2403AHS_Wk11_Lecture_Pathology of Respiratory Diseases_1pp-1-45.pdf

Cardiovascular disease Ramona Clark Learning Outcomes • Describe the pathophysiology of respiratory diseases (including asthma, COPD, bronchiectasis, pneumonia, cystic fibrosis) • Identify the common risk factors, ages and stages of presentation for these pathologies • Explain the mucociliary esc...

Cardiovascular disease Ramona Clark Learning Outcomes • Describe the pathophysiology of respiratory diseases (including asthma, COPD, bronchiectasis, pneumonia, cystic fibrosis) • Identify the common risk factors, ages and stages of presentation for these pathologies • Explain the mucociliary escalator and how different pathologies effect its action ASTHMA What is Asthma? • A common chronic inflammatory condition of the airways characterised by widespread narrowing of the airways • Asthma in childhood slightly different pathology – dependent on pathogen exposure Asthma - prevalence • 1 in 9 Australians have asthma (AIHW, 2017-18) • ~11% of population • ↑ABTI, rural, lower SES, F>M • ~10% of children 0-14 years (AIHW, 2018) • 441 deaths due to asthma in 2017 • 29% of total Burden of disease due to resp. condition AIHW 2014-15 Asthma Cardinal signs: 1. Reversible airway obstruction 2. Airway inflammation 3. Airway hyperresponsiveness (twitchy) • Increased sensitivity to airway narrowing stimuli • → excessive bronchoconstriction Asthma – Airway irritation Allergen or irritant exposure Immune response IL-4 IgE Mast cell degranulation Vasodilation Vascular permeability Cellular infiltration Neutrophils, lymphocytes, eosinophils Chemical mediators Neurotransmitters Asthma – Airway irritation → Airway obstruction Vasodilation Vascular permeability Cellular infiltration Chemical mediators Neutrophils, lymphocytes, eosinophils Bronchospasm, vascular congestion, mucous secretion, impaired mucociliary function, thickening of airway walls, bronchoconstriction Neurotransmitters Desquamation Fibrosis Bronchial hyperresponsiveness Airway obstruction Inflammation - vasodilation • ↑ vascular permeability • ↑ extracellular fluid • Exudate → oedema • Vascular congestion arteriole smooth muscle bronchiole alveoli capillary Inflammation - vasodilation • ↑ vascular permeability • ↑ extracellular fluid • Exudate → oedema • Vascular congestion arteriole smooth muscle bronchiole alveoli capillary Inflammation - bronchoconstriction Inflammation • ↑ Exudate Inflammation - bronchoconstriction Bronchoconstriction • ↓ airway diameter • → Secretions line the wall • Increased fluid • Thick, tenacious secretions • Further decreases diameter • Increased resistance • Thickened airways (lumen) Inflammation – Cellular infiltration • Disruption of epithelium • ↑ Cellular debris • → ↓ diameter • → ↑ resistance • Impaired mucociliary function Mucociliary escalator First line of defence to protect lungs • Move debris (e.g. pathogens, dust particles) from airways to glottis Healthy • Mobile cilia (co-ordinated beat) • Watery mucous • Cough/swallow when reach glottis Mucociliary escalator (Healthy) • Periciliary fluid (Sol layer) coats the cilia • Debris stick to mucous (Gel) layer • Periciliary layer Airway Lumen Goblet cells produce thin layer of mucous that floats on top • Mucous layer Smooth muscle Goblet cell Basal cell Cilia beat to move debris to Ciliated columnar epithelial cell glottis Basement membrane Mucociliary escalator (Asthma) • Narrowed airways • Thickened basal membrane • Increased secretions • Epithelial shedding Oedema, mucus, muscle spasm Asthma Resistance to airflow Impaired expiration Air trapping Alveolar hyperinflation Uneven ventilation / perfusion Decreased pulmonary blood flow Decreased alveolar ventilation Impaired gas exchange Respiratory failure Hypercapnia Hypoxaemia Asthma: Obstruction • Obstruction → decreased expiration • Air trapping • ↓ ventilation . . • V/Q mismatch • Impaired gas exchange O2 • Hypoxaemia • Hypercapnia V = ventilation, Q = perfusion ↑ CO2 Asthma: Symptoms • SOB • Wheeze (expiratory) → no sound (no air) • Hypercapnic (increased PaC02) SOB: Shortness of breath Asthma: Physiotherapy Physiotherapy implications: • Nil / minimal role in acute phase • Airway clearance techniques later (based on clinical findings) • Timing medications: pre / post-exercise • Bronchodilator (e.g. Ventolin) → Reversible airway limitation • Wheeze in other obstructive diseases e.g. Brx Brx / BE = Bronchiectasis Chronic Obstructive Pulmonary Disorder COPD – Cardinal signs Chronic obstructive pulmonary disease is characterised by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases 1. Persistent airflow limitation (obstruction) 2. Chronic inflammation COPD - Prevalence ▪ ~5.1% of Australians ▪ 1 in 20 aged >45yrs (AIHW 2018) ▪ increases with age ▪ 2.5 x ABTI ▪ COPD 5th leading cause of death (AIHW 2018) ▪ 4th cause of total burden (AIHW 2011) COPD (Not all patients → Old definition) • COPD is two disorders (chronic bronchitis and emphysema) • → this is an older definition that is inaccurate COPD = Chronic Bronchitis Presence of cough and sputum production 3+ months over 2 + yrs But… present only in a minority of patients And can have chronic cough without spirometry changes + Emphysema Destruction of the gasexchange surfaces But… more than one structural abnormalities present Gold report, 2020 COPD (all patients → newer more accurate definition) • Applies to all COPD patients therefore more accurate description COPD = Chronic Inflammation Chronic inflammation Narrowing of small airways + Airflow limitation Small airways disease Structural changes Parenchymal destruction Airflow limitation Emphysema Persistent bacteria in airway Chronic cough (Mucopurulent) ↓ Lung elastic recoil Gold report, 2020 COPD: Lung inflammation Genetic predisposition Airway irritant ↓ Ability to protect lung tissue Long-term smoking, pollution, infection Free radicals Inactive lung anti-proteases Lung inflammation • Chronic (repeated) inflammation • Typically from noxious stimuli (eg smoking) Yu, 2013 COPD: Inflammation • Chronic (repeated) inflammation • Increase oxidative stress • Inflammatory cytokines • Protease function Lung inflammation Repeated injury to bronchial tree Destruction of lung parenchyma Infiltration neutrophils ↓ elastic recoil Goblet cell proliferation Airway structural support Death ciliated epithelium Alveolar enlargement Chronic inflammation Repeated and on-going • Narrowed airway • Vascular permeability • Vascular congestion • Oedema Barnes, 2015 Chronic inflammation 1. Oxidative stress (by-product of the inflammation) 2. Protease imbalance (increase in elastase) 3. Specific inflammatory cells → CD8 cells (differs from asthma) Mucociliary escalator (COPD) • Narrowed airways • Goblet cells proliferation* • → ↑ secretions* • Epithelial shedding • → ↑ cellular debris • Shortened cilia Risk of infection: influenza / pneumonia *Not all patients – predominantly those with additional diagnosis of Chronic Bronchitis COPD – Airflow limitation • Parenchymal destruction • Loss of alveolar attachments • Decrease in elastic recoil • Decrease surface area → decrease gas exchange Viglio, 2020 COPD – Airflow limitation 1. Air trapping (hallmark of COPD) 2. Gas exchange abnormalities (emphysema) Harder for pt to get O2 into blood Pulmonary hypertension • Hypoxic vasoconstriction • Blood diverts from alveoli that no longer provide 02 • Vasoconstriction and shunt blood to other areas • Smaller areas → increase pressure COPD: Symptoms • Dysponea / SOB • Exp wheeze • Hyperinflation → high lung volumes (due air trapping) • ↓ Thoracic expansion (due hyperinflation) • +/- cough and sputum production • +/- wheeze COPD: Hyperinflation • Air trapping → Increase TLC, but increase+++ residual vol (O’Donnell, 2006) COPD severity • Spirometry = gold standard for diagnosis • Confirmed post-bronchodilator by: FEV1 <80% or FEV1/FVC < 70%. Mild Moderate Severe FEV1 = 60-80% pred. FEV1 = 40-59% pred. FEV1 < 40% pred. SOB mild exertion SOB level walking SOB min exertion ADLs unaffected Limited ADLs Signif. ↓ ADLs Infrequent cough Cough + sputum Chronic co. + sputum++ chest infections Chest infection + Abs Freq chest infections COPD: Physiotherapy Physiotherapy implications: • Large role in acute and management phases • Airway clearance techniques (based on clinical findings) • Pulmonary rehabilitation Medications: • Bronchodilators (β2-agonists, antimuscarinics) • Inhaled corticosteroids • Antibiotics Pneumonia Pneumonia • Acute inflammatory consolidation of alveoli; or inflammation / infiltration of interstitial tissues with inflammatory cells, or combination of both Pneumonia - Prevalence ▪ ~5.1% of Australians ▪ Aged > 70+ or < 1 yr ▪ Co-morbidities (incl. diabetes, cancer, chronic respiratory disease, immunocompromised) ▪ Viral / bacterial infection already ▪ Hx smoking ▪ ABTI Chest infection URTI • Common • Breathe in bacteria (airborne) LRTI • Less common • Alveolar → pneumonia Respiratory Infection • Categorised by: • URT vs LRT • Location • Bacteria/Virus/fungal Aetiology of pneumonia • Viral (50%) → influenza A,B, COVID-19 • Bacteria (30%) → (e.g. strep*, haemophilus) • Mycoplasma (20%) • Fungal (severely immuno-compromised → aids, chemo) • Aspiration • Stroke, vomiting *Streptococcus pneumonia; Haemophilus influenzae Pneumonia Types • Lobar • Bronchial • Segmental • Full lung Classifications • Community-acquired • Nosocomial (hospital acquired • Ventilator associated