Fine Structural Morphometry on Biopsy Specimens of Human Lung: 2. Diffuse Idiopathic Pulmonary Fibrosis

Abstract

Stereologic techniques were applied to an electronmicroscopic study of random samples from nine normal human lungs and nine with diffuse idiopathic interstitial pulmonary fibrosis. Relative fractional volumes of lung components, alveolar and capillary surface areas, and arithmetic and harmonic mean thickness of alveolar-capillary membranes were compared in the two groups to enable a more precise assessment of the changes responsible for the diffusion abnormalities present in this disease. Arithmetic mean thickness of the alveolar-capillary membranes in diseased lungs was increased to 2.1 times the normal mean value and harmonic mean thickness to 1.7 times normal. This increase by itself appears insufficient to account for the associated abnormalities of gas transfer and is incompatible with the traditional concept of alveolar-capillary block. When compared with normal lung, there was a threefold increase in mean volumetric fraction of septal intercapillary tissue and a decrease to one third the anticipated values of mean surface areas of alveoli and capillaries. Although uniformity of distribution of these changes cannot be determined by this method, our study suggests that abnormalities of gas transfer between alveolar air and capillary blood in diffuse idiopathic interstitial pulmonary fibrosis result primarily from a decrease in the surface areas available for diffusion. Increase in membrane thickness then becomes important only insofar as abnormalities of other diffusion factors make this parameter critical. Stereologic techniques were applied to an electronmicroscopic study of random samples from nine normal human lungs and nine with diffuse idiopathic interstitial pulmonary fibrosis. Relative fractional volumes of lung components, alveolar and capillary surface areas, and arithmetic and harmonic mean thickness of alveolar-capillary membranes were compared in the two groups to enable a more precise assessment of the changes responsible for the diffusion abnormalities present in this disease. Arithmetic mean thickness of the alveolar-capillary membranes in diseased lungs was increased to 2.1 times the normal mean value and harmonic mean thickness to 1.7 times normal. This increase by itself appears insufficient to account for the associated abnormalities of gas transfer and is incompatible with the traditional concept of alveolar-capillary block. When compared with normal lung, there was a threefold increase in mean volumetric fraction of septal intercapillary tissue and a decrease to one third the anticipated values of mean surface areas of alveoli and capillaries. Although uniformity of distribution of these changes cannot be determined by this method, our study suggests that abnormalities of gas transfer between alveolar air and capillary blood in diffuse idiopathic interstitial pulmonary fibrosis result primarily from a decrease in the surface areas available for diffusion. Increase in membrane thickness then becomes important only insofar as abnormalities of other diffusion factors make this parameter critical.