1. © 2007 McGraw-Hill Higher Education. All rights reserved. Chapter 3 Chronic Obstructive Pulmonary Disease

2. © 2007 McGraw-Hill Higher Education. All rights reserved. Topics Emphysema Chronic Bronchitis Pressure-volume curve Dynamic airway compression Ventilation-perfusion inequality

3. © 2007 McGraw-Hill Higher Education. All rights reserved. Case Study #3: Chuck Used car salesman SOB over the last 3 years –Chronic cough for 15 yrs Yellow, purulent sputum 45 yr smoking history 2 packs a day Intermittent swelling of the ankles Respiratory infection history No family history of lung disease

4. © 2007 McGraw-Hill Higher Education. All rights reserved. Case Study #3: Chuck Dyspneic Florid appearance Cyanotic BP: 150/80 Barrel shaped chest Ankle edema Whistling lung sounds

5. © 2007 McGraw-Hill Higher Education. All rights reserved. Chuck Hb: 17 g/dl X-ray –Showed over inflation Ppa: 30 mmHg Vo 2 max: 1.2 L/min Treatment –Bed rest, oxygen therapy, bronchodilators, diuretics –Advised to stop smoking –COPD rehab program

6. © 2007 McGraw-Hill Higher Education. All rights reserved. Chuck 6 mo later –Admitted with acute chest infection –Marked dyspnea –Purulent sputum –Cyanosis –Rales –Obvious ankle edema –PaO 2 : 42 mmHg –PaCO 2 : 55 mmHg –pH 7.30 –died

7. © 2007 McGraw-Hill Higher Education. All rights reserved. Autopsy –Lungs voluminous and lacked elastic recoil, some bronchi filled with mucus secretions, much destruction, with alveolar destruction prominent –Definite Chronic Bronchitis (blue bloaters) and emphysema (pink puffers), which caused respiratory failure Chronic Bronchitis

8. © 2007 McGraw-Hill Higher Education. All rights reserved. Pathology Structure –Alveolar destruction –Enlarged airspaces –Emphysema: –From the latin to inflate –Characterized by enlargement of the air spaces distal to the terminal bronchioles w/ destruction of the alveolar walls

9. © 2007 McGraw-Hill Higher Education. All rights reserved. COPD and lung function Chronic bronchitis –Marked by hypertrophied mucus glands –Inflammatory response due to irritants in smoke –Airways are swollen and blocked by mucus –Increased sputum production

10. © 2007 McGraw-Hill Higher Education. All rights reserved. Increasing SOB –Thickened bronchial walls –Obstruction –Poorly supported airways –Airway collapse –Florid with central cyanosis Elevated Hb Low SaO 2 Low Po 2 –Release of EPO Physiology & pathophysiology

11. © 2007 McGraw-Hill Higher Education. All rights reserved. Overinflation: inc. lung volume Whistling sounds caused by increased turbulence Neck vein engorgement, ankle edema and enlarged liver consistent with pulm hypertension –Right axis deviation is consistent with hypertrophy of the RV Physiology & pathophysiology

12. © 2007 McGraw-Hill Higher Education. All rights reserved. Pulmonary function tests

13. © 2007 McGraw-Hill Higher Education. All rights reserved. Gives you the compliance curve –Gives information about the elasticity of the lung –Pleural pressure is the negative pressure created by the outward pull of the ribcage and the inward pull of the lung –The lung will inflate as this pressure becomes more negative –Hysteresis –Transpulmonary pressure: pressure differential across the lung Diff betw intrapulmonary and intrapleural pressures Pressure volume curve

14. © 2007 McGraw-Hill Higher Education. All rights reserved. Volume change per unit pressure change (ΔV/ΔP) Lung very compliant in the middle of the curve; very stiff on the ends Emphysema Increases the compliance and reduces the elasticity of the lung Compliance

15. © 2007 McGraw-Hill Higher Education. All rights reserved. Regional differences in Ventilation Uneven –Higher in lower lung units, lowest in upper Posture dependent Laying supine –Highest in posterior lung

16. © 2007 McGraw-Hill Higher Education. All rights reserved. Why? Intrapleural pressure less negative at base –Due to the weight of the lung –Upper lobes are already somewhat distended –Lower lobes thus fill more (larger unit change in volume) Regional differences in Ventilation At low lung volumes Now intrapleural pressures are uniformly less negative (lung is smaller); base is now being compressed and ventilation is impossible; so apex is now better ventilated; typically apex is better ventilated

17. © 2007 McGraw-Hill Higher Education. All rights reserved. Airway closure Compressred regions do not have all the air squeezed out –Small airways close first –Traps gas –Usu. Occurs only at low lung volumes –In aging the volume this occurs at rises; why? Dependent regions of the lung are poorly ventilated

18. © 2007 McGraw-Hill Higher Education. All rights reserved. Forced expiration Measured with spirometer –FEV 1.0 –FVC –Measured after breath to TLC –FEF 25-75% Measure of elasticity of lung

19. © 2007 McGraw-Hill Higher Education. All rights reserved. Descending limb is invariant because it is “effort independent” What limits flow? Only at high volumes does increased effort result in increased flow Dynamic compression of Airways

20. © 2007 McGraw-Hill Higher Education. All rights reserved. Airways are compressed as intrathoracic pressure increases A: opening pressure of 5 cmH 2 O B: Opening pressure of 6 cmH 2 O C: Opening pressure of 8 D: Closing pressure of 11 cmH 2 O Thus, maximal flow decreases with lung volume Lung volume changes here are entirely due to elastic recoil Worse in emphysematous lungs as elastic recoil is reduced Dynamic airway compression

21. © 2007 McGraw-Hill Higher Education. All rights reserved. PaO 2 declines somewhat with age Cause: –V A /Q mismatch –Po 2 is determined by the ratio of ventilation to blood flow Blood gases

22. © 2007 McGraw-Hill Higher Education. All rights reserved. Ventilation-perfusion inequality –A: normal V A /Q –B: No ventilation; so V A /Q of 0 –C: No blood flow: V A /Q of ∞ –Note how V A /Q is different betw apex and base of lung

23. © 2007 McGraw-Hill Higher Education. All rights reserved. Areas with very high V A /Q add very little to oxygen to blood; thus PaO 2 is dominated by areas of low V A /Q Also shape of O 2 - Hb dissociation curve dictates that areas of very high V A /Q cannot increase the oxygenation of the blood very much, while areas of low V A /Q can lower Po 2 considerably Ventilation-perfusion

24. © 2007 McGraw-Hill Higher Education. All rights reserved. Normal lung, A-aDO 2 is about 4 mmHg due to V A /Q mismatching Disease can increase this by quite a bit MIGET –Inert gases with range of solubilities infused intravenously –Measure concentrations in arterial blood and expired air –No blood flow to unventilated areas (no shunt) Ventilation- perfusion

25. © 2007 McGraw-Hill Higher Education. All rights reserved. Alveolar-arterial Po 2 difference –P A O 2 = P I O 2 – [P A CO 2 /R] –Chuck: –149-[49/0.8] = 88 mmHg –PaO 2 = 58 –AaDO 2 = 30 PaCO 2 –Chuck: 49 mmHg V A /Q mismatch Hypoventilation: Pco 2 = [Vco 2 /V A ]*K pH: falls due to elevated Pco 2 (respiratory acidosis) Measurement of ventilation- perfusion inequality

26. © 2007 McGraw-Hill Higher Education. All rights reserved. Acclimatization and High-altitude diseases Hyperventilation –Hypoxemia stimulates peripheral chemoreceptors; blows off Co 2, raises P A O 2 –P B 250 mmHg do calculation –Renal compensation reduces HCO 3 - Polycythemia –Increased Hct and [Hb] –Increases O 2 carrying capacity: draw eq. –EPO form kidney Other features –Rightward shift in O 2 -Hb dissociation curve (Leftward at extreme altitude) Improves off-loading of O 2 at the tissues Caused by ↑2,3 DPG at altitude Increased capillary-to-fiber volume ratio –Muscle mass drops at altitude

27. © 2007 McGraw-Hill Higher Education. All rights reserved. Acute mountain sickness –Headache, dizziness, palpitations, insomnia, loss of appetite and nausea Hypoxemia and resp. alkalosis Chronic mountain sickness –Cyanosis, fatigue, severe hypoxemia, marked polycythemia High altitude pulmonary edema –Severe dyspnea, orthopnea, cough, cyanosis, crackles and pink, frothy sputum –Life threatening –Associated with elevated Ppa (hypoxic pulm vasoconstriction) High altitude cerebral edema –Confusion, ataxia, irrationality, hallucinations, loss of consciousness and death –Fluid leakage into brain Acclimatization and High-altitude diseases