplies the right ventricle and apex * **Left Coronary Artery:** Branches into left circumflex artery and LAD * **Left Anterior Descending Artery:** Supplies interventricular septum, left ventricle and some of right ventricle * **Left Circumflex Artery:** Supplies left atrium and ventricle * **Left Obtuse Marginal Artery:** Supplies left ventricle * **NB:** Both the anterior and posterior descending arteries follow the anterior/posterior interventricular groove towards the apex of the heart where they generally anastomose * **NB:** Right coronary artery and left circumflex artery travel along left/right atrioventricular grooves

Answer 19

**_MACROSCOPIC FEATURES_** * **Normal Coronary Arteries** 1. Wide lumen 2. No occluded blood flow 3. Lumen not encroached by plaques 4. Undisturbed arterial walls (no deposits, inflammation, clots or narrowing) 5. Smooth endothelial surface * **Atherosclerosis** 1. Reduced lumen size 2. Fatty streaks (flat yellow spots to elongated streaks) 3. Tunica intima thickening 4. Fibrous plaques (white-yellow and encroach on the lumen) seen on intimal surface 5. Calcium deposits (white granules) 6. Superimposed thrombus (red-brown) over ulcerated plaques 7. Patchy eccentric lesions (not circumferential)

Answer 20

**_MICROSCOPIC FEATURES/HISTOLOGY_** * **Normal Coronary Arteries** 1. Normal tunica intima (layer of flattened endothelial cells) 2. Normal tunica media (bulk middle layer of smooth muscle cells and elastin) 3. Normal adventitia (thin outer layer of connective tissue) * **Atherosclerosis** 1. Superficial fibrous cap composed of smooth muscle cells and dense collagen and elastin 2. Beneath cap is infiltration of macrophages, T cells, and smooth muscle cells 3. Deep to cap is necrotic core with cholesterol, (lipid), dead cell debris, foam cells and fibrin

Answer 21

**Types of Disease:** 1. Congenital Disease 2. Acquired Disease (Traumatic, Inflammatory, Degenerative and Neoplastic)

Answer 22

**Myocardial Diseases:** 1. **Myocarditis (Inflammatory)** 1. Infective Myocarditis 2. Immune Myocarditis 3. Idiopathic Myocarditis 2. **Cardiomyopathy (Degenerative)** 1. Dilated Cardiomyopathy 2. Hypertrophic Cardiomyopathy 3. Restrictive Cardiomyopathy 4. Secondary Cardiomyopathy **Pericardial Diseases:** 1. Pericarditis 2. Cardiac Tamponade **Neoplasms** 1. Atrial Myxoma 2. Rhabdomyoma 3. Angiosarcoma 4. Metastases

Answer 23

**Myocardial Diseases:** **Myocarditis (Inflammatory):** Primary inflammation of the myocardium, pathologically seen as myocyte necrosis and inflammatory cell infiltration. * **Infective Myocarditis:** Viruses most common causes (e.g. Coxsackie A and B, ECHO, Influenza, HIV and CMV), but can be caused by bacteria (Chlamydia, Rickettsia, Meningococcus, Diphtheria and Borrelia), fungi (candida), helminths (Trichinella) or protozoa (Chaga's disease and Toxoplasmosis). * **Immune Myocarditis**: Can occur post-viral or post-bacterial infection through cross-reactivity and development of an autoimmune condition. Also due to systemic immune disease (SLE, rheumatic fever or polymyositis), drug hypersensitivity (antibiotics, diuretics, antihypertensives) and transplant rejection. * **Idiopathic Myocarditis:** Due to sarcoidosis and giant cell myocarditis

Answer 24

**Cardiomyopathy (Degenerative):** A disorder in which the heart muscle is structurally (wall thickness and chamber size) and functionally (mechanical and electrical) abnormal. Primary myopathy can be genetic, whilst secondary myopathy is due to many causes including toxins, metabolic, drugs, infiltrates, depositions, neuromuscular. 1. **Dilated Cardiomyopathy:** Dilation and impaired contraction of one or both ventricles (dilation can result in increased mass and eccentric hypertrophy). Common causes are viral myocarditis (Coxsackie virus) and genetics, but can also occur with drugs, alcohol and pregnancy 2. **Hypertrophic Cardiomyopathy:** Increased ventricular wall thickness or mass not caused by pathologic loading conditions. Common causes are athletics and intense endurance training and genetics (mutations in genes coding for sarcomere proteins) 3. **Restrictive Cardiomyopathy:** Nondilated ventricles with increased ventriuclar stiffness and impaired ventricular diastolic filling. Can occur idiopathically or due to amyloid, radiation fibrosis, sarcoidosis and metastatic tumours. 4. **Secondary Cardiomyopathy**: Caused by cardiotoxic drugs, catecholamine excess, iron overload and thyroid disease

Answer 25

**Figure 12.30** Causes and consequences of dilated and hypertrophic cardiomyopathy. Some dilated cardiomyopathies and virtually all hypertrophic cardiomyopathies are genetic in origin. The genetic causes of dilated cardiomyopathy involve mutations in any of a wide range of genes. They encode proteins predominantly of the cytoskeleton, but also the sarcomere, mitochondria, and nuclear envelope. In contrast, all of the mutated genes that cause hypertrophic cardiomyopathy encode proteins of the sarcomere. Although these two forms of cardiomyopathy differ greatly in subcellular basis and morphologic phenotypes, they share a common set of clinical complications. *LV,* left ventricle.

Answer 26

**Pericardial Diseases:** **Pericarditis:** Inflammation of the pericardium classified according to the composition of the fluid that accumulates around the heart (serous, fibrinous, purulent or haemorrhagic). Caused commonly by viral infection, but can also be due to bacterial infection, autoimmune conditions, post-MI, chest trauma, cancer or idiopathic. **Cardiac Tamponade:** Compression of the heart caused by fluid collecting in the sac surrounding the heart (pericardial cavity). Caused by pericarditis, chest trauma, complications of cardiac surgery, cancer, kidney failure, connective tissues diseases, hypothyroidism and aortic ruptures.

Answer 27

**Neoplasms of the Heart:** **Atrial Myxoma:** Rare heart disorder in which a rare tumour grows in the left heart chamber **Rhabdomyoma:** Benign tumour of striated muscle **Angiosarcoma:** Rare type of cancer that forms in the lining of the blood vessels and lymph vessels **Metastases:** More common than primary cardiac tumours. Pericardial are most common, followed by epicardial and myocardial metastases. Can manifest as a lung mass or mediastinal mass with direct invasion of the adjacent heart, as a central mass extending into the left atrium via the pulmonary veins, as pericardial effusion and nodularity, or as myocardial nodules.

Answer 28

**Definition of IHD:** Disturbance in myocardial O2 supply and demand **Decreased Supply:** Due to mechanical obstruction (atheroma, thrombosis, spasm, stenosis), or decreased flow of oxygenated blood to myocardium such as with anaemia, hypoxia, hypotension, tachycardia (shortened diastole) and carboxyhaemoglobulinaemia (carbon monoxide poisoning) **Increased Demand:** Due to increased cardiac output such as with hyperthyroidism or thyrotoxicosis, or myocardial hypertrophy such as from aortic stenosis or hypertension.

Answer 29

**Clinical Features of IHD** 1. Chest Pain (Central) → Pain/Tightness/Pressure/Discomfort, Radiation to Jaw/Shoulder/Neck, On exertion (SA) or at rest (USA) 2. Dyspnoea/Shortness of Breath 3. Reduced Exercise Tolerance 4. Sense of Impending Doom 5. Palpitations 6. Sweating

Answer 30

**Complications of IHD:** * Stable Angina * Unstable Angina * Acute Myocardial Infarction (STEMI/NSTEMI) * Mortality * **Day 1-3 Post MI:** 1. Cardiac Dysrhythmia 2. Pericarditis (Early) or Dressler’s Syndrome (Delayed) 3. AV Block 4. Cardiogenic Shock * **Day 3-5 Post-MI:** 1. Ventricular Free Wall Rupture 2. Ventricular Septal Rupture 3. Papillary Muscle Rupture 4. Acute Mitral/Tricuspid Regurgitation 5. Ventricular Pseudoaneurysm * **Day 5-10 Post-MI:** 1. Ventricular Mural Thrombus 2. Atrial Thrombus 3. DVT and Pulmonary Embolism * **Day 10 + Post-MI:** 1. Congestive Heart Failure 2. Ventricular Aneurysm (VF or VT)

Answer 31

**_Management of Stable Angina_** **General:** 1. Treat underlying conditions (i.e. anaemia or hyperthyroidism) 2. Manage co-morbidities (i.e. diabetes or hypertension) 3. Evaluate risk factors and reduce risk where possible 4. Symptomatic treatment should be started with the vasodilator sublingual or buccal nitrate to relieve acute episodes of stable angina **Specifics** 1. **Nitrates:** For coronary vasodilation 2. **β-Blockers and/or Ca2+ Channel Blockers:** To prevent acute episodes 3. **Statins:** To reduce cholesterol 4. **Aspirin:** Anti-platelet 5. **ACE Inhibitor:** To treat other conditions (i.e. hypertension, heart failure, chronic kidney disease)

Answer 32

**_Management for Acute Coronary Syndrome_** **General:** 1. *Same as with Angina* 2. **High-Risk Patients:** Require urgent coronary angiography and intervention 3. **Low-Risk Patients:** Managed with oral aspirin, clopidogrel, beta-blockers and nitrates **Specifics** 1. **Analgesic:** Such as morphine for pain management 2. **Oxygen:** For hypoxia, as needed 3. **Nitrates:** For coronary vasodilation 4. **Anti-Platelet Agents:** Such as aspirin and clopidogrel to reduce risk of MI or death 5. **Antithrombins:** Such as heparin to reduce risk of MI or death 6. **β-Blockers:** To reduce myocardial ischaemia by blocking circulating catecholamines, reducing HR and BP, reducing myocardial oxygen consumption 7. **Plaque Stabilisation Agents:** HMG-CoA reductase inhibitor drugs (statins) and ACE inhibitors are routinely administered to produce plaque stabilization, improve vascular and myocardial remodelling, and reduce future cardiovascular events **Revascularisation:** 1. Percutaneous Coronary Intervention (PCI) 2. Coronary Artery Bypass Grafting (CABG)

Answer 33

**ECG Features of Myocardial Ischaemia:** 1. ST depression (at rest ECG normalises) 2. T wave inversion

Answer 34

**ECG Features of Myocardial Infarction** * ST elevation (starts at J point) * ECG can be normal at start until tissue death * **STEMI:** 1. Persistent elevation \>1mm in 2 limb leads 2. Persistent elevation \>2mm in 2 contiguous chest leads 3. New LBBB * **NSTEMI** 1. ST depression \> 0.5mm 2. T wave inversion \> 2mm * **Old Infarct (Death of Muscle)** 1. Pathological Q waves where there is no contraction (persist long term) 2. T wave inversion (can correct long-term)

Answer 35

**ECG Features of Myocardial Infarction** * ST elevation (starts at J point) * ECG can be normal at start until tissue death * **STEMI:** 1. Persistent elevation \>1mm in 2 limb leads 2. Persistent elevation \>2mm in 2 contiguous chest leads 3. New LBBB * **NSTEMI** 1. ST depression \> 0.5mm 2. T wave inversion \> 2mm * **Old Infarct (Death of Muscle)** 1. Pathological Q waves where there is no contraction (persist long term) 2. T wave inversion (can correct long-term)

Answer 36

**Cardiac Ultrasound Features of Myocardial Ischaemia:** 1. Abnormal wall motion due to damaged/dead tissue 2. Decrease in myocardial thickening due to damage and necrosis 3. Decrease in valve movements of heart due to damage 4. May have abnormal wall thickness or chamber size due to underlying hypertrophy 5. May have reduced ejection fraction due to damage to heart muscle 6. May have altered diastolic or systolic motion 7. Perhaps post-complications such as thrombus, valve disease, aneurysm or rupture

Answer 37

**Dyspnoea:** Sensation of difficult or uncomfortable breathing (subjective experience perceived by the patient) **Orthopnoea:** Dyspnoea that develops when a patient is supine, occurs because in an upright position the patient’s interstitial oedema is redistributed **Paroxysmal Nocturnal Dyspnoea:** Severe dyspnoea that wakes the patient from sleep so that he or she is forced to get up gasping for breath. This occurs because of a sudden failure of LV output with an acute rise in pulmonary venous and capillary pressures which leads to transudation of fluid into the interstitial tissues, increasing the work of breathing

Answer 38

**Heart Failure with Reduced Ejection Fraction (HFrEF):** Pump dysfunction (systolic HF) * **Dysfunction**: Inadequate emptying of ventricles during systole resulting in decreased EF ( ≤ 40) * **Causes**: 1. Decreased contractility/force of contraction due to myocardial infarction or myocarditis 2. Decreased blood supply to the heart due to coronary artery disease 3. Increased afterload due to hypertension 4. Impaired mechanical function due to valve disease **Heart Failure with Preserved Ejection Fraction (HFpEF):** Filling dysfunction (diastolic HF) * **Dysfunction**: Inadequate relaxation and filling of ventricles during diastole, leading to decreased EDV and SV and resulting in preserved EF ( ≥ 50) * **Causes**: 1. Restrictive cardiomyopathy e.g. amyloidosis or sarcoidosis) 2. Valve disease 3. Hypertension

Answer 39

**Left Sided Heart Failure Pathophysiology:** ***Overall:** Decreased LV contractility or EDV → Decreases SV → Decreases CO → Not enough blood is pumped into systemic circulation to meed body's demands → Blood backs up into lungs → Pulmonary congestion/oedema → Pulmonary hypertension* **Systolic Dysfunction:** LV can't pump well so EF decreased (many different causes) 1. **Dilated Cardiomyopathies** 2. **Mitral/Aortic Regurgitation** 3. **Myocardial Infarction** 4. **Severe Hypertension/Advanced Aortic Stenosis**

Answer 40

***LEFT SIDED HEART FAILURE - SYSTOLIC DYSFUNCTION*** **Dilated Cardiomyopathies:** Progressive dilation of LV via eccentric hypertrophy → Increased EDV → Increased contractility at first (Frank Starling Law) → Eventual weakening and thinning → Decreased LV contractility

Answer 41

***LEFT SIDED HEART FAILURE - SYSTOLIC DYSFUNCTION*** **Mitral/Aortic Regurgitation:** Chronic LV volume overload → Progressive dilation of LV via eccentric hypertrophy → Increased EDV → Increased contractility at first (Frank Starling Law) → Eventual weakening and thinning → Decreased LV contractility

Answer 42

***LEFT SIDED HEART FAILURE - SYSTOLIC DYSFUNCTION*** ## Footnote **Myocardial Infarction:** Necrotic non-functional myocytes (non-conductive, non-contractile) → Decreased LV contractility

Answer 43

***LEFT SIDED HEART FAILURE - SYSTOLIC DYSFUNCTION*** **Advanced Aortic Stenosis:** Increased TPR → Increased LV afterload → Chronic LV pressure overload → Concentric LV hypertrophy → Increased O2 demand BUT squeezed coronary arteries and reduced supply → Decreased LV contractility

Answer 44

**Left Sided Heart Failure Pathophysiology:** **Diastolic Dysfunction:** LV can't fill well so EF preserved (many different causes) 1. **Cardiac Tamponade/Myocardial Ischemia/Hypertrophic Cardiomyopathy:** Decreased LV relaxation and/or diastolic filling → Decreased EDV 2. **Myocardial Fibrosis/Restrictive Cardiomyopathy/Hypertrophic Cardiomyopathy:** Increased LV wall stiffness → Reduction in LV compliance -\> Decreased EDV

Answer 45

**Severe Hypertension:** Increased TPR → Increased LV afterload → Chronic LV pressure overload → Concentric LV hypertrophy → Increased O2 demand BUT squeezed coronary arteries and reduced supply → Decreased LV contractility

Answer 46

***LEFT SIDED HEART FAILURE - DIASTOLIC DYSFUNCTION*** **Cardiac Tamponade/Myocardial Ischemia/Hypertrophic Cardiomyopathy:** Decreased LV relaxation and/or diastolic filling → Decreased EDV

Answer 47

***LEFT SIDED HEART FAILURE - DIASTOLIC DYSFUNCTION*** **Myocardial Fibrosis/Restrictive Cardiomyopathy/Hypertrophic Cardiomyopathy:** Increased LV wall stiffness → Reduction in LV compliance → Decreased EDV

Answer 48

**Right Sided Heart Failure Pathophysiology:** **Overall:** Decreased RV contractility → Decreases SV → Decreases RV CO → Increased RA pressure → Blood backs up into systemic venous vasculature (elevated JVP) → Hydrostatic pressure and bulk flow pushes fluid out of capillaries into systemic tissues (pitting oedema) and congestion of fluid in liver and spleen (hepatosplenomegaly). RV also still needs to pump against high afterload → RV pressure overload → Concentric RV hypertrophy → Further decrease of pumping ability **NB:** *Cor Pulmonale* is RV hypertrophy, dilation, and/or dysfunction due to pulmonary hypertension secondary to pulmonary disease (COPD, pulmonary fibrosis, upper airway obstruction, obstructive sleep apnoea, obesity-hypoventilation syndrome or chest wall irregularities such as kyphoscoliosis)

Answer 49

**_Right Sided Heart Failure Pathophysiology:_** * **Cardiac Disease (Systolic HF)** 1. Dilated Cardiomyopathies 2. Tricuspid Regurgitation 3. Myocardial Infarction 4. Pulmonic Valve Stenosis * **Diseases of Lung Parenchyma:** Results in *Cor Pulmonale* HF 1. COPD 2. Interstitial Lung Disease 3. Chronic Infection * **Diseases of Pulmonary Vasculature:** Results in *Cor Pulmonale* HF 1. Embolism 2. Pulmonary Hypertension

Answer 50

***RIGHT SIDED HEART FAILURE*** ## Footnote **Dilated Cardiomyopathies:** Progressive dilation of RV via eccentric hypertrophy → Increased EDV → Increased contractility at first (Frank Starling Law) -\> Eventual weakening and thinning → Decreased RV contractility

Answer 51

***RIGHT SIDED HEART FAILURE*** **Tricuspid Regurgitation:** Chronic RV volume overload → Progressive dilation of RV via eccentric hypertrophy → Increased EDV → Increased contractility at first (Frank Starling Law) → Eventual weakening and thinning → Decreased RV contractility

Answer 52

***RIGHT SIDED HEART FAILURE*** ## Footnote - **Myocardial Infarction:** Non-functional myocytes → Decreased RV contractility - **Pulmonic Valve Stenosis:** Increased TPR → Increased RV afterload → Chronic RV pressure overload → Concentric RV hypertrophy → Decreased RV contractility - **Left Heart Failure:** Pulmonary hypertension → Chronic increased RV afterload → Chronic RV pressure overload → Concentric RV hypertrophy → Decreased RV contractility

Answer 53

***RIGHT SIDED HEART FAILURE*** **Diseases of Lung Parenchyma:** Results in *Cor Pulmonale* HF **COPD, Interstitial Lung Disease, Chronic Infection:** Pulmonary vasoconstriction → Increased pulmonary hypertension → Chronic increased RV afterload → Concentric RV hypertrophy → Decreased RV contractility

Answer 54

***RIGHT SIDED HEART FAILURE*** **Diseases of Pulmonary Vasculature:** Results in *Cor Pulmonale* HF **Embolism or Pulmonary Hypertension**: Chronic increased RV afterload → Concentric RV hypertrophy → Decreased RV contractility

Answer 55

**Biventricular Heart Failure:** Heart failure in which both the LV and RV are affected (usually due to LV failure) resulting in backward and forward heart failure

Answer 56

**_Clinical Signs and Symptoms of Heart Failure_** * **Both** 1. Diaphoresis, Tachycardia, Tachypnoea (Compensatory SNS Stimulation due to reduced CO) 2. Cool Clammy Peripheries (Reduced CO and Peripheral Vasoconstriction) 3. Dyspnoea (Exertional and/or Rest) and Reduced Exercise Tolerance 4. Fatigue * **Left Sided Heart Failure** 1. Pulmonary Oedema 2. Orthopnoea and Paroxysmal Nocturnal Dyspnoea 3. Bilateral Basal Lung Crackles (Pulmonary Oedema) 4. Pink (Whitish) Frothy Sputum and Cough 5. Lung Congestion and Pleural Effusion (Dullness to Percussion) 6. Confusion (Poor Perfusion to Brain) 7. Syncope and Presyncope 8. Nocturia (Increased Fluid Retention due to RAAS) * **Right Sided Heart Failure** 1. Peripheral Oedema 2. Elevated JVP 3. Pitting Oedema (Ankles/Sacrum) 4. Ascites and Abdominal Bloating (Dullness to Percussion) 5. Hepatosplenomegaly and RUQ 6. Discomfort 7. Weight Gain (Fluid Retention)

Answer 57

**Complications of Left Sided Heart Failure** 1. Arrhythmias 2. Pulmonary Oedema 3. Pulmonary Hemorrhage (Congested Capillaries Burst) 4. Pleural Effusion 5. Renal Insufficiency (Reduced Perfusion) **Complications of Left Sided Heart Failure** 1. Arrhythmias 2. Eventual Failure of Left Heart Tricuspid Regurgitation 3. Peripheral Oedema 4. Congestive Hepatopathy 5. Cardiac Cirrhosis and Liver Failure Cardiac Cachexia

Answer 58

**Features of Left Heart Failure on CXR** 1. Cardiomegaly 2. Cephalization 3. Perihilar Haze 4. Peribronchial cuffing 5. Kerley-B lines 6. Opacified/White Interlobular fissures 7. Pleural effusion 8. Air bronchogram 9. Widespread airspace opacificity

Answer 59

**Clinical Approach to Fever of Unknown Origin:** Think infection, autoimmune, inflammation or neoplasm * **Bacteraemia:** The transient presence of bacteria in the blood (usually asymptomatic) caused by local infection or trauma * **Clinical Features:** 1. Fever, chills 2. Rigors 3. Anorexia 4. Tiredness/Lethargy 5. Delirium (elderly) * **Clinical Approach** 1. History 2. Examination 3. Investigation 4. Differentials List

Answer 60

**Pyrexia of Unknown Origin:** A fever of 38.3°C or greater for at least 3 weeks with no identified cause after three days of hospital evaluation or three outpatient visits, commonly due to infections, neoplasms or connective tissue disorders. **Bacteraemia:** The transient presence of bacteria in the blood (usually asymptomatic) caused by local infection, wounds or trauma, which can lead to infection, sepsis or both. **Septicaemia/Blood Posioning:** The presence and multiplication of bacteria in the blood caused by spread of infections throughout the body, including the lungs, abdomen, and urinary tract, which can quickly progress to sepsis. **Sepsis:** Term used to describe the signs and symptoms of a systemic inflammatory response syndrome (SIRS) to a localised primary site of infection. **Severe Sepsis:** The presence of the sepsis syndrome (presence of either a positive blood culture or clinical features of fever, tachypnoea, tachycardia, suspected infection), complicated by organ dysfunction, hypotension or hypoperfusion and manifested by low blood pressure, oliguria, hypoxia, acute confusion and lactic acidosis. **Septic Shock:** Defined as the sepsis syndrome plus organ dysfunction and hypotension unresponsive to adequate fluid replacement.

Answer 61

**Mechanisms of Antibiotic Resistance:** * **1) Prevent Entry of the Antibiotic** 1. Lack of entry transporter 2. Decreased membrane permeability 3. Efflux pumps (i.e. PmrA in *S. pneumonia,* NorA in *S. aureus,* ArcB in *E.coli* and MexB in *P.aeruginosa*) 4. Porin channel reduction * **2) Destroy the Antibiotic** 1. Enzymatic inhibition or degradation (i.e. penicillinases produced by *S.aureus*) 2. B-lactamases (intrinsic in anaerobes and common in gram-negatives and ESBLs) 3. AmpC cephalosporinase (inducible with antibiotic use) * **3) Change the Structure of the Antibiotic Target** 1. Point mutations (ribosomal subunits or DNA changes) 2. Change surface proteins/antigens (i.e. *S. pneumonia* lowers affinity of PBPs to Penicillin G) 3. Plasmid mediated resistance genes (i.e. Van A gene in VRE/VRSA, TEM gene in gram negative rod that creates an enzyme that hydrolyses penicillins, Mec A gene in MRSA for resistance to B-lactams) 4. Alter target site on ribosome to prevent antibiotic from binding (i.e. *S. pneumoniae* causes erythhromycin ribosomal methylase) * **3) Overproduce the Target** 1. FolA gene and overproduction of DHFR and DHPS to become resistant to co-trimoxazole 2. Overproduction of PBPs

Answer 62

**Mechanisms of** ***Staphylococci Spp.*** **Resistance:** Acquired via plasmid transfer via bacterial conjugation (horizontal gene transfer) or spontaneous gene mutation and positive selection.

Answer 63

**Types of Valves:** 1. **Semilunar Valves (Pulmonary and Aortic):** Three semilunar cusps of dense connective tissue covered by endothelium with no chordae tendineae 2. **Atrioventricular Valves (Tricuspid and Mitral):** Triangular-shaped cusps of dense connective tissue covered by endothelium with chordae tendineae attached to free edges - **Chordae Tendineae:** Attach to cusps of the right tricuspid valve and the left mitral valve to prevent them going back into the atrium - **Papillary Muscles:** Pulls on chordae when ventricle contracts to assist

Answer 64

**Anatomy of Heart Valves:** **Tricuspid Valve (Right Atrium → Ventricle):** * Three thin leaflets (anterior, posterior and septal) built for low pressure * Multiple chordae and 3-5 papillary muscles (less arranged than the mitral valve) * Septal attachments * AV junction on medial side of tricuspid annulus near septum * Prone to regurgitation from annular and RV dilatation * Surrounded by the RCA * More apically oriented (towards apex) than mitral on ECHO

Answer 65

**Pulmonary Valve (Right Ventricle → Pulmonary Trunk):** * Three leaflets (right, left and anterior cusps) * No coronary arteries * Pulmonary stenosis and/or regurgitation usually congenital

Answer 66

**Mitral/Bicuspid Valve (Left Atrium → Ventricle):** * Two leaflets (anterior and posterior) * Two papillary muscles (medial and lateral) * No septal attachments * Anterior leaflet has as one scallop * Posterior leaflet has three scallops (P1, P2, P3 with P1 lateral) * Looks like smiley face when open * Double kick action for passive flow, diastasis and atrial contraction * Medial to the mitral valve is the cardiac crux, the right heart and the conducting system * Posterior to the mitral valve is the annulus and pericardial space

Answer 67

**Aortic Valve (Left Ventricle → Aorta):** * Three leaflets (right coronary, left coronary and non-coronary cusps) * Two coronary arteries in the aortic sinuses * Looks like Mercedes sign when closed * “Crescendo-decrescendo” blood flow as it increases to peak systole than decreases * Anterior to the annulus is the right ventricle (best seen on ECHO) * Medial is the right atrium, posterior is the left atrium/mitral valve and lateral is left atrium

Answer 68

**Auscultation of Valves:** **Aortic Valve Auscultation Point:** Right 2nd intercostal space right parasternal edge **Pulmonary Valve Auscultation Point:** Left 2nd intercostal space next to sternum **Tricuspid Valve Auscultation Point:** Left 4th or 5th intercostal space next to sternum **Mitral Valve Auscultation Point:** Left 5th intercostal space at midclavicular line

Answer 69

**Basic Causes of Valvular Pathology:** 1. **Congenital:** Valvular abnormalities 2. **Traumatic:** Valve rupture 3. **Infective:** Infective endocarditis 4. **Immune:** Valvular disease 5. **Degenerative:** Age-related changes

Answer 70

**_Valvular Heart Disease - Mitral Regurgitation_** * **Pathophysiological Effects:** Increased LV EDV → Backflow of Blood from LV → Increased LA Volume → LV and LA Dilation → LV Dysfunction → Reduced CO → CHF and Pulmonary HTN → RV Failure * *NB: Volume dilates first and then hypertrophies later due to increased filling pressure* * ***Clinical Signs and Symptoms*** 1. *Can be present for many years before symptoms appear* 2. Signs of pulmonary oedema 3. Signs of peripheral oedema 4. Palpitations (AF and Increased SV) 5. Fatigue, lethargy, syncope and presyncope (reduced CO) 6. Displaced apex 7. Pansystolic murmur at apex to axillar 8. Apical systolic thrill

Answer 71

**_Causes of Mitral Regurgitation_** 1. **Valve Degeneration:** Calcification\*, rheumatic\*\*, endocarditis or connective tissue disorders 2. **Dilated Fibrous Ring:** Marfan's or LVF 3. **Fixed Fibrous Ring:** Calcification 4. **Leaflet Retraction:** Carcinoid syndrome or rheumatic disease 5. **Leaflet Perforation:** Infective endocarditis or surgery 6. **Leaflet Prolapse:** Mitral valve prolapse (MVP) 7. **Long Chordae Tendinae:** MVP Syndrome 8. **Short Chordae Tendinae:** Rheumatic or post-MI displacement and leaflet tethering 9. **Ruptured Chordae Tendinae:** Downward vegetation growth 10. **Ischaemic/Ruptured/Fibrotic Papillary Muscles:** MI and post-MI 11. **Ventricular Abnormalities:** Dilated cardiomyopathy or post-MI necrosis and fibrosis

Answer 72

**Mitral Stenosis** → Rheumatic Heart Disease **Mitral Prolapse →** MVP/Barlow's/Floppy Valve Syndrome: Connective tissue disorder causing weakened connective tissue of mitral valve, leads to translucent billowing parachute-like leaflets and lengthening and thinning of chordae tendinae **Aortic** **Stenosis** → Congenital**:** Bicuspid or unicuspid valve & **Valve** Degeneration**:** Calcification (old age) or rheumatic

Answer 73

**_Causes of Aortic Regurgitation_** 1. **Congenital:** Quadricuspid, bicuspid or prolapsed valve 2. **Valve Degeneration:** Calcification, endocarditis, rheumatic or trauma 3. **Cusp Perforation:** Infective endocarditis and trauma (chest blow) 4. **Cusp Retraction:** Rheumatic valvular disease, carcinoid valvular disease, syphilis and bicuspid aortic stenosis with prolapse of smaller cusp under bigger one 5. **Aortic Root Dilation:** Aortic aneurysm, syphilis, rheumatic arthritis, ankylosing spondylitis, giant cell aortitis, Reiter's syndrome 6. **Aortic Wall Weakening:** Marfan's syndrome, idiopathic and Osteogenic Imperfecta

Answer 74

* **Tricuspid Stenosis and Regurgitation** 1. Congenital 2. Valve Degeneration: Rheumatic or infective endocarditis from IV drug use * **Pulmonary Stenosis and Regurgitation** 1. Congenital * **\* Calcification normally occurs at the age of 75 or greater, but bicuspid aortic valve can calcify in children \*\* Rheumatic disease usually results in fusion of cusps resulting in small rigid opening*** * **NB: Diagnosis of valvular disease is through clinical assessment, ECHO and angiography***

Answer 75

**Pathophysiology of Rheumatic Fever and Heart Disease:** 1. Exposure to Group A streptococcal bacteria (i.e. *S. pyogenes*). 2. Infection with Group A streptococcal bacteria (presents as pharyngitis and sore throat or skin sores). 3. Host immune system develops delayed autoimmune reaction triggered by molecular mimicry and antigen cross-reactivity between the cell wall M proteins of the infecting *S. pyogenes* and cardiac myosin and laminin 4. Activation of auto-reactive lymphocytes 5. Tissue injury and inflammation, valvular injury and neuronal cell surface targeting leading to cell signalling and dopamine release (Sydenham's chorea) 6. Acute Rheumatic Fever (joint swelling and pain (migratory polyarthritis), carditis (myocardial Aschoff body), fever, heart problems, chorea (jerky movements), erythema marginatum (skin rash) and subcutaneous painless nodules on elbows, wrists, knees, ankles and near spine) 7. Recurrent infection and acute rheumatic fever 8. Chronic permanent damage to one or more heart valves (stretched and/or scarred) that remains after the episodes of acute rheumatic fever is resolved 9. Rheumatic Heart Disease that presents with mitral leaflet thickening, commissural fusion and shortening and thickening and fusion of chordae and papillary muscles 10. Complication of rheumatic heart disease such as valvular disease, heart failure, arrythmias (AF), stroke, endocarditis and pregnancy complications.

Answer 76

**_Valvular Heart Disease - Mitral Stenosis_** * **Pathophysiological Effects:** Obstruction to LV → Increased LA Pressure (Protected LV) → LA Dilatation → Increased Pulmonary Vascular Resistance → Pulmonary HTN and RV Failure → Eventual LV Decreased EDV → Reduced CO and CHF * **Clinical Signs & Symptoms** 1. *No symptoms until the valve is moderately stenosed* 2. Signs of pulmonary oedema 3. Signs of peripheral oedema 4. Palpitations (AF) 5. RV heave 6. Opening snap and loud S1 sound Mid-diastolic rumble at apex 7. Mitral facies (rosy cheeks/blue tongue)

Answer 77

**_Valvular Heart Disease - Aortic Regurgitation_** * **Pathophysiological Effects:** Backflow of Blood from Aorta → Increased LV Volume → LV Dilation → LV Dysfunction → Reduced CO * **Clinical Signs & Symptoms** 1. *Significant symptoms occur late and do not develop until LV failure* 2. Signs of pulmonary oedema Syncope and angina (reduced CO) Palpitations (increased LV size) 3. Displaced apex 4. Collapsing pulse 5. Wide pulse pressure 6. Decrescendo early-diastolic murmur

Answer 78

**_Valvular Heart Disease - Aortic Stenosis_** * **Pathophysiological Effects:** Outflow Obstruction → Increased LV Afterload → Increased LV Pressure → LV Hypertrophy → LV Dysfunction → Reduced CO → LV Failure → Pulmonary HTN and RV Failure * **Clinical Signs & Symptoms** 1. *No symptoms until aortic stenosis is moderately severe* 2. Exercise-induced syncope, angina, dyspnoea (muscle outgrows oxygen supply) 3. Signs of pulmonary oedema 4. Signs of peripheral oedema 5. Systolic thrill 6. Systolic ejection click 7. Mid-systolic crescendo-decrescendo murmur radiating to carotids

Answer 79

**_Valvular Heart Disease - Tricuspid Regurgitation_** * **Pathophysiological Effects:** Backflow of Blood from RV → Increased RA Volume → RV and RA Dilation → RV Dysfunction → Systemic Venous Congestion * **Clinical Signs & Symptoms** 1. *Signs of peripheral oedema* 2. *Palpitations (AF)* 3. *A blowing pansystolic murmur, best heard on inspiration at the lower left sternal edge*

Answer 80

**_Valvular Heart Disease - Tricuspid Stenosis_** * **Pathophysiological Effects:** Obstruction to RV → Increased RA Pressure → RA Hypertrophy → Systemic Venous Congestion → Eventual Heart Failure and Reduced CO * **Clinical Signs & Symptoms** 1. Signs of peripheral oedema 2. Pre-systolic pulsation felt over liver 3. A rumbling mid-diastolic murmur heard best at the lower left sternal edge and is louder on inspiration

Answer 81

**_Valvular Heart Disease - Pulomary Regurgitation_** * **Pathophysiological Effects:** Backflow of Blood from Pulmonary Trunk → Increased RV Volume → RV Dilation → RV Dysfunction → Systemic Venous Congestion * **Clinical Signs & Symptoms** 1. *Usually causes no symptoms* 2. A decrescendo early-diastolic murmur, beginning with the pulmonary component of the second sound that is difficult to distinguish from the murmur of aortic regurgitation

Answer 82

**_Valvular Heart Disease - Pulmonary Stenosis_** * **Pathophysiological Effects:** Outflow Obstruction → Increased RV Afterload → Increased RV Pressure → RV Hypertrophy → RV Dysfunction → RV Failure → Systemic Venous Congestion and Heart Failure * **Clinical Signs & Symptoms** 1. *Severe pulmonary obstruction is incompatible with life, but lesser degrees of obstruction give rise to symptoms* 2. Fatigue and syncope 3. Signs of peripheral oedema 4. RV heave 5. A harsh mid-systolic ejection murmur, best heard on inspiration, to the left of the sternum in the 2ICS

Answer 83

**_Valvular Heart Diseases - Infective Endocarditis_** * **Pathological Features** 1. Valvular Vegetations 2. Perivalvular Abscesses 3. Impaired Valve Function * **Complications** 1. Heart murmur, heart valve damage and heart failure 2. Stroke 3. Paralysis or paresis 4. Seizure 5. Abscesses that develop in the heart, brain, lungs and other organs 6. Pulmonary embolism 7. Kidney damage 8. Enlarged spleen

Answer 84

**_Valvular Heart Diseases - Valve Stenosis_** * **Pathological Features** 1. Narrowed Valve Opening 2. Calcification 3. Fibrotic Scarring 4. Abnormal No. of Cusps/Leaflets * **Complications** 1. *Depends on Site of Valve Damage* 2. LV dysfunction and failure Pulmonary HTN and oedema RV dysfunction and failure 3. Peripheral oedema 4. Heart failure 5. Atrial fibrillation and arrhythmias 6. Stroke (due to dilated ventricle and transmural thrombus)

Answer 85

**_Valvular Heart Diseases - Valve Regurgitation_** * **Pathological Features** 1. Impaired Closure of Valve Calcification 2. Fibrotic Scarring Stretched/Dilated Chamber 3. Cusp/Leaflet Perforation, Retraction or Prolapse 4. Short, Long or Ruptured Chordae Tendinae 5. Ischemic/Ruptured/Fibrotic Papillary Muscles 6. Vessel Dilation or Wall Weakening * **Complications** 1. *Depends on Site of Valve Damage* 2. As above

Answer 86

**_Acute Rheumatic Fever Prevention_** * **Primordial Prevention:** * Reduce overcrowding * Improve respiratory and skin hygiene * **Primary Prevention:** * Treatment of Group A Streptococcal infection * Develop Group A Streptococcal vaccine (not yet developed) * **Secondary Prevention:** * Antibiotic prophylaxis (about every 3.5-4 weeks up to the age of 25 or further if necessary) * Regular ECHO to detect asymptomatic rheumatic heart disease cases * **Tertiary Prevention:** * Medical management of heart failure and complications of rheumatic heart disease * Access to surgical interventions for valve lesion * ECHO screening of high-risk groups for rheumatic heart disease * Access to dental care, contraception and regular clinical review

Answer 87

**Infective Endocarditis:** An endovascular infection of cardiovascular structures, including cardiac valves, atrial and ventricular endocardium, large intrathoracic vessels and intracardiac foreign bodies (i.e. prosthetic valves, pacemaker leads and surgical conduits). **Risk Factors for Infective Endocarditis:** 1. Infection 2. Poor dental hygiene 3. Recent dental treatment 4. Intravenous drug use 5. Tattoos and body piercings 6. Soft tissue infections 7. Intravascular devices 8. Cardiac surgery 9. Permanent pacemakers 10. Prosthetic heart valves 11. Co-morbidities such as structural, valvular, rheumatic or congenital heart disease 12. Chronic hemodialysis 13. HIV infection 14. Immunosuppression 15. History of endocarditis

Answer 88

**Pathology of Infective Endocarditis:** * The presence of organisms in the bloodstream (episode of bacteremia) * Abnormal cardiac endothelium facilitating their adherence and growth 1. Endothelial damage can be due to aberrant jet streams and turbulent flow in the setting of diseased cardiac valves and septal defects or direct trauma from intravascular devices 2. Damaged endocardium promotes platelet and fibrin deposition which allows organisms to adhere and grow, leading to an infected vegetation 3. Aortic and mitral valves are most commonly involved in infective endocarditis apart from intravenous drug users in whom right-sided lesions are more common

Answer 89

**Microbiology of Infective Endocarditis:** * **Streptococci spp. (50-80% of Cases):** *S. viridans* normally found in the upper aerodigestive tract, may disseminate during tonsillectomy, dental extraction, dental cleaning resulting in bacteremia. *S. viridans* causes subacute and chronic bacterial endocarditis. * **Staphylococci spp. (20-30% of Subacute and 50% of Acute Cases):** *S. aureus* and *S. epidermidis* common in patients with indwelling central venous catheters, IVDA, diabetes, chronic haemodialysis and prosthetic valve endocarditis. Staphylococcal endocarditis can affect functionally normal native valves and cause extensive tissue damage and septic emboli. Prosthetic valve endocarditis is mainly due to coagulase negative staphylococci (S*. epidermidis*). *S. aureus* causes acute bacterial endocarditis. * **Enterococci spp. (5-15% of Cases):** *S. faecalis, S. bovis* and *S. faecium* * **HACEK Organisms:** *Haemophilus parainfluenza, Haemophilus aphrophilus, Actinobacillus (Haemophilus) actinomycetemcomitans, Cardiobacterium hominis, Eikenella species,* and *Kingella species* * **Less Common Organisms:** *Candida, Aspergillus, Histoplasma*, and *Brucella* (common in IVDA, alcoholics, and patients with prosthetic heart valves)

Answer 90

**Manifestations of Infective Endocarditis** * **Systemic Inflammatory Effects** 1. Fever (with no obvious source) 2. Elevated CRP and ESR Increased WCC 3. Anaemia 4. Haemolysis 5. Microscopic haematuria 6. Other markers (lactate, low platelets, renal impairment, low complement) 7. Arthralgia 8. Malaise 9. Splenomegaly and tender spleen Weight loss * **Vascular Phenomena** 1. Emboli 2. Janeway lesions (blanching non painful erythematous lesions on palms and soles) 3. Splinter hemorrhages (nail and conjunctiva) 4. Skin petechiae * **Immunological Phenomena** 1. Osler’s Nodes (painful nodules on fingertips) 2. Roth Spots (retinal hemorrhages) 3. Glomerulonephritis (haematuria) ***NB:** Vascular effects are due to septic emboli whilst immunological effects are due to immune complex depositions* ***NB:** Other manifestations also include murmurs, dyspnoea and chest pain*

Answer 91

**Infective Endocarditis - Complications:** Depends on valve and exact location of vegetation 1. Heart problems such as heart murmur, heart valve damage and heart failure 2. Stroke 3. Paralysis or paresis 4. Seizure 5. Abscesses that develop in the heart, brain, lungs and other organs 6. Pulmonary embolism 7. Kidney damage 8. Enlarged spleen

Answer 92

**Prophylaxis and Prevention of Infective Endocarditis:** 1. **Antibiotic Prophylaxis:** 1. Prosthetic heart valves 2. Congenital heart disease or surgery 3. Prior endocarditis 4. Heart transplant 5. Rheumatic heart disease in indigenous patients 6. Tooth extraction or reimplantatio 7. Periodontal procedures or dental surgery such as implants 2. Avoid high risk behaviours (IV drug use or tattoos) 3. Maintain good dental hygiene 4. Identify and treat underlying bacteraemia early 5. Manage comorbidities such as HIV and structural, valvular, rheumatic or congenital heart disease

Answer 93

**Diagnosis of Infective Endocarditis:** Modified DUKE Criteria * **Major Criteria:** Positive blood cultures (before antibiotics administered) and/or cardiac imaging (transoesophageal imaging) showing vegetation, abscess or other signs * **Minor Criteria:** 1. Predisposing factors such as valve replacement or intravenous drug use 2. Fever greater than 38 degrees 3. Vascular phenomena such as emboli, haemorrhages, or Janeway lesions 4. Immunological phenomena such as Osler's nodes, Roth's spots and rheumatoid fever

Answer 94

**Common Antibiotics for Infective Endocarditis:** Usually 4-6 Weeks of IV therapy (two weeks in hospital) 1. **Broad Spectrum:** IV Penicillin (1.8 g 4 hourly) and Gentamicin (4 mg/kg/d) and Vancomycin (MRSA) 2. **Prosthetic Valve or MRSA Risk:** Vancomycin 3. **Specific IV Antibiotics:** Target to specific bacteria **Principles of Antibiotic Treatment:** 1. Initially start with broad spectrum to relieve fever and signs of sepsis, then change when the exact organism is known 2. If stable, wait for definitive organism first 3. If unstable, treat immediately after blood cultures 4. Once the bug is known, choose the right antibiotic for the bacteria and start intense IV therapy in hospital

Answer 95

**Mechanisms of Fever Production:** 1. Tissue inflammation via infection, trauma, autoimmunity, hemorrhage, tumours, thrombosis and heat stroke 2. Macrophages or monocytes release pyrogens/cytokines (IL-1B, TNF-a and IL-6) 3. Cytokines induce cyclooxygenases 2 (COX-2) that convert arachidonic acid into prostaglandins 4. This results in increased production of prostaglandins in the vascular and perivascular cells of the hypothalamus 5. Prostaglandins (specifically PGE2) stimulates the production of neurotransmitters 6. Neurotransmitters reset the temperature set point at a higher level 7. Increased metabolic rate, rigors and peripheral vasoconstriction help the body generate and conserve heat

Answer 96

**Lifecycle of Plasmodium:** **Exo-Erythrocytic Cycle** 1. During a blood meal, a malaria-infected female *Anopheles* mosquito inoculates sporozoites into the human host 2. Sporozoites infect liver cells which begins the exo-erythrocytic stage of the life cycle where asexual multiplication occurs 3. Within hepatocytes sporozoites mature into schizonts in the liver 4. Schizonts rupture and release merozoites into circulation, ending the exo-erythrocytic cycle ***NB:** In the case of P. vivax and P. ovale, a few parasites remain dormant in the liver as hypnozoites which may reactivate at any time causing relapsing infection*

Answer 97

**_Lifecycle of Plasmodium -**_ _**Erythrocytic Cycle_** 1. The merozoites invade RBCs where they undergo another asexual cycle called the erythrocytic cycle 2. During this stage the merozoites develop to form immature or ring stage trophozoites which then progress to mature trophozoites 3. The mature trophozoites develop into schizonts 4. At the end of the erythrocytic cycle, the infected RBCs burst, releasing the merozoites 5. At this stage, merozoites can either infect new RBCs to begin the erythrocytic cycle again, or they can develop into gametocytes

Answer 98

**Lifecycle of Plasmodium -** **Sporogonic Cycle** 1. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an *Anopheles* mosquito during a blood meal, beginning the sporogonic cycle 2. While in the mosquito’s stomach, the microgametes fertilise the macrogametes generating zygotes 3. The zygotes become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts 4. The oocysts grow, rupture, and release sporozoites which go to the mosquito’s salivary glands 5. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle

Answer 99

**Epidemiology of Malaria:** * In 2017, there were 219 million cases of malaria in 90 countries * In 2017, malaria deaths reached 435,000 * Africa carries a disproportionately high share of the global malaria burden. In 2017, the region was home to * 92% of malaria cases and 93% of malaria deaths. * Malaria endemic areas include Africa, South America, and Asia (tropical and sub-tropical areas)

Answer 100

**Pathogenesis of Malaria:** 1. Host becomes infected with *Plasmodium* sporozoites via a bite from an infected anopheline mosquito 2. *Plasmodium spp. invade RBCs and digest hemoglobin. As hemoglobin is digested, a toxic metabolite hemozoin (a polarizable crystal) is produced.* 3. The intracellular parasites modify the erythrocytes in several ways 1. They derive energy from anaerobic glycolysis of glucose to lactic acid (hypoglycaemia and lactic acidosis) 2. Parasites reduce RBC membrane deformability, resulting in hemolysis and accelerated splenic clearance (splenomegaly and anaemia) 3. Alterations to uninfected RBCs, such as the addition of *P. falciparum* glycosylphosphatidylinositol (GPI) to the membrane, may play a role in increased clearance of uninfected cells (anaemia) 4. Once RBCs rupture (according to the parasite life cycle), cell membrane remnants and the hemozoin crystal are phagocytised by circulating macrophages 5. Activated macrophages release pro-inflammatory cytokines such as TNF-a, IFN-y, IL-1, IL-6 and IL-8 6. Cytokines results in headache, fever and rigors, nausea and vomiting, diarrhea, anorexia, tiredness, aching joints and muscles, thrombocytopenia, immunosuppression, coagulopathy, and central nervous system manifestations 7. In *P. falciparum* malaria, RBCs containing schizonts adhere to the lining of capillaries in the brain, kidneys, gut, liver and other organs which can cause mechanical obstruction and rupture, releasing toxins and stimulating further cytokine release

Answer 101

**Clinical Features of Malaria:** 1. Fever (paroxysmal) 2. Headache 3. Malaise 4. Chills 5. Fatigue 6. Abdominal pain 7. Vomiting and/or diarrhoea 8. Hepatosplenomegaly 9. Anaemia * Incubation period is 10–21 days, but can be longer * In cases with *P. vivax* and *P. ovale*, relapses may occur weeks or months after being infected * *P. falciparum* symptoms are more severe and include behavioural changes, confusion, seizures, anaemia, respiratory failure, kidney failure, coma and shock * If not treated immediately, *P. falciparum* malaria can lead to death

Answer 102

**Prevention:** 1. Antimalarial medication 2. Anti-mosquito sprays or lotions 3. Sleeping under a permethrin-treated bed net

Answer 103

**Causes of Fever in Travellers:** **Malaria:** Infection with *plasmodium* spp. (*P. falciparum, P. vivax, P. ovale, P.malariae*) following a female Anopheles mosquito bite **Dengue:** Infection with dengue virus (four different antigenic varieties) transmitted by the daytime-biting *Aedes* aegypti mosquito or *Aedes albopictus* mosquito (less common), which breed in standing water in refuse dumps in inner cities in tropical and subtropical areas **Typhoid:** Infection with *Salmonella Typhi* transmitted via faecal-oral route such as with contaminated water or food, or close contact with infected prson **Hepatitis:** Infection with Hepatitis A or E virus via faecal-oral route (contaminated food or water) or infection with Hepatitis B, C or D via exchange of blood or body fluids (tattoos, sex, needles, transfusion, mother) **Diarrhoeal Illness:** Infection with gastrointestinal pathogen such as *S. auerus*, *B. cereus, C. perfringens, C. botulinum, C. difficile, E. coli, V. cholera, C. jejuni, Salmonella spp., Shigella spp.,* Rotavirus or Norovirus through contaminated food or water

Answer 104

**Thrills:** Palpable murmurs **Murmurs:** Abnormal heart sounds due to turbulent blood flow across heart valves or vascular abnormalities

Answer 105

**Cardiac Murmurs** 1. Timing and Duration 2. Intensity → **Crescendo:** Increasing intensity, **Decrescendo:** Decreasing intensity, **Crescendo-Decrescendo:** Diamond-shaped 3. Area of Greatest Intensity and Radiation 4. Grading (Loudness and Harshness): Levine’s Grading System 5. Presence of a Thrill 6. Changes During Respiration or with Dynamic Manoeuvres

Answer 106

**Cardiac Murmurs -** **Timing and Duration:** * **Systolic** **Murmur**: Occur between S1 and S2 * **Diastolic** **Murmur**: Occur between S2 and S1 * **Pan/Holo-Systolic**: Lasting for all of systole * **Mid-Systolic**: Starts after S1 and ends before S2, in crescendo-decrescendo manner * **Late Systolic**: Starts after S1 and extends up to S2, usually in a crescendo manner * **Early Diastolic**: Starts immediately after S2 and extends through diastole, in a decrescendo manner * **Mid-Diastolic**: Starts later in diastole after S2 and may be short or extend right up to S1 * **Pre-Systolic**: Just before S1 * **Continuous Murmur**: Lasting for all of diastole and systole

Answer 107

**Area of Greatest Intensity and Radiation**

Answer 108

**Grading (Loudness and Harshness):** **Levine’s Grading System** * **Grade 1/6:** Very soft and not heard at first (often audible only to consultants and to those students who have been told the murmur is present) * **Grade 2/6:** Soft, but can be detected almost immediately by an experienced auscultator * **Grade 3/6:** Moderate, there is no thrill * **Grade 4/6:** Loud, thrill just palpable * **Grade 5/6:** Very loud, thrill easily palpable * **Grade 6/6:** Very, very loud, can be heard even without placing the stethoscope on the chest

Answer 109

**Added Sounds:** **Extra S3 Sound ("Kentucky"):** Low-pitched mid-diastolic sound indicative of increased ventricular filling due to reduced ventricular compliance **Extra S4 Sound ("Tennessee"):** Late diastolic sound indicative of increased ventricular filling, due to a high- pressure atrial wave reflected back from a poorly compliant ventricle **Systolic Ejection Click:** An early systolic high-pitched sound that is heard over the aortic or pulmonary and left sternal edge areas due to the abrupt doming of the abnormal valve early in systole Example: Aortic stenosis or pulmonary stenosis

Answer 110

**Features of Cardiac Ultrasound:** 1. Structure of valves 2. Size of chambers 3. Wall motion and contraction 4. Direction and velocity of blood flow (regurgitation/stenosis) 5. LV wall thickness 6. **E/A Ratio:** Marker for the function of the LV and represents the ratio of peak velocity blood flow from gravity in early diastole (the E wave) to peak velocity flow in late diastole caused by atrial contraction (the A wave) 7. **Bernoulli Equation:** ∆P = P2-P1 = 4(V22 – V12) which calculates pressure gradient from velocity to assess degree of obstruction of valves (often used for aortic stenosis)