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Block 3 – Respiratory Learning Objectives Arunan Sriravindrarajah The following lecture objectives were ordered thematically TABLE OF CONTENTS Anatomy ................................................................................................................................................................. 4 Thorax – Thoracic Cage Wall, Boundaries, Breast and Surface Anatomy .............................. 4 Thorax – Internal Organisation and Lower Respiratory System ................................................ 4 Head and Neck – Scalp, Face, Mastication, Neck ............................................................................ 4 Head and Neck – Nose, Sinuses, Mouth ............................................................................................. 4 Head and Neck – Pharynx, Larynx ........................................................................................................ 5 Head and Neck – Eye ................................................................................................................................. 5 Head and Neck – Ear .................................................................................................................................. 5 Head and Neck – Cranial Nerves ........................................................................................................... 5 Head and Neck – Clinical Anatomy ....................................................................................................... 5 Head and Neck – Development .............................................................................................................. 6 Imaging ................................................................................................................................................................... 6 Normal Chest X-Ray.................................................................................................................................... 6 Head and Neck: Radiology ....................................................................................................................... 6 Respiratory Physiology ........................................................................................................................................... 7 The Gas Exchange Unit – Function ....................................................................................................... 7 Mechanics of Breathing – Part I ............................................................................................................. 8 Mechanics of Breathing – Part II............................................................................................................ 9 Control of Breathing and Respiratory Failure .................................................................................. 10 Normal Lung Function .............................................................................................................................. 11 Exocrine Secretion ..................................................................................................................................... 12 Respiratory Pathophysiology ................................................................................................................................ 13 Respiratory Signs and Symptoms ....................................................................................................... 13 Mechanisms of Asthma ............................................................................................................................ 14 Bronchodilators and Asthma Treatment............................................................................................ 15 Pathophysiology of Interstitial Lung Disease 1 and 2 .................................................................. 16 Mechanisms of Symptamology in COPD ........................................................................................... 17 Pathophysiology of Airways Dysfunction in COPD ......................................................................... 17 Biochemical Consequences of Oxygen Deficit and Excess ......................................................... 19 Case Conference – Clinical Grand Rounds........................................................................................ 19 Respiratory Acid-Base Disorders .......................................................................................................... 19 Smoking ................................................................................................................................................................ 20 Evidence for Tobacco as a Cause for Disease ................................................................................. 20 Advocacy and Lobbying for Tobacco Control ................................................................................... 21 1 Smoking and Anaesthetic Risk.............................................................................................................. 22 Smoking Related Lung Disease and Smoking Cessation ............................................................ 22 Pathology Related to Smoking .............................................................................................................. 23 Sleep ..................................................................................................................................................................... 23 Physiology of Sleep ................................................................................................................................... 23 Sleep Disorders ........................................................................................................................................... 24 Pathophysiology of Sleep Apnoea ........................................................................................................ 27 Sleepiness in the Workplace .................................................................................................................. 28 Cystic Fibrosis ....................................................................................................................................................... 28 Cystic Fibrosis as a Multi-System Disease ....................................................................................... 28 Cystic Fibrosis as a Genetic Disorder ................................................................................................. 29 Infections in Cystic Fibrosis.................................................................................................................... 30 Immunology / Infectious Diseases ........................................................................................................................ 31 IgE Mediated Responses ......................................................................................................................... 31 Microbiology of Pneumonia in Australia ............................................................................................. 32 Antimicrobial Action in Respiratory Disease .................................................................................... 33 Dermatology ......................................................................................................................................................... 34 Mechanisms of Cutaneous Hypersensitivity ..................................................................................... 34 Other..................................................................................................................................................................... 36 Psychological Effects of Trauma ........................................................................................................... 36 Overview of Emergency Medicine ........................................................................................................ 37 Hearing Impairment and Deafness in the Community ................................................................ 37 Children in Hospital ................................................................................................................................... 38 PPD ....................................................................................................................................................................... 39 Uncertainty in Medical Practice ............................................................................................................. 39 Communicating Certainty and Uncertainty to Patients ............................................................... 40 Stress and Coping ...................................................................................................................................... 41 Population Medicine............................................................................................................................................. 42 Support Services for Patients and Families ..................................................................................... 42 Immunisation .............................................................................................................................................. 43 Seminars ............................................................................................................................................................... 43 Road Trauma – Active and Passive Safety ....................................................................................... 43 Lung Function Tests – Airflow Obstruction ....................................................................................... 44 Globalisation and Public Health – One World One Health .......................................................... 45 Honesty in Medical Practice.................................................................................................................... 46 Prevention and Awareness of Asthma................................................................................................ 47 2 Lung Function Tests – Restrictive Lung Disease ............................................................................ 48 Lung Disease Resulting From Occupational Exposure ................................................................. 48 Spirituality and Meaning of Medicine .................................................................................................. 49 Microbiology of Pneumonia .................................................................................................................... 50 Physiotherapy in Cystic Fibrosis ........................................................................................................... 51 Critical Appraisal of Observational Studies ...................................................................................... 52 3 ANATOMY THORAX – THORACIC CAGE WALL, BOUNDARIES, BREAST A ND SURFACE ANATOMY The structural components and organisation of the lower respiratory system - ... The structure-function relationship of the thoracic wall, boundaries and lower respiratory system - ... The relationship between the surface anatomy landmarks of the thorax and the underlying respiratory system, and its relevance in the clinic - ... THORAX – INTERNAL ORGANISATION AND LOWER RESPIRATORY SYSTEM The structural components and organisation of the walls and boundaries of the thorax - … The anatomy of the breast and the surface anatomy of the thorax - ... The structural components and organisation of the lower respiratory system - ... The structure-function relationship of the thoracic wall and lower respiratory system - ... How the structure of the thoracic cavity relates to its function in a clinical context - ... HEAD AND NECK – SCALP, FACE, MASTICATION, NECK Detailed anatomical organisation of the scalp, face and neck, including the following associated with scalp, face and neck: o Bones o Joints (e.g. Temporomandibular); and o Muscles (Facial Expression, Neck and Mastication) - …. HEAD AND NECK – NOSE, SINUSES, MOUTH Detailed anatomical organisation of the nose, sinuses and mouth, including: o Major Parts 4 o o o - Functions Blood Supply; and Neural Innervation … HEAD AND NECK – PHARYNX, LARYNX Detailed anatomical organisation of the pharynx and larynx, including: o Cartilages, Ligaments and Muscle o Function (Swallowing and Phonation) o Blood Supply; and o Neural Innervation - ... HEAD AND NECK – EYE Detailed anatomical organisation and function of the eye, including: o The different tunics of the globe o Blood supply of the globe o Neural innervations of the globe and associated structures o The different extraocular eye muscles, their innervations, functions and clinical testing o The bones that make up the cave of the orbit - ... HEAD AND NECK – EAR Detailed anatomical organisation and function of the: o Greater ear complex o Internal, middle and external ears o The bony and cartilaginous frameworks o Neural Innervations; and o Clinical applications - ... HEAD AND NECK – CRANIAL NERVES Detailed anatomical organisation of the cranial nerve system, including: o Their peripheral distributions including major branches o Patterns of innervations o The functional fibres that each nerve may carry to target structures; and o The clinical signs and symptoms after lesion - ... HEAD AND NECK – CLINICAL ANATOMY The major clinical features of the head and neck - ... The key anatomical structures and their clinical relevance - ... 5 HEAD AND NECK – DEVELOPMENT The main features of the development of the head and neck o Cranium o Pharyngeal Apparatus o Thyroid Gland; and o Palate - ... Consider some major abnormalities associated with head and neck embryology, for example cleft palate/lip, holoprosencephaly and acrania - ... IMAGING NORMAL CHEST X-RAY Demonstrate an understanding of the anatomy of the basic structures forming the visible thoracic cage on CXR (ribs, vertebral bodies, diaphragms) Demonstrate an understanding of the structures forming the visible borders of the mediastinum in the frontal CXR Demonstrate an understanding of the main shadows visible in the lateral CXR (Right ventricle, left atrium, aortic arch, hilar structures in particular) Describe the main features which markedly affect the quality of a CXR (with regard to inspiration, rotation and position of the patient at the time of the CXR - Chest X-Rays are preferable on full inspiration as this make the lung markings more noticeable by separating the structures more o In contrast, X-Rays on expiration will result in crowding of the lung markings at the base of the lungs Rotation can be assessed by comparing the distance between the Spinous Process and the left and right clavicles; this should be equidistant in a non-rotated patient The best way to image will be to have the structures of interest closer to the film as this will minimise the level of magnification (i.e. Chest X-Rays are preferable in the PA View rather than the AP View) o However, many Chest X-Rays cannot be done PA as the patient is too sick to stand up; this results in the Chest X-Ray being taken in different positions and so the resultant image will be skewed accordingly - Explain the main advantages of using CT scan of the chest rather than a CXR (with regard to density differences and cross sectional demonstration of structures) - CT Scans can identify significantly more densities than the 5 densities in X-Rays o Special views can be developed that show only the tissues that had a particular range of densities (i.e. only bones, only soft tissue, only lung, etc.) o The use of IV contrast can also make it easier to view particular areas / compartments HEAD AND NECK: RADIOLOGY The major radiological features of the head and neck - ... 6 RESPIRATORY PHYSIOLOGY THE GAS EXCHANGE UNI T – FUNCTION The significance and function of the gas exchange unit - Exchange of oxygen and carbon dioxide with the atmosphere is the unique and most important function of the lung o Over time, this must reflect the metabolic requirement of the whole body to maintain homeostasis o Transport takes place through diffusion and convection – physical processes (NOT Chemical Processes) Convection will transport air through the major airways (as well as through the Arterial Blood to the tissues), whilst diffusion transports air through the smaller airways and across the Alveolar / Capillary Membrane (as well as across the Artery to the Tissues / Mitochondria) o The transport of oxygen and carbon dioxide is based on the pressure gradient (these gases will move from the areas of high pressure to low pressure) The airways will repeatedly branch dichotomously over and over again, such that the surface area will increase lower in the airways (i.e. surface area of the Alveoli is ~70sq m (half a tennis court) vs. surface area of the Trachea (~5sq cm, which is size of 10c coin) Alveolar buds will only begin to appear at approximately Generation 19 o This is the point at which gas exchange commences o The earlier Generations of airways are purely conductive (i.e. transport air through the airways and NOT exchange gas) and are known as the ‘Deadspace’ o Most of the gas exchange will occur after Generation 23, at which the Bronchioles have become Alveolar Ducts (i.e. purely Alveolar walls) The Alveolar Capillary membrane is extremely thin (between 1-4 microns in length), but very strong o The thinness of the membrane readily enables the diffusion of gas o Alveolar spaces are on either side of the capillary, which facilitates the exchange on gas to / from the capillary The resting ventilation (i.e. amount of air that enters the lungs at rest) is ~7.5L per minute o Only ~5.2L / min will reach the Alveolar Ducts of the Lungs (the remaining ~2.3L / min remains in the Deadspace) o The partial pressure of Oxygen in the atmosphere is ~150mmHg, though this reduces to ~100mmHg at the Alveoli as Carbon Dioxide diffusing back across the membrane takes up some of the space o The partial pressure of Oxygen in Arterial blood will then be ~90mmHg, which then diffuse into Tissue / Mitochondria due to the pressure gradient (as these cells have a partial pressure of Oxygen of ~5mmHg) o The de-oxygenated blood returning to the Lung will have a partial pressure of Oxygen of ~2040mmHg The following gas exchange problems may arise: o Hypoventilation o Poor Cardiac Output o Ventilation Perfusion Mismatch (V/Q Mismatch) o Diffusion impairment o Anaemia or dysfunctional haemoglobin ‘Acinus’ is the smallest function gas exchange unit in the lung o The partial pressure of Oxygen and Carbon Dioxide within the Acinus is effectively homogenous (though it may be different in a different Acinus) o Most lung diseases (e.g. COPD, Asthma) will affect the lung in a non-homogenous manner, which will result in Ventilation Perfusion inequality between the different Acini and ultimately impair gas exchange - - - - - - 7 - - - - - - The main determinant of the partial pressure of Oxygen and Carbon Dioxide in this Acinus is the Ventilation Perfusion Ratio (i.e. NOT the absolute levels of Ventilation or Perfusion but rather the ratio between them) There is more ventilation in the bottom of the lungs compared to the top of the lungs due to the effect of gravity o Bottom of lungs are less stretched due to gravity and have greater capacity to expand with new air (i.e. ventilation) o Similarly, hydrostatic forces will result in greater bloodflow in the bottom of the lungs o As the increase in bloodflow is greater than the increase in ventilation at the bottom of the lungs, this area has a lower Ventilation Perfusion Ratio than the top of the lungs which has a higher Ventilation Perfusion Ratio Whilst partial pressure of Carbon Dioxide in blood will typically increase in respiratory disease, increased ventilation levels will enable the stabilisation of the carbon dioxide levels o However, the oxygen levels in the blood will continue to decrease despite the increased ventilation o This is the due to differences in the shape of the Disassociation Curve, whereby additional ventilation may reduce the Carbon Dioxide content but will not increase the Oxygen content (due to maximum Oxygen carrying capacity of Haemoglobin) Greater Ventilation Perfusion Mismatch will mean that maintaining the same partial pressure of Carbon Dioxide will require an increase in Ventilation Diffusion impairment in the lungs is not usually a problem (except at altitude) o Diffusion will be directly proportional to the Surface Area, Pressure Gradient and Diffusion Constant for the Substance as well as being inversely proportional to its Thickness Partial Pressure of Oxygen at Altitude is reduced, which means Pressure Gradient and hence Diffusion is lower o The Diffusion Constant for the Substance is directly proportional to its solubility and inversely proportional to the square root of its Molecular Weight o Thickened Alveolar Membrane will slow down the diffusion and increase the time required for a red blood cell to remain in the capillary to be fully loaded with oxygen The consumption levels of Oxygen do not change as a result of Respiratory Disease, so the body will attempt to adapt in a manner to increase the diffusion of oxygen o This will result in the body reducing the level of partial pressure of Oxygen in the body o This reduction in partial pressure will increase the pressure gradient and hence the amount of oxygen diffused into the blood o A similar mechanism applies to Carbon Dioxide too (i.e. increase partial pressure of Carbon Dioxide in the blood to diffuse additional carbon dioxide out of the body) o Therefore, Respiratory Diseases will typically manifest as a change in the partial pressure of Oxygen and Carbon Dioxide in the blood; Respiratory Failure involves a: Reduction in arterial oxygen tension (PaO2) below 80 mmHg breathing air at sea level; and or Normal PaO2 80 – 100 mmHg Increase in arterial carbon dioxide tension (PaCO2) above 45 mmHg Normal PaCO2 35 – 45 mmHg MECHANICS OF BREATHI NG – PART I Describe the anatomy of the respiratory system and its mechanical properties that allow it to function as a gas exchanging organ o The respiratory system is a complex elastic structure which has been arranged to function efficiently with respect to moving air in and out of the lungs and for exchanging oxygen and carbon dioxide o The generation of a more negative pleural pressure by the contraction of the inspiratory muscles (mainly the diaphragm) draws air through the conducting airways to the respiratory zone o Relaxation of the inspiratory muscles allows the elastic system to passively return to its preinspiratory state, thus achieving exhalation - The right bronchus is more straight compared to the left bronchus 8 - - - - - - - - o When people aspirate, contents will more commonly travel down the right bronchus The Right Lung has three lobes (Upper, Middle, Lower) whilst the Left Lung has two lobes (Upper and Lower) o The Lingula of the Left Lung is a part of the Left Upper Lobe will be located in the same general location as the Right Middle Lobe (though it is not a separate lobe) o The Right Lung does not have a Lingula but instead has a Middle Lobe The Terminal Bronchiole is the last Bronchiole before the Respiratory Bronchiole and Alveoli emerges o The Terminal Bronchiole is where gas exchange commences with additional gas exchange occurring in the Respiratory Bronchiole o Alveoli Ducts do not specifically have walls, but rather have a series of Alveoli creating a border / duct o The ‘Acinus’ refers to the Terminal Bronchiole, Respiratory Bronchiole and Alveoli The cross-sectional area of the lung will increase exponentially further into the lower respiratory tract o Resistance to breathing will generally be in the largest parts of the lung (i.e. trachea, bronchi) o Flow velocity of air is highest in these areas too, which generate the breathing sounds Terminal and Laminar Flow occurs due to the negative pressure gradient in the lung (which draws air deeper into the lungs) o In contrast, Diffusive Flow occurs due to Diffusion (i.e. high concentration to low concentration) o The distance that needs to be travelled in Diffusion is very small which means Diffusion relatively efficient especially given the large surface area of the Alveoli The high velocity flow of air in the upper airways will make it difficult for aerosols to travel deep into the lungs o The aerosols will travel very fast and contact with the branched areas and not continue to travel deeper into the lungs o Doctors will typically ask patients to breathe in slowly and deeply to minimise this issue and maximise the probability of the aerosol entering deep into the lungs o Medications also aim to reduce the size of aerosol particles as this will assist in the aerosol from travelling deeper into the lungs Collateral Ventilation involves canals / channels between Alveoli and / or Acinus; this can occur in diseases such as Emphysema o This is a problem as it interferes with the normal flow of air through the lungs, which can result in the collapse of airways and reduced oxygen absorption o This can be helpful when one channel gets blocked (e.g. due to mucus) as it provides another channel for air to enter / exit Mucous in the lungs is an important protective mechanism to capture foreign particles; however, abnormal increases / changes in mucous are characteristic of many respiratory diseases o Cilia is critical for clearing mucous and other particles o Problems with Cilia can give rise to several different infections / diseases Diaphragm is the main muscle of respiration Forced expiration is mainly assisted by the Abdominal Muscles (rather than the Intercostal Muscles) Pleural Space is a single bag in-between the lungs and chest wall (between Visceral and Parietal Pleura respectively) o There is a small amount of fluid (~20mL) in this space that aims to reduce friction and this space is negative pressure o There are several pain sensors on the Parietal Pleura (Pleuritis is a very painful disease) MECHANICS OF BREATHI NG – PART II The anatomy and mechanical properties of the respiratory system dictate how breathing and gas exchange occurs o Because of the apical to basal gradient of ventilation, blood flow must also match this gradient to allow efficient gas exchange - Lung Elastic Recoil Pressure will increase significantly above 75% of Lung Volume (this is the kink in the curve) 9 o - - - - - - - This makes it harder to reach maximum lung volume (TLC) as a significantly greater force is required for expansion of lung to greater than 75% of full volume There is a direct relationship between the lung volumes and airway calibre o The higher the lung volume, the more wide open the airways o Peak flow of airways will occur at the maximum lung volume; this is due to: Higher elastic recoil pressure at higher lung volumes Higher Airway Calibre at higher lung volumes Respiratory Abdominal Muscles are at a mechanical advantage at higher lung volumes (and hence exert a greater force) o In contrast, low airway volumes result in narrower airways / closure (e.g. wheeze, cessation of breathing) The Diaphragm is not attached to the lung and so its movement downwards does not directly pull down the lungs o However, the contraction of the Diaphragm (i.e. its movement down) expands the Thoracic Cavity o The increase in the Thoracic Cavity will decrease the Intra-Pleural Pressure (per Boyle’s Law); this increases the pressure gradient between the Intra-Pleural and Intra-Pulmonary spaces causing the lungs to expand o The expansion of the lungs increases the volume and hence decreases the Intra-Pulmonary Pressure (per Boyle’s Law); this will result in air flowing from outside into the lungs (i.e. from high to low pressure), which results in the further inflation of the lungs Contraction of Diaphragm pulls against elastic recoil of lung and chest wall as well as resistance in airways o Relaxation of diaphragm will hence result in a passive recoil of the lungs (i.e. expiration of air) Gravity will increase the level of pressure at the top of the lung (and hence result in more elastic distension, bigger alveoli and more constricted blood vessels) compared to the bottom of the lung o There is greater capacity for ventilation (i.e. fresh air entering the lung) at the bottom of the lung as the alveoli has a smaller size at FRC (which means the change in size with full inspiration is greater at the base of the lung compared to the top of the lung) o Therefore, more perfusion and ventilation will occur from the bottom of the lung (though perfusion increase is higher than ventilation increase, so Ventilation Perfusion Ratio is actually lower at the base of the lungs) Distension / Dilatation of the Airways will compress the blood vessels associated with the Alveoli and vice versa o Therefore, blood flow (and blood pressure) with decrease during inspiration and increase during expiration Elasticity of lungs will decrease with age; this will result in increased closure of the airways at the base of the lungs as there is less pressure to open the airways o This closure of airways will affect more of the lungs when the patient is supine (especially if patient is obese) as the gravitational effects are affecting a larger proportion of the lung Airways Resistance = (Pressure at Alveoli – Pressure at Mouth) / Flow Understanding the basic concepts of how disease affects the normal functioning of the lung provides a sound basis of clinical assessment of respiratory disease - Asthma results in an increase in airways resistance (which results in a reduction in flow) Emphysema results from a reduction in both the pressure gradient and flow (which results in an overall increase in resistance) Obstructive airways disease results in airway narrowing and / or closure as well as hyperinflation of the lungs In contrast, Interstitial Fibrosis results from an increase in the pressure gradient (due to smaller, harder lungs) and flow (which results in an overall decrease in resistance) - CONTROL OF BREATHING AND RESPIRATORY FAILURE 10 The normal physiological regulation of breathing - Diaphragm is controlled from the Brain Stem (which sends signals down the Spinal Cord from which emerge the Phrenic Nerve, which innervates the Diaphragm) o In contrast, the Heart is independent in its operation and will work with Neurological input o Chemoreceptors will provide input to Brain Stem regarding the Carbon Dioxide levels and will result in the Brain Stem adjusting respiration accordingly (through its impact on the Diaphragm) Exchange of Oxygen from the atmosphere into the body is a passive process rather than an active process o Diffusion of oxygen into the bloodstream occurs due to a pressure gradient in the lungs Ventilation determines how much oxygen is delivered to the gas exchange area and how much carbon dioxide is eliminated; rate of ventilation depends on: o Central Chemoreceptors – these will increase ventilation if CO2 exceeds a threshold level (as higher ventilation reduces CO2 levels) Central chemoreceptors are located in the Medulla are very sensitive to the pH of the CSF (which will be impacted by the levels of Arterial Carbon Dioxide) o Peripheral Chemoreceptors – these will increase ventilation if Blood Oxygen levels fall below a threshold level The Carotid Body is a small cluster of Peripheral Chemoreceptors located near the fork of the Carotid Artery that will respond to Oxygen Saturation levels The Carotid Body will be stimulated when Oxygen Saturation Levels drop below 90% (i.e. Arterial Oxygen Pressure of ~60mmHg) and trigger increased ventilation Respiratory Failure is defined as Arterial Oxygen Pressure <60mmHg at rest (NOT after exercise) o Arterial Oxygen Pressure of 60mmHg is the equivalent of Oxygen Saturation of ~89% o Reduction of Arterial Oxygen Pressure below this level will result in a significant drop in oxygen saturation (due to Haemoglobin Oxygen Association Curve) o Note the level of the Arterial Carbon Dioxide pressure can be high, low or normal during respiratory failure This is due to Carbon Dioxide having the ability to be converted into different forms and stored in the body In contrast, oxygen can only be located in the body in red cells and the lungs There are two types of respiratory failure o Hypoxic Respiratory Failure (i.e. Type A or ‘Pink Puffer’) Low arterial O2 with normal or low CO2 o Hypercapnic Respiratory Failure (i.e. Type B or ‘Blue Bloater’) Low arterial O2 with high CO2 - - - - The disease states that alter normal control of respiration - Both obstructive (e.g. COPD) and restrictive (e.g. ILD) lung diseases will affect respiration The acute & chronic consequences of respiratory failure - Acute respiratory failure will involve a difficulty breathing and a resulting increase in ventilation rate Chronic respiratory failure will involve the body /chemoreceptors adapting to the changed breathing patterns and having a higher arterial level of CO2 in the stable state NORMAL LUNG FUNCTION The lung function tests used commonly in the assessment of patients with respiratory disease and the determinants of both normal and abnormal lung function - In the Office: o Spirometry o Peak expiratory flow 11 - o Expiratory flow volume curves In the Respiratory Laboratory: o Lung volumes (e.g. Pressure Plethysmograph) o Diffusing capacity o Blood gas tensions/oximetry o Bronchial provocation o Exercise testing o Specialised lung function (airway resistance, nitrogen washout, MIPS and MEPS, lung elasticity) EXOCRINE SECRETION The 2-stage hypothesis for function of exocrine glands and its implications for exocrine gland function in cystic fibrosis - Thaysen’s 2-stage hypothesis was that: o Stage 1 Primary fluid is produced in the coil Composition of fluid in coil is same regardless of the rate of flow Primary fluid is usually (but NOT always) plasma-lie o Stage 2 The duct changes the composition of the primary fluid by transporting Na+ and Clout and K+ and HCO3- into the fluid o When the flow rate is slow, there is greater opportunity for the duct to adjust the fluid and transport any excess quantities of ions However, when the flow rate is high, these is less opportunity for the duct to adjust the fluid o Cystic Fibrosis is a disease of Protein Kinase A activated Cl- ion channel called CFTR, which prevents the Cl- ions (and hence Na+ ions) from people pumped out of the sweat Similarly, the failure of the Cl- ion channel in the lungs results in excessive function of an alternative system that results in excessive Na+ ion loss from the lungs - The mechanisms by which sweat ducts, pancreatic ducts, colonic crypts and respiratory epithelium transport ions and how the function of these affected organs is affected by cystic fibrosis - There are ion channels the apical and basal surfaces of the epithelium that are responsible for the transportation of Na+ and Cl- ions across the epithelium Some of these Na+ channels (e.g. on basal membrane) are ATP activated and result in the outflow of Na+ from the Epithelium into the blood Other channels are passive channels that will enable flow based on the concentration gradients The malfunctioning of the CFTR gene inhibits some of the Cl- ion channel in the body, resulting in malfunction in ion transport across the epithelium - The various mechanisms by which mutations in the CF gene lead to abnormal function - Mutations in the CF gene will affect the Kinase A activated Cl- ion channel called CFTR o This will affect the flow of Cl- (and other) ions in the sweat glands and lungs o The impact in the lungs is slightly different from the sweat glands due to the existence of an Cl- ion Secretory System in the Lungs The physiological basis of pharmacological therapies for cystic fibrosis - Gene therapies for Cystic Fibrosis aim to add functional CFTR genes to cells in order to restore proper functioning of the Cl- ion channel 12 - Pharmacological treatments aim to activate the mutated CFTR genes in cells, which will avoid the failure of the Cl- ion channels to operate correctly Other approaches include do not target the CFTR gene but rather aim to correct for the adverse effects (e.g. down regulate Na+ channel to avoid excessive loss of Na+ ion from the lungs [as this results in viscous mucous]) RESPIRATORY PATHOPHYSIOLOGY RESPIRATORY SIGNS AND SYMPTOMS The principles of taking a history and undertaking an examination of the respiratory system - Differential Diagnosis list can be developed based on initial signs and symptoms of the patient (there are various pneumonics / tools can help develop this list) o Additional questions will help prioritise this list (e.g. timing of onset) o This list will help direct the history and examination to help rule in / rule out various conditions To discuss the origins of the symptoms (breathlessness, cough, haemoptysis, pain and wheeze) and signs of respiratory ill health - Key respiratory symptoms and signs include: o Dyspnoea – An uncomfortable awareness of breathing (i.e. sense of effort to breathe); may be due to: Increased central respiratory drive Increased respiratory load Lung irritation o Cough – Reflex used to expel particulate matter from the lungs (e.g. particles, excess mucous, etc.) o Sputum – Mucous secretion from glands in the tracheobronchial tree (any irritant will increase sputum production) Green colour sputum more likely to indicate bacterial infection o Haemoptysis – coughing up blood / blood-stained sputum; may be due to: Foreign body Bronchiectasis Pneumonia Lung Cancer Tuberculosis Trauma ...and many more o Chest Pain – relatively non-specific and may signify a long list of differentials; may be due to: Angina Myocardial Infarct Pulmonary Embolism Pulmonary Hypertension Bacterial Pneumonia Pneumothorax Pericarditis ...and many more o Clubbing – characteristic bulging of the distal finger and nail bed; may be due to: Respiratory illnesses Lung Cancer / Lymphoma Cardiac illnesses (e.g. Infective Endocarditis) Gastrointestinal (e.g. Cirrhosis, Inflammatory Bowel Disease) o Percussion – tapping of the fingers over the chest wall /back 13 o Low density tissue will vibrate with greater resonance when percussing compared to high density tissues (which will percuss with dull sound) Auscultation Crepitation – Non-continuous popping sounds caused by opening of obstructed airways; may be caused by: Pneumonia (Coarse Crepitation) COPD (Coarse Crepitation) Pulmonary Oedema (Coarse Crepitation) Pulmonary Fibrosis (Fine Crepitation) Wheeze – Polyphonic, high-pitched sound typically on expiration; may be caused by: Asthma Pulmonary Oedema Small Airway Trauma Stridor – loud, monophonic noise with constant pitch that results from any large airway obstruction; may be caused by: Tumour Foreign body Aspiration Vocal Cord Dysfunction Pleural Rubs – rubbing / scratching sound heard over inflamed pleura due to loss of normal pleural lubricant; may be caused by: Pleurisy Pulmonary Embolism Pneumonia Tuberculosis Bronchial Breath Sounds – indicates consolidation of lung tissue (e.g. Pneumonia) Vocal Resonance (or Fremitus) – character of a patient’s voice when auscultated (or palpated) increased resonance suggests consolidation, whilst decreased resonance suggests pleural effusion MECHANISMS OF ASTHMA Describe the prevalence of asthma in Australia - 10% of Australian suffer from Asthma (~2 million people) Prevalence is highest in children / adolescents List the risk factors for asthma - Atopy in infants (e.g. eczema, rhinitis) Positive family history of Asthma Maternal smoking Male Indoor Allergen Exposure (e.g. house dust, moulds) Explain airway hyperresponsiveness (AHR) and list the triggers for AHR - This refers to extreme sensitivity of the airways to physical, chemical and pharmacological stimuli o AHR correlates with severity of asthma and can be improved with inhaled corticosteroids Triggers for AHR / Bronchoconstriction include: o Exercise o Antigens o Chemicals (e.g. Histamine, Methacholine, Mannitol, AMP) - Describe the cells involved in the pathogenesis of asthma 14 - - Acute Asthma involves an antigen / trigger causing Mast Cells to release inflammatory cytokines (e.g. histamine), which results in Bronchial Smooth Muscle contraction (EARLY RESPONSE) Subsequently, several hours after exposure to the antigen / trigger, there is an influx and activation of inflammatory cells (e.g. Eosinophils) (LATE RESPONSE) o Eosinophils will result in Epithelial Shedding which will eventually result in scarring and a reduction in the size of the lumen o Furthermore, the shedding of the Epithelium will interfere with Mucociliary Clearance which increases the probability of other respiratory problems Chronic Asthma will involve smoother muscle hyperplasia and hypertrophy (unlike in Acute Asthma) o This bigger smooth muscle will result in a smaller lumen (i.e. airway constriction) and also magnify the level of constriction in bronchospasm (as muscles are bigger) o There will also be additional mucous discharge from Goblet Cells, which gives rise to Mucous Plugs List asthma drugs which act on the pathogenic pathways of asthma - Beta-Agonists (e.g. Ventolin, Salbutamol) Inhaled Corticosteroids (ICS) (e.g. Fluticasone, Ciclesonide, Budesonide, Beclomethasone) Combination of Long-Acting Beta-Agonists and ICS (e.g. Seretide, Symbicort) Describe the mechanism of action of these drugs - Beta-Agonists are used to relieve bronchoconstriction Inhaled Corticosteroids are used as a long-term regular therapy, as it is the only drug which reduces airway hyper-responsiveness Combination of ICS with Long-Acting Beta-Agonists (LABA) allows the same effect as ICS but with lower dosage levels of the ICS - List the effects of corticosteroids which contribute to efficacy in treating asthma - Corticosteroids are used as a long-term regular therapy, as it is the only drug which reduces airway hyper-responsiveness (which is the key underlying feature of Asthma) BRONCHODILATORS AND ASTHMA TREATMENT List the classes of bronchodilators with a couple of examples of drugs in each class - Beta-Adrenoceptor agonists (e.g. Isoprenaline [Beta-1 and 2], Salbutamol [Beta-2 selective], Salmeterol [Long-Acting Beta-2]) Anticholinergic drugs (e.g. Atropine, Ipratropium, Tiotropium [Long-Acting]) Phosphodiesterase inhibitors (e.g. Theophylline [non-selective], Roflumilast [PDE4 selective]) Describe the mechanism of action of β adrenoceptor agonists as bronchodilators - Relax airway smooth muscle (ASM) by binding to Beta-2 receptors on surface of ASM cells; this will relieve bronchoconstriction List other actions of β adrenoceptor agonists which are beneficial in the treatment of asthma - Inhibit release of Histamine and Leukotrienes from Mast Cells (which result in bronchoconstriction) Increase Mucocilliary clearance (by increasing beating frequency of cilia) Inhibit release of Acetylcholine (ACh), which leads to smooth muscle relaxation 15 Describe the mechanism of action of muscarinic receptor antagonists - Blocking the M3 Acetylcholine Receptors via Anticholinergics will prevent Bronchial Smooth Muscle Constriction (i.e. results in Bronchial Smooth Muscle relaxation) Describe the mechanism of action of phosphodiesterase inhibitors - Increase the levels of Cyclic AMP, which interferes with the contraction pathway and hence result in relaxation of smooth muscle List the usual drug treatment of asthma - Short-Acting Beta Agonists are used as needed for symptoms (e.g. wheezing, before exercise) Inhaled Corticosteroids (ICS) are a long-term preventative treatment (to reduce Airway Hypersensitivity) for all but the mildest asthma Combination of ICS and Long-Acting Beta-Agonists (LABA) are used for moderate to severe asthma o Using two drugs using different classes / mechanisms can have additive effects o This enables a higher effect without have to increase the dosage of a single drug (which would increase the risk of the drug) Describe the differences between asthma and COPD - Asthma o o o o o COPD o o o o o - Symptoms are variable Onset at childhood Course is variable with remission possible Smoking sometimes but not always present Bronchodilators and Corticosteroids are very effective Symptoms are persistent Onset at >45 years Course is progressive Smoking usually present Bronchodilators not effective, whilst Corticosteroids have modest effectiveness List the usual drug treatment of COPD - Bronchodilators are used for symptoms (e.g. Beta-Agonists, Anticholinergics, Phosphodiesterase Inhibitors) o These are the same treatments in Asthma, although they will not be as effective Long-Acting Beta-Agonists (e.g. Salmeterol) and Long-Acting Anticholinergics (e.g. Tiotropium) Inhaled Corticosteroids for advanced disease (this has no effect on lung function, but will decrease rate of exacerbations) - PATHOPHYSIOLOGY OF I NTERSTITIAL LUNG DISEASE 1 AND 2 The concept of obstructive and restrictive lung disorders - Restrictive Lung Disorders are characterised by decreased lung volume (TLC <80%) o This involves the lung being unable to expand (i.e. decreased lung compliance) and let air into the lungs o This may be due to Pulmonary causes (e.g. ILD) or Extra-Pulmonary causes (e.g. Pleural disease, Chest Wall abnormality, etc.) Obstructive Lung Disorders are characterised by a FEV1/FVC ratio < 70% o This involves the lungs not being able to expire air due to an obstruction o This will result in the lung hyperinflating (i.e. increased lung compliance) - 16 The diagnosis, assessment and monitoring of lung diseases using lung function tests - Lung Function Tests are not specific for diagnosis of ILD; however, they are useful for assessing the severity of the disease Restrictive Lung Disease should have lung function results where: o Reduced lung volumes (FVC, TLC) o Elevated FEV1/FVC ratio o Low DLco, preserved KCO Obstructive Lung Disease should have lung function results where: o FEV1/FVC ratio < 70% o KCo will be decreased in Emphysema - - MECHANISMS OF SYMPTAMOLOGY IN COPD The major clinical features of chronic obstructive pulmonary disease - Key symptoms include: o Shortness of Breath / Dyspnoea (initially on exertion, at rest in end-stage disease) o Chronic Cough (may include sputum production) o Wheeze o Anorexia / Weight Loss o Ankle Oedema (common in end-stage disease) Key features of Obstructive Pulmonary Disease include: o Obstruction to Airflow (especially expiratory) o FEV1/FVC Ratio < 70% o Expiratory Flow Rates decreased o Lung hyperinflation (i.e. increase in RV, FRC, TLC and decrease in IC, VC) Pathological changes include: o Loss of elastic recoil of lungs o Abnormal gas exchange - - The main mechanisms that generate this condition - Obstruction limits their flow-volume loop, which means patients is limited when at rest o Dynamic Hyperinflation occurs where the patient begins taking more air in the lungs (i.e. increase in FRC) to avoid this limitation (may be triggered by exercise) and also reduce airways resistance o However, this requires greater energy leading to greater metabolic demands and weight loss o This also results in a reduction in IC, leading to dyspnoea Obstruction also prevents air from being expired in normal time, so expiration is still ongoing when the next breath in is needed o This results from the equal pressure point of the lungs being deeper in the lungs due to the lungs possessing less elastic coil o This makes it more difficult to expire air resulting in greater levels of gas trapping o This will result in higher RV and TLC (and hence lower VC) Difficulty eating due to Dyspnoea will also contribute to weight loss / anorexia Poorer gas exchange in the lungs will result in higher pulmonary blood pressure; this will eventually result in right heart failure (which eventually causes Oedema) o Hyperinflation will also inhibit venous return and reduce cardiac output, which again triggers an increase in Pulmonary Blood Pressure - - PATHOPHYSIOLOGY OF AIRWAYS DYSFUNCTION I N COPD Understand the pathology of small airways disease, chronic bronchitis and emphysema 17 - - - - Small Airways Disease o Involves variably severe chronic airflow obstruction characterised by loss of bronchioles, mucous plugs and variable amounts of inflammation and fibrosis this will include a range of diseases such as Emphysema, Bronchiolitis, etc. o Small Airways are those that are more peripheral to the main bronchi and proximal bronchioles o Smaller airways have a large cross-sectional surface area compared to the larger airways, and so restrictions here are less likely to be identified in a lung function test (as there is more surface area available) Chronic Bronchitis o Inflammation of the mucous membrane of the bronchi o Diagnosed if there is productive cough on most days for at least 3 consecutive months over not less than 2 consecutive years Not necessarily associated with airflow limitation BUT in the presence of obstruction leads to more exacerbations and more rapid decline of lung function Emphysema o Abnormal permanent enlargement of airspaces distal to the terminal bronchioles (i.e. larger alveoli) with destruction of their walls and without obvious fibrosis. o This will lead to loss of elasticity of the lungs (i.e. increased compliance) and hyperinflation COPD will typically consist of a combination of Emphysema and Airway Obstruction (rather than only one of them) o Equal Pressure Point moves deeper into the lungs and hence reduces the Expiration ability of the lungs In Emphysema, this is due to the loss of elastic recoil of the lungs resulting in lower inward pressures in the lung In Airway Obstruction, this is due to the loss of pressure towards the mouth being more rapid as the airways are narrower (which increases frictional resistance to airflow) Understand the principles of spirometry - Spirometry measures the speed of expiratory airflow (FEV1) and the total volume of air expired (FVC) o Reduction in FEV1 is greater than the reduction in FVC in COPD, so the ratio of FEV1 to FVC will go down o FEV 1 level and Ratio of FEV1/FVC are important clinical measures; FEV1<80% of predicted and FEV1/FVC Ratio < 70% after bronchodilator use is diagnostic of COPD Bronchodilator Reversibility (i.e. the effectiveness of Bronchodilators) is highly variable within COPD patients (i.e. patients may respond sometimes and not respond other times to Bronchodilators) Spirometry can be used to measure the severity of the disease / level of lost lung function (though alternative, more accurate measures exist [e.g. BODE Index]) - Understand the reasons for and consequences of loss of elastic recoil in emphysema - Destruction and enlargement of the alveoli result will result in the loss of elastic tissue in the alveoli walls The loss of elastic recoil will result in lower inward pressures in the lung o This causes the Equal Pressure Point to move deeper into the lungs and hence reduces the Expiration ability of the lungs - Appreciate the abnormalities in the lung volume subdivisions and the effects on work of breathing - All the lung volumes are increased in COPD (i.e. increase in FRC, TLC and RV) o This is partly because the airways are obstructed and the air cannot get out 18 - o Furthermore, Emphysema will result in larger alveolar spaces resulting in larger lung inflation Higher lung volumes result in higher pressures (per the pressure-volume curve); this requires more energy / work to breathe Understand the concept of flow limitation and its effects on operating lung volumes and exercise limitation - Normal people will have no flow-limitation (i.e. shaded area) at rest o In contrast, the patient is at their flow-limitation at rest and hence cannot exercise o However, breathing at higher lung volumes (EELV) will reduce the level of flow-limitation and increase the capacity for expansion of ventilation The limitation of breathing at higher lung volumes is that greater pressure is required to breath at these volumes (per the volume-pressure curve) This requires more energy and patients will get more easily fatigued and breathless Understand the abnormalities of gas transfer in emphysema - Emphysema will involve a reduction in the surface area of the of the alveoli (as there will a smaller number of bigger alveoli), which reduces the level of diffusion Emphysema will also result in the destruction of the capillary bed surrounding the alveoli, which reduces the rate of uptake of oxygen by Haemoglobin (Hb); this reduces overall ability to transfer oxygen - BIOCHEMICAL CONSEQUE NCES OF OXYGEN DEFICIT AND EXCESS TBA - new in 2012 - Study showed lower mortality in pre-term infants with higher oxygen saturation levels o However, there can be oxygen toxicity in these pre-term infants as the higher oxygen levels may disrupt growth factor production and vascular development o Excess oxygen has also disrupted / damaged vascular development in the Retina Excess Oxygen can lead to Reactive Oxygen Species, which can have multiple different effects, some of which are destructive (e.g. DNA Damage) whilst others are useful (e.g. Iron Homeostasis) Oxygen Deficit may lead to (via the production of Hypoxia Induced Factor [HIF]: o Expression of growth factors / Angiogenesis o Cell survival and expansion o Erythrocyte generation (EPO) o Oxygen delivery o Metabolism uncouples Glycolysis from Citric Acid Cycle - CASE CONFERENCE – CLINICAL GRAND ROUNDS TBA o o - It is CRITICAL to know the location of the different lobes of the lung on a Chest X-Ray o Ensure that labelling Upper and Lower (and Middle for the Right Lung) Lobes are correct!!! Movement of Diaphragm downwards will increase Abdominal Pressure; this pressure will affect the chest wall at the Zone of Apposition (i.e. adjacent to the Abdominal area) resulting in the expansion of the chest wall o Biggest physiological difference between elite athletes and normal people is the ability to increase cardiac output (rather than any specific respiratory difference) - This session explores a case of a patient with lung disease The case is used to highlight key aspects of lung structure and function RESPIRATORY ACID-BASE DISORDERS 19 The lung's role as a rapid regulator of arterial blood pH, through the control of the partial pressure of carbon dioxide in the arterial blood - H+ concentration is kept within a narrow bounds in the blood (~35-45nmol/L); equivalent of pH of 7.35 to 7.45 o This is done using a Bicarbonate Buffer, where H+ (and HCO3-) ion concentration ion can be decrease / increased by converting to / from Bicarbonate o Bicarbonate though is dissolved CO2, so changing the level of CO2 will enable regulation of H+ ion concentration Lungs control arterial blood pH by adjusting ventilation, which adjusts the partial pressure of CO2 (which affects the H+ ion concentration) - How this is disturbed by disease - Disease can affect the pH levels in the blood; the type of problem can be interpreted by: o Is pH acid or alkaline side of 7.40? If acid, is PaCO2 high = 1o respiratory If acid, is BE (HCO3-) low = 1o metabolic If alkaline, is PaCO2 low = 1o respiratory If alkaline, is BE (HCO3-) high = 1o metabolic o Has other variable moved opposite (compensation)? o Is compensation partial or complete? Note: Base excess (BE) is calculation of base (or acid) required to bring the measured pH back to 7.4 after correcting the PCO2 to 40 mmHg o BE is normally between +2 to -2 mmol/L o Negative base excess means there is excess acid in the blood sample after the above correction Ventilation-Perfusion is matched when Alveolar Oxygen Pressure = Inspired Oxygen Pressure (~150mmHg with Room Air) – 1.25 x Arterial Pressure of Carbon Dioxide o There is an allowable difference of ~15mmHg from this above calculation; otherwise a wide A-a gradient for oxygen may indicate there is a V/Q Mismatch o This calculation will only be valid when there is a steady-state Respiratory and Metabolic Acidoses tend to be compensated, BUT Alkaloses tend not to be compensated o Metabolic Alkalosis not compensated because CO2 rise not tolerated (chemoreceptors will trigger increase ventilation) o Respiratory Alkalosis is too transient to be compensated (kidneys take 24 to 48 hours to deliver metabolic compensation) - - - SMOKING EVIDENCE FOR TOBACCO AS A CAUSE FOR DISEASE Identify diseases for which evidence is sufficient to conclude that smoking causes these diseases - Cancer (e.g. lung, nasal, oropharyngeal, laryngeal, oesophageal, stomach, cervical, pancreatic, liver, bladder, etc.) Cardiovascular disease (e.g. Atherosclerosis, Coronary Heart Disease, etc.) Respiratory disease (e.g. COPD, Pneumonia, Asthma, etc.) Reproductive disease (e.g. SIDS, Low Birth Weight, Foetal Death, etc.) Other disease (e.g. Cataracts, Hip Fracture, Osteoporosis, etc.) Outline in broad terms the types of epidemiological studies that have been used to investigate the effects of smoking on the risk of diseases, and limitations of these studies 20 - - Range of case control and cohort studies that have shown statistically significant associations between smoking and diseases (e.g. RR of ~13 for Lung Cancer) o Dose-Response studies have shown the link between increased smoking and increased risk The association between increased smoking rates and increased disease o The same increase in disease appears in women ~20 years after men; this was important as the increase in smoking in women was ~20 years after men too Explain the principles by which we determine causality - The exposure precedes the outcome The association is unlikely to be due to chance The association is unlikely to be due to bias The association is unlikely to be due to confounding Other criteria to consider are: o The association is strong o There is a dose-response relationship o The association is consistent o The association is coherent with other epidemiological data o The association is specific o The association is biologically plausible Interpret statistics that are used to quantify the burden of disease from smoking in individuals (Relative Risk, Attributable Fraction) and in populations (Population Attributable Fraction) - Relative Risk is the increase risk of an outcome with exposure to the intervention of interest (i.e. smoking) (e.g. RR of ~13 for Lung Cancer) Attribution Fraction is the proportion of the disease in an exposed group that is due to exposure o AR% = ((Incidence in Exposed – Incidence in Non-Exposed) / Incidence in Exposed) x 100 Population Attribution Fraction is the Attribution Fraction multiplied by the proportion of the population which is exposed to that exposure o This provides an estimate of impact on the population as a whole - ADVOCACY AND LOBBYING FOR TOBACCO CONTROL The role and process of public health advocacy in bringing about change in law, regulations, resource allocations and institutional practices relevant to public health - Public Health Advocacy has led to a series of changes across a range of different dimensions (e.g. law, regulations, resource allocations, social norms, institutional practices, etc.) that has significantly reduced smoking and the resultant morbidity / mortality Changes have included: o Cigarette Taxes o Plain Packaging o Smoking restrictions / denormalisation (e.g. smoke-free pubs) o Mass reach / health campaigns o Publicity regarding adverse health outcomes of smoking - The key role of mass media in this process - Mass Media played a key role in the promotion and increase in cigarette smoking prevalence The removal of cigarette advertising from Mass Media was an important action to reduce the promotion and usage of cigarettes Media campaigns work MORE with low SES smokers (who have the highest rates of smoking) o Media campaigns are more effective that Nicotine Replacement Therapies or other pharmacological treatments at reducing smoking prevalence - 21 SMOKING AND ANAESTHE TIC RISK The factors that make tobacco a major identifiable risk factor relating to surgery and the perioperative period - Smoking is associated with increased risks during anaesthesia o Cardiac Complications (e.g. Ischaemia or arrhythmia) o Vascular Events (e.g. Stroke, Transient Ischaemic Attack [TIA]) o Respiratory Problems (e.g. COPD, Emphysema) Smoking is associated with increased postoperative complications o Cardiac Complications (e.g. Heart Attack or arrhythmia) o Stroke (related to Atherosclerosis) o Bronchopulmonary Infections (due to poor sputum clearance, sputum retention, Pneumonia) there is a 6x increase in post-operative pulmonary complications for smokers Smoking is associated with poorer outcomes from surgery (e.g. increased post-operative complications, delayed healing, additional surgery, etc.) In order to reduce post-surgical complications, patients will need to cease smoking for at least ~6-8 weeks (this is the time taken for immune function to normalise) o Minimum of at least 4 weeks of smoking cessation prior to surgery to get any improvement in outcomes related to surgery - - SMOKING RELATED LUNG DISEASE AND SMOKING CESSATION Understand the spectrum of smoking-related lung disease - There are a range of different diseases resulting from smoking through the main three are: o Lung Cancer o COPD (+ Other Respiratory Diseases) o Coronary Heart Disease + Other Vascular Events (e.g. Stroke) Describe the key behavioural elements that contribute to dependence on tobacco - Context (e.g. Time / Place such as after meal, breaks, etc.) Ritual (i.e. process of lighting up and smoking) Sensory inputs (e.g. touch and feel of cigarette, smell of tobacco, smell and light of flame, etc.) Reinforcing (nicotine) stimulus (i.e. addictiveness of nicotine) Comprehend basic pharmacology of nicotine as it relates to dependence and of the treatments used for smoking cessation - Nicotine crosses blood-brain barrier and will trigger the release of Dopamine onto the part of the Brain that creates a sense of pleasure / reward Continued smoking results in down-regulation / alteration of receptors; additional nicotine is then needed to prevent withdrawal symptoms Treatments for smoking cessation may involve nicotine replacement to avoid these pleasure / withdrawal symptoms that drive people to smoke o Provision of nicotine in alternate manner will break the ritual, context and sensory inputs of smoking, which will assist with longer-term smoking cessation - Explain the complementary nature of behavioural interventions that aid smoking cessation - Behavioural interventions are important as brief advice to quit is the most cost-effective community strategy for smoking cessation This can increase number of quit attempts, which will lead to greater levels of smoking cessation - 22 Discuss at a basic level issues related to e-cigarette use - E-Cigarettes involve nicotine delivery from non-combustible sources around for long time (i.e. heating tobacco rather than burning, non-tobacco) o However, there is no reduction in nicotine or Carbon Monoxide Effectiveness of E-Cigarettes in quitting is unproven (maintenance of part-vaping and part smoking nicotine dependence may have no health benefit) These should never be recommended o Quietly counsel to use another strategy o Discourage long-term e-cigarette use - PATHOLOGY RELATED TO SMOKING The major pathological features related to smoking - Major smoking related diseases include: o Cardiovascular disease (e.g. Hypertension, Ischemic Heart Disease, Cardiac Arrest, etc.) o Respiratory disease (e.g. Emphysema, Chronic Bronchitis, Infections, etc.) o Foetal compromise (e.g. SIDS, low birth weight, prematurity, etc.) o Cancer Lip, oral cavity, pharynx Larynx Trachea/bronchus/lung (Bronchogenic Carcinoma) Oesophagus Urinary tract & Bladder Pancreas Cervix Stomach Features of these cancers include: o Typically spread towards the area / tissue of least resistance (e.g. through vessels) o Lymphatic Spread o Mucosal invasion Other features from other diseases include: o Black lungs (due to tar particles) o Gastric ulcers / haemorrhage Emphysema will involve: o Bigger Alveoli o Uneven-sized Alveoli Chronic Bronchitis will involve: o Mass influx of Neutrophils and other inflammatory / immune cells o Massive thickening of basement membrane o Goblet Cell Metaplasia Cardiovascular Disease will involve: o Atheromatous change (i.e. massive infiltration of Macrophages that will result in a reduction in the size / space of the vessel) o Myocardial Infarction o LV Hypertrophy o Stroke / Haemorrhage - - - - - SLEEP PHYSIOLOGY OF SLEEP To introduce concepts of normal and abnormal sleep and circadian physiology 23 - - Sleep is a reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment o Very low or high reported hours of sleep associated with higher death rates Sleep is a homeostatic phenomenon (i.e. pressure for sleep increases with increasing time awake); this is discharged with sleep o Physiological basis of homeostatic drive not fully understood Sleepiness is also determined by the time of day (i.e. Circadian Physiology) o Circadian Clock is managed by the Suprachiasmatic nucleus (SCN) of anterior hypothalamus o Circadian Clock will determine release of Melatonin and changes to core temperature, which affect propensity to sleep o Note: Circadian Clock regulates not only sleep patterns, but also metabolism, hormones, feeding, etc. Systems related to sleep and arousal inhibit each other to maintain stability The effects of insufficient or disrupted sleep will be discussed - Function of sleep is not known, but there are many proposed reasons (e.g. Energy conservation, thermoregulation, cellular repair, neural maturation, learning & memory, etc.) o Whatever its purpose, sleep appears necessary o With prolonged wakefulness, it becomes progressively more difficult to prevent episodes of sleep Lapses or microsleeps inevitable with prolonged wakefulness Sleep restriction (i.e. not sufficient sleep per night) will accumulate over time, such that someone sleep 6 hours per night will have considerable number of lapses after two weeks o Other adverse effects of insufficient sleep include: Blurred vision Mood changes / Irritability Nausea Hallucinations / Delusions Behavioural or performance impairments (e.g. poorer memory) - - SLEEP DISORDERS The common sleep disorders, their epidemiology and modes of presentation, basic differential diagnosis, consequences - Common list of sleep disorders include o Insomnia o Sleep Apnoea o Narcolepsy o Disorders of Arousal (NREM) / REM Behaviour Disorders o Restless Leg Syndrome (RLS) o Sleep Schedule Disorders Insomnia involves a difficulty of sleeping despite adequate opportunity and circumstances for sleep resulting in daytime sleepiness, fatigue, cognitive impairment, mood disturbance, etc. o Epidemiology ~30-40% of adults have experienced Insomnia More likely in women (1.5x vs. men) More likely in elderly More likely in those working unconventional work week Insomnia is commonly associated with a range of other co-morbidities (85% of Insomnia will occur with another co-morbidity) o Drivers Predisposing Factors (e.g. genetics, hyperarousal, depression, etc.) Precipitating Factors (e.g. acute stress, illness, medications, etc.) - 24 - - - Perpetuating Factors (e.g. dysfunctional attitudes to sleep, increased time in bed, etc.) o Consequences Increased risk for psychiatric disorders (overlap with depression) Decreased quality of life Increase health care utilisation and costs Increased absenteeism/occupational performance Falls Motor Vehicle Accidents Increase pain sensitivity Cardiovascular disease o Treatments include behavioural (e.g. sleep hygiene) and pharmacologic (e.g. benzodiazepines, melatonin, etc.) Obstructive Sleep Apnoea (OSA) is characterised by repeated upper airway closure during sleep o Risk Factors Age Male Central Obesity “Facial shape” Endocrine Disorders (hypothyroidism, acromegaly) Smoking Allergic disease o Symptoms Restless Sleep Loud Snoring Excessive Daytime Sleeping (EDS) Morning Headaches o Consequences Motor Vehicle Accidents Occupational Accidents Cardiovascular Disease (e.g. Hypertension, Stroke, Coronary Heart Disease, etc.) Erectile Dysfunction o Treatment improves sleepiness, cognitive performance and quality of life and can include Weight Loss / Exercise Positional Therapy (i.e. don’t sleep on back) Cessation of Alcohol and Smoking CPAP Oral appliances (e.g. Mandibular advancement splints) Surgical Procedures (e.g. Palatal Surgery) Hypercapnic OSA (Obesity Hypoventilation Syndrome) defined by extreme obesity and alveolar hypoventilation during wakefulness (hypercapnic respiratory failure) o This will involve patients that may have Pulmonary Hypertension, Right Heart Failure, OSA, Obesity and evidence of respiratory failure (e.g. low oxygen levels, high CO2 levels) o This disease is associated with significant morbidity and mortality (and significant health care costs) o Treatment includes CPAP, BIPAP and Weight Loss Central Sleep Apnoea is similar to OSA, but occurs due to a central failure to indicate to the body to ventilate (and NOT an obstruction) o Central Sleep Apnoea involves a centrally mediated reduction in ventilation (no effort to ventilate), whilst Obstructive Sleep Apnoea involves a blockage of the airways (and there are efforts to ventilate) o Risk Factors Very Elderly Prior Stroke (i.e. brainstem injury) Cheyne-Stokes Respiration Opioid Use 25 o - - - - When present, often overlaps with OSA (and can also cause sleep disruption, daytime sleepiness) Narcolepsy is a chronic neurological condition that involves Excessive Daytime Sleepiness, Cataplexy (i.e. loss of muscle tone), sleep paralysis, sleep hallucinations o Risk Factors Adolescent Onset Obesity Disturbed Nocturnal Sleep o Consequences / Symptoms Excessive Daytime Sleepiness (EDS) Cataplexy (i.e. short-term loss of muscle tone [e.g. less than 2 minutes]) (typically triggered by emotion such as laughter or anger) Sleep Paralysis Sleep Hallucinations Motor Vehicle Accidents Short, irresistible sleep episodes (that are refreshing) Short sleep latency (i.e. quicker to go from awake to asleep) There is a very rapid transition to REM sleep and out of REM sleep CSF levels of Hypocretin < 110 pg/ml (<1/3 normal) o Treatment Proper sleep hygiene Avoidance sleep deprivation Maintain regular sleep-wake schedules (avoid shift work) Regular scheduled daytime naps (-15 minutes) Stress avoidance Pharmacological Approaches EDS Treatment (e.g. Amphetamines, Modafinil) Cataplexy Treatment (e.g. TCA, SSRI) (these are both REM sleep suppressors) Idiopathic Hypersomnolence o Similar to Narcolepsy except: EDS even after sufficient or even increased amounts of night time sleep and without cause Longer naps that are unrefreshing o Idiopathic Hypersomnolence (IH) patients have a unique CSF that inherently activates GABA receptors (which are critical for sleep) This is akin to being on sleeping pills all the time o Risk factors include EDS, Viral Illness and Adolescence o This condition is diagnosed after excluding all other sleep disorders o This condition may spontaneously resolve for ~15% of patients, but those who continue with this condition have less favourable outcomes Recurrent Hypersomnia is characterised by periods of EXTREME sleepiness (e.g. multiple days, one week, etc.) o This condition will include a range of other symptoms too (e.g. hypersexuality, hyperphagia [increased hunger], etc.) Parasomnias are disorders of arousal / partial arousal and sleep stage transition, with undesirable physical phenomena occurring predominantly in sleep o Non-REM Sleep Disorder examples include night terrors, sleep walking, confusional arousals o REM Sleep Disorder Risk Factors Male (9x vs. Female) Elderly (>60) Acute – Substance / Medication-induced Chronic – ~60% idiopathic, otherwise neurodegenerative Increase EMG tone is required prior to be able to make a diagnosis of a REM Sleep Disorder 26 o Restless Leg Syndrome (RLS) involves URGE Urge to move limbs Rest or inactivity precipitates or worsens symptoms Getting up or moving improves the sensation Evening or nighttime appearance or worsening of symptoms Note: This is typically not a major problem for those with the condition Risk Factors include: Family History Iron deficiency End Stage Renal Failure Pregnancy (particularly 3rd trimester) Medications (e.g. TCA, SSRI, Lithium, Dopamine antagonists) Treatments include Dopamine precursors and /or agonists, Gabapentin or Lyrica PATHOPHYSIOLOGY OF S LEEP APNOEA How abnormalities of breathing during sleep lead to the clinical syndrome of obstructive sleep apnoea and its physiological consequences - Apnoea is defined as cessation of airflow at the mouth and nose for ~10 seconds during sleep (10 seconds is ~two cycles of breathing (i.e. missing more than a breath)) Obstructive Sleep Apnoea (OSA) is characterised by recurrent upper airway obstructions during sleep o There are recurrent episodes of apnoea and hypopnoea (i.e. Respiratory Disturbance Index (RDI) ≥5 events/hour of sleep) and symptoms of functional impairment o Upper airway obstruction occurs when collapsing force of negative airway pressure exceeds the dilating force of upper airway dilator muscle activity Risk factors include: Male Elderly Obesity Genetics Cranio-facial anatomy Alcohol Arousal from sleep is responsible for terminating obstructive events (though these arousals do not usually lead to complete awakening) The fragmentation of sleep due to repeated arousals required to reopen airway and resume breathing in OSA results in cognitive dysfunction, memory loss, social disharmony, etc. OSA also results in decreases in oxyhaemoglobin saturation which lead to: o Pulmonary and Systemic Hypertension o Cardiac Arrhythmias, including atrial fibrillation o Myocardial Infarction and Stroke o Probable decreased survival - - The pathophysiological mechanisms contributing to upper airway obstruction and central apnoea during sleep - Causes of Upper Airway Obstruction / Collapse include: o Anatomical narrowing of the upper airway o Excessive loss of upper airway muscle tone o Defective upper airway protective reflexes (which activate upper airway muscles when there is negative airway pressure) o Frequent arousals (which may lead to hyperventilation post-apnoea, resulting in hypocapnia and reduced ventilation drive) Central Sleep Apnoea is a neurological disease (rather than a respiratory / upper airway disease) where the drive for ventilation is reduced - 27 o o o Central Apnoea due to Hypoventilation is characterised by blunted chemoreceptor responsiveness During sleep, wakefulness stimulus to breathe disappears → alveolar hypoventilation → central apnoea → arousal → restore ventilation Central Apnoea due to Hyperventilation results from abnormally high awake ventilatory responses Hyperpnoea → ventilatory overshoot → hypocapnia → central apnoea → mild hypercapnia → restore rhythmic respiration → hyperpnoea → repeat cycle Central apnoea results if arterial PaCO2 is lowered below a highly sensitive “apnoeic threshold” Central Apnoea due to Cardiac Failure results as heart failure will reduce circulation time of blood This means that it will take longer for the ventilation drive to occur when CO2 levels are high (as the high CO2 blood will take longer to reach the chemoreceptors) The delay in ventilation drive will results in the apnoeic episodes SLEEPINESS IN THE WORKPLACE The effects of shiftwork and extended work hours on neurobehavioural and physiological variables - Shiftwork and extended work hours will disrupt Circadian Rhythms (which are critical for sleep and other metabolic purposes), resulting in acute sleep loss and chronic sleep restriction; this will ultimately result in fatigue Shiftwork will result in a series of adverse physiological changes in the body o Increased risk of cardiovascular events o Changes in appetite / hunger (more craving for carbohydrates and fats) o Reduction in metabolism o Decreased fertility o Reduced immune function o Sleep disorders Shiftwork will result in a series of adverse neurobehavioural changes on areas such as: o Concentration o Memory o Reaction / Response Time o Decision Making o Attention o Sleep Onset o Errors / Accidents / Injuries - - The occupational impact of sleep disorders - Fatigue / tiredness resulting from sleep disorders will increase rates of errors, accidents and injuries in the workplace Many fatigue-related problems occur when the person is conducting a monotonous, routine task (rather than something new), but at a time when they normally would be sleeping Note: There are some people who are able to maintain their performance despite sleep deprivation (though people who are affected by sleep deprivation may lack the awareness as to the extent of their cognitive impairment) - CYSTIC FIBROSIS CYSTIC FIBROSIS AS A MULTI-SYSTEM DISEASE The aetiology and pathogenesis of multi-organ damage in cystic fibrosis 28 - CF results from mutations on Chromosome 7; there are thousands of possible mutations though the most common is F508del These mutations encode an abnormal CFTR protein; the reduction of function of the CFTR protein in the plasma membrane results in : o Decreased Airway Cl- secretion o Upregulated Na+ re-absorption from Airways o Increased mucous production and viscosity (due to lack of Na+ ions) o Decreased volume of airway surface lining fluid (which is needed for cilia to operate) o Decreased muco-ciliary clearance o Increased production of pro-inflammatory cytokines The pathogenesis of the clinical features of cystic fibrosis - Excessive Na+ re-absorption from airways results in more viscous, thicker mucous Dysfunctional CFTR protein results in decreased volume of airway surface lining fluid (which is needed for cilia to operate), and hence decreased muco-ciliary clearance Increased mucous in lungs increases risk of infection / inflammation Malnutrition occurs due to malabsorption in the Gastrointestinal Tract, which results in loss of calories, fat and protein Distended abdomen due to Meconeum Ileus, which is a thickening of the mucous in the bowel, resulting in distended bowels Clubbing can be another sign of Cystic Fibrosis; this reflects the underlying lung disease (in particular the Bronchiectasis) - The multidisciplinary team approach to management of cystic fibrosis - - Multidisciplinary Team is critical for managing patients with CF (e.g. Respiratory Physician, Gastroenterologist, Nursing Staff, Chest Physiotherapist, Social Worker, Dietician, CF Foundation, CF Community Nurse, etc.) CF patients have a range of needs (e.g. medical, supportive, education, social / financial, development approach) that are best satisfied by a multi-disciplinary approach Goals of multi-disciplinary approach are: o Delay / prevent disease progression o Attain optimal growth / nutrition o Maintaining quality of life for child patient and family o Encourage developmental independence o Support transition to adult care The impact of chronic disease on child and family - Chronic disease can be difficult for child and family given the large amount of time needed for daily management of the illness and its impact on the normal development of a child Difficulties of the child’s chronic disease may result in family breakdowns, so increased support for these families are needed Social workers can provide support for the family and help them integrate CF into their lives; furthermore, they assist with crises and directing them to other financial / disability support - - CYSTIC FIBROSIS AS A GENETIC DISORDER The value of DNA genetic diagnosis - Cystic Fibrosis is an Autosomal Recessive disorder Identifying the particular genes and alleles that have mutated will: o Clearly diagnose the particular disease; and o Provide an indication as to the severity of the disease (as different mutations have different impacts) 29 - DNA Genetic Diagnosis can also provide a diagnosis prior to apparent symptoms appearing; this will enable more rapid and prompt treatment prior to the degeneration of the individual (e.g. better outcome for newborns that have CF screening) Describe the significance of the CFTR gene and appreciate the role of family counselling and DNA mutation scanning - CFTR gene (Cystic Fibrosis Transmembrane Regulator) is the gene whose mutation is responsible for Cystic Fibrosis o Over 1,700 different types of CF mutations have been discovered, but most are VERY rare (70% of patients with CF have the F508del mutation) o The particular allele that has mutated will determine the severity of the CF o Variants in other areas of the gene will also affect the incidence of particular symptoms / effects of CF Family / genetic counselling can be provided to: o Parents who have had a child with CF, and are planning to have more children o People who have CF and are planning a family o Other relatives of a person with CF o CF carriers in the general population Genetic counselling aims to provide proper information to the couple regarding prognosis, treatment and risks / benefits of pre-natal tests so they can make an informed decision about becoming pregnant DNA Mutation Scanning with provide a pre-natal diagnosis that can be used to provide the couple with information whether the foetus / embryo is positive for CF (and hence whether to continue with the pregnancy / implant a different embryo) - - INFECTIONS IN CYSTIC FIBROSIS TBA - Cystic Fibrosis involves a defective CFTR gene, which will prevent chloride ions moving out of mucusproducing cells, leading to a mucus that is deficient in salts, extremely dehydrated (sticky) and static o Thick static mucus (sputum) is not cleared regularly (i.e. a good microbial habitat) o Infection begins in infancy with uncleared bacteria and probably viruses attaching to and invading respiratory airway epithelial cells Infections of the CF upper and lower airways are commonly polymicrobial communities that can grow as mixed biofilms o Bacterial species include: Staphylococcus aureus, Haemophilus influenzae, Burkholderia cenocepacia, Pseudomonas aeruginosa o Fungi include: Cryptosporidium sp., Aspergillus fumigatus, Candida albicans o Viruses include: Respiratory Syncytial Virus (RSV), Human metapneumovirus (hMPV), Adenovirus, parainfluenza virus There is a mixed range of different bacteria that will infect younger patients with CF (especially Staphylococcus Aureus) o However, as CF patients age, the diversity in bacterial infections decrease with the majority of infections (~52.5%) relating to Pseudomonas aeruginosa Bacterial pathogenesis is dependent on actively expressed virulence factors; for example, B. cenocepacia has the following virulence factors: o Quorum Sensing – Ability to attract other of the same species to the same site; bacteria attracting to this site from this method are much more efficient at entering the cell and forming a biofilm o Iron Uptake – Utilise the systems of the cell for itself; this will re-direct iron to the bacteria rather than the cell, ultimately causing the demise of the cell o Lipopolysaccharide / Exopolysaccharide – Senses the environment to finds attachment sites and ward off the host immune response o Antimicrobial Resistance (Efflux Pumps) – Pushes out any antibiotics that may target the bacteria - - - 30 o - - - - Flagella / Cable Pilus – Enable immediate movement of the bacteria away and attachment to different sites Staphylococcus aureus is the most prevalent organism among US CF children with a peak prevalence between ages 11–15 years o Its ability to form biofilms decreases effectiveness of antibiotic treatment o Small Colony Variants (SCV) have an increased ability to adhere to host components, to form biofilms and to invade and persist within host cells o Treatment is via antibiotics such as Flucloxacillin or Methicillin However, treatment of Staphylococcus aureus may lead to higher rates of infection with Pseudomonas aeruginosa Haemophilus influenza is a gram negative rod that is a common infector early in childhood, decreasing as patients get older o This bacteria is present in encapsulated and non-encapsulated phenotypes Burkholderia cepacia complex (Bcc) comprises 17 species of group of catalase +ve, non-lactosefermenting, Gram-negative bacteria infecting plants and animals o This is an opportunistic pathogen of immunocompromised people, including CF o Infections by ET12 serovars of B. cenocepacia have the most serious health outcomes Resistance to almost all clinically relevant antibiotics and patient-to-patient transmission further complicates treatment/prevention o B. cenocepacia are intracellular parasites, surviving well within epithelial cells and macrophages. This provides a reservoir for bacterial persistence o Treatment may include ceftazidime, doxycycline Pseudomonas aeruginosa is a Gram negative bacillus found ubiquitously in environment (soil, water, synthetic surfaces) (and hence is commonly inhaled) o This bacteria is highly antibiotic resistant and a prolific biofilm former (increases persistence) o Due to its antibiotic resistance, persistence and prevalence, P. aeruginosa is responsible for most adult CF patient deaths (it also becomes the dominant species over time) o At acute infection, environmental strains are more virulent; however, expression of certain virulence factors (e.g. protease, elastase, pyocyanin) decreases with chronic infection o Certain P. aeruginosa strains are more deadly, especially epidemic strains such as the LES, Manchester strain, AES-1 and AES-2 o Treatment Antibiotics that may succeed include: aminoglycosides, quinolones, cephalosporins, carbapenems, polymixins and monobactams (though note this bacteria is highly antibiotic resistant and so these may not be effective) IMMUNOLOGY / INFECTIOUS DISEASES IGE MEDIATED RESPONSES Immunobiology of IgE antibody responses, including their role in protective immunity to parasites and in hypersensitivity to environmental and other allergens - Purpose of IgE is to provide immunity / protection against parasites (function of mediators released from Mast Cells are to damage and kill parasites) o Clinical manifestations of allergies result from the release of mediators (e.g. Histamine) from Mast Cells Immunological mechanism of IgE will first involve sensitisation to an antigen following initial exposure, and then a provocation response to subsequent exposures o Sensitisation involves the antigen being taken up by an APC, which then activates a T-Cell the T-Cell will then activate a B-Cell to produce antibodies against that antigen, which then attach to Mast Cells There are a range of different mechanisms through which allergic sensitisation can occur (e.g. inhalation, ingestion, insect bite, injection, trans-placental, etc.) o Provocation response involves the antigen interacting with the antibody attached to the Mast Cell, which triggers the release of mediators from the Mast Cells (e.g. Histamine) - 31 - An initial ‘Early Phase Response’ occurs from the mediators immediately released (e.g. Histamine) However, Mast Cells also have a ‘Late Phase Response’, which is driven by the Mast Cells releasing chemokines that attract Eosinophils which arrive several hours later Mast Cells also interact with nerve endings, which provides a sensory warning for potentially dangerous exposures This will enable the person to avoid these exposures and protect them from these potentially noxious stimuli o Note: IgE and Mast Cells are located all over the skin and mucous membranes across the entire body Hypersensitivity involves genetic predisposition to generate an IgE antibody response to common, otherwise harmless environmental antigens o There is some evidence that people with allergic responses have an immune system more likely to have Th2 and TReg cells rather than Th1 and Th17 cells Th2 cells are more likely to respond to allergen exposure, and so this increased level may be responsible for Allergies o This hypersensitivity may lead to Anaphylaxis, Sneezing, Urticaria, Angioedema, Atopic Eczema, Asthma, Rhinitis, Allergic Conjunctivitis, o These people may suffer from the ‘Allergic March’ (i.e. development of additional allergies over time) Initially as an infant, these patients will have Atopic Eczema and will eventually progress to develop Allergic Rhinitis and Asthma MICROBIOLOGY OF PNEU MONIA IN AUSTRALIA The importance of age and underlying disease in predicting the most likely causative organisms in pneumonia - The prevalence of particular organisms causing Pneumonia will vary with age; for example (most likely at the top): o 1-3 months afebrile Chlamydia trachomatis Respiratory Syncytial Virus (RSV) o 1-24 months Respiratory Syncytial Virus (RSV) Other Respiratory Viruses Streptococcus pneumonia o 2-5 years Respiratory viruses Streptococcus pneumonia Haemophilus influenza o 6-18 years Mycoplasma pneumonia Streptococcus pneumonia Chlamydia pneumonia o 18+ years Streptococcus pneumonia Viruses Mycoplasma pneumonia Haemophilus influenza Similarly, the presence of underlying diseases will change the prevalence of the microbe causing the Pneumonia: o Without Co-existing disease Streptococcus pneumonia Mycoplasma pneumonia Viruses Chlamydia pneumonia - 32 o Haemophilus influenza With Co-existing disease Streptococcus pneumonia Viruses Haemophilus influenza Aerobic Gram Negative Bacteria Staphylococcus aureus The methods available for examining specimens, including immunofluorescence, and for viruses, interpretation of sputum gram stains, use of antigen detection methods, use of blood cultures and serological methods - The following specimens can be obtained: o Unsterile Examination of Sputum Prior antibiotic use will reduce the reliability of Sputum analysis This will be due to certain microbes having already been eliminated, with other microbes increasing growth to fill the space left behind Nasopharyngeal Swab Nasopharyngeal Aspirate Nasal Washing Urine Antigen Detection Note: Issue with using non-sterile sites are that several different microbes are expected to exist here and hence any identified microbes may not be the real cause of the Pneumonia o Uncontaminated (normally Sterile) Transtracheal Aspirate Bronchoscopy o Sterile Blood Pleural Fluid Lung Aspirate Lung Biopsy The different tests available include: o Culture o Staining o Biochemistry o Histology Additional Special Tests available include: o PCR o Serology o Immunofluorescence o Urine Antigen Testing Microbiologic diagnosis of Pneumonia is rare in routine practice and still quite uncommon in hospital settings o Instead, management guidelines are largely based on epidemiologic studies - - - ANTIMICROBIAL ACTION IN RESPIRATORY DISEASE The mechanisms of anti-microbial action in respiratory disease - The following types of anti-microbials have the following targets / mechanisms of action: o Beta-Lactams (e.g. Penicillin) and Glycopeptides inhibit bacterial cell wall synthesis o Macrolides, Ketolides, Streptogramins, Lincosamides, Oxazolidinones, Aminoglycosides and Tetracyclines inhibit protein synthesis within bacteria o Fluoroquinolones target the bacterial DNA 33 - - - The following types of anti-fungals have the following targets / mechanisms of action: o Polyenes target the Ergosterol plasma membrane integrity o “–azoles” inhibit biosynthesis of Ergosterol o Echinocandins inhibit Glucan synthesis The choice of antimicrobial will depend not only on the infecting organism but also host factors / environment Current Therapeutic Guidelines for Community-acquired Pneumonia in Australia indicate using a narrower spectrum of antibiotics for moderate Pneumonia (vs. stronger broad-spectrum antibiotics for Severe Pneumonia) o However, doctors in hospital commonly prescribe stronger broad-spectrum antibiotics (e.g. 3rd generation Cephalosporin) for even moderate Pneumonia o Penicillin + either Macrolide or Tetracycline will provide coverage for ~95% of bacteria causing Pneumonia There are a range of different bacterial resistance mechanisms such as: o Active efflux (i.e. reduced entry of antibiotic into cell) o Modified target (i.e. modification / mutation of binding cite for the antibiotic) o Inactivating enzymes (that target / inactivate the antibiotic) o Note: These above resistance mechanisms can either be intrinsic or acquired Key requirement for effectiveness of the antibiotic is the time in which the antibiotic concentration is above the MIC (rather than the magnitude above which the antibiotic concentration exceeds the MIC) o If the antibiotic concentration is above MIC for >50% of the dosage time, then the antibiotic will be effective o In contrast to other antibiotics, the key to Aminoglycosides are the ratio of the Peak Concentration to the MIC (rather than the % of dosage time above the MIC) Different areas of the body can achieve different maximum concentrations of antibiotics due to the physiology of the area o It is important to understand which part of the body the antibiotic will need to act in, as this will determine whether the antibiotic concentration will exceed the MIC for ~50% of the dosage time (and hence whether or not it is effective) DERMATOLOGY MECHANISMS OF CUTANE OUS HYPERSENSITIVITY Diseases caused by hypersensitivity in skin, according to Gell and Coombs classification, their diagnosis and treatment - Immune system plays a role in most skin diseases, and hence is critical when considering the skin The skin diseases can be classified as; o Type I (IgE Mediated) Anaphylaxis Urticaria/ Angioedema o Type II (Antibody Mediated) Bullous Diseases o Type III (Antigen-Antibody Complex Mediated) Vasculitis o Type IV (Cell Mediated) Contact Hypersensitivity (CHS) Delayed Type Hypersensitivity (DTS) Type I diseases make Mast Cells degranulate and include: o Anaphylaxis Systemic Anaphylaxis may be triggered by penicillin, bee stings, etc. Symptoms include difficulty breathing, vomiting, abdominal pain, urticaria / angioedema, swelling of tongue, wheeze, etc. - 34 - - Treatment of systemic anaphylaxis includes adrenaline (e.g. Epipen), anti-histamines and removal of the trigger (e.g. bee sting, nuts, etc.) o Urticaria (i.e. Hives) Triggers include local anaphylaxis, temperature, pressure, sun exposure, cholinergic exposure and stress Symptoms include ‘Wheels’ (i.e. Hive Wheels, which are red or skin-colour welts with clear edges) Lesions (i.e. ‘hives’) from Urticaria are short-term and will not persist beyond a few minutes or hours Treatment includes: Avoid precipitating factors and direct mast cell degranulators (e.g. Aspirin, NSAIDs, Alcohol) Antihistamines: H1, H2 Immunosuppresants (e.g. Prednisone, Phototherapy, Colchicine) only used for severe Urticaria Type II diseases can include organ-specific (e.g. Addison’s Disease), non-organ specific (e.g. RA, Sjogrens) or somewhere in-between: o Pemphigus This involves the immune system (antibodies) reacting against the upper most layer of the epidermis resulting in the epidermis falling apart and blistering The mechanism involves the antibodies reacting against the Desmosome junction between the keratinocytes in the epidermis Mucous membrane involvement is usually prominent This disease appears like a burn, and also involves fluid loss and a higher risk of infection There are many different types of the Pemphigus disease (e.g. Vulgaris, Foliaceus, etc.) Treatment includes: Stop any causative drugs Oral Corticosteroids will involve high dosage (1-2mg per kg for the patient) o Alternatively use Methotrexate, Cyclosporin, Azathiprine or Cyclophosphamide IVIG / Plasmapheresis Rituximab (anti-CD20) o Other Bullous Disorders (e.g. Bullous Pemphigoid, Dermatitis Herpetiformis) Bullous Pemphigoid involves the antibodies affecting antigens inside the basement membrane; this results in the epidermis rising, which creates the formation of a raised blister Treatment options are the same as Pemphigus Type III diseases involve complement activation against the Antigen-Antibody complex, resulting in tissue damage and influx of inflammatory cells o Allergic Vasculitis/ Leukocytoclastic Vasculitis (LCCV) / Polyarteritis Nodosa Triggers include Infection, Drugs, Autoimmune Disorders, Malignancy or Idiopathic Diagnosis will involve taking an appropriate history for above triggers Investigation of kidneys will provide insight into the extent of the disease (involvement of the kidneys signifies a more serious Vasculitis that requires more aggressive treatment) Vasculitis will typically resolve by itself with rest; more aggressive treatment though is possible with Steroids / NSAIDs, though this is generally not required Treatment options includes: Remove antigen Rest, warmth, compression stockings NSAIDs / Steroids Dapsone (more persistent or severe cases) Colchicine (more persistent or severe cases) Immunosuppresants (more persistent or severe cases) 35 - Type IV diseases involve cell mediates responses; they will not occur immediately but require ~72 hours to peak: o Contact Hypersensitivity (CHS) commonly occurs with nickel belt-buckles or necklaces Patch Testing is available where a range of different materials are applied to the skin, which is then observed a few days later for a reaction These diseases respond very well to Topical Steroids (Oral Systemic Steroids would rarely be required) o Type IV Atopic Eczema may be triggered by Dust Mite or contact dermatitis to topical agents Key diagnostic features include Pruritus (i.e. extreme itchiness), Personal / Family History of Atopy, Chronic Dermatitis and typical morphology and distribution of skin lesions Emollients (i.e. skin moisturisers) are an important treatment to minimise dryness and itchiness, though Topical Steroids can also be used OTHER PSYCHOLOGICAL EFFECT S OF TRAUMA A patient who suffers a traumatic injury may suffer a multitude of psychological effects by a number of avenues. This lecture illuminates a variety of possible psychological effects with special reference to posttraumatic stress disorder which is described in the Learning Topics - Post-Traumatic Stress Disorder (PTSD) results from exposure to actual or threatened death, serious injury or sexual violence o This exposure may be via: Direct experience Witness of the event as it occurred to others Learning that the traumatic event occurred to a close family member or friend Experiencing repeated or extreme exposure to aversive details of events (e.g. as a first responder) o A traumatic event does not necessarily require the individual to suffer from the trauma but can also result from the individual perceiving that they are experiencing the trauma Sufferers of PTSD will: o Re-experience the event through: Intrusive and distressing memories Dreams Feeling the event is happening again (e.g. Flashbacks, Hallucinations) Distress at exposure to reminders o Avoid stimuli associated with the trauma (which may result in associated social withdrawal or occupational difficulties) o Negative alterations in cognitions and mood associated with the trauma, such as: Loss of memory around the trauma Exaggerated negative beliefs about the oneself, others or the world Tendency to blame self or others Persistent fear, horror, anger, guilt, shame Feelings of detachment or estrangement from others Inability to experience positive emotions o Altered arousal and reactivity Increased irritability and anger Reckless or self-destructive behaviour Hypervigilance Exaggerated startle response Decreased concentration Disturbed sleep PTSD onset typically occurs weeks or months after stressor; symptoms must continue one month to meet criteria for diagnosis - - 36 - - Children suffering from trauma may have specific manifestations of trauma such as: o Repetitive play (e.g. play where their doll will repeatedly die) o Trauma-specific fear will arise from not only the traumatic event but similar events (e.g. child attacked by Doberman will begin to fear all dogs) as well as resulting in greater propensity for fear of other stimuli (e.g. more likely to be scared of the dark) o Children may believe there were omens that foresaw the traumatic event and be averse to these omens in the future Furthermore, they may feel guilt for the traumatic event as they feel they should have stopped the traumatic events after seeing the omen Childhood sexual abuse is particularly severe form of trauma resulting in a range of long-term effects such as loss of trust, sexualisation of normal affection, guilt, routine use of extreme defence mechanisms (e.g. disassociation), etc. OVERVIEW OF EMERGENCY MEDICINE Describe the role of the Emergency Department to stabilise, evaluate, treat and arrange disposition for all patients presenting o The wide range of severity of illness and patient complexity mandates the Emergency Department triage patients needs and priorities o Life threatening processes must be anticipated and dealt with in an immediate, ordered initial assessment. This assessment attends first to the most potent life threats of airway, breathing and circulation o When stability is secure then a more thorough evaluation with history and examination, which can identify processes requiring treatment or formal investigations o Emergency Department organisation and procedures are essential to deal with both the urgency and breadth of its role from management of medical and surgical emergencies to the management of trauma, assault, toxicological problems and pre-hospital care - Emergency Medicine is unique compared to other specialities as incoming patients are undifferentiated and the doctor needs to be able to diagnose the patient without any background information Emergency Medicine will involve providing treatment almost immediately whilst further investigations are being conducted o There may not be sufficient time to wait for tests / investigation results to return, so treatment is provided in the interim o Response (or failure to respond) to treatment can be a source of information in itself that can assist with obtaining a clear diagnosis There is significant time pressure in Emergency Medicine diagnoses and decisions need to made quickly even where these is limited information Triage involves a rapid assessment to determine the level of priority for seeing the patients o There are five stages / categories of Triage based on the level of urgency and severity A Trauma Team will ideally have a team leader who steps back and doesn’t conduct any procedures o This will allow the team leader to think about the broader situation and direct the team accordingly instead of getting tunnel-vision about a specific procedure - - HEARING IMPAIRMENT AND DEAFNESS IN THE COMMUNITY The different classifications of hearing loss, together with main cause of hearing loss in children and in adults - Hearing loss refers to impairment of hearing (compared to deafness which refers to total loss of hearing) The different classification of hearing loss are: o Conductive Hearing Loss = When sound cannot conduct through the ear (commonly caused by ear wax) o Sensory Hearing Loss = When the Cochlear isn’t working properly - 37 o - Neural Hearing Loss = When there is something wrong with the nerve innervating the Cochlear Main causes of hearing loss are: o Conductive Wax Perforated Tympanic Membrane Otitis Media with Effusion Dislocation of Ossicles (e.g. due to Cholesteatoma, Trauma, etc.) Otosclerosis (i.e. fixed [rather than vibrating] Stapes) o Sensory Loss of hair cells in the inner ear Congenital (may be indicated by Genetics, Birth Problems, Intrauterine Viral Illnesses) Acquired Infection Noise (e.g. people exposed to >90dB for >8 hours per day will eventually incur hearing loss) Trauma Ototoxic Medications (e.g. those with the suffix ‘-mycin’) Autoimmune Disorders Meniere’s Disease Late Onset Genetic Old Age CHILDREN IN HOSPITAL The major reasons for, and issues associated with, the hospitalisation of children - Hospitalisation of children may be needed for treatment not available at home, investigations, consultations, observation and / or education o Hospitalisation of children may be needed for not only treatment, but also sub-specialty consultation or investigations Sub-specialty consultations in out-patient services can be extremely difficult to organise (especially if multiple sub-specialities need to be conferred with) As a result, it may be easier to hospitalise the child to obtain access to this subspecialties Common reasons for hospitalisation of children include: o Respiratory infections / asthma o Dehydration o Trauma o Elective surgery o Other infections o Birth Most hospitalisation of children is for simple problems with a short length of stay; however, there exists problems needing prolonged stays (e.g. Prematurity, Anorexia Nervosa, Leukaemia, etc.) Adverse effects of hospitalisation include: o Infection o Family disruption o Loss of normal activity / school o Lack of stimulation o Treatment side-effects o Over-investigation o Reinforcement of sick role - - 38 - - - - - o Cost Principles to consider when contemplating hospitalisation of a child is: o Safety o Clinical Outcomes o Convenience for the Family o Efficiency o Note: You don’t need to be in hospital just because you’re sick Alternatives to admission include: o Ambulatory care / short-stay units (e.g. for Salbutamol stretching in Asthma) o Acute review clinics (appointment within 24 hours; parents can be taught the different treatments / mechanisms to manage their child’s condition) o Hospital in the home (may involve a patient being provided a Canula through which a nurse can visit the patient at home and provide IV antibiotics) o Home Visits Special considerations for children in hospital o Physiology – children have different physiology and so the risk thresholds for vital signs are different o Play – good environment including Play will make children happier, more accommodating and have an overall better experience o Procedures – avoid if possible as most procedures on children have the potential to be traumatic experiences for everyone o School o Parents / communication – need to involve 3rd party (i.e. parent) in decision-making o Child-friendly environment Impact of a hospital experience will vary by child due to differences in: o Health care variables (e.g. nature of condition) o Child variables (e.g. response to separation from family, understanding of condition, etc.) o Family variables (e.g. availability to child during hospital stay) o Environmental variables (e.g. contact with strangers, loss of autonomy, etc.) Each child in hospital should be provided with: o Play (assists child in becoming more comfortable in environment) o Preparation (this will help child understand what will happen, which make the child more accommodating and hence everything go smoother) o Procedural Support (ensures the procedure occurs efficiently and smoothly) o Follow Up Post Procedure (i.e. debrief with the child to explain what happened and what could be better) o Environment (make more child friendly [e.g. bring child’s favourite toy and blanket, decorated walls, etc.]) PPD UNCERTAINTY IN MEDICAL PRACTICE Understand the centrality of uncertainty to all medical practice - In the real world of clinical care, symptoms are elusive, test results unclear and decisions complex and distorted by emotion Uncertainty is ever-present! Be aware of the variation in uncertainty tolerance that exists between societies, professions and individuals - Difference cultures / societies, professions and individuals will have a different preferences such as tolerance for uncertainty (e.g. Australia has more tolerance for Uncertainty than rest of world) 39 Understand the potential psychological consequences for practitioners of concealing or managing large amounts of uncertainty - There is pressure on doctors to deny uncertainty, such as: o Denial of uncertainty may not merely be expected but often demanded by patients (who viewed expression of uncertainty as less competent) o Doctors want to act like they are competence and knowledgeable, and wish to deny their uncertainty (especially younger doctors) Doctors who are relatively intolerant of ambiguity are: o More likely to experience a greater frustration and anxiety o More likely to order excessive diagnostic tests and additional treatment o Less likely to discuss this uncertainty with their patients and are less likely to engage in shared decision making - Understand what is meant in patient safety systems theory by ‘latent errors’ - ‘Latent errors’ are deficiencies in design, organisation, maintenance, training, management, etc. that create the conditions in which people are more likely to make mistakes o These latent errors are in some ways pre-destined to occur due to the prevailing conditions Be able to describe the major cognitive errors in diagnostic reasoning and relevant de-biasing strategies - Availability heuristic o Tendency to accept a diagnosis because of ease in recalling a past similar case rather than on the basis of prevalence or probability o De-bias by verifying prevalence based on proper statistics Anchoring heuristic o Tendency to fixate on first impressions—selected symptoms or signs or simple investigation results as predictors of specific diagnosis o De-bias by thinking beyond the most favoured; reconsider in light of new data or unexpected course of illness Confirmation bias o Selective seeking out of information that seems to confirm favoured diagnosis and ignoring data that are inconsistent with the diagnosis o De-bias by looking for highly sensitive features of the favoured diagnosis that should be present and take note of findings that are highly specific for alternative diagnoses Premature Closure o Acceptance of a diagnosis before it has been fully verified by considering alternatives and searching for data that challenge the preliminary diagnosis o De-bias by reconsidering the case when refreshed and less distracted; consider extremes or “red flags” (i.e. what’s the diagnosis I don’t want to miss?) Framing effect o Tendency to opt for candidate diagnoses based on how the problem is perceived or framed according to past history, clinical setting, previous diagnostic labels, and other contextual factors o De-bias by deliberately consider the case from different angles: “Let’s play devil’s advocate” - - - - COMMUNICATING CERTAI NTY AND UNCERTAINTY TO PATIENTS Be able to describe the features of shared decision making - Shared Decision Making will involve: o Information about Options being provided by Clinician to Patient o Information about Preferences being provided by Patient to Clinician o Deliberation and Decision being made by Patient AND Clinician together Shared Decision Making requires information exchange is occurring in both directions with mutual deliberation and agreement required - 40 Be able to describe some major issues in communicating with patients about complex evidence and how decision aids can assist - The information involved in medical decision making can be quite complicated and needs to be communicated in a manner that enables the patient to understand the information, engage in the process and make informed decisions Patients may also be quite anxious and lack the prior knowledge to understand the medical terminology being used (or just lack basic health literacy) o Decision Aids have been shown to be effective across a range of dimensions, though their level of usage is less than optimal o Other decision supports such as question prompt lists, patient coaching and option grids may be useful - STRESS AND COPING Understand contemporary models of stress exposure and stress response - Stimulus-Based Model o Stress is external to person, who will experience a reaction in response to this stress o Weakness is that is treats the person as a passive respondent, with no contribution to the event / outcome Response-Based Model o Focuses on the physiological, psychological and behavioural responses of the person to stress o Weakness is it mainly concerned with the symptoms of stress, without considering how the person can alter the response to stress Transaction Model o Regards the stress process as an interaction between the person and the environment (i.e. Stressor Response related to Stressor Exposure AND Stressor Appraisal by the individual) o This is the current preferred model of stress as it provides the person with the opportunity to adjust to / deal with the Stress exposure and results in different people experiencing the same stressful exposure in different ways - - Understand the effects of acute and chronic stressors on biopsychosocial health parameters - Acute responses include: o Arousal of Sympathetic Nervous System and HPA Axis (i.e. secretion of hormones) o Heightened CV, respiratory and skeletal muscle function o Reduced blood flow to skin and digestive tract o Decreased skeletal muscle tone o Decreased immune response o Heightened alertness / narrowed attention Chronic responses include: o Accelerated Atherosclerosis o Bone demineralisation o Metabolic Syndrome (e.g. Diabetes, Central Obesity, Hypertension) o Poor problem solving / task performance o Decreased ability to relate socially o Reduction in memory o Increase CV Events (e.g. Arrhythmias, Heart Attack, Ischaemia) o Increased Infectious Diseases and Cancer Progression - Understand the difference between appropriate and inappropriate coping behaviours - Coping behaviours are efforts to manage stress 41 - Appropriate coping behaviours include problem-focused coping (reduce stressor intensity) and response-focused coping (manage stress response) Inappropriate coping behaviours are those that do NOT accept the circumstances and engage is delusion / projection (e.g. delusional beliefs, projective identification) POPULATION MEDICINE SUPPORT SERVICES FOR PATIENTS AND FAMILIES The issues involved in living with cystic fibrosis from the time of diagnosis, managing during childhood, adolescence and adulthood, and finally in the terminal stages - There are critical times when parents and people with CF need support: o Diagnosis o Declining Health o Terminal Stages Support at diagnosis includes helping parents cope with the following issues: o CF is a chronic condition for which there is no cure o It is a condition with an unpredictable prognosis o It requires rigorous daily treatment but in spite of this the condition will progressively worsen o It is a genetic condition with implications for parents planning to have more children Families may need support with: o Information, becoming knowledgeable about condition & sound parenting skills o Secure relationship between partners o Encouragement, commitment to treatment plan o Emotional Support, acceptance of situation o Respite & strong, involved support group o Financial Support o Normalisation o Hope, appropriate expectations Issues with adults include: o Transition from paediatric to adult care o The daily routine of fitting in inhalations, airway clearance, taking enzymes with everything you eat whilst trying to lead a “normal” life o Developing relationships with friends and partners, how to tell people about CF and when o Hospitalisations which mean time away from education and work o Dealing with the progression of CF involving decreased exercise tolerance and perhaps having to restrict work o Complications such as CF related diabetes and liver disease o Living independently o Financial difficulties such as the cost of medications o Parenthood – Men are generally infertile o Loss of friends with CF o Transplantation option as health declines Social workers can assist adults with CF by: o Finding the way through the Centrelink maze – not easy! o Seeking accommodation that is suitable and working through the NSW Housing maze o Helping people deal with depression that is a consequence of declining health o If transplantation is recommended then people often require help in adjusting to the fact that their health is reaching a crisis point o When an adult with CF dies their friends in the CF community need support and counselling o Helping Young adults accepting and grasping their chronic illness Support services can include teaching CF patients different coping strategies (e.g. Fight [Aggressive], Face [Assertive], Flight [Passive]) depending on the nature of the condition - - - - - 42 IMMUNISATION The nature and mechanisms of action of vaccines - Vaccines operate by induction of antibodies and / or induction of T-Cells against the disease o The initial primary immune response will be moderate, but the subsequent secondary immune response to future exposures (such as the actual real-life microbe) will be much stronger and quicker o Hence, the vaccination will enable quicker and more effective eradication of the microbe (and hence prevent disease) This induction involves the patient ingesting or injecting either a live attenuated version of the microbe (that is insufficient to cause anything more than mild disease) or an inactivated version of the microbe o Live vaccines are marginally more dangerous, but do stimulate a stronger immune response that typically provides life-long protection o Inactivated vaccines are safer (especially for the immunocompromised), though several doses may be needed for lifelong protection - The range of vaccines that are used, their effectiveness and impact on the health of populations - Vaccinations have significantly reduced the mortality and morbidity from these diseases; they save ~2-3million lives per year Vaccines have been able to prevent (and in some cases eradicate) the following previously horrifying diseases: o Smallpox o Polio o Diphtheria o Measles Vaccinations are generally provided to children (based on a vaccination schedule after birth), though there benefits apply not only to children but also adults (who avoid contracting illnesses from these vaccinated children) There have been concerns about the over-vaccination of children and the potential adverse sideeffects, though several studies have shown the side-effects to be minimal and the concern to be based on misunderstanding and /or misinformation - - - SEMINARS ROAD TRAUMA – ACTIVE AND PASSIVE S AFETY Describe the extent to which road traffic crashes contribute to injury-related death and disability in Australia and internationally - 1.3 million deaths worldwide per year due to Road Trauma o Over 75% of all deaths in Low & Middle Income Countries o Deaths due to Road Trauma are predicted to increase by over 60% in next 20 years Road Trauma is the leading cause of death for young people worldwide Annual Road Death in Australia in 2009 were 1,616 (7.8/100,000) Describe the trends in injury related death and disability that has occurred globally over the last three decades - Global road injuries have increased by 46% in the twenty years to 2010 and account for almost a third of the world’s injury burden Deaths from Road Trauma are declining in developed countries, but expected to increased in developing countries - 43 Understand the respective roles of human and vehicle factors along with physical and social environmental factors in the causal pathways for motor vehicle crash and injury - Risk Factors for Road Trauma Injury are: o Driving Exposure (e.g. travel modes, land use, road design, etc.) o Crash Exposure (e.g. driver experience, speed, alcohol, fatigue, distractions, number of passengers, etc.) o Crash Severity (e.g. speed, alcohol, non-use of seat-belts, unforgiving roadside objects, insufficient vehicle crash protection, etc.) Risk factors influencing severity of post-crash injuries o Human tolerance / health o Automatic vehicle alerts o Vehicle design for ease of extraction Therefore, there are a range of different factors / considerations to consider in the causal pathways for MVA and injury - - Use the Haddon Matrix to identify strategies for prevention of motor vehicle crash and injury - Haddon matrix is a conceptual model in which the principles of public health were applied to the problem of traffic safety. This approach led to substantial advances in the understanding of the behavioral, road-related and vehicle-related factors that affect both the number and severity of road traffic related injuries Matrix considers four factors (i.e. Human, Vehicle, Environmental, Social) across three timeframes (i.e. Pre-crash, Crash, Post-crash) - Identify and discuss the evidence for the effectiveness of these strategies - Strategies developed include: o Safer drivers (e.g. provisional licensing system, limits on # of passengers) o Bans of mobile phone use o Prohibition of alcohol / drugs (e.g. RBT, Speed Cameras) o Speed limits /restrictions (especially for inexperienced drivers) o Safer vehicle design (e.g. Seatbelts, ABS Brakes, Electronic Stability Control, Airbags) o Road Environment (e.g. well-designed road corners, reduction in roadside objects, etc.) o Automatic Vehicle Alerts post-crash o Streamlined emergency response procedures LUNG FUNCTION TESTS – AIRFLOW OBSTRUCTION Concept of airflow limitation or obstruction - Airflow limitation / obstruction is where something exists in the airways that narrow the size of the airways hence increasing resistance This will make it more difficult to expire air from the lungs The methods that underpin measurement of airflow limitation - Spirometry is used to measure airflow limitation / obstruction The following metrics are measured: o Forced Expiratory Volume in 1 sec (FEV1) o Forced Vital Capacity (FVC) By expressing FEV1 as a percent of Vital Capacity – FEV1/FVC - you get an absolute measure of airways resistance o FEV1/FVC 80% = Normal Airways Resistance - 44 - o FEV1/FVC <70% = Airways Limitation / Obstruction (after use of bronchodilator) Peak Flow Rate (maximum flow rate achieved after maximal inhalation followed by forced exhalation) is also a measure of airways obstruction o Peak Flow Rate is a cheaper, simpler method to measure airway obstruction GLOBALISATION AND PU BLIC HEALTH – ONE WORLD ONE HEALTH What is globalisation? - Globalisation is the process of increasing international interconnectedness, such that there is an interdependence between the various countries of the world This applies to not only economic and social areas, but also health and environmental areas What is the concept behind 'One Health"? - One Health considers the interplay between human, animal and environmental health o There is recognition that it is increasingly difficult, and not sensible, to focus on one aspect without taking the others into account. o There is recognition of the importance of ecology and environment to human health How has globalisation impacted public health practice locally and internationally? - Globalisation has highlighted the different public health needs / focus in different countries o Many of the major diseases in developing countries are attributable to environmental factors o Many of the major diseases in developed countries are attributable to lifestyle factors o There is significant inequality in the health burden across different countries (e.g. high health burden in Sub-Saharan Africa vs. Australia) Furthermore, the increased linkages between countries has also made it very relevant to consider the health progress / status of countries throughout the world, as a disease may develop in one country and quickly spread throughout the world (e.g. SARS Virus, HIV/AIDS) - How well are local and international policies and services keeping up? - The impact of climate change and reduced biodiversity are concerning as local and international policies have not proven sufficient yet to tackle these global issues Certain local steps have been taken, which have been effective at a local level, but broader global action will be needed on other critical issues - What are the emerging challenges and opportunities facing public health in an increasingly interconnected world? - Opportunities include: o Food from around the world can be sent to areas of hunger and malnutrition, which will help resolve this significant health and wellbeing issue o Best practice techniques can be shared throughout the world Challenges include: o The lack of coordination and agreement regarding the best solution / approach to many broader issues that will ultimately affect health (e.g. climate change) o Diseases developing in one part of the world are at risk of spreading throughout the world very rapidly improvements in transportation / travel significantly increase the risk of a future global pandemic - What part do future medical practitioners play in addressing those challenges and opportunities? 45 - Medical practitioners need to be aware of these challenges and opportunities and respond accordingly o Report diseases of public health importance to authorities o Consider potential animal/environmental exposures in the medical history (pets, wildlife, vectors) and counsel clients about risks o Consider information about clinical disease in animals as potentially relevant to human health o Advocate for global solutions for global problems HONESTY IN MEDICAL P RACTICE Be aware of the different types of certificates - The main categories of certificates are: o Sick – Work, Study, Centrelink o Fitness – Driving, Diving, Pre-Employment, Travel o Entitlement – Disabled Parking, Carer’s Pension, Centrelink o Legal – Birth, Death, Cremation, Passport Have an understanding of the principles underlying medical certification - Medical certification leverages the trust society places in the medical profession Doctors should sign certificates honestly, truthfully, ethically and morally o It is critical to ensure documents signed should not be incorrect or misleading, regardless of whether the consequences of that document are small or large o Your reputation (and the reputation of the medical community) is at stake and will be sullied by signing / certifying a misleading document Be able to discuss doctor, patient and societal issues regarding certification - Key issues to consider are: o Patient and Doctor honesty o Patient privacy & confidentiality vs. Third-Party needs o Doctor conflict – needs of the patient vs. need to be honest o Who is paying for the doctor’s services? o Effect on doctor-patient relationship Understand why ‘speaking up for safety’ is hard and why it matters - Doctors are reluctant to identify and openly speak about errors / problems with other doctors practice o It can be very difficult / awkward to have this discussion and can be easier to try and get around it o However, it is important to be able to speak up rather than try and avoid the problem (e.g. directing own patients away from the doctor) as there will still be patients being treated by the offending doctor receiving substandard care (e.g. Dr Jayant Patel) Know what is meant by whistle blowing - Whistleblowing refers to revealing / reporting misconduct, dishonest behaviour, violations of law / ethics, etc. occurring within an organisation This typically involves acting against the prevailing norm in the organisation to speak out o Ostracisation of whistleblowers commonly occurs, especially as whistleblowing by definition rocks the boat and upsets the status quo Articulate the main dimensions of incident disclosure policy 46 - - It is important to treat patients with respect and be open about clinical incidents o When an error has been made, doctors should express regret and seek forgiveness o Provide the patients / families with a factual explanation of what happened, discuss the possible consequences and explain the steps being taken to manage the adverse event and prevent recurrence o Patients / families should also be provided an opportunity to relate their experience and their feelings It is important to realise this is a TWO-WAY discussion that may occur over a period of time Identify the priorities of patients harmed by incidents and of their relatives - Patients and their families often just want to: o Understand what happened o How it happened; and o What will be done to prevent recurrence Patients and their families are not usually seeking to apportion blame / sue Discuss the main strategies central to effective incident disclosure communication - Pro-actively discuss / raise the incident with the patient and their families When an error has been made, doctors should express regret and seek forgiveness (and not offer a qualified, ‘non-apology’ instead) Provide a factual explanation of what happened, discuss the possible consequences and explain the steps being taken to manage the adverse event and prevent recurrence o Be open and honest about the issue, instead of trying to hide / mislead o Do not minimise the extent of the issue as this may appear dismissive to patients - PREVENTION AND AWARE NESS OF ASTHMA The importance of preventative measures in the management of asthma - Asthma is a highly prevalent disease with ~10.2% of the population having Asthma Preventative measures are needed to minimise deaths (~400 / year compared to ~1,000 per year in the 1980’s), hospitalisations (~20,000 / year in NSW) and reductions in quality of life Preventive measures can: o Primary prevention - preventing an illness or injury before it starts o Secondary prevention - treatment of an asymptomatic illness to achieve remission or cure o Tertiary prevention - prevention in people with an illness or injury to reduce the severity The content and limitations of current preventative strategies - Primary Prevention strategies include avoiding maternal / parental smoking, encouragement of breastfeeding and diet with increased fruit and vegetables o Other primary strategies such as minimising exposure to house dust mites, avoid early antibiotic use, childhood infections, etc. have been proposed but there is a lack of clear evidence as to their efficacy Secondary Prevention strategies include reduction in HDM, cat and cockroach allergen levels is possible in the home with appropriate intervention o However, the specific strategies undertaken must be tailored to the individual based on their environment and allergen sensitivities o Secondary Prevention aims to prevent the ‘Allergic March’ Tertiary Prevention strategies include use of Bronchodilators (e.g. Short-Acting Beta-Agonist, LongActing Beta Agonist [LABA]), Inhaled Corticosteroids (ICS) or a combination of LABA + ICS o Ensure patient has the proper technique for use of these inhalers - - 47 o o Another technique involves the patient taking an additional dosage of ICS and LABA when their Asthma worsens above and beyond their baseline levels of ICS + LABA Other techniques include avoidance of triggers, avoid smoking, management of comorbidities (e.g. reflux, OSA) The best means communicating these strategies to the patient and the community - Development of a clear Asthma Action Plan will help communicate the different strategies for the patient o Asthma Action Plan should be developed in conjunction with the patient o Ensuring a collaborative process will increase the likelihood of compliance / usage of the Asthma Action Plan Continued education and reinforcement are needed with patients to ensure they fully understand how to best manage their Asthma Guidelines / handbooks are also available for patients / the community to understand the different strategies available - LUNG FUNCTION TESTS – RESTRICTIVE LUNG DISEASE The principles that underlie a number of lung function tests, including lung volumes (VC, TLC, FRC and RV) and diffusion capacity (DLCO) - With restrictive lung disease, air cannot enter the lungs, resulting in a fall in TLC and VC o Restricted lungs have limited capacity to expand, and so the amount of air inhaled with be limited (this will limit / reduce the Peak Flow Rate) o Note: The FEV1/FVC Ratio will remain normal, as both FEV1 and FVC both fall but by the same proportions o Restrictive Lungs will also have V/Q Mismatch and hence reduced diffusing capacity Actual values of FRC and RV can be measured by calculating the change in a known concentration of a gas after breathing it in a closed system o This is due to the equilibrium level of the new concentration having to equal the concentration in the lungs o This fact can then be used to estimate the volume of the lungs Diffusion Capacity (DLCO) involves measuring the difference in concentration of Carbon Monoxide inspired vs. expired after holding the breath for 10 seconds o The difference in concentrations will indicate the level of diffusion (with adjustment made for dilution of Carbon Monoxide within the blood) - - LUNG DISEASE RESULTI NG FROM OCCUPATIONAL EXPOSURE Provide an overview of main occupational lung diseases - Identifying Occupational Lung Diseases is critical as appropriate identification will enable removal of the patient from this environment / exposure and the prevention of a long-term problems Main Occupational Lung Diseases are: o Asthma o COPD o Lung Cancer o Mesothelioma o Pneumoconioses (e.g. Asbestosis, Silicosis, Coal Worker’s Pneumoconioses) o Pneumonitis o Inhalational Fevers o Extrinsic Allergic Alveolitis (e.g. Farmer’s Lung, Cheese Worker’s Lung) o Infections - 48 Provide an overview of causative exposures of occupational lung diseases - Types of exposures that result in Occupational Lung Diseases include: o Gas o Fumes o Vapour o Mists o Dusts o Aerosols Causes of Occupational Lung Diseases include: o Biological causes (e.g. grain, flours, fungi, fur, etc.) o Chemical causes (e.g. welding fumes, alcohols, CFCs, Isocyanates, Asbestos, Coal Dust, Silica Dust, etc.) Top three specific causes of Occupational Lung Diseases are: o Asbestos o Silica o Diesel Exhaust - - Provide an overview of approaches to diagnosis, treatment and prevention - Diagnosis will require a careful, detailed history and examination o Look for temporal association with work o Look for appearance of similar symptoms in co-workers o Changes in FEV1 and Peak Expiratory Flow Rate (PEFR) Treatment will involve: o Targeting ‘Hierarchy of Control’ (which refers to different approaches available to deal with occupational exposures) to minimise further exposures Elimination of exposure Substitute exposure Isolate from exposure Engineer solution to minimise exposure Change system of work to minimise exposure PPE against exposure Note: The best options are the top of the hierarchy (i.e. Eliminate), whilst the worst options are at the bottom of the hierarchy (i.e. PPE) Normal medical treatments for that type of lung disease (e.g. Occupational Asthma = Same Treatment as Asthma, Asbestosis = Same Treatment as ILD) - - SPIRITUALITY AND MEA NING OF MEDICINE Explain the relationships between spirituality, religion and health and their role in the experience of suffering - Patient’s spirituality will influence: o How they understand health, illness, diagnoses, recovery and loss o Strategies they use to cope with illness o Their resilience, resources and sense of support o Decision making about treatment, medicine and self-care o Expectations of, and relationship with, health staff o Day-to-day health practices and lifestyle choices o Overall health outcomes Suffering is an individual, subjective experience based on the historical, cultural and social context which is unique to each individual Spirituality / Religion play a important role in how people perceive their health situation and the level of suffering experiences o It is important to understand how the patient views suffering as the provided medical intervention may not be suitable to relieve this suffering (and indeed may cause suffering) - 49 - Healthcare needs to incorporate the importance of spirituality / religion and support patients with the spiritual support they desire Spirituality is associated with superior health outcomes such as longevity, pain relief, recovery from illness, adjustment to disability, improved palliative care outcomes and coping with illness Recognize some of the spiritual issues patients may want to explore in relation to acute or chronic illness and the place of a spiritual history - Number of studies have shown most patients desire their doctor to know about their spiritual beliefs and how these beliefs influenced their approach to a severe illness o Holistic patient care should therefore involve understanding the patient as an individual including how spirituality influences them o Spiritual History may therefore be appropriate for these patients (though need to be careful to respect patient’s beliefs and NOT to impose one’s own beliefs) Appreciate the influence of spirituality on patient decision making in treatment and therapy - Spirituality is critical for providing patients with support through their illnesses / diseases o Doctors should respect this important role of spirituality and attempt to tailor the treatment / therapy in a manner that allows the patient to follow their spirituality o This may require changing from the ideal ‘best practice’ therapy, but this trade-off may be appropriate if the support and hope the patient obtains from their spirituality is more important Spirituality may be particularly relevant in end of life scenarios, so it is important to support the patient in their expression of their spiritual needs - Understand the role of chaplains/pastoral care workers in the health system and when referral is appropriate - Chaplains / Pastoral Care Workers in the health system provide religious counselling / spiritual support to not only to patients and their families, but also staff members in hospitals o They play an important role as part of a multi-disciplinary team treating patients and should be included as part of this broader team Referral of patients to Chaplains / Pastoral Care Workers may be appropriate for patients in need of support o This support may take various forms whether they are spiritual or non-spiritual (e.g. listening, praying, following up referrals, providing sacramental support (e.g. blessings, baptisms) or services (including memorials or funerals)) - MICROBIOLOGY OF PNEU MONIA To understand clinical and public health importance of the most common causes of pneumonia and mechanisms of their transmission - Pneumonia is a respiratory illness and can be transmitted via airborne spread o However, aspiration of gastric contents is a common cause of pneumonia (as many bacteria are able to enter the lungs) o Commensal Flora may also be the cause of pneumonia, so this needs to be considered (will affect treatment needed) Different bacteria / viruses are more likely to affect particular parts of the respiratory system understanding the different types of pneumonia-causing bacteria will enable isolation of the site of infection Understanding the different causes of pneumonia are important as public health measures can be implemented to prevent these causes - - 50 To understand differences in aetiology, clinical significance and methods of laboratory diagnosis of community- and hospital-acquired pneumonia - Community-acquired pneumonia develops in immunocompetent individuals outside of hospitals or who have been in hospital for less than 48 hours Community vs. Hospital-Acquired Pneumonia are caused by different organisms o Community -Acquired Pneumonia is monomicrobial and mainly Streptococcus pneumonia (i.e. Pneumococcus) or Haemophilus influenza Other types of Community-Acquired Pneumonia include Mycoplasma pneumonia, Chlamydia pneumonia or Legionella species (which are all causes of ‘atypical pneumonia’) o Hospital-Acquired Pneumonia may be monomicrobial or polymicrobial; common causes are Klebsiella pneumonia, E-Coli, Pseudomonas aeruginosa, Staphylococcus aureus, etc. Key difference in hospital-acquired pneumonia is the bacteria causing the pneumonia are much more drug resistant than community-acquired pneumonia (and hence prognosis is worse) Laboratory Diagnosis will include Sputum Culture (e.g. Gram Stain), Blood Culture (more reliable than Sputum as blood is a sterile sample), Urine Test and / or Serology - - PHYSIOTHERAPY IN CYSTIC FIBROSIS The physiological effects of excess secretions and the impact on these on various mucous clearance techniques - Abnormal mucous (e.g. more viscous, excessive volume) in CF can result in mucous plugs that obstruct breathing o Stagnant sputum creates ideal conditions for infection o The resulting inflammation will damage the bronchial tissue resulting in permanent dilatation of the bronchi and increased airway collapsibility (which will impair ventilation and gas exchange) Coughing will only clear sputum in more central areas of the lung (but not necessarily the peripheral areas of the lung) and will take a lot of energy - The range of techniques for mucous clearance - Speed up the movement of mucous; this can involve: o Taking a slow deep breath in and then rapid exhalation (e.g. ACBT) o Specific expiration techniques (e.g. Autogenic Drainage, Huff) o Postural Drainage / Percussion and Vibration of the lungs to mobilise the mucous Prevent airway collapse or blockage o PEP Devices o Relaxed Breathing Techniques Make mucous less thick o Oscillation o Hypertonic Saline / Mannitol o Antibiotics o Exercise - - The physical effects of some of these techniques - ‘ACBT’ refers to Active Cycle of Breathing Technique o Thoracic Expansion Exercises will involve taking deep breaths that open up the airways (which make it easier to retrieve and expel mucous from the peripheries) o Huffs will mobilise mucous and bring the mucous further up the airways, which will make it easier to clear with one subsequent cough Autogenic Drainage reaches the highest airflow each generation of bronchi without airway collapse (aim for a mucous rattle rather than a wheeze) - 51 - - - - - Positive Expiratory Pressure will open up collateral channels to areas of the lung that are blocked off from mucous plug o This will assist with expelling the air in these ‘blocked off’ channels, which can push out the sputum from these peripheries and hence open up the airways again o Furthermore, Positive Expiratory Pressure can open up floppy central airways that may be partially obstructed ‘PDPV’ refers to the Postural Drainage Percussion Vibration technique; this loosens the thick, sticky mucous in the lungs so it can be removed by coughing Oscillation approximated the cilia ‘beat’ frequency to maximise vibration of bronchial walls and hence increase ease of clearance o Oscillation also ruptures the mucous gel and reduces sputum viscosity, thus making it easier to clear Hypertonic Saline disrupts bacterial biofilm and reduces viscosity of sputum, which improved mucocilliary clearance o Similarly, Mannitol alters mucous properties in a way that improves mucocilliary clearance Inhaled antibiotics reduce the concentration of bacteria, thus reducing the infection and inflammation that makes mucous thicker o A bronchodilator is initially used to open up the airways, before inhaling antibiotics (as the antibiotics will get deeper into the lungs) Exercise will reduce mucous elasticity, thus making it easier to clear o Resistance training will improve posture, which also assists with mucous clearance CRITICAL APPRAISAL OF OBSERVATIONAL STUD IES Review learning about observational studies in the Research Methods Block - Commonly used observational study designs in clinical epidemiology o Cohort (Prospective OR Retrospective) o Case-Control o Cross-Section o Case Series Cohort study involves assembling a group of people at risk of an outcome / disease and dividing them into two groups based on exposure to factor of interest o Members of each groups are then observed to determine who developed the outcome / disease of interest o Rates of outcome / disease of interest in exposed vs. non-exposed groups are compared o Cohort studies are the best evidence available when randomisation (i.e. RCT) is not possible Case-Control study involves assembling a group with the outcome / disease of interest already as well as a control group and looking back retrospectively to identify prior exposures for each group o This is a useful study design for rare outcomes or those needing lengthy follow-up Key biases that may be present in observational studies are: o Selection Bias o Measurement Bias o Confounding Criteria for causality: o Exposure preceded by onset o Dose-response gradient o Dechallenge-rechallenge study o Association consistent o Biological sense - - - - Introduction to critical appraisal of observational studies o Understand what critical appraisal is Critical appraisal is the systematic assessment of evidence from a research study using pre-specified ‘rules of evidence’ to determine if the research is: 52 o Understand how to approach the critical appraisal of observational studies o Relevant Valid Important Test relevance by assessing whether research question addresses the clinical question of interest Test validity by assessing: Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause? Were treatments/exposures and outcomes measured in the same ways for both groups? (was the assessment of outcomes either objective or blinded to exposure?) Was the follow-up of the study patients long enough (for the outcome to occur) and complete (so that no or very few patients were lost to followup)? Were objective outcome criteria applied in a blind fashion? If subgroups with different prognosis identified was there adjustment for important prognostic factors? Do the results of the harm study fulfil some of the diagnostic tests of causation? Test importance by assessing: What is the magnitude of the association between exposure and outcome? What is the precision of the estimate of the association between exposure and outcome? Practise critical appraisal by applying a ‘checklist’ to observational ‘Harm’ and ‘Prognosis’ studies 53
