RCSI Year 1 RESPIRATORY DISEASE PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Bronchiectasis/Asthma and Vasculitis Class Course Lecturer Date Year 1 RESPIRATORY DISEASE Pathology Dr Clive Kilgallen Dr Fatima Al Hashimi 27th April 2023 LEARNING OUTCOMES • Define bronchiectasis • Describe the path...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Bronchiectasis/Asthma and Vasculitis Class Course Lecturer Date Year 1 RESPIRATORY DISEASE Pathology Dr Clive Kilgallen Dr Fatima Al Hashimi 27th April 2023 LEARNING OUTCOMES • Define bronchiectasis • Describe the pathogenesis, aetiology and symptoms of bronchiectasis • Define pleural effusions • Describe the pathogenesis, aetiology and symptoms of pleural effusions • Define asthma • Describe the pathogenesis, aetiology and symptoms of asthma • Discuss vasculitic disease that affect the lung BRONCHIECTASIS • Abnormal irreversible dilatation of the bronchi caused by destruction of the muscle and elastic tissue • Classified as an obstructive lung disease • Disease involves a vicious circle of transmural infection and inflammation with mediator release • Prognosis depends on underlying cause and extent of lung involved WHAT ARE THE CAUSES OF BRONCHIECTASIS? CAUSES OF BRONCHIECTASIS 1. INFECTION • Sequel to bronchopneumonia and bronchiolitis in childhood which has imperfectly resolved • Pneumonia complicating measles or whooping cough § Incidence reduced due to effective childhood immunisation strategies • Allergic Bronchopulmonary Aspergillosis (ABPA) • Chronic tuberculous cavities • Primary Mycobacterium avium complex infection 2. CONGENITAL CONDITIONS • Primary ciliary dyskinesia § Poorly functioning cilia contribute to retention of secretions and recurrent infections • Alpha-1-antitrypsin deficiency • Cystic Fibrosis • Young’s syndrome § § Chronic sinopulmonary infections Male infertility • Marfan syndrome (very rarely) • Kartageners Syndrome § § § Characterised by a triad of dextrocardia, bronchiectasis and severe sinusitis. Autosomal recessively inherited condition Affects the mobility of the cilia 3. IMMUNODEFICIENCY • Persons with humoral immunodeficiency syndromes involving deficiencies of IgG, IgM and IgA (i.e. Hypogammaglobulinaemia) • Immunodeficiency due to malignancy e.g. myeloma, lymphoma • Immunoglobulin replacement reduces the frequency of infections and prevents ongoing airway destruction 4. BRONCHIAL OBSTRUCTION Obstruction of central bronchi by: • Inhaled / aspirated foreign bodies • Tumour • Mucus plugs in asthma • Compressive lymphadenopathy • Chronic aspiration 5. RHEUMATIC CONDITIONS • Sjogrens Syndrome • Systemic Lupus Erythematosus • Rheumatoid arthritis • Also associated with inflammatory bowel disease especially ulcerative colitis PATHOGENESIS • The induction of bronchiectasis requires two factors: § An infectious insult § Impairment of drainage, airway obstruction • Involved bronchi are dilated, inflamed and easily collapsible, resulting in airflow obstruction and impaired clearance of secretions SYMPTOMS • Productive cough with purulent sputum • Sputum may be mucoid, mucopurulent, thick or viscous • Blood streaked sputum or copious haemoptysis may result from erosive airway damage due to acute infection • Dyspnoea and wheezing in 75% • Pleuritic pain in 50% • Recurrent LRTI Physical Findings • Crackles, coarse crepitations and rhonchi on auscultation • Clubbing a common finding in the past, rare now 3% • Major confounding disease is COPD WHAT ARE THE COMPLICATIONS OF BRONCHIECTASIS? COMPLICATIONS OF BRONCHIECTASIS Complications: • Massive haemoptysis • Respiratory failure • Pneumonia • Pleural effusion • Brain abscess • Amyloidosis Respiratory pathogens are staphylococcus aureus, haemophlyus influenza, pseudomonas aeruginosa PLEURAL EFFUSION • Accumulation of fluid in the pleural space • Empyema: accumulation of infected fluid in the pleural space • Normally a small amount of thin, pale yellow fluid is present in the pleural space to allow movement of the visceral pleural against the parietal pleura • Pleural effusions are classified as: § TRANSUDATE § EXUDATE EXUDATE PLEURAL EFFUSIONS HAVE A LOW PROTEIN. A.True B.False TRANSUDATE VERSUS EXUDATE • Transudates have low specific gravity, low protein and few cells • Causes include heart failure, fluid overload, nephrotic syndrome, Peritoneal dialysis • Exudates have high specific gravity, high protein and lots of cells • Causes include infection, malignancy, pulmonary emboli PATHOPHYSIOLOGY • Pleural fluid will accumulate when the rate of pleural fluid formation is greater that the rate of pleural fluid removal by the lymphatics • A transudative effusion occurs when alterations in the systemic factors that influence pleural fluid movement result in a pleural effusion. Examples are elevated visceral pleural capillary pressure with left heart failure, elevated parietal pleural capillary pressure with right heart failure, decreased serum oncotic pressure with nephrotic syndrome, hepatic cirrhosis PATHOPHYSIOLOGY (CONTINUED) • A exudative effusion occurs when the pleural surfaces are altered. Inflammation of the pleura, leading to increased protein in the pleural space is the most common cause of exudative effusion PLEURAL EFFUSION CHEST X-RAY • • • • CXR +/- CT Thorax Blood tests Thoracocentesis WHAT DO YOU UNDERSTAND ABOUT THE TERM ASTHMA? • Asthma is an inflammatory disorder characterised by hyper-responsiveness of the airway to various stimuli resulting in wide spread narrowing of the airways • The changes are reversible, either spontaneously or with therapy • The inflammatory response includes T lymphocytes, mast cells in eosinophils and is associated with exudation of plasma, oedema and smooth muscle hypertrophy, deposition of matrix, mucus plugging and epithelial damage ASTHMA – DEFINITION • Episodic, reversible bronchospasm (airflow obstruction) resulting from exaggerated bronchoconstriction in response to various stimuli • Chronic inflammatory disorder of the airways • Recurrent episodes of wheezing, breathlessness, chest tightness and coughing • Heterogeneous disease triggered by a wide variety of inciting agents ASTHMA • Asthma is common • 300 million people worldwide • 10-15% of children, 7-10% of adults • Young children commonest; boys>girls • Adolescents least common, higher frequency in adults • Childhood asthma has a good prognosis PATHOPHYSIOLOGY • Inflammation of the airways • Smooth muscle surrounding airway becomes oedematous and tightens airway • Reduces amount of air that can pass through leading to wheeze • Airway epithelium becomes oedematous, erythematous and inflamed • Inflammatory mediators include: § Type 2 T helper lymphocytes, IL-4, IL-5, IL-13 § Eosinophils, IgE, Mast cells, histamine, leucotrienes SYMPTOMS § Episodic SOB § Wheeze § Chest tightness § Cough § +/- sputum production § Generally worse in morning § History: elicit triggers CAUSATIVE FACTORS • Allergic and Intrinsic (Non-allergic) • Atopic related disease (Allergic) as evidenced by increased IgE levels and immediate hypersensitivity on skin testing predominates in childhood asthma • Non-allergic or intrinsic asthma is associated with an older age and may be difficult to manage. Often associated with COPD • Genetic factors – no single gene but several, in combination with environmental factors, influence development • Environmental factors – early childhood exposure to allergens and maternal smoking – house dust mite allergens, cockroach allergy in U.S.A, • Viral infections – rhino virus – RSV • Occupational sensitizers – 250 materials in workplace cause occupational asthma, isocyanates, wood dust, bleaches, allergens from animals CAUSATIVE FACTORS (CONTINUED) • Cold air and exercise – exercise-induced wheeze is drive by release of histamine, prostaglandins (PGs) and leukotrienes (LTs) from mast cells • Atmospheric pollution and irritant dusts – many patients with asthma experience worsening of symptoms on exposure to tobacco smoke, car exhaust fumes, solvents, sulphur dioxide, ozone etc. • Diet – increased intake of fresh fruit & vegetables shown to be protective • Emotion – emotional factors influence asthma both acutely and chronically • Drugs § NSAIDs, aspirin, ibuprofen are implemented in triggering asthma - 5% of patients (particularly prevalent in patients with nasal polyps and asthma) § Beta blockers – direct parasympathetic innervation that tends to produce bronchoconstriction MICROSCOPIC FEATURES • • • • • • Airway infiltration by neutrophils and eosinophils Mast cell degranulation Basement membrane thickening Loss of epithelial integrity Occlusion of bronchial lumen by mucus Hyperplasia and hypertrophy of bronchial smooth muscle and goblet cells NATURAL HISTORY OF ASTHMA NOT PRECISELY DEFINED • In majority of patients it is not progressive (contrast with chronic bronchitis, cystic fibrosis, bronchiectasis) • Some (minority) patients do develop irreversible changes in lung function • Clinical course is characterised by remissions and exacerbations VASCULAR LUNG DISEASES • Pulmonary embolism • Pulmonary infarction • Haemorrhage • Vasculitis PULMONARY THROMBOEMBOLISM • Pulmonary embolism is a complication arising from deep vein thrombosis that results in a blood clot blocking the pulmonary artery or its branches • Source: Venous and right side of heart § >95% arise from thrombi in deep veins of lower legs (popliteal vein or above) § Thromboemboli do not usually arise from superficial or smaller leg veins • Results in 50,000 deaths / year in USA • True incidence of non-fatal pulmonary emboli is unknown RISK FACTORS • Immobilisation: § Prolonged bed rest § Surgery • Severe trauma • CCF • Pregnancy • OCP • Malignancy • Hypercoagulable states: § Factor V leiden mutation § Protein C, Protein S deficiency § Antithrombin III deficiency § Lupus anticoagulant § Homocysteinuria • Connective tissue disease Wirchovs Triad PATHOPHYSIOLOGY AND SYMPTOMS • Depends on size of the embolism, which in turn dictates the size of the occluded pulmonary artery • Consequences: § Increase in pulmonary artery pressure from blockage of flow and vasospasm caused by neurogenic mechanisms and release of mediators § Ischaemia of downstream pulmonary parenchyma § Occlusion of a major vessel causes a sudden increase in pulmonary artery pressure, diminished cardiac output, acute cor pulmonale and possibly sudden death § Occlusion of a smaller vessel is less catastrophic and may even be clinically silent CLINICAL MANIFESTATIONS • Silent (60-80%) § Small and embolic mass is removed by fibrinolytic activity § Bronchial circulation sustains viability of affected lung parenchyma • Sudden death (5%) § Acute cor pulmonale, cardiovascular collapse when >60% of the vasculature is obstructed • Obstruction of small to medium pulmonary branches (10-15%) § Causes pulmonary infarction; patients complain of dyspnoea, haemoptysis, pleuritic chest pain CLINICAL MANIFESTATIONS (CONTINUED) • Recurrent PE’s (3%) § May lead to pulmonary hypertension, chronic right sided heart stain (chronic cor pulmonale, pulmonary vascular sclerosis • Classic presentation: § Sudden onset pleuritic chest pain § SOB § Hypoxia § Syncope, seizures § Decreased level of consciousness § New onset atrial fibrillation § Haemoptysis INFARCTION • • • • Usually peripheral Wedge shaped with the base at the pleural surface Haemorrhage and appear as raised red-blue areas in early stage Adjacent pleural covered in a fibrinous exudate; can cause pleuritic chest pain and effusion NON THROMBOTIC EMBOLI • Air embolism • Fat embolism • Amniotic fluid embolism • Foreign body embolism • Bone marrow embolism DIFFUSE ALVEOLAR HAEMORRHAGE • Present as a triad § Haemoptysis § Anaemia § Diffuse pulmonary infiltrates • Prototype: Goodpasture syndrome • Secondary causes: § Necrotizing bacterial pneumonia § Bleeding diathesis § Passive venous congestion GOODPASTURE SYNDROME • Rapidly progressive glomerulonephritis plus haemorrhagic interstitial pneumonitis • Renal and pulmonary lesions are caused by antibodies to antigens common to glomerular and pulmonary basement membranes • Example of type II cytotoxic antibody mediated hypersensitivity • Antibodies can be detected in the serum in >90% of patients (Anti glomerular basement membrane antibodies; also called anti-GBM disease) GOODPASTURE SYNDROME (CONTINUED) • Lungs shows focal necrosis of alveolar walls associated with intra-alveolar haemorrhages, fibrous thickening of septae • Haemosiderin laden macrophages seen in the acute setting • Management: Plasmapheresis and immunosuppressive therapy • Plasma exchange removes offending antibodies and immunosuppressive drugs inhibit antibody production VASCULITIS AFFECTING LUNG • Pulmonary angiitis and granulomatosis (GPA; aka Wegener granulomatosis) • Churg-Strauss syndrome • Collagen vascular disorders GRANULOMATOSIS WITH POLYANGIITIS (GPA) - (WEGENER'S GRANULOMATOSIS; ANCA ASSOCIATED VASCULITIS) • Hallmark: § Pauci-immune vasculitis of small to medium sized vessels § Necrotising granulomatous inflammation • Antineutrophil Cytoplasmic antibody (ANCA) § Cytoplasmic ANCA (c-ANCA) directed against PR3 is most specific for GPA § Some patients with GPA express perinuclear staining ANCA (p-ANCA) specific for myeloperoxidase (MPO) • Radiology § CXR, CT Thorax (nodular densities, may cavitate), CT sinus • Biopsy (only in atypical presentation) § Lungs: necrotising vasculitis, parenchymal necrotising granulomatous inflammation § Vessels: acute and chronic inflammation with fibrinoid necrosis of vessel wall CLINICAL PRESENTATION • Recurrent RTI’s, fever, night sweats, fatigue, lethargy, weight loss, anorexia • Ophthalmic § Conjunctivitis, episcleritis • ENT § Chronic sinusitis, rhinitis, epistaxis • Pulmonary § Pulmonary infiltrates, cough, haemoptysis, dyspnoea, diffuse alveolar haemorrhage due to alveolar capillaritis CLINICAL PRESENTATION (CONTINUED) • Musculoskeletal § Myalgia, arthralgia • Renal § Crescentic necrotising glomerulonephritis • CNS • Cutaneous § Vasculitic ulcers • Cardiac § Pericardial rub EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA; CHURG-STRAUSS DISEASE) • Rare systemic necrotising, granulomatous vasculitis, affects small to medium sized vessels, associated with severe asthma and blood and tissue eosinophilia • ANCA associated vasculitis (like GPA and microscopic polyangiitis) EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA; CHURG-STRAUSS DISEASE) • Clinical presentation § Allergic rhinitis / asthma § Eosinophilic infiltrative disease (e.g. eosinophilic pneumonia, gastroenteritis) § Vasculitis (small and medium sized vessels with granulomatous inflammation) • Investigations § Bloods: ESR, CRP, U&E, FBC (eosinophilia), IgE, rheumatoid factor positive (low titre), p-ANCA + § Bronchoscopy: Lavage fluid shows raised eosinophils • Constitutional symptoms § Malaise, fever, weight loss, myalgia • Asthma • Paranasal sinusitis • Allergic rhinitis § Recurrent sinusitis § Polyposis • Pulmonary symptoms § Cough, haemoptysis • Arthralgia • Skin § Purpura, bullae, nodules, digital ischaemia • Cardiac § Myocarditis, pericarditis, MI • GIT § Eosinophilic gastroenteritis • Peripheral neuropathy § Mononeuritis multiplex LUNG IN COLLAGEN VASCULAR DISORDERS • Collagen vascular disorders § SLE, rheumatoid arthritis, scleroderma, dermatomyositis-polymyositis • Pulmonary manifestations § Interstitial pneumonia -> diffuse interstitial fibrosis § Pulmonary hypertension § Pulmonary vasculitis § Diffuse alveolar haemorrhage § Pleuritis • END OF LECTURE • THANK YOU