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RESTRICTIVE DISEASES OF THE LUNG. Definition: TLC decreased by 20% compared to predicted values based on height, age, gender. Fig. 13.16. Air filled lung without surfactant. Fluid filled lung. Air filled lung. Volume. Pressure. water molecule. surfactant molecule.
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RESTRICTIVE DISEASES OF THE LUNG Definition: TLC decreased by 20% compared to predicted values based on height, age, gender
Air filled lung without surfactant Fluid filled lung Air filled lung Volume Pressure
water molecule surfactant molecule
Lung Pressure Volume Curves Full term Preemie Volume Pressure
CAUSES OF PULMONARY EDEMA • Cardiogenic • Myocardial infarction • Hypertensive left heart failure • Increased capillary permeability • Inhaled or circulating toxins • Endotoxin • High O2 over long periods of time • Radiation • SO2, NO2 • Bacterial and viral pathogens
Cardiogenic pulmonary edema left atrial pressure pressure in pulmonary vein Pcap fluid flux across the endothelium • Usually self correcting: • increased fluid flux increases PIF • increased fluid flux concentrates proteins in capillaries, increasing pcap
Increased capillary permeability Inflammation Increased permeability of pulmonary capillaries Increased protein leak across capillaries ↓ pcap ↑ fluid flux across capillaries • Usually not self limiting • fluid that leaks out has protein in it, increasing the oncotic pressure of • the interstitial spaces
Symptoms • dyspnea • cough (particularly in the recumbent position) • the cough is often non-productive in the early stages, • but in the advanced stages, it may bring up pink foam, • and cyanosis may be present
Pulmonary Function • the PV curve of the lung is shifted downward and to the right • resistance to flow through airways may increase • -(fluid forms around airways and isolates them from retractive forces • of the lung parenchyma) • TLC, VC, FRC decrease
How does edema affect lung compliance? “Good” lung “Good” lung Air Air
Breath goes evenly to both lungs Compliance = V/ P “Good” lung “Good” lung Air Air
Breath only goes to good lung Compliance = V/ P 2 “Good” lung “Bad” lung (very stiff) Air Fluid and pus
Gas Exchange • If only interstitial edema is present • little change in blood gases • If alveolar edema is present • decreased PaO2 (due to shunt) • PaCO2 normal or even low (hyperventilation). • Reason for hyperventilation: • low PaO2 • stimulation of lung receptors by high transpulmonary pressures • (lung is stiffer, so it requires greater pressures for ventilation)
Pulmonary alveolar proteinosis 1 2 3 4 5 6 7 8 9 10 Lavage Number
Proteinaceous material filling the alveoli, but no inflammatory cells
How does obesity impact: • Pulmonary mechanics • Pattern of breathing • Blood gases • Pulmonary Disease
How does obesity impact: • Pulmonary mechanics • Lung volumes • PV curves • Airway caliber • Airway responsiveness • Pattern of breathing • Blood gases • Pulmonary disease
How does obesity impact: • Pulmonary mechanics • Lung volumes • PV curves • Airway caliber • Airway responsiveness • Pattern of breathing • Blood gases • Pulmonary disease
From : Shore, S.A. Environmental Perturbations: Obesity. • Comprehensive Physiology, 263-282, 2010.
(293 subjects) ERV RV VC TLC FRC RV airway closure Lean Obese Adapted From: Rubinstein et al Ann Intern Med 112:828-832, 1990.
How does obesity impact: • Pulmonary mechanics • Lung volumes • PV curves • Airway caliber • Airway responsiveness • Pattern of breathing • Blood gases • Pulmonary disease
lean obese From: Johnston et al, Am J PhysiolRegulIntegr Comp Physiol 290: 126-33, 2006
How does obesity impact: • Pulmonary mechanics • Lung volumes • PV curves • Airway caliber • Airway responsiveness • Pattern of breathing • Blood gases • Pulmonary disease
Airway Resistance Lung Volume
Gaw is corrected for absolute lung volume Gaw = 1/Raw From: King et al: Eur. Respir. J. 25:896-901, 2005
Interim conclusion The airways of obese subjects are narrowed. The airway narrowing is more than could be expected on the basis of reduced lung volume alone. What else is causing airway narrowing?
FACTORS PRODUCED BY ADIPOSE TISSUE CYTOKINES TNFa IL-6 IL-1 PBEF TGFb IL-10 ACUTE PHASE REACTANTS Serum amyloid A C-reactive protein PAI-1 a1-acid glycoprotein CHEMOKINES IL-8 Eotaxin MCP-1 MIP-1a ENERGY REGULATING HORMONES Leptin Adiponectin Resistin OTHER FACTORS Angiotensinogen Complement B, C3, D Acylation-stimulating protein VEGF IL-1RA Retinol-binding protein-4
How does obesity impact: • Pulmonary mechanics • Lung volumes • Airway caliber • Airway responsiveness • Pattern of breathing • Blood gases • Pulmonary disease
Weight gain increases the likelihood of developing AHR From Litonjua et al Thorax 57:581-585, 2002
How does obesity impact: • Pulmonary mechanics • Pattern of breathing • Blood gases • Pulmonary disease
Obesity leads to decreased tidal volume and increased frequency Adapted from Sampson and Grassino, J. Appl. Physiol. 55:1269-1276, 1983.