Effects of pulmonary fibrosis on the distribution of edema. Morphometric analysis.

Abstract

We tested the hypothesis that in advanced pulmonary fibrosis, edema is redistributed away from the relatively noncompliant interstitium and predominantly floods alveoli. Severe left lung fibrosis was produced in six dogs with radiation and intratracheal bleomycin and, 24 mo later, hydrostatic edema was induced by infusing 20% body weight Ringer's lactate. Previously we had found, by computed tomography scanning and gravimetry, that similar amounts of water per unit volume accumulated in control and fibrotic lungs; semiquantitative light microscopic grading showed less interstitial and more alveolar edema in the fibrotic lungs. In the present study, we extended these observations with detailed morphometric assessment of volume fractions and absolute volumes of the pulmonary compartments, and we examined the lungs with electron microscopy. We found a twofold rise in the volume fractions of connective tissue and alveolar edema (p < 0.05) and a 50% reduction of air and of interstitial edema in fibrotic lobes (p < 0.05). There was a marked reduction in the absolute volume of edema, paralleling the reduction in lung volume in fibrosis, and minimal gravity-dependent edema gradients in both control and fibrotic lungs. In the latter, evidenced by electron microscopy, the interstitial edema was randomly distributed, whereas in the control lungs, 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.

Pulmonary ischemia/reperfusion injury: A quantitative study of structure and function in isolated heart‐lungs of the rat

“…Our stereologic approach allowed to estimate the volumes of the respective compartments to quantitate the particular contributions of interstitial and intraalveolar edema. Several studies clearly showed that, suitable fixation procedures given, LM and TEM are appropriate techniques to demonstrate and quantify edema accumulations in the peribronchovascular space (Michel et al, 1986; 1987; Zwikler et al, 1994) as well as in the alveolar space (Bachofen et al, 1993; Wu et al, 1995). There is no doubt that cryofixation is the best means to retain fluid in lung samples (Bastacky et al, 1995; Luchtel et al, 1991).…”

Pulmonary ischemia/reperfusion injury: A quantitative study of structure and function in isolated heart‐lungs of the rat

“…Our stereologic approach allowed to estimate the volumes of the respective compartments to quantitate the particular contributions of interstitial and intraalveolar edema. Several studies clearly showed that, suitable fixation procedures given, LM and TEM are appropriate techniques to demonstrate and quantify edema accumulations in the peribronchovascular space (Michel et al, 1986;1987;Zwikler et al, 1994) as well as in the alveolar space (Bachofen et al, 1993;Wu et al, 1995). There is no doubt that cryofixation is the best means to retain fluid in lung samples (Bastacky et al, 1995;Luchtel et al, 1991).…”

The extracellular matrix of the lung and its role in edema formation

“…In an experimental model of fi brosis there was a marked reduction in the absolute volume of edema, in parallel with a reduction in lung volume, suggesting that fi brosis deeply affects the distribution of edema in the lung (Zwinkler et al 1994). …”