Chapter 3 Chronic Obstructive Pulmonary Disease © 2007 McGraw-Hill Higher Education. All rights reserved. Topics • • • • • Emphysema Chronic Bronchitis Pressure-volume curve Dynamic airway compression Ventilation-perfusion inequality © 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 © 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Chuck • Hb: 17 g/dl • X-ray – Showed over inflation • Ppa: 30 mmHg • Vo2 max: 1.2 L/min • Treatment – Bed rest, oxygen therapy, bronchodilators, diuretics – Advised to stop smoking – COPD rehab program © 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 – PaO2: 42 mmHg – PaCO2: 55 mmHg – pH 7.30 – died © 2007 McGraw-Hill Higher Education. All rights reserved. Chronic Bronchitis • 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 © 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 © 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Physiology & pathophysiology • Increasing SOB – Thickened bronchial walls – Obstruction – Poorly supported airways – Airway collapse – Florid with central cyanosis • Elevated Hb • Low SaO2 • Low Po2 –Release of EPO © 2007 McGraw-Hill Higher Education. All rights reserved. Physiology & pathophysiology • 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Pulmonary function tests © 2007 McGraw-Hill Higher Education. All rights reserved. • Pressure volume curve 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Compliance • 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 © 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Regional differences in Ventilation • 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) © 2007 McGraw-Hill Higher Education. All rights reserved. •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 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Forced expiration • Measured with spirometer – FEV1.0 – FVC – Measured after breath to TLC – FEF25-75% Measure of elasticity of lung © 2007 McGraw-Hill Higher Education. All rights reserved. Dynamic compression of Airways • Descending limb is invariant because it is “effort independent” • What limits flow? • Only at high volumes does increased effort result in increased flow © 2007 McGraw-Hill Higher Education. All rights reserved. Dynamic airway compression • Airways are compressed as intrathoracic pressure increases • A: opening pressure of 5 cmH2O • B: Opening pressure of 6 cmH2O • C: Opening pressure of 8 • D: Closing pressure of 11 cmH2O • 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 © 2007 McGraw-Hill Higher Education. All rights reserved. Blood gases • PaO2 declines somewhat with age • Cause: – VA/Q mismatch – Po2 is determined by the ratio of ventilation to blood flow © 2007 McGraw-Hill Higher Education. All rights reserved. Ventilation-perfusion inequality – – – – A: normal VA/Q B: No ventilation; so VA/Q of 0 C: No blood flow: VA/Q of ∞ Note how VA/Q is different betw apex and base of lung © 2007 McGraw-Hill Higher Education. All rights reserved. Ventilation-perfusion • Areas with very high VA/Q add very little to oxygen to blood; thus PaO2 is dominated by areas of low VA/Q • Also shape of O2Hb dissociation curve dictates that areas of very high VA/Q cannot increase the oxygenation of the blood very much, while areas of low VA/Q can lower Po2 considerably © 2007 McGraw-Hill Higher Education. All rights reserved. • Ventilationperfusion Normal lung, A-aDO is 2 about 4 mmHg due to VA/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) © 2007 McGraw-Hill Higher Education. All rights reserved. Measurement of ventilationperfusion inequality • Alveolar-arterial Po2 difference – PAO2 = PIO2 – [PACO2/R] – Chuck: – 149-[49/0.8] = 88 mmHg – PaO2 = 58 – AaDO2= 30 • PaCO2 – Chuck: 49 mmHg • VA/Q mismatch • Hypoventilation: Pco2 = [Vco2/VA]*K • pH: falls due to elevated Pco2 (respiratory acidosis) © 2007 McGraw-Hill Higher Education. All rights reserved. Acclimatization and High-altitude diseases • Hyperventilation – Hypoxemia stimulates peripheral chemoreceptors; blows off Co2, raises PAO2 – PB 250 mmHg do calculation – Renal compensation reduces HCO3• Polycythemia – Increased Hct and [Hb] – Increases O2 carrying capacity: draw eq. – EPO form kidney • Other features – Rightward shift in O2-Hb dissociation curve (Leftward at extreme altitude) • Improves off-loading of O2 at the tissues • Caused by ↑2,3 DPG at altitude • Increased capillary-to-fiber volume ratio – Muscle mass drops at altitude © 2007 McGraw-Hill Higher Education. All rights reserved. Acclimatization and High-altitude diseases • 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 © 2007 McGraw-Hill Higher Education. All rights reserved.