Respiratory Notes PDF

Respiratory Notes Hypersensitivity Hypersensitivity - Adaptive immune response - inappropriate - Detrimental response in the host Allergen - Any antigen eliciting a hypersensitivity reaction (self or non self) - Organ system affected is variable - Asthma - LRT - H...

Respiratory Notes Hypersensitivity Hypersensitivity - Adaptive immune response - inappropriate - Detrimental response in the host Allergen - Any antigen eliciting a hypersensitivity reaction (self or non self) - Organ system affected is variable - Asthma - LRT - Hay fever - URT Common Allergens - Plant pollens - Dander of animals - Mould spores - Dances of small animals (dust mites) - Insect venoms - Vaccines and drugs - Food - Plant leaves - Metal - Synthetic chemicals and industrial products Reactions TYPE 1 - IgE - IMMEDIATE HYPERSENSITIVITY (2-30min) - Soluble antigen - often environmental - Produce IgE and Mast cell activation -> degranulation - Allergic rhinitis, asthma, systemic anaphylaxis - Discomfort to death reactions - Phases of Allergies - Phase 1 = Sensitization - First exposure to antigen eg; pollen - Extraction of antigen and activation of specific T cells - Production of IgE and binds to mast cells - Phase 2 = Elicitation - High affinity IgE receptor (FCRI) on mast cell  - Cross linked activated receptors transmit signal and release of preformed granules containing histamine =degranulation - Adrenaline (epinephrine) can combat blood pressure loss in anaphylactic reaction = changes in vascular permeability and SM - Histamines-> causes vasodilation (which leads ot warm of skin), increased permeability of venules (which causes swelling) and smooth muscle contraction (which causes bronchospasms) - Eicosanoids (Leukotrienes, prostaglandins and thromboxanes)-> derived form arachidonic acid TYPE 2 - IgG (or IGM) - Mainly from drug adminstation - 5-8 hours but can occur between 2-24h - IgG or IgM binds to self or forign antigens on cells like rbc,wbc, platelet - Cell death via phagocytosis, NK cell activity or complement mediated lysis - Pathology occur when destruction of tissue leads to illness in host - Cell or matrix associated antigen - FCR+ cells (phagocytes and NK cells) - Examples of reaction against blood cell and platelets - Drug allergies like penicillin - Via chemicals like formaldehyde - Transfusion reactions - Hyperacute graft reaction - few min to 48h after transplant  - Natural reactions - haemolytic disease of newborn - Erythroblastosis fetalis - Potentially fatal in newborn - Maternal IgG ab directed against antigens expressed on foetal RBC and target rhesus + blood group antigen on RBC - RH - mother and Rh+ baby, in 2nd preg = rbc from baby enter blood and stimulate RH-IgG ab which crosses into placental causing lysis/opsonization of fetus rbc = anemia TYPE 3 - IgG - Immune complex disease involving FCR cell complement (immune complexes) - 2-8 hours - Immune complex form every time ab meet antibodies and IC are generated - It is caused by the deposition of immune complexes in BV and tissue - Normal clearance exists to avoid hypersensitivity as immune complexes (covered in C3b) are bound to RBC (cr1) transported to liver and spleen for removal of complex from RBC by fixed tissue macrophages and larger are cleared most efficiently but sometimes not all are cleared - Patients with low level of clearance have poor binding of IC to RBC = reduced removal by liver and spleen - Soluble antigen - Serum sickness, arthus reaction, post strep glomerulonephritis, farmers lung and pigeon fanciers lung TYPE 4 - Reaction develop hours to days (24-96h) after contact (delayed type hypersensitivity) - Type 4 include type 1 DM, RA, contact hypersensitivity - Mediated by t cells and macrophages - NOT AB - TH1 (macrophage activation) - COntact dermatitis, tuberculin reaction - TH2 (eosinophil activation) - Chronic asthma, chronic allergy - CTL - cell associated antigen (cytotoxicity) - Contact dermatitis Contact hypersensitivity (CHS) - Also known as contact dermatitis - Antigens simple chemicals like nickel, plant, topically applied drugs,soaps and cosmetics - Initial contact sensitizes and memory TH1 cells migrate to tissue - Second contact leads to erythema, itching, eczema, or necrosis of skin within 12-48 h Anatomy of the Lung Muscles of Intercostal Diaphragm External intercostals – Elevate ribs - Musculo-tendinous partition splitting Internal intercostals – Depress ribs thoracic and abdominal cavities Innermost intercostals – depresses ribs? - Chief muscle of respiration - Innervated by phrenic nerve by motor and some sensory (C3,C4,C5) = Internal thoracic artery, posterior intercostal artery, thoracic aorta = intercostal vein, intercostal artery, intercostal aorta Airway Control Respiratory pressures - P-ATM: 760mmHg (Negative 760mmHg) Intrapulmonary pressure (Ppul) - Increase and decrease with phases - Eventually equalises with ATM pressure - Determines direction of airflow Intrapleural Pressure (Pip) - Pressure in the pleural cavity - Always 4mmHg less than Ppul - Maintains pull on lungs Transpulmonary pressure (Ptpul) - Difference between Ppul and Pip - Px lungs from collapsing Mechanics and pressure changes Inspiration 1. Inspiratory muscle contract (diaphragm descend and rib cage elevates) 2. Thoracic cavity increase in volume 3. Lungs are stretched: intrapulmonary volume increases 4. Intrapulmonary pressure drops 5. Air flows into lungs down the pressure gradient until intrapulmonary pressure is 0 Mechanics and pressure changes Expiration 1. Inspiratory muscles relax- diaphragm rises and rib cage descend 2. Thoracic cavity volume decreases 3. Elastic lung recoil passively - intrapul vol decreases 4. Intrapul pressure rises 5. Air flows out of lungs until intrapulmonary pressure is 0 Factors Affecting Pulmonary Ventilation 1. Airway resistance 2. Alveolar surface tension 3. Lung compliance Airway Resistance - Resistance to airflow - Inversely proportional to airway diameter - Decreases increases resistance - Bronchodilators decrease resistance and increase air flow - Mucus narrows airways - Irritants, inflamm chemicals activate parasymp reflexes = bronchoconstriction - Greatest resistance in bronchi near trachea in large bronchioles  - SM in bronchial wall is sensitive to neural control and chemicals - Resistance in smaller bronchioles important to disease (smaller in size, muscular contraction, oedema in walls, mucus collection in lumen) Alveolar surface tension - Caused by alveolar fluid - At water and air interface - water has strong attractive force for each other - Inside alveoli water attempts to contract and = force air out via alveoli collapse - Net effect: elastic contractile force in the lungs -> Surfactant - Secreted by type 2 alveolar epithelial cells - Contain phospholipid, proteins and ions - RED surface tension and increase lung compliance Lung compliance - Extent to which lung volume will expand for given increase in transpul pressure - Due to - Elasticity of lung tissue - Alveolar surface tension - Healthy lungs = high compliance - Reduced compliance results in increase force to fill and empty lung - Decease elasticity (fibrosis) = decrease compliance - Decrease surfactant production = decrease compliance - Decrease thoracic mobility (arthritis and paralysis) = decrease compliance - Alveolar damage (emphysema) = increase compliance NERVOUS CONTROL OF BRONCHIAL MUSCLE - Direct control of bronchioles via sympathetic nerves is very minor - Circulating Adrenaline - Acts of B2 receptors located airway SM mast cells, epithelium, glands - Bronchodilation - mediator release from mast cells (anti-inflam) and increase mucociliary clearance - Parasympathetic innervation dominates - Vagus nerve - Ach acts of M3 in SM - Bronchoconstriction - Fibres innervate airway SM (bronchodilation), vascular SM (vasodilation), glands (mucus secretion) NERVOUS CONTROL OF BRONCHIAL MUSCLE Other neurotransmitter/Modulators - Non-adrenergic, non-cholinergic, NNC Inhibitory (cause bronchodilation) - NO - inhibitory neurotransmitter - Vasoactive intestinal Peptide VIP - cotransmitter with ACh Excitatory (cause inflammation, bronchoconstriction) - Substance P, neurokinin A (neurokinins) - peptide neurotransmitters - 5-HT (serotonin) Local Control of Bronchial SM - Local secretory factors often cause bronchoconstriction - Histamine - Slow reactive substance of anaphylaxis - Released by mast cells in the lung during allergic reaction - eg to pollen - Irritants such as smoke, dust, sulphur dioxide, acid smog can act directly on lung tissue to initiate local, non nervous reaction reactions that cause constriction - Prostaglandins, leukotrienes, cytokines Respiratory Defence Mech - Inhalation of debris/pathogen will cause damage to resp exchange surface - Nose - Coarse hairs in nostrils remove large particles - Turbulent precipitation of particles - Airways - Nasal passageway warms and moisten conditions air - Goblet cells and submucosal glands in resp passageways produce mucus to trap particles and moisten airways - Ciliated epithelium continually sweeps mucus down to and up to pharynx (mucociliary escalator) - Lungs - Alveolar macrophages engulf trapped particles Nasal Conchae - During inhalation, the conchae and nasal mucosa filter, heat and moisten air - During exhalation these structures reclaim heat and moisture Mucocillairy escalator - Ciliated pseudostratified columnar epithelium with goblet cells produce a moving mass of mucus Respiratory Membrane - Alveolar macrophage SPIROMETRY - Measuring Ventilator Function Volume/Time Curve (spirogram) - VC, FCV, FEV1 calculated manually Flow/Volume loop - Use more common clinically Portable Spirometers - Automatically calculate indices - Stores pt data, calculate ref values Peak Flow Metres - Peak expiratory flow (PEF) - Pt use Anatomy of Pharynx and Larynx *Respiratory Acid-Base disorder Hydrogen - Contributes to PH - Has positive charge and is very reactive due to its large charge to size ratio - This means high affinity for negatively charged molecules such as proteins - Acids donate protons making a solution more acidic Non Volatile (Fixed acids) - Do not leave the solution and must be excreted eg: sulphuric acid, phosphoric acid (from breakdown of amino and nucleic acids) - Organic acids (lactic acid, ketones, fatty acids) are metabolised rapidly so don't usually accumulate unless large amounts are produced Volatile Acids - Can leave solution and enter atmosphere - Ie: lungs can breathe out CO2 Weak Acids - Are effective buffers because they can neutralise excess hydrogen ions by binding to them when the PH decreases and can release hydrogen ions when the PH increases Buffer Systems - Lungs and kidneys are largely responsible for regulating acid base balance of blood by independently controlling CO2 and HCO3 - Largest source of acid is CO2 production which occurs during oxidation of carbs, fats, and most amino acids - When we breathe out we prevent H production, metabolism also produces non-volatile acids which the lungs cannot handle - Metabolism also produces non-volatile which the lungs cannot handle, these acid also produce non volatile bases which end up as in bicarbonate - Kidneys excrete acid and also reabsorb/generate bicarbonate - Limitations - Requires normal respiratory function to eliminate CO2 - Dependent on bicarb availability (alkaline reserve) - Normally large alkaline reserve of NaHCO3 and HCO3 produced in kidneys Chemical - Acts immediately Respiratory - Acts within a few minutes Renal - Acts within a few hours to days Respiratory Control of Acid-Base Balance - Respiratory system controls alveolar ventilation (volume of fresh air that reaches the alveoli per min, which is available for gas exchange) - Because CO2 ultimately turns into H+ our breathing can provide short term and immediate control of blood PH - Hypoventilation - when H+ decrease, co2 accumulates through decreased ventilation (H+ decreases = rise in PH) - Hyperventilation - when H+ increase, co2 expelled through increased ventilation (H+ increases = drop in PH) Immediate chemical buffering, the lungs are second line of defence against PH disturbances If H+ increase = it will bind with bicarbonate and form CO2 -> breathe out to decrease H+ If H+ decrease = it will accumulate bind with water and form H+ -> to increase H+ If a healthy individual pCO2 is maintained 40mmHg, this is achieved by expelling the CO2 that is produced by cellular metabolism through the lung Any disturbance in the ability to eliminate CO2 may cause a change in blood PH so alveolar ventilation maintains normal pCO2 to px acute changes in PH Alveolar ventilation controlled by chemoreceptors located centrally in medullary and peripherally in the carotid body and aortic arch Renal Control of Acid-Base balance - The kidney can excrete acid load and maintain plasma HCO3 at round 24 mmol/L - The renal system provides a long term control of PH and can eliminate metabolic acids such as phosphoric acid, uric acid, lactic acid and ketones - The most important renal mech for regulating acid base balance are - Reabsorption of filtered HCO3 - Generation of new HCO3 by acid excretion - Formation of HCO3 by ammonium NH4 excretion - When the H decreases in the blood, it leads to an increase in PH (alkosis), the amount of free bicarbonate ions in the blood need to reduce as fewer H ions to neutralise - When the H+ increases in the blood it leads to a decrease in PH, to buffer this excess H+ bicarb ions needs to be available to neutralise the hydrogen ions Acid-Base Disorders - If acid-base imbalance is due to malfunction of a physiological buffer system, the other one compensates: respiratory system attempts to correct metabolic acid-base imbalances and kidney attempt to correct respiratory acid-base imbalances - Changes in arterial pCO2 results in respiratory acid-base disorders - Changes in plasma bicarbonate results in metabolic acid-base disorders Cause Clinical Manifestations Acute Depression of medullary resp centre CNS Resp Failure of resp muscle and chest wall motor - n&V, restless, headache, confusion, Acidosis function seizures Airway obstruction - Increased cerebral flow due to Ventilator defects vasodilation - Hypercapia - increase intracranial pressure Cardio - Increase bp and hr Renal - Renal vasodilation from mild hypercapnia but vasoconstriction due to severe hypercapnia Chronic Depression of medullary resp centre Less severe due than acute due to ph near Resp Failure of resp muscle and chest wall motor normal due to renal compensation Acidosis function - Symp with acuity and severity of co2 Airway obstruction & Ventilator defects retention  - Headache, restless, blur, lethargy, twitching, tremor, convulsion, coma - Resp rapid but adapts gradually - No cyanosis skin can be pink Acute Resp Alkalosis Obstructive Lung Diseases Types of diseases - Asthma = Bronchi - Chronic Bronchitis = Bronchi - Bronchiectasis = Bronchi - Emphysema = Alveoli Obstructive Lung Disorders - Lung disorders which obstruct the airway = resistance to the airflow - Reduced airflow especially due to expiration - Characterised by - Prolonged and deep expiration = More force required to expel air - Spirometry = Decreased FEV/FVC ratio (25-50%) - Wheezing is a common symptom/sign - Examples - Usually co exist - Asthma - Chronic Bronchitis - Emphysema - Bronchiectasis - Permanent dilation of bronchi and bronchioles with chronic necrotizing infection - Triggers - Smoking, allergy, pollution, infection, stress Chronic Bronchitis - Persistent productive cough - at least 3 months consecutive over 2 years - Persistent obstruction of bronchioles and bronchi - Largely irreversible due to mucus secretion and airway thickening as a result of chronic inflammation - Clinical Entitiy Emphysema - functional/morph entity - Abnormal enlargement of airways (distal bronchioles) and destruction of alveolar walls - Voluminous lungs with increase compliance - Obstruction in emphysema due to changes in alveolar tissue - Bronchitis and emphysema usually coexist Spirometry for Restricitve vs Obstructive Obstructive - Fev1, fev1/fvc is decreased, fvc is either decreased or the same  - Longer line in comparison to restrictive and Normal lung - Cashew nut = concave shape Restrictive - Fvc decreased, fev1 decreased or same and fev1/fvc is increased - Shorter line than normal lung and obstructive - Almond nut = convex shape CASE 1 Pt PC 62y M presents with progressive SOB - copious yellow-green sputum - Occasionally blood streak sputum - Tx for similar episodes in past 2 years - Smokes 1 pack per day Pt Clinical Appears blue Presentation Pitting edema of the ankle Pt Diagnosis Chronic Bronchitis (Blue Bloaters) - Hypoxia drivers respiration - Central cyanosis (hypoxia drives vasoconstriction) - Low o2 and high co2 = TYPE 2 RESP FAILURE RISK Clinical Excess body fluids manifestations Chronic Cough SOB on exertion Increased sputum Cyanosis (late sign) Weight gain Pathogenesis 1. Long standing irritation by cigarette smoke, pollutants (SO2, NO2), dust = chronic airway inflammation (lymphocytes not eosinophils)  2. Loss of cilia and squamous metaplasia -> lung cancer 3. Goblet cell hyperplasia of small airways AND submucosal gland hypertrophy of airways (trachea/bronchi/ioles) a. Increase bronchial wall thickness b. Hypersecretion of mucus -> microbial infection 4. Airflow obstruction decrease fev1 and fev1/fvc and pefr 5. Dyspnea due to hypoxemia, hypercapnia, ccf Tobacco affects on lungs - Transcription of mucin gene MUC5AC in bronchial epithelium - Production of proteases from activated neutrophil elastase cathepsin, material metalloprotienases and macrophages - Inactivate normal lung anti oxidants - IL13 by T lymp = proinflammatory - Smoke damages cillia of resp epithtelium Path and Micro CASE 2 Pt PC 42y M presents with increasing SOB - Febrile = 38c and increased RR - Increasing Productive cough - SOB walking short distances and speaking - Nil chest pain - Smoke 2 packs per day for 25 years - Fam hx of eczema + Pt Clinical Shallow and fast breathing Presentation Hyperventilating (Pink relative term) Pursed lips (puffer fish term) Barrel Chest and accessory muscle use Poor chest expansion on palpation Decreased tactile vocal fremitus (dampened by trapped air) Hyperresonance percussion -bone percussion echos back via trapped air Diminished breath sounds of auscultation Decreased vocal resonance Pt Diagnosis Emphysema - Pink Puffer Clinical - Accessory Muscle Use to breathe manifestations - Pursed lips - Minimal Absent cough - Leaning forward to breathe - Thin stature Pathogenesis 1. Tobacco smoke fuels are environmental exposures 2. Reactive o2 spp, free radical injury 3. Causes imbalance between proteases and antiproteases OR 1. genetic TGFB1 polymorphisms A1 antitrypsin deficiency 2. Tgfb gene regulates CT = inadequate elastin repair 3. Loss of elastic recoil due to irreversible damage to CT elastin 4. Permanent dilation of alveoli without fibrosis = Inflammatory cells release cytokines and proteases which causes epithelial cells to necrosis or apoptosis also affecting mesenchymal cells = Alveolar parenchymal destruction Path and Micro Investigations 1. FBC - increased PCV and WCC 2. Arterial Blood gasses - High CO2 and Low O2 = type 2 resp failure 3. PFT = obstructive pattern 4. Naso PCR and sputum culture = rule out viral/bact infection 5. ECG = rule out RHF 6. Chest X ray Complication Acute/Infective exacerbation - IECOPD Bronchietasis RHF Spontaneous Pneumothorax Resp Failure Predispose to cancer Sleep Apnea Case 3 Pt PC 55y M presents with persistent productive cough - Foul smelling sputum - Chest pain - Frank blood in sputum Pt Clinical - Rigors Presentation - Febrile - Clubbing Pt Diagnosis Bronchiectasis - Permanent dilation of bronchi and bronchioles in affected area due to destruction of lung tissue and chronic necrotising infection Ddx - Lung cancer, pulmonary TB, lung abscess, necrotising pneumonia Clinical Fever-high grade with chills manifestations Severe persistent cough with expectoration of foul smelling sputum Blood streaks of frank blood (hemoptysis) Weight Loss Clubbing Pathology Start in lower lobes and Loss of Cillia Irreversible dilation of distal bronchi and bronchioles Necrotic inflammation = pus and mucus Peri bronchial fibrosis Diagnosis FBC Sputum MCS Nasophargngeal swab (not as helpful as mostly bacterial) Tx and Tx Complication - Postural drainage - Ab IV/oral 4-6 weeks - Bronchodilators - Surgical Lobectomy Complication - Lung abscess - bacterial or fungal - Brain abscess - renal, bone abscess Case 4 Pt PC 19y F presents with episodic breathing difficulties - Wheeze - Chest tightness - Episodes short lasting, intermittent, semi regular and mostly in spring/autumn early mornings and night Pt Diagnosis Asthma Clinical Paroxysmal (intermittent/episodic) and reversible usually manifestations Acute episodic narrowing of airways and hyper responsiveness to triggers If repetitive then causes chronic inflam changes SOB, wheeze, chest tight, cough Pathology Allergen activates immune system  Airway tissues infiltrated by immune cells (neutrophils, eosinophils) Mast cells release inflammatory mediators = bronchoconstriction/bronchospasm = inflammation, increase mucus production, contractile response of smooth muscle and SM thickening (Type 1 hypersensitivity reaction) Pathology Restrictive Lung Diseases Restrictive (Diffuse Interstitial) Lung Disease - Characterized by the inflammation and fibrosis of the pulmonary CT, principally the most peripheral and delicate interstitium in the alveolar walls. - Diseases which reduce lung capacity to expand (reduction in compliance) - Pulmonary or extrapulmonary causes (pleural or chest wall) Classification of RLD - Acute: Acute Respiratory Distress Syndrome (ARDS) - Chronic: Chronic restrictive Lung disease ACUTE Definition Acute RLD - Severe acute lung injury - Inflammation associated increase in pulmonary vascular permeability leading to lung epithelium and endothelial damage (alveolar) Causes Common - Direct lung injury - Pneumonia and Aspiration of Gastric Contents - Indirect Injury - Sepsis and severe trauma with shock Pathogenesis Endothelial and epithelial injury = damage in alveolar capillary membrane Imbalance between pro and anti inflammatory markers  Formation of hyaline membranes = characteristic of ARDS resulting from inspissation of protein rich edema fluid that entraps debris of damaged epithelial cell Clinical Dyspnea, tachypnea followed by cyanosis and resp failure Presentation Hypoxia = unresponsive to oxygen Uneven distribution leading to VQ mismatch and hypoxemia Pathology Hyaline membranes are glassy, structureless, acellular proteinaceous material that stains eosinophilic. The entomology of hyaline related to a colorless transparent substance = meaning glassy Complication Mortality 40% = multiorgan failure, sepsis or direct lung injury Fibrosis and scarring leads to chronic condition in minority cases Resolution Treat the precipitating cause and support failing organs including resp support - ITU care Histopathologically - Reabsorb exudate and removal of dead cell by macrophage - Replace endothelium by migration from uninjured capillaries from marrow progenitor cells - Replacement of epithelium by surviving type 2 pneumocytes and bronchoalveolar stem cells CHRONIC Definition Bilateral patchy progressive restriction of the pulmonary interstitium (alveolar septum) Classification Fibrosing - Idiopathic pulmonary fibrosis - Non specific interstitial pneumonia - Cryptogenic organising pneumonia - Pneumoconiosis - Drug Reactions - Radiation Pneumonitis Granulomatous - Sarcoidosis - Hypersensitivity pneumonitis Eosinophilic Smoking related - Desquamative interstitial pneumonia - Respiratory bronchitis associated ILD  Other - Pulmonary alveolar proteinosis Clinical Dyspnea, presentation Tachypnonea Eventual cyanosis (NIL wheeze or obstruction signs) Reduction in CO diffusing capacity, lung volume and compliance Diagnosis Chest X ray - Bilateral infiltrative lesions in forms of SMALL NODULES, IRREGULAR LINES OR GROUND GLASS SHADOWS Complication Secondary pulmonary HT and RHF CASE 1 PC 72y M presents with SOB (mild) - Hx of smoking - Treated with bronchodilators (presumed COLD) but no improve - Pulmonary function test show restriction and impaired diffusing capacity for CO - Chest x ray show bibasilar interstitial marking Diagnosis Idiopathic pulmonary fibrosis Pathogenesis Repeated cycles of epithelial activation/injury = fibrosis Role of TGF-B1 Fibroblastic foci Pathology CASE 2 PC 76y M presents with SOB (progressively worse) - Chronic cough and NIL chest pain - 45 pack year smoking hx but stopped at age 50 - Nil fam hx of lung disease - Joint swelling and stiffness - Normal auscultation Diagnosis Pneumonitis - Non neoplastic lung reaction due to inhalation of dust and matter - Asbestosis, silicosis, anthracosis, bagassosis Pathogenesis Particles escape lung defenses such as nasal filtration, cough reflex, muco-ciliary action and escape macrophage removal and survive macrophage produced proinflammatory cytokines -L-1β and IL-18 Coal Randing from asymptomatic to simple CWP to complicated CWP = leading to PMF Contaminating silica in the coal dust can favour prognosis Usually benign but can lead to PHT and cor pulmonale Silicosis Most prevalent chronic occupational disease Crystaline sillica - more fibrogenic than amorphous Increased sucessibility to TB Silica particles in macrophages cause granuloma Asbestosis Family of crystalline hydrated silicates Long fibres - dangerous - Serpentine: flexible and curly - Amphibole : start sharp and stiff Complocation - Lung carcinoma, mesothelioma, neoplasms extrapulmonary (colon cancer) Asbestosis Pathology Bagassosis Interstitial lung disease- hypersensitivity pneumonitis attributed to exposure of mouldy molasses (bagasse) Drug associated Antineoplastic drugs can cause damage to alveolar lining cells and to with interstitial interstitium indirectly fibrosis Amiodarone is a common antiarrythmic drug causing pneumonicitis Other eg: Bleomycin, Methotrexate, Nitrofurantoin Radiation Well known complication of therumatic radiation of thoracic tumours  pneumonitis 1-6 m after irradiation, acute pneumonitis occurs in 10-20% pt If not resolved = chronic radiation pneumonitis Epithelial cell atypia and foam cells within vessel walls are a characteristic Emerging Causes of RLD: Obesity and Smoking Obesity - Major cause due to increased work of breathing - Atelectasis Smoking - Can be obstructive or restrictive - Desquamative interstitial pneumonia - large collection of macrophages in air space - Resp bronchiolitis associated ILD - pigmented intraluminal macrophages within 1st and 2nd order bronchioles *Resp Mechanics *Resp Pharm Chest X-Ray Indications for Ordering a CXR (MAAACHI) - Major trauma - exclude widened mediastinum, pneumothorax, haemothorax - Acute chest pain - exclude pneumothorax, perforated viscus and aortic dissection - Asthma/Bronchiolitis - when diagnosis unclear or not responding to therapy - Acute Dyspnoea - exclude HF and pleural effusion - Chronic Dyspnoea - exclude HF, effusion and interstitial lung disease - Haemoptysis - suspected mass, metastasis or lymphadenopathy - Infection - exclude pneumonia Scan Approach - Entire lung boundaries vs Scanning with fovea over each part of lung How to read Chest X-Rays AIRWAYS - Tracheal deviation - Bronchi - Hilar vessels (lymphadenopathy) - Is there air where it shouldn't be (pneumothorax, pneumomediastinum, pneumoperitoneum) BREATHING - Lung zones and lobes - Plural line (shouldnt be visible) - Costophrenic recess CIRCULATION - Heart size and location - Heart borders - Widened mediastinum - Aortic knob DIAPHRAGM  - Height and shape - Rib intersection - Air below the diaphragm EVERYTHING - Bones - fractures and tumours - Soft tissue - Equipment (tube and pacemakers) - Review areas of pathology - apices, retrocardiac and periphery and hilar regions Normal Chest X ray How to count ribs - Shaft of rib 1 and 2 directly overlie clavicle - Count using anterior or posterior enders: superior to inferior direction - Check if medial ends of clavicle are equidistant Pneumonia consolidation - Fever - Productive cough - SOB - Fatigue - Increased density in lobar pattern - Appearances of air bronchograms - Should not be associated with volume loss Atelectasis (Lung Collapse) - Superiorly displaced horizontal or other fissures - Volume loss displaces fissures due to obstruction or compression of the lung by pleural fluid via pleural fluid or pnuemothroax - Sharly define passivity obscuring vessels without air bronchogram - Volume loss resulting in displacement of diapharm, fissures, hilar or mediastinum Right upper lobe atelectasis - Hyperdense right upper zone due to collapse of right upper lobe - Fissure is raised because volume loss of the collapsed right upper lobe - Contour of obstrucitng mass is visible and causes fissure to appear S shaped - Goldeen S sign = predictive of lung cancer obstructing the R upper lobe and bronchus Suspected Inflammation on the bronchioles Emphysema - Flattened hemidiaphragm on lateral examination - Increase in retrosternal space (normal is less than 2.5cm) - Prominent pulmonary artery (Secondary pulmonary HT) - Confusion, hallucination dx with metabolic encephalopathy to pneumonia (chest pain and SOB) - PLUERAL EFFUSION - collection of fluid in the plural space - Blurring of the costophrenic angle, blunting of angle, fluid within horizontal or oblique fissure Tension Pnuemothroax - Right sided tension pnuemothorax with right sided lucency and leftward mesistinal shift - Radiolucent hyperexpanded right hemithorax - Absent bronchvascular markings - Significant widening of intercostal spaces - Mediastinal shift to contralateral side Left lung Atelectasis - whiteout /radiopacity with increased attenuation of left lung and position of trachea pulled toward opacified side LUL atelectasis - Veil like appearance on left lung and aortic knuckle well decided due to adjacent upper lobe being full of air - Left heart border obscured and left hemidiaphram is raised indicating lung vol loss - Left upper lobe collapse - Mass visible at left hilum causing collapse of L upper lobe Pathology of Lung Cancer Lung Cancer Epidemiology - Leading cause of cancer death and 4th most commonly diagnosed cancer - More males died from lung cancer (ranked 2nd and 4th for females) - Australia was lower than the rates of other westernised countries - but higher than australia and africa Causes - Tobacco smoke - cigarette, pipe, and cigar smoking - exposure to radon, asbestos, environmental tobacco - Exposures to other hazardous materials - Industrial pollution contributes Tobacco Smoking - Main ingredient in cigarettes is tobacco - Tobacco plants are picked, fried and broken into small pieces - Artificial flavourings and other chemicals to keep cigarettes to keep them burning - Over 4000 chemicals in cigarettes, 51 are carcinogenic - Nicotine tar and CO Lung Cancer Location - Most are BRONCHIAL carcinomas - Lung cancer can originate anywhere in the lung - Most cancer arise in the main bronchi and near subdivisions CP - Cough - Sputum - Haemoptysis - SOB - Weight loss - Fever - Fatigue - Numerous metastasis Classifications - Small cell carcinoma - Non small cell carcinoma - Squamous cell carcinoma - Adenocarcinoma - Large cell carcinoma - Others SMALL CELL CARCINOMA Definition Small cell carcinoma arises from epithelial cells that line surface of central located bronchi - Most aggressive type of lung cancer, spread widely throughout course of disease (not always tx by surg- prefered chemo/rad) Cause Predominantly caused by lung cancer Prevalence 11.8% of lung cancer in Australia & 5 Year survival less than 5% Path Features Endobronchial 1-10cm Neuroendocrine Mitoses Necrosis Chromogranin, Synaptophysin, CD56 Diagnosis SQUAMOUS CELL CARCINOMA Definition Carcinoma arising from squamous epithelial cells characterised by proliferation of atypical pleomorphic squamous cells Graded as well, moderately or poorly differentiated = well differentiated carcinomas are usually associated with keratin production Epidemiology More common in males but decrease in proportion overall 5 year survival rate = 20% Pathological Prognosis Grade not important but STAGE is very important ADENOCARCINOMA Definition Bronchoalveolar carcinoma, minimally invasive adenocarcinoma of the lung Epidemiology Increased in adenocarcinoma due to filtered cigarettes and the increase in dose of nitrosamines, MOST COMMON IN WOMEN Increasing incidence, arises more peripherally -over 40% of lung cancer Prognosis - best of all lung cancers Types Acinar Predominant Adenocarcinoma Papillary Predominant adenocarcinoma Micropapillary predominant adenocarcinoma Solid Predominant adenocarcinoma Invasive mucinous adenocarcinoma Histology Lepidic, acinar, papillary, micropapillary and solid types - histology subtypes Lepidic pattern defined as tumour lining alveolar with no disruption and no lymph or pleural invasion Aciniar pattern is chatacterised by glandular formation  Papillary pattern displays fibrovascular cores lined by tumour cells replacing alveolar lining Micropapillary composed of ill defined projection Solid pattern defined as solid sheets and nest of tumour Pathology EGFR and ALK mutations possible LARGE CELL CARCINOMA Definition Poorly differentiated adenocarcinoma and squamous cell carcinoma Some are large cell neuroendocrine tumours Tumours lack morphologic and immunohistochemical evidence of glandular, squamous or neuroendocrine differentiation Characteristics Large, polygonal and anaplastic cells growing in sheets or solid nests Moderately abundant cytoplasm, well defined cell borders, vesicular nuclei, prominent nucleoli Foci of central necrosis and haemorrhage may be present  Pathological Metastases from Primary Lung Cancer - Regional lymph nodes - Adjacent organs - Via blood stream to bone and liver etc Tumours of Primary Pleural - Mesothelioma - Abstheos related - Tumour of mesothelial cells - Similar tumoirs in peritenoeum and scrotal sac Mesothelioma Definition Malignancies involving mesothelial cells that line pleura (also peritoneum and pericardium) Diagnosis More than 90% pleural mesothelioma present with pleural effusion - decreases after thoracentesis No cure Clinopath Micro of cytology and histology Relations Closely related to asbesthosis - in the past and present - Floor tiles, dry wall, ceiling tiles, insulin and fibro-roofs *Therapies in Malignancies *Clinical Aspects of Resp Disorders