© 2007 McGraw-Hill Higher Education. All rights reserved. Chapter 5 Diffuse Interstitial Pulmonary Fibrosis

© 2007 McGraw-Hill Higher Education. All rights reserved. Topics Pathology of diffuse interstitial pulmonary fibrosis Normal alveolar wall structure Reduced lung volumes and compliance Pressure-volume curves Diffusion across the blood-gas barrier Diffusing capacity

© 2007 McGraw-Hill Higher Education. All rights reserved. Case Study #5: Elena 40 yr old Blues singer Dyspnea and fatigue 5 years ago symptoms worsened Weight loss and unusual fatigue Irritating, unproductive cough No family history of pulm disease No apparent toxic exposure

© 2007 McGraw-Hill Higher Education. All rights reserved. Physical exam #5: Elena Drawn Rapid, shallow breathing Poor inspiratory movement Crackles on inspiration Clubbed fingers Loud pulmonary second sound (indicative of R side HF)

© 2007 McGraw-Hill Higher Education. All rights reserved. Investigations Normal hemoglobin and cell counts Small contracted lung and rib cage Raised diaphragm

© 2007 McGraw-Hill Higher Education. All rights reserved. Exercise and pulm function tests Vo 2 max: 2.2 L/min Stopped because of SOB Look at very low Po 2 values Why? DLCO

© 2007 McGraw-Hill Higher Education. All rights reserved. Definitive diagnosis –Marked thickening of alveolar walls Extensive collagen deposition Capillary obliteration Cause: unknown Lung Biopsy

© 2007 McGraw-Hill Higher Education. All rights reserved. Normal histology and Pathology Restrictive lung disease –No obstruction –Small volumes –Interstitial disease affects the parenchyma (tissue) Normal vs. restrictive alveolar wall

© 2007 McGraw-Hill Higher Education. All rights reserved. Alveolar anatomy Normally –Blood-gas barrier: ~ 0.3 um Alveolar epithelium, interstitium, capillary endothelium –Type I cell Chief structural cell of alveoli Structural Collagen –Type II cell Epithelial Globular Little structural support Metabolically active Forms surfactant In injury, transformed into type I cells

© 2007 McGraw-Hill Higher Education. All rights reserved. Other cells –Macrophages Scavenge foreign particles and bacteria –Fibroblasts Synthesize collagen and elastin –In fibrosis; large amts of collagen are laid down in interstitium of alveolar wall Alveolar anatomy II

© 2007 McGraw-Hill Higher Education. All rights reserved. Interstitium –Space between alveolar epithelium and capillary endothelium –Usu. Thin –Provides integrity and strength to BG barrier –Vulnerable to stress Alveolar anatomy III

© 2007 McGraw-Hill Higher Education. All rights reserved. Pathology of Diffuse Interstitial Pulmonary Fibrosis Many synonyms –Idiopathic pulmonary fibrosis –Interstitial pneumonia (inflammation and flooding) –Cryptogenic fibrosing alveolitis Principal features –Thickening of the interstitium Collagen deposition Infiltration with lymphocytes Fibroblasts lay down collagen Desquamation: cellular exudate (containing macrophages) in alveoli Destruction of alveolar architecture “Honeycomb” lung; scarring of lung (resists stretching)

© 2007 McGraw-Hill Higher Education. All rights reserved. Clinical findings –Chief complaint: dyspnea Caused by stiff lung Reduced compliance Shallow, rapid breathing Physical exam –Crepitations on inspiration caused by fibrotic lesions –Loud 2cd pulmonary sound: hypertension Caused by wholesale destruction of pulm caps Chest radiograph –Small lung Physiology and pathophysiology

© 2007 McGraw-Hill Higher Education. All rights reserved. Right shifted compliance curve (low) Very low lung volumes Pulmonary function tests

© 2007 McGraw-Hill Higher Education. All rights reserved. Pulmonary function in fibrosis Relaxation pressure-volume curve –Fig 5-6 –FRC: lung and chest wall forces are equal Above FRC: –Lung+chest wall forces are positive »Greater tendency for recoil Below FRC: –They are negative »Greater tendency for expansion Obstructive disease: FRC increases; why? Restrictive disease: FRC decreases; why?

© 2007 McGraw-Hill Higher Education. All rights reserved. FVC decreased FEV 1.0 /FVC: normal Elevated FEF 25-75% Rapid exhalation; why? –Little dynamic compression –Scarring supports the airways and holds them open Forced expiration

© 2007 McGraw-Hill Higher Education. All rights reserved. Arterial blood gases Hypoxemia; why? –V A /Q mismatch Destruction of capillaries Derangement of alveolar architecture –Diffusion limitation Thickened BG barrier

© 2007 McGraw-Hill Higher Education. All rights reserved. Diffusion across Blood-gas barrier Diffusion limitation vs perfusion limitation CO: diffusion limited –Binds very strongly to Hb Thus, partial pressure changes very little; why? No back-pressure Transfer limited by properties of blood-gas barrier N 2 O: perfusion limited –NO combination with Hb –Dissolves in plasma –Partial pressure rises rapidly –Transfer limited by blood flow O 2 ? –Can be both

© 2007 McGraw-Hill Higher Education. All rights reserved. Diffusion across Blood-gas barrier So, O 2 is perfusion limited in health, where the rise in partial pressure is rapid due to the lower affinity of Hb for O 2 and the very high diffusing capacity In disease, when the diffusion capacity is reduced, then O 2 becomes diffusion limited Also, diffusion of a gas depends upon it’s solubility in both the BG barrier AND the blood –If the same, no diffusion limitation –If different, diffusion limited Thus, BG barrier thickness increase can limit diffusion

© 2007 McGraw-Hill Higher Education. All rights reserved. Measurement of diffusing capacity Carbon monoxide: –Diffusion limited gas –V gas = A/T x (P 1 -P 2 ) x D –V gas = D L (P 1 -P 2 ) D L = diffusing capacity of the lung –Includes area, thickness and diffusive properties of membrane and gas D L = Vco/(P 1 -P 2 ) D L = Vco/P A co Vol of CO transferred per unit pressure CO

© 2007 McGraw-Hill Higher Education. All rights reserved. Usu. Subject takes a breath of dilute CO mixture (0.3%) and exhales –Conc difference between inspired and exhaled measured; rate of disappearance measured Rx rate with Hb –Not all resistance to transfer lies in membrane –Some lies in the Rx rate with Hb Two stages –Diffusion through BG barrier (includes plasma and RBC membrane) –Rx rate with Hb Measurement of diffusing capacity

© 2007 McGraw-Hill Higher Education. All rights reserved. These two “resistances” produce the overall “resistance to diffusion” Overall “conductance” is the inverse of these resistances (see Fig. 5-9) D L = diffusing capacity of the lung D M = diffusing capacity of the “membrane” Θ = rx rate with Hb Vc = capillary blood vol Measurement of diffusing capacity

© 2007 McGraw-Hill Higher Education. All rights reserved. Why is Elena’s diffusing capacity reduced? Reduced membrane conductance Reduced Vc Perhaps also due to unequal V A /Q