Obstructive lung disease Notes


Osmosis High-Yield Notes

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Alpha 1-antitrypsin deficiency



Chronic bronchitis

Cystic fibrosis

NOTES NOTES OBSTRUCTIVE LUNG DISEASE GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Obstruction of airflow from lungs ▪ Increased resistance to airflow → airtrapping ▪ Classifications ▫ Narrowing of lumen wall (e.g. asthma, chronic bronchitis) ▫ Increasing pressure external to airway/loss of lung parenchyma (e.g. emphysema) ▫ Obstruction of airway lumen (e.g. bronchiectasis, chronic bronchitis) COMPLICATIONS ▪ Cor pulmonale, right ventricular hypertrophy SIGNS & SYMPTOMS ▪ Cough, thick mucus, dyspnea, wheezing DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray/CT scan LAB RESULTS ▪ Sputum culture ▪ Arterial blood gas (ABGs) 886 OSMOSIS.ORG OTHER DIAGNOSTICS Spirometry/pulmonary function test (PFTs) ▪ Tidal volume (TV) ▫ Volume of air inspired, expired during quiet breathing ▪ Residual volume (RV) ▫ Volume of air left in lung after maximal expiration ▪ Forced vital capacity (FVC) ▫ Maximum volume of air that can be expired after maximal inspiratory effort ▪ Forced expiratory volume (FEV) ▫ Volume of air forcibly exhaled per unit of time ▪ Peak expiratory flow rate (PEFR) ▫ During FEV, maximum flow of expiration ▪ Functional residual capacity (FRC) ▫ Volume of air left in lungs after quiet expiration TREATMENT ▪ See individual diseases
Chapter 126 Obstructive Lung Disease ALPHA 1-ANTITRYPSIN (A1AT) DEFICIENCY osms.it/a1at-deficiency PATHOLOGY & CAUSES ▪ Autosomal dominant (codominant) genetic disorder ▫ Decreased production/absence of A1AT → overaction of proteases → damaged alveoli → damaged lungs, liver ▪ Lungs ▫ Damaged alveoli inflammation → neutrophils secrete elastase → absence of/decreased A1AT → elastase overacts, inflames → increased breakdown of elastin → alveoli lose elasticity, integrity → chronic obstructive pulmonary disease (COPD) ▪ Liver ▫ Genetic mutation → misfolded A1AT build up in endoplasmic reticulum of hepatocytes → kill hepatocytes → cirrhosis CAUSES ▪ Smoking ▫ Earlier onset of COPD in individuals with A1AT deficiency ▪ Genetics ▫ Serine protease inhibitor, clade A, member 1 (SERPINA1) encodes A1AT protein, located on long arm of chromosome 14 ▪ Pi*M ▫ Normal allele ▪ Pi*Z (most common) ▫ Mutated/diseased allele ▫ Misfolded A1AT proteins aggregate → stick in endoplasmic reticulum of hepatocytes → kill hepatocytes ▪ PiMZ ▫ Heterozygous (one normal allele, one diseased allele) ▫ Mutated gene contributes 10% normal amounts A1AT proteins ▫ Heterozygous individuals have 60% normal levels (enough to protect lungs in non-smokers) ▫ Increased risk of lung/liver disease ▪ PiZZ ▫ Homozygous ▫ Individuals only have 15–20% normal levels ▫ Much higher risk of lung/liver disease ▫ Can live without lung/liver disease if environmental exposures minimal ▫ Infants can develop liver failure during first years of life ▫ Individuals with no production of A1AT = no liver disease COMPLICATIONS ▪ COPD (emphysema, bronchiectasis, chronic bronchitis), hepatocellular carcinoma, liver cirrhosis, chronic hepatitis SIGNS & SYMPTOMS ▪ COPD: shortness of breath, wheezing, mucus production, chronic cough ▪ Liver damage, cirrhosis, impaired liver function: inability to make coagulation factors, hepatic encephalopathy, portal hypertension, esophageal varices, jaundice, hepatocellular carcinoma OSMOSIS.ORG 887
DIAGNOSIS DIAGNOSTIC IMAGING Liver ultrasound Chest X-ray/CT scan ▪ Hyperinflated/damaged lungs, basilar emphysema, panlobular emphysema ▫ Smoking: apically distributed emphysema LAB RESULTS ▪ Serum A1AT levels ▪ Family history, genetic testing ▪ Liver biopsy OTHER DIAGNOSTICS ▪ PFT ▫ Measure rate air exits lungs ▪ Periodic acid-Schiff (PAS) ▫ Diastase-resistant pink globules in liver biopsy ▫ Stains A1AT pink TREATMENT MEDICATIONS ▪ Augmentation therapy ▫ Intravenous (IV) infusions of A1AT protein from plasma donors ▫ Not curative, only slows progression ▪ Inhalers, supplemental oxygen ▫ COPD ▪ Lactulose ▫ Prevent hepatic encephalopathy ▫ For liver cirrhosis SURGERY ▪ Liver transplant ▫ Esp. homozygous infants, liver failure during first years ▪ Lung transplant Figure 126.2 A CT scan of the chest in the axial plane demonstrating panlobular emphysema as a consequence of alpha 1-antitrypsin deficiency. Figure 126.1 The histological appearance of the liver in an individual with alpha 1-antitrypsin deficiency. There are globular inclusions within periportal hepatocytes. 888 OSMOSIS.ORG
Chapter 126 Obstructive Lung Disease ASTHMA osms.it/asthma PATHOLOGY & CAUSES ▪ Hyperresponsiveness disorder, reversible airflow obstruction ▪ Chronic inflammation, narrowing of airways ▪ Acute (Type 1 hypersensitivity reaction) ▫ Initial sensitization to allergen → production of cluster of differentiation 4 (CD4), T helper 2 (Th2) cells → release interleukin 4 (IL4), interleukin 5 (IL5) → environmental trigger → eosinophils, mast cells release inflammatory mediators in bronchial walls (e.g. histamine, leukotrienes) → degradation of lipids, proteins, nucleic acids → tissue destruction → strong inflammatory reaction in bronchiolar walls → smooth muscle of bronchioles spasm, mucus in narrow airways increases → difficulty breathing ▫ Vasodilation of pulmonary vasculature, increased capillary permeability → edema ▫ Increased mucus production by goblet cells → impaired mucociliary function ▪ Chronic inflammation → scarring, fibrosis → thickening of epithelial basement membrane → permanently narrows airway ▪ Th2 cells release IL5 → attract, activate eosinophils ▪ Neutrophils release cytokines ▫ Interleukin 8 (IL8) ▫ More severe for individuals with neutrophilic asthma ▪ Triggers ▫ Air pollution, cigarette smoke, dust, pet dander, cockroaches, mold, pollen, medications (e.g. aspirin, beta-blockers) TYPES Extrinsic ▪ Type 1 hypersensitivity reaction triggered by extrinsic allergens (e.g. dust, mold) ▪ Individuals with atopic family history to allergies ▪ Atopic triad ▫ Asthma, atopic dermatitis, allergic rhinitis Intrinsic ▪ Nonimmune ▪ Viral infections, stress, exercise, smoking SIGNS & SYMPTOMS ▪ Coughing, chest tightness, dyspnea, difficulty breathing, wheezing, whistling during expiration ▪ Curschmann spirals in sputum ▫ Spiral-shaped mucus plugs ▫ Casts from small bronchi ▫ Blocks air exchange, inhaled medications from reaching inflammation ▪ Charcot–Leyden crystals in sputum ▫ Needle-shaped, formed from breakdown of eosinophils DIAGNOSIS OTHER DIAGNOSTICS ▪ Trigger test, spirometry, peak air flow ▪ Classifications based on frequency of symptoms (esp. night/morning), forced expiratory volume in one second (FEV1), PEFR, frequency of medication use (intermittent, mild persistent, moderate persistent, severe persistent) TREATMENT OTHER INTERVENTIONS ▪ No cure; treatments manage symptoms, prevent asthma attack ▪ Avoid triggers OSMOSIS.ORG 889
Chapter 126 Obstructive Lung Disease Figure 126.3 A chest radiograph demonstrating hyperinflation in an individual with chronic asthma. There is a pneumothorax in the right lower zone. BRONCHIECTASIS osms.it/bronchiectasis PATHOLOGY & CAUSES ▪ Chronic inflammation → permanent dilation of bronchi, bronchioles → destruction of airways ▫ Damage to mucociliary “elevator” → mucus, bacteria accumulates CAUSES Chronic inflammation ▪ Primary ciliary dyskinesia ▫ Absence of dynein arm in cilia → cilia move abnormally → mucus stuck in airways → bacteria in mucus multiply → pneumonia → chronic inflammation ▪ Cystic fibrosis (most common) ▫ Mucus too sticky → hard for cilia to sweep → mucus accumulates → recurrent pneumonias → chronic inflammation, infection Airway obstruction ▪ E.g. tumor inside/outside airway, lodged foreign object ▪ Blockage prevents mucociliary escalator from clearing mucus → recurrent pneumonias → chronic inflammation Infections ▪ E.g. aspergillosis, tuberculosis, adenovirus, Haemophilus influenzae, Staphylococcus aureus; hypersensitivity response → inflammation ▫ Chronic inflammation → immune cells, cytokines damage cilia, elastin fibers → airways dilated, clogged with mucus → fibroblasts deposit collagen → loss of elastin, buildup of collagen → lungs less elastic → more difficult for air to move smoothly → lung function declines → hypoxia → pulmonary arterioles constrict to divert blood away from damaged areas of lung → increased OSMOSIS.ORG 891
pulmonary vascular resistance → right ventricular hypertrophy → cor pulmonale → inflammation of pleura SIGNS & SYMPTOMS ▪ Wheezing, productive cough, foul smelling mucus, dyspnea, hemoptysis, recurrent/ persistent pneumonia, basilar crackles ▪ Long term hypoxia ▫ Digital clubbing DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Dilated bronchi/bronchioles Chest X-ray ▪ Increased bronchial markings at lung periphery LAB RESULTS ▪ Sputum culture ▪ Genetic testing Figure 126.4 The gross pathological appearance of the lungs in a case of severe bronchiectasis. OTHER DIAGNOSTICS ▪ Spirometry ▫ FEV1 decreased, FEV1/FVC ratio decreased ▪ Sweat test TREATMENT MEDICATIONS ▪ Bronchodilators; beta-2 agonists (e.g. albuterol) ▪ Inhaled corticosteroids (e.g. fluticasone ▪ Antibiotics ▫ Recurrent pneumonias OTHER INTERVENTIONS ▪ Percussion, postural drainage ▫ Recurrent pneumonias ▪ Pulmonary hygiene ▪ Adequate hydration 892 OSMOSIS.ORG Figure 126.5 The histological appearance of bronchiectasis complicated by fungal colonisation. There is a heavily dilated bronchus containing an aggregation of fungus known as an aspergilloma.
Chapter 126 Obstructive Lung Disease CHRONIC BRONCHITIS osms.it/chronic-bronchitis PATHOLOGY & CAUSES ▪ Preventable, progressive pulmonary disease ▫ Chronic airway inflammation, limited airflow ▫ Bronchial tubes in lungs inflame → productive cough ▪ Subset of COPD ▪ Exposure to irritants → hypertrophy/ hyperplasia of bronchial mucous glands, goblet cells in bronchioles, cilia less mobile → increased mucus production, less movement → mucus plugs → obstruction in bronchioles → air-trapping → productive cough ▪ Blocked airflow, air-trapping → increased partial pressure of CO2 in lungs → less O2 reaches blood → cyanosis (if severe); individuals referred to as “blue bloaters” RISK FACTORS ▪ Smoking (primary cause), cystic fibrosis, sulfur, nitrogen dioxide, dust, silica, family history, genetic predisposition COMPLICATIONS ▪ Pulmonary hypertension, increased workload of right ventricle, cor pulmonale, infections distal to mucus blockages, fibrosis of terminal bronchioles, compensatory polycythemia SIGNS & SYMPTOMS ▪ Wheezing (due to mucus, narrow airway), crackles/rales (small airways pop open during air movement due to narrow passageway) ▪ Hypoxemia, hypercapnia (due to mucus plugs blocking air flow) → cyanosis → tissue hypoxia DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Large, horizontal heart, increased bronchial markings LAB RESULTS ▪ ABGs ▫ Respiratory acidosis (arterial PCO2 > 45mmHg, bicarbonate > 30mEq/L) OTHER DIAGNOSTICS ▪ Productive, mucinous cough ▫ At least three months over two consecutive years ▪ PFTs ▫ Increased TLC, air-trapping; decreased FVC1/FVC ratio ▪ Postmortem measurement ▫ Reid index (measure ratio of thickness of bronchial mucinous glands, total thickness of airway, epithelium to cartilage) ▫ > 40% (due to hyperplasia, hypertrophy of glands) TREATMENT MEDICATIONS ▪ Supplemental oxygen, bronchodilators, inhaled steroids, antibiotics ▫ Manage symptoms ▪ Prophylactic vaccination against influenza, Streptococcus pneumoniae (S. pneumoniae) OTHER INTERVENTIONS ▪ Smoking cessation, pulmonary rehabilitation OSMOSIS.ORG 893
CYSTIC FIBROSIS (CF) osms.it/cystic-fibrosis PATHOLOGY & CAUSES ▪ Autosomal-recessive multisystem disorder ▫ Affects lungs, digestive system, reproductive system, sweat glands ▪ Caused by CFTR gene defect (located on long arm of chromosome 7) ▫ Encodes cyclic adenosine monophosphate–regulated chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) ▫ Various mutations: including lack of protein production; protein trafficking defect, degradation within cellular endoplasmic reticulum, Golgi body ▪ Genetic defect → impaired sodium, chloride transport across epithelial cell surface → thick, tenacious secretions ▫ Classic triad: ↑ sweat chloride levels, chronic sinopulmonary disease, pancreatic insufficiency ▪ Bronchi effects ▫ Goblet cell hyperplasia, submucosal gland hypertrophy → production of viscous mucus, mucus plugging → airway inflammation → elastase released from neutrophils → tissue destruction → ↑ thickness of airway walls, bronchiectatic cysts, ventilationperfusion mismatch → hypoxemia RISK FACTORS ▪ Family CF history; especially carrier parents ▪ ↑ incidence in white people of Northern, Central European descent COMPLICATIONS ▪ Chronic respiratory tract infections ▫ Common bacteria: Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae (especially younger children) ▫ Invasive fungal disease may occur → allergic bronchopulmonary aspergillosis 894 OSMOSIS.ORG (ABPA) ▪ Sinusitis ▫ Related to chronic inflammation ▪ Significant hemoptysis ▫ Related to enlarged, tortuous bronchial arteries ▪ Bronchiectasis ▫ Due to mucus plugging ▪ Pneumothorax ▫ Related to ruptured emphysematous bullae ▪ Secondary pulmonary hypertension ▫ Related to small pulmonary artery hypertrophy ▪ Nasal polyps ▫ Related to chronic inflammation ▪ Respiratory failure ▪ Non-pulmonary complications ▫ Cirrhosis; gallstones; pancreatitis; heat exhaustion, dehydration; hypochloremic alkalosis (excessive salt-loss in sweat); rectal prolapse; infertility (azoospermia); fat-soluble vitamin deficiency; anemia; nail clubbing SIGNS & SYMPTOMS ▪ Highly variable presentation ▫ Related to specific mutation, gene penetrance, environmental factors ▪ Specific pulmonary manifestations ▫ Chronic, productive cough; dyspnea; ↑ anterior-posterior chest diameter; digital clubbing; basilar crackle; expiratory wheeze; generalized hyperresonance
Chapter 126 Obstructive Lung Disease DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound ▪ May detect hyperechogenic bowel, meconium peritonitis Chest X-ray ▪ Hyperinflation, air trapping, atelectasis, flattened diaphragm, peribronchial thickening, bronchovascular markings, peribronchial cuffing, parallel lines (related thickened bronchial walls—”tram tracks”) CT scan ▪ Inspissated bronchial secretions; detects degree of bronchiectasis LAB RESULTS ▪ Genetic testing ▪ CFTR mutation identification ▪ Sweat chloride test ▫ ↑ sweat chloride concentration ▫ Pilocarpine administered → stimulate sweat; collected, analyzed for chloride content Figure 126.6 A plain chest radiograph demonstrating tram-track opacities and ring shadows in an individual with cystic fibrosis. They are particularly well demonstrated in the left upper zone. OTHER DIAGNOSTICS ▪ Newborn screening ▫ Detects CF in neonatal period; initiate early intervention ▪ Pulmonary function tests ▫ ↓ FEV1 FEV1/FVC ▫ ↑ residual volume to total lung capacity (RV/TLC) ratio ▫ ↓ total lung capacity ▫ ↓ vital capacity TREATMENT MEDICATIONS Figure 126.7 A CT scan of the chest in the coronal plane demonstrating bilateral widespread bronchiectasis in a twenty five year old female with cystic fibrosis. ▪ CFTR modulators ▪ Medications to clear respiratory secretions; inhaled hypertonic saline ▪ Anti-inflammatory medications (e.g. glucocorticoids) ▪ Antibiotics ▫ Infections ▪ Bronchodilators ▫ ↓ airflow obstruction ▪ Prevention ▫ Annual influenza vaccine; pneumococcal vaccine OSMOSIS.ORG 895
SURGERY ▪ Lung transplantation ▪ Respiratory support ▫ Respiratory failure → invasive ventilation OTHER INTERVENTIONS ▪ Address complications ▪ Chest physiotherapy ▫ Mobilize retained secretions ▪ Respiratory support ▫ Supplemental oxygen ▫ Positive-pressure ventilation EMPHYSEMA osms.it/emphysema PATHOLOGY & CAUSES ▪ COPD subset ▫ Exposure to irritants → degrades elastin in alveoli, airways → air-trapping, poor gas exchange. ▪ Irritants (e.g. cigarette smoke) → attraction of inflammatory cells → release leukotrienes, chemical mediators (e.g. B4; IL8; TNF alpha/proteases, elastases/ collagenases) → destroy collagen, elastin → lose elasticity → low pressure during expiration pulls walls of alveoli inward → collapse → air-trapping distal to collapse → septa breaks down → neighboring alveoli coalesce into larger air spaces → decreased surface area available for gas exchange ▫ Loss of elastin → lungs more compliant (lungs expand, hold air) ▫ Alveolar air sacs permanently enlarge, lose elasticity → exhaling difficult TYPES Centriacinar/centrilobular emphysema ▪ Most common ▪ Damage to central/proximal alveoli of acinus sparing distal alveoli ▫ Individuals who smoke (irritants can’t reach distal alveoli); upper lobes of lungs Panacinar emphysema ▪ Entire acinus uniformly affected ▫ A1AT deficiency; lower lobes of lungs 896 OSMOSIS.ORG Paraseptal emphysema ▪ Distal alveoli most affected ▫ Lung tissue on periphery of lobules near interlobular septa ▫ Ballooned alveoli on lung surface rupture → pneumothorax CAUSES ▪ Smoking, A1AT deficiency COMPLICATIONS ▪ Hypoxic vasoconstriction → cor pulmonale ▫ Poor gas exchange → vessels vasoconstrict to shunt blood to better gas exchange → pulmonary hypertension → increased workload for right heart → right ventricular hypertrophy → cor pulmonale ▪ Hypoxemia ▪ Pneumothorax SIGNS & SYMPTOMS ▪ Barrel chest (air-trapping, hyperinflation of lungs), apparent respiratory distress with use of accessory muscles, tripod positioning, weight loss, exhaling slowly through pursed lips (“pink puffers”), hyperventilation ▪ Pursing lips increases pressure in airway → keeps airway from collapsing → weight loss ▪ Dyspnea, cough (with less sputum)
Chapter 126 Obstructive Lung Disease DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Increased anterior-posterior diameter, flattened diameter, increased lung field lucency (air-trapping) OTHER DIAGNOSTICS ▪ Increased TLC ▪ FVC decreased (esp. FEV1) TREATMENT MEDICATIONS ▪ Bronchodilators ▪ Inhaled steroids ▪ Combination inhalers ▫ Bronchodilators + inhaled steroids ▪ Oral steroids ▫ Adverse effects: oral candidiasis, weight gain, diabetes, osteoporosis ▪ Antibiotics (e.g. azithromycin prevents exacerbations) ▪ Supplemental oxygen Figure 126.8 The gross pathological appearance of emphysema. There are numerous dilated airspaces in a peripheral distribution. SURGERY ▪ Lung volume reduction ▫ Removal of areas of damaged lung tissue to create extra space in chest cavity for healthy lung tissue to expand ▫ Can improve quality of life and prolong survival ▪ Lung transplant ▪ Bullectomy ▫ Removal of bullae (large air spaces) to improve air flow OTHER INTERVENTIONS ▪ Pulmonary rehabilitation program ▫ Customized education plan consisting of exercising training, nutrition advice, and lifestyle counseling Figure 126.9 The histological appearance of emphysema There are numerous hyperexpanded alveoli. OSMOSIS.ORG 897
MNEMONIC: P vs. B Emphysema vs. Bronchitis EmPhysema: Pink Puffer Chronic Bronchitis: Blue Bloater 898 OSMOSIS.ORG

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This Osmosis High-Yield Note provides an overview of Obstructive lung disease essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Obstructive lung disease by visiting the associated Learn Page.