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© 2007 McGraw-Hill Higher Education. All rights reserved.
Chapter 5Diffuse 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• Vo2 max: 2.2 L/min
• Stopped because of SOB
• Look at very low Po2 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
• FEV1.0/FVC: normal
• Elevated FEF25-75%
• 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?– VA/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
• N2O: perfusion limited– NO combination with Hb– Dissolves in plasma– Partial pressure rises rapidly– Transfer limited by blood flow
• O2?– Can be both
© 2007 McGraw-Hill Higher Education. All rights reserved.
Diffusion across Blood-gas barrier
• So, O2 is perfusion limited in health, where the rise in partial pressure is rapid due to the lower affinity of Hb for O2 and the very high diffusing capacity
• In disease, when the diffusion capacity is reduced, then O2 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 (P1-P2) x D– V gas = DL (P1-P2)
• DL = diffusing capacity of the lung
– Includes area, thickness and diffusive properties of membrane and gas
• DL = Vco/(P1-P2)• DL = Vco/PAco• 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)
• DL = diffusing capacity of the lung
• DM = 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 VA/Q