Chapter 5 Diffuse Interstitial Pulmonary Fibrosis

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Chapter 5Diffuse Interstitial Pulmonary

Fibrosis


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


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


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)


Investigations

• Normal hemoglobin and cell counts

• Small contracted lung and rib cage

• Raised diaphragm


Exercise and pulm function tests• Vo2 max: 2.2 L/min

• Stopped because of SOB

• Look at very low Po2 values

• Why?• DLCO


• Definitive diagnosis– Marked thickening

of alveolar walls• Extensive

collagen deposition

• Capillary obliteration

• Cause: unknown

Lung Biopsy


Normal histology and Pathology• Restrictive lung disease

– No obstruction– Small volumes– Interstitial disease affects the parenchyma (tissue)

• Normal vs. restrictive alveolar wall


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


• 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


• Interstitium– Space between

alveolar epithelium and capillary endothelium

– Usu. Thin– Provides integrity

and strength to BG barrier

– Vulnerable to stress

Alveolar anatomy III


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)


• 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


• Right shifted compliance curve (low)

• Very low lung volumes

Pulmonary function tests


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?


• 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


Arterial blood gases

• Hypoxemia; why?– VA/Q mismatch

• Destruction of capillaries

• Derangement of alveolar architecture

– Diffusion limitation• Thickened BG

barrier


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


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


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


• 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



• 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



Why is Elena’s diffusing capacity reduced?

• Reduced membrane conductance

• Reduced Vc• Perhaps also due to

unequal VA/Q

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Chapter 5 Diffuse Interstitial Pulmonary Fibrosis

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