Quiz Yourself - Respiratory

1. Quiz Yourself - Respiratory

2. The FEV1 is reduced when: • airway obstruction is present as with these diseases: • Asthma • Emphysema • FEV1/FVC ratio is reduced when • airway obstruction is present. The normal ratio is: • 70-75 • The FVC is reduced with • restrictive lung disease • Pulmonary fibrosis

4. Lung Volumes in Disease States What does each of these represent?

5. What is the alveolar gas equation? • PAO2 = FIO2 x (PB – PH2O) – PaCO2/RQ What is the standard version (room air/temp)? • PAO2 = 150 – PaCO2/RQ RQ = 0.8 – 1.0

6. What are the 2 ways to alter V/Q ratio? Dead space • Regions of the lung that are ventilated but not perfused • Anatomic? • Normal. Like the trachea. About 30% of tidal volume. • Physiologic? • Includes anatomic, but in theory, when there are unperfused regions, as with a pulmonary embolism Shunt • Regions of the lung that are perfused but not ventilated! • V/Q mismatch = incomplete shunt. Responsive to O2 therapy • Shunt is refractory to O2 therapy Key pt: regions with a high V/Q ratio cannot compensate for regions with a low V/Q ratio b/c the high V/Q is normal!

7. What are the causes of hypoxemia and how do we distinguish them? • We distinguish between them using blood gas and A-a gradient • Hypoventilation • indicated by hypoxemia with a high pCO2, normal A-a. • Increasing frequency of breathing while lowering tidal volume increased the proportion of dead space ventilation to alveolar ventilation • V/Q mismatch • Shunt • indicated by hypoxemia with a HUGE A-a difference • Common causes include intracardiac lesions, structural abnormalities of the pulmonary vasculature, filling of alveolar spaces w/ fluid or complete alveolar collapse • Low inspired O2 (Low altitude)

8. What is the diffusing capacity? • Measured by DLCO • Impacted by diffusion barrier and aggregate surface area of alveoli • Measured with CO (but possible errors if the hemoglobin levels are low) • What does emphysema do? • reduces the area  reduced DLCO • What does fibrosis do? • increases the thickness  reduced DLCO

9. What are the volume patterns for the following diseases? • Obstructive diseases? • larger TLCs • Chronic bronchitis? • increased RV, increased FRC • Emphysema? • increased RV, VERY increased TLC • Restrictive diseases? • smaller TLCs • Fibrosis? • all lung volumes decreased • Obesity? • FRC reduced • Inspiratory muscle weakness? • TLC reduced • Expiratory muscle weakness? • RV is elevated

10. Mechanisms of Hypoxemia • Hypoventilation • V/Q Mismatch • Shunt • Low Inspired pO2 • How do we measure lung volumes? • Helium dilution • Used to measure absolute FRC • Doesn’t work if there’s lots of obstructed airways where a • Plethysmography • The small sealed box • Makes measurements using Boyle’s law

11. What patterns of impairment are associated with: • Obstructive lung disease? • Diminished rates of expiratory flow (increased FEV1, decreased FEV1/FVC) • Restrictive lung disease? • Diminished lung volumes • Preserved expiratory flow • What gives a characteristic scooped appearance in the expiratory phase of flow-volume loops? • Airway obstruction like emphysema • When is obstruction increased during inspiration? • When it’s an extra-thoracic variable obstruction • When is obstruction increased during expiration? • When it’s an intra-thoracic variable obstruction

12. What’s this? Normal Alveoli!

13. Dilated bronchi Muco-Purulent Debris in Dilated Bronchi Bronchiectasis

14. Bronchiectasis • What is it? • A chronic dilation of bronchi or bronchioles secondary to inflammation or obstruction • Pre-disposing syndromes? • Cystic fibrosis (CF) • Primary ciliary dyskinesia syndrome (Kartagener’s s.) • Radiology? • Airway dilation which extends to the periphery • Pathology? • Permanent dilation of bronchi • peri-bronchial inflammation and organization (fibrosis) • Can sometimes see mucopurulent debris in bronchioles

15. Eosinophil What disease is this? Charcot-Leyden crystals – eosinophil granule contents This is ASTHMA!!!! Asthma Curschmann Spirals – mucus casts

16. Asthma • Clinical: • Airway hyperresponsiveness • Triggers: antigens, exercise, drugs, infections, stress • Acute, usually reversible diffuse bronchial narrowing • Sxs: Wheezing, dyspnea • Radiology: • Alternating atelectasis and overexpansion • Pathology: • Edema • smooth muscle thickening • BM thickening • mucous cell hyperplasia • increased submucosal eosinophils • thickened intralumenal mucus • Curschmann spirals – mucus casts • Charcot-Leyden crystals – eosinophil granule contents

17. Increased numbers of mucinous glands in submucosa Chronic Bronchitis • A Clinical Diagnosis! • Definitional: Productive cough > 3months/year x > 2 years • Radiology is non-specific • Pathology: • Mucous cellular and glandular hyperplasia • May have submucosal chronic inflammation • May have respiratory bronchiolitis • Might look like this:

18. Centrilobular Emphysema in COPD

19. Emphysema • Clinical: • Associated with cigarette smoking (component of COPD) • 1-antitrypsin deficiency, esp PIZZ mutation • Radiology: • Increased lucency (dark region) • Upper>lower lobe suggests centrilobular type • Lower>upper lobe suggests panlobular type • Possible increased AP diameter • Possible flattened diaphragm • Pathology: • Dilation of distal airspaces with septal destruction • Locations: • Centrilobular: Cigarette smoke • Panlobular: A1AT deficiency or cigarette smoke • Increased elastase activity

20. Bronchiolitis Obliterans/Organizing Pneumonia (BOOP) • Clinical: • Acute onset cough, dyspnea, fever, and malaise • Multiple associations, e.g. collagen-vascular dz • Most patients respond to corticosteroids • Radiology: • Multiple patchy airspace infiltrates • Pathology: • Patchy fibromyxoid plugs in distal bronchioles – the BO • Fibromyxoid plugs in alveoli, +/- endogenous lipid pneumonia – the OP • Think bronchiolar and alveolar airspace fibroblasts

21. Intrinsic Asthma- No allergic or (personal family) history Usually adult onset Often follows severe respiratory illness Symptoms usually perennial More refractory to treatment, become other diseases, progress to vasculitis Eosinophils still impt Extrinsic Asthma- Strong family history of allergies Usually onset at a young age Other allergic manifestations in patients History of specific allergic association triggers (e.g. pollen, animal dander) Correlation with skin and inhalation responses to specific antigens Type I hypersensitivity rxn IgE mast cell and eosinophils Classification of Asthma

22. What does this demonstrate? What is it? ALLERGIC SHINER: Edema/ Discoloration Around the Eye

23. What are the important cells in asthma? • Eosinophils (in sputum) • B lymphocytes in mediating the asthma – more impt • What’s the point of the methacholine challenge? • It demonstrates that there’s something different in the architecture of the asthmatic’s airways that makes them non-specifically hyperreactive • What is a key feature of the pathophysiology of asthma that contributes to death? • Mucous plugs occluding airways • What are Creola bodies? • Agglomerated bronchial epithelial cells, seen in asthma • What happens when you administer a beta-agonist? • You initially decrease the O2 saturation via V/Q mismatch. • What is AM dipping? • When peak flow is decreased in the morning; associated w/ more severe asthma • What is the late phase reaction? • Delayed reduction in FEV1 due to IgE and influx of inflammatory cells • What is the cornerstone of asthma therapy? • Corticosteroids (effective in reducing late phase reaction)

24. Findings/Diagnosing Asthma? • Spirometry Increase lung volumes (TLC, FRC, RV) Decreased peak flow, FVC, FEV1, FEV1/FVC • Auto peak end expiratory pressure (auto-PEEP)-with rate respiratory rate. • DLCO Increased - useful in establishing dx • Methacholine challenge Hyper-responsive • b-agonist Reversible airflow obstruction when treated; albuterol • Eosinophils Increased in blood and found in sputum • ABG Low PO2, low PCO2

25. Treatment of Asthma • Avoid asthmatic triggers • Use bronchodilators • Sympathomimetics – usually B2-AR specific to increase cAMP. • albuterol • Salmeterol is a long acting B2 • Methylxanthines – inhibits PDE  increased cAMP • Anticholinergics – reserved for COPD • Use anti-inflammatory drugs • Corticosteroids – the cornerstone of therapy • Cromolyn and nedocromil – inhaled prophylactics • Zileuton, Zafirlukast – decreases leukotrienes • Omalizumab – anti IgE antibody

26. General Strategy for Management of Asthma • Infrequent attacks? • Inhaled sympathomimetics (B2) • More frequent? • Add an anti-inflammatory as maintenance, usually a corticosteroid • Still not good enough? • Regular use of inhaled B2 agonists • Add methylxanthines (theophylline) • Significant attack? • Systemic steroids • Status asthmaticus? • IV corticosteroids • Aggressive bronchodilators

27. Classification of asthma? • Mild intermittent • Mild persistent – more than 2X/week, but <1QD • Moderate persistent – daily symptoms • Severe persistent – continual symptoms

28. Common precipitating stimuli of asthma? • Allergen exposure – involves histamines, leukotrienes • Leukotrienes = why NSAIDS can precipitate asthma! • Inhaled irritants • Respiratory tract infections • Exercise (cool air) • When is airflow most compromised in asthmatics? • Expiration • Why is FRC chronically increased in asthma? • Dynamic hyperinflation – can’t fully exhale all air • Persistent activity of inspiratory muscles • What are the common symptoms of asthma? • Cough • Dyspnea • Wheezing – airflow through narrowed airways • Chest tightness • What is the mechanism of low PO2, low PCO2 in asthmatics? • V/Q mismatch

29. What are the 2 disorders under COPD? Basic defs? • Chronic bronchitis – diagnosis based on chronic cough and sputum production • Emphysema – diagnosis based on destruction of lung parenchyma and enlargement of air spaces distal to the terminal bronchiole • What’s the pathogenesis of alveolar destruction? • Protease and protease inhibitors are in balance in lung • Smoking inhibits protease inhibitors • Neutrophils and macrophages in inflammation release damaging proteases • What are the risk factors for COPD? • Cigarette Smoking (also 2nd hand) • Hyperresponsive Airways • Occupational Factors (firemen) • Alpha1-antitrypsin Deficiency – PIZZ is BAD! • Normally keeps elastase in check to maintain lung elastin

30. Mechanisms of Airflow limitation in COPD? • loss of alveolar attachments • obstruction of the airway due to inflammation • airway-wall fibrosis • airway smooth muscle constriction • luminal obstruction with mucus. • Loss of elastic recoil in emphysema results in: • Decreased expiratory flow rates • Lower driving pressure for expiratory airflow • Loss of radial traction from supporting alveolar walls • Functional abnormalities in COPD? • Decreased FVC, FEV1, FEV1/FVC • Increased RV, FRC, TLC • Decreased DLCO in emphysema • Increased Reid index in chronic bronchitis • Hypoxia • Hypercapnia in chronic bronchitis

31. Major secondary problem with COPD? Causes? • Pulmonary HTN  cor pulmonale (more common in chronic bronchitis patients) • Major Cause: Hypoxia  vasoconstriction • Hypercapnia • Polycythemia • Destruction of the pulmonary vascular bed • What is the protease-antiprotease hypothesis? • Alveolar integrity is maintained via a balancing act • Smoke increases the # of PMNs in the lung • PMNs produce elastase  degrades elastin • Smoke oxidants, oxidants from inflammatory cells impair A1AT anti-elastase activity • Neutrophil elastase stimulate mucus release • PMNs and macrophages make matrix metalloproteinases  shift balance towards degradation

32. Clinical Distinctions Between Blue Bloater and Pink Puffer COPD Pathophysiology

33. Treatment of COPD • Bronchodilators • Antibiotics • Corticosteroids • Supplemental O2 • Exercise rehab • Chest PT, postural drainage • Surgery (last resort) • Lung transplant • Lung volume reduction • Vaccines: pneumovax, flu • Plasma A1AT if the patient is A1AT deficient • Mechanical ventialtion

34. Major Points from SmokingCessation Lecture • Tobacco dependence is chronic and requires repeated intervention • If at first you don’t succeed, try, try again! • ALL pts who smoke should be offered at least ONE tobacco dependence treatment. • Pharmacotherapy CAN be helpful • Nicotine withdrawal can be fairly severe • Clinicians, hospitals, etc must institute consistent ID, documentation, and tx of tobacco users • Brief tobacco dependence tx is VERY effective – all pts should be offered at least brief tx • Strong dose-response relation between tobacco dependence tx and it’s effectiveness

35. Major Points from SmokingCessation Lecture • The 3 types of counseling/behavioral therapy found to be very effective and should be used: • Social Support within treatment • Social Support outside treatment • Skills training/problem solving • Unless contraindicated, use of effective pharmacotherapies for smoking cessation in all pts trying to quit should be used • Tobacco dependence treatments are both clinically effective and cost-effective relative to other medical and disease prevention interventions • Setting a quit date is IMPT! • Set up follow-up dates after quit date to see your pt. • People tend to gain weight upon quitting…

36. 5 first line pharmacotherapies for smoking abstinence that WORK • Bupropion SR • Nicotine gum • Nicotine inhaler • Nicotine nasal spray • Nicotine patch 2 second line pharamcotherapies for smoking: - clonidine - nortiptyline

37. What is the most successful self-help format to quit smoking? • Hotline “quitlines” • Person-to-Person contact – how much helps? • Even <3min is (moderately) better than none! • 10min or more is best • Asking your pt to quit smoking helps/doesn’t help? • It DOES! • What are 3 things associated with unsuccessful attempts at quitting? • Not practicing total abstinence • Drinking alcohol • Other smokers in da’ house

38. Peribronchovascular space Is dilated Giant cell Sarcoidosis What disease?

39. Sarcoidosis • Clinical: • Multi-system granulomatous disease • Adults, B>W, F>M • Dyspnea • Radiology: • Interstitial infiltrates in bronchovascular distribution (= lympagenic distribution) • Usually have hilar adenopathy (picked up on routine CXR) • Pathology: • Tight, well-formed non-caseating granulomata • Def of granulomata: Focal accumulations of epithelioid histiocytes

40. Hypersensitivity Pneumonia Loose Granulomas Interstitial expansion Peri-Bronchiolar Expansion

41. Hypersensitivity Pneumonitis(Extrinsic Allergic Alveolitis) • Clinical: • Organic dusts • Doesn’t mean carbon based • Means related to organic products • Occupational or environmental exposure • Acute and chronic: dyspnea, cough, fatigue • Radiology: • Bilateral interstitial linear or nodular pattern • Pathology: • Patchy peri-bronchiolar and interstitial chronic inflammation with loosely formed granulomata

42. Coal dust macules Coal-worker’s Pneumoconiosis

43. Patchy Sub-Pleural Fibrosis Ferruginous Body Asbestosis

44. Fibrotic Nodules Late Silicosis

45. UIP: Sub-pleural fibrosis adjacent to normal lung UIP

46. Usual Interstitial Pneumonia (UIP) • Clinical: • Syn. with “Idiopathic pulmonary fibrosis (IPF)” • Adults, mean 51 yo; poor response to steroids, 66% mortality • Radiology: • Patchy subpleural infiltrates, DDx asbestos, rheum • Pathology: • Patchy interstitial inflammation; fibrosis alternating with normal parenchyma • Temporally heterogeneous = ongoing injury to lung • Morph overlap with rheum dzs, e.g. scleroderma

47. Fibroblasts in the interstitium Alveolus Proliferative phase DAD

48. Proliferative (Organizing) Phase Diffuse Alveolar Damage (DAD) • Clinical: • > 1-2 wks after identifiable acute lung injury (ex: MVA, septic shock, kidney stone, inhalation of noxious chemical) • Decreased pulm compliance -> mechanical ventilation • 50% mortality • Radiology: • Diffuse, interstitial>alveolar pattern • Pathology: • Interstitial + intra-alveolar fibroblastic proliferation • Temporally uniform • If it’s temporally heterogeneous = UIP • You HAVE to see interstitial fibroblastic proliferation • If it’s purely intra-alveolar = BOOP

49. What characterizes Pulmonary function in Restrictive Lung Disease? • Characterized by reduced FVC, normal or high FEV1/FVC ratio Identify which is interstitial lung disease, obesity, and inspiratory & expiratory muscle weakness. Muscle Weakness Obesity Normal ILD TLC TLC TLC TLC FRC FRC RV FRC FRC RV RV RV

50. What’s the differential diagnosis for bilateral diffuse infiltrates that mimic diffuse parenchymal disease? • Congestive heart failure • Pulmonary infection • Lymphangitic carcinomatosis • What are known causes of diffuse parenchymal lung disease? • Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis • Inhaled organic antigens  hypersensitivity pneumonitis • Iatrogenic (drugs – amniodirone, radiation) • What are unknown etiological diffuse parenchymal lung diseases? • IPF/UIP • Sarcoidosis • BOOP • Goodpasture’s • Wegener’s • And many more… (Connective tissue disease associated, Chronic eosinophilic pneumonia, Lymphangioleiomyomatosis, Pulmonary Langerhan’s cell histiocytosis, Alveolar proteinosis, Pulmonary vasculitides)