The effects of pulmonary fibrosis on the distribution of lung edema

The normal lung with its air-filled alveoli is designed primarily to function in gas-exchange. Pulmonary edema, particularly in its alveolar flooding phase, is life-threatening because it interferes with this gas-exchange function. An important safety factor against alveolar flooding is the pulmonary interstitium that has a high compliance to accommodate edema fluid. We tested the hypothesis that if we decreased the compliance of the interstitium by experimental fibrosis, lung edema would be redistributed from the interstitium and predominantly flood alveoli. To study this, severe left lung fibrosis was produced in six dogs with radiation and bleomycin. Twenty-four months later, hydrostatic edema was induced by fluid infusion and lungs were studied pre- and post-edema with computed tomography (CT) scanning. Gravimetry and morphology were used to assess the amounts and distribution of edema between fibrotic left and control right lungs. Fibrosis, pre-edema, produced a 11-fold decrease in lung volume and a 2.2-fold increase in tissue density. We found, by CT and gravimetry, that similar amounts of water accumulated per unit volume in control and fibrotic lungs. Morphometry and semi-quantitative light microscopic grading showed a two-fold rise in the volume fractions of connective tissue and alveolar edema, and a 50% reduction of air and of interstitial edema in the fibrotic lobes. By electron microscopy, the interstitial edema in the fibrotic lungs was randomly distributed, whereas in the controls it was found primarily around extra-alveolar vessels and airways, not in the alveolo-capillary septa. We conclude that fibrosis profoundly affects the distribution of edema in the lung.