1. 1 Respiratory Disorders II

2. 2 Lecture Outline 1- Spirometry: Volume/Time & Flow/Volume Curves 2- Use of Spirometry in Obstructive & Restrictive Lung Diseases 3- Spirometry Live Demonstration 4- Aetiology & Pathological Features of Chronic Bronchitis 5- Aetiology & Pathological Features of Emphysema 6- Effect of Obstructive Lung Disease on Lung Volumes & Capacities 7- Aetiology & Pathological Features of Restrictive Lung Disease 8- Respiratory Function Tests- Diagnostic Significance

3. 3 Spirometry in the wards = 2 types - 1-Vol-time - 2- Flow- vol Spirometry

4. 4 Spirometry- Vol/Time Volume (L) 0 1 2 3 4 5 6 Time (s) 01234 FEV 1 Normally, FEV 1 /FVC ratio= 0.8 or FEV 1 = 80% FVC Forced Vital Capacity FVC From fully inspired state patient expels all air in their lungs as forcefully as possible 25% 75% Slope of the initial line gives the flow rate FEF 25% -75%

5. 5 Forced Expiratory Flow (FEF 25% – 75% ) Measure of expiratory flow rate (  V/  t) over middle half of the FVC curve More conveniently done on Flow-Vol spirometry … Directly read off from the curve SIG = Early airflow obstruction

6. 6 Vol-Time Spirometry in Obstructive Lung Disease Volume (L) 0 1 2 3 4 5 6 Time (s) 01234 Obstructive Lung Disease Total Volume (TLC and FVC) may be normal but FEV 1 is reduced And FEV 1 /FVC ratio <0.8 (<50% here) Forced Vital Capacity FEV 1

7. 7 Vol-Time Spirometry in Restrictive Lung Disease Volume (L) 0 1 2 3 4 5 6 Time (s) 01234 Restrictive Lung Disease: Total Volume reduced and FVC reduced, FEV 1 reduced But FEV 1 /FVC ratio = NORMAL! FEV 1 Forced Vital Capacity

8. 8 Spirometry: Flow/Volume Loop Flow (L s -1 ) Expired Lung Volume (L) 0 2 4 6 2 4 6 Expiration Inspiration 12345 FEF 75 FEF 25 Vital Capacity 1 s mark Measurement of flow rates; contemporary technique ● 1 sec ● PEF

9. 9 Spirometry: Demonstration

10. 10 Flow/Volume Loops in Obstructive Lung Disease Flow (L s -1 ) Lung Volume (L) 0 2 4 6 2 4 6 Expiration Inspiration 12345 FEF 50 FIF 50 ● ● 1 sec PEF Scooped out appearance

11. 11 Flow (L s -1 ) Lung Volume (L) 0 2 4 6 2 4 6 Expiration Inspiration 12345 FEF 50 FIF 50 ● 1 sec ● PEF Flow/Volume Loops in Restrictive Lung Disease

12. 12 Chronic Bronchitis Clinical definition : “A cough productive of sputum on most days for three months of the year, for at least two consecutive years”- WHO- CD10 Airways show Hypersecretion of mucus with mucus gland Hyperplasia = an increase in airflow resistance in the large airways The airway obstruction is due to Luminal Narrowing and Mucus Plugging Could be part of underlying disease process; eg asthma, cystic fibrosis, Dyskinetic cilia syndrome…etc – Not 1 ry diagnosis Chronic Obstructive Lung Diseases (COPDs)

13. 13 Chronic Bronchitis Metaplasia: Ciliated Columnar Ep cells Replaced by Squamous Ep cells Hypertrophy of submucosal glands & Hyperpalsia of goblet cells

14. 14 Chronic Bronchitis Chronic Bronchitis leads to: 1. Alveolar Hypoventilation 2. Hypoxaemia (low arterial PO 2 ) 3. Hypercapnia (↑blood CO 2 ) 4. Respiratory Failure may occur Individuals are typically cyanosed but may not have Dyspnoea (Respiratory distress) In some cases chronic bronchitis may lead to Hypoxic Pulmonary Vasoconstriction, and Secondary Pulmonary Hypertension This may lead to right sided heart failure

15. 15 Emphysema Permanent enlargement (dilation) of any part respiratory acinus (distal to the bronchi) Destruction of alveolar walls (without scarring) Loss of elastic recoil in the lungs as the respiratory tissue is destroyed Thus: area for gas exchange is reduced There are two patterns: 1. CENTRIACINAR 2. PANACINAR Acinus = Terminal duct + alveoli

16. 16 The Acinus in Emphysema

17. 17Emphysema Acinus in Emphysema

18. 18 Air trapping, Increased RVEmphysema Increased FRC, TLC

19. 19 Emphysema Proposed to be caused by unregulated activity of extracellular proteases secreted from inflammatory cells This is a response to chronic exposure to cigarette smoke or other inhaled irritants Linked to an imbalance of protease and the protease inhibitor  1-antitrypsin Proteases (particularly Elastase) cause the breakdown of alveolar walls and collapse of small airways

20. 20 Aetiology of Emphysema Antielastase activity  1 Antitrypsin Deficiency (genetic) Smoking Elastase Elastic Damage Emphysema

21. 21 Emphysema The classic presentation = barrel-chested and dyspnoeic Patients have prolonged expiration and may sit forward in a hunched position attempting to squeeze the air out of the lungs The loss of elastic recoil and structural support leads to: 1. Trapping of air in lungs 2. Over inflated lungs 3. Decreased rate of airflow on expiration

22. 22 Emphysema Reduced oxygen uptake despite increased ventilation blood oxygenation may be maintained by rapid respiration, but subjects breathless on the slightest exertion and become hypoxic Patients are known as ‘PINK PUFFERS’ Cyanosis, hypercapnia and cor pulmonale (enlargement of the right ventricle) occur late in the disease after progressive decline in lung function

23. 23 Emphysema progresses slowly and worsens over time. Increased effort in breathing leads to progressive breathlessness Some do not progress (Pink Puffers) In some cases the disease progresses leading to chronic hypoxia and hypercapnia (Blue Bloaters) Emphysema

24. 24 Effects of Obstructive Disease on Lung Volumes TLC is elevated (why?) Residual Volume is elevated Expiratory Capacity is elevated So FRC is elevated (What about IRV & IC?) Elevations are due to air trapped in lungs following expiration Vital capacity may be reduced FEV 1 is reduced

25. 25 Effects of Obstructive Disease on Lung Volumes Airflow is reduced due to airway obstruction. VC and FEV 1 are reduced but  FEV 1 is >  FVC Therefore FEV 1 /FVC ratio is much lower than the normal 70% - 80% of FVC (as low as 25%)

26. 26 Restrictive Lung Diseases Restrictive lung diseases are caused by a reduction in total lung capacity Features include: 1. Increased Lung Density (Stiff Lung). 3. Reduced Compliance (  V/  P) 4. Breathlessness (Dyspnoea) 5. Greater Effort to Inflate Lungs 6. Abnormality of Alveolar Walls which renders them rigid

27. 27 Restrictive Lung Diseases Characterised by damage to the alveolar walls and capillaries An increase in interstitial fluid or fibrosis produce a stiff lung Damage to the alveolar epithelium and vasculature produce abnormalities in the ventilation/ perfusion ratio (normally 5/6 ~ 0.8)

28. 28 Restrictive Lung Disease ACUTE - Adult Respiratory Distress Syndrome (ARDS) Trauma or acute illness Inflammation of lung paranchyma- pulmonary edema- eg Pneumonia CHRONIC - Pneumoconiosis- occupational lung disease- Asbestosis silicosis, byssinosis (cotton dust) - Idiopathic Pulmonary Fibrosis (IPF) -unknown cause - Sarcoidosis- immune system disorder- small inflammatory nodules (granulomas)- leading to fibrosis

29. 29 Chronic Restrictive Lung Diseases Develop over months/years and leads to a slowly decreasing respiratory efficiency With chronic interstitial fibrosis leading to ‘honeycomb’ lung There is an infiltration of macrophages and microcyst formation. Clinically patients exhibit dyspnoea, cough and in advanced cases hypoxemia and cyanosis, eventually respiratory failure

30. 30 Honeycomb lung

31. 31 Proposed Mechanism for Fibrosis T Lymphocyte B Lymphocyte Activated Macrophage Unknown Antigen Immune complexes cytokines Oxidants & Proteases Injury to type I pneumocytes (epithelial cells) Fibrogenic cytokines Fibroblasts

32. 32 Macrophage in alveolus

33. 33 Effects of Restrictive Disease on Lung Volumes Reduced FVC Reduced FEV 1 Relatively Normal FEV1/FVC ratio Relatively Normal PEFR TLC is reduced (Why?) Inspiratory capacity is reduced. Residual Volume is normal Reflect loss of compliance

34. 34 Respiratory Function Tests – Diagnostic Significance Peak Expiratory Flow Rate - Reduced with obstructive lung disease. FEV 1 - * Reduced with obstructive disease * Reduced with pulmonary fibrosis (restrictive) Forced Vital Capacity (FVC) - * Reduced in COPD * Reduced with a corresponding decrease in total lung volume in fibrosis or oedema * Reduced with muscle weakness

35. 35 Respiratory Function Tests – Diagnostic Significance Forced Expiratory Ratio: FEV 1 /FVC - * Low in obstructive lung disease * Normal or high in restrictive defects

36. 36 Thanks & Good Luck!