Comprehensive Physiology Wiley Online Library

Functional Morphology of Lung Parenchyma

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Elements of Lung Structure
1.1 Epithelium
1.2 Surface Lining of Air Spaces
1.3 Endothelium
1.4 Interstitial Space and Structures
2 Elements of the Fiber System
2.1 Collagen and Reticulin Fibers
2.2 Elastic Fibers
2.3 Integral Fiber Strand
3 Fiber Continuum of the Lung
3.1 Axial Fiber System
3.2 Peripheral Fiber System
3.3 Alveolar Septal Fiber System
4 Design of the Alveolar Septum
5 Alveolar Surface Lining Layer
6 Deformation of the Alveolar Septum Under the Effect of Interacting Forces
7 Geometry and Mechanics of the Acinus
8 Conclusions
Figure 1. Figure 1.

A: alveolar septum of dog lung showing delicate fiber bundle in septum and strong bundle at free edge forming the alveolar entrance ring as boundary of alveolar duct. Note collagen (CF) and elastic (EL) fibers, fibroblasts (F), and smooth muscle cell (SM). Capillaries (C) lined by endothelial cells (EN), alveolar surface lined by epithelium made of cuboidal type II (EP2) and squamous type I (EP1) cells. Scale, 2 μm. B: entrance ring at higher power. Scale, 0.5 μm.

Figure 2. Figure 2.

Fine structure of collagen (CF) and elastic (EL) fibers in perivascular sheath. Collagen fibers are bundles of banded fibrils seen in longitudinal and transverse section. Elastic fibers are made of amorphous core surrounded by microfibrils (arrows) that are partly embedded in core in thicker fibers. Scale, 0.5 μm.

Figure 3. Figure 3.

Integral fiber system seen by interference‐contrast microscopy of subcutaneous tissue of rat. Elastic fibers (EL) form network of straight fibers associated with wavy collagen fibers (CF). Scale, 50 μm.

Figure 4. Figure 4.

Section of fetal human lung showing continuity of loose peripheral mesenchymal bed from pleura (PL) to deeper parts of lung, and condensed mesenchyme (arrows) around bronchi (B) and within lobules as anlage of axial fiber system. Note location of pulmonary veins (V) and arteries (A) in loose mesenchyme. Scale, 200 μm.

Figure 5. Figure 5.

Acinar airways of perfusion‐fixed rabbit lung. Note that the wall of alveolar ducts (AD) is formed by network of coarse fiber bundles around alveolar mouths that represent the acinar extension of the axial fiber system from terminal (TB) and respiratory (RB) bronchioles. Peripheral fiber system is represented by pleura (PL) and a small septum with a branch of the pulmonary vein (arrow). Scale, 200 μm.

From Weibel
Figure 6. Figure 6.

Thick section of acinar airways in human lung with elastic fiber stain. Fiber strands in wall of alveolar ducts (AD, heavy arrows) decrease in thickness toward periphery. Light arrows outline peripheral fiber strands that extend from pleura (PL). Scale, 200 μm.

From Weibel
Figure 7. Figure 7.

Subpleural region of human lung with 2 interlobular septa (S) extending from pleura (PL). Gomori fiber stain. AD, alveolar duct. Scale, 200 μm.

Figure 8. Figure 8.

Thick slice of dried human lung showing hierarchy of interlobular septa (arrows). PL, pleura. Scale, 1 mm.

Figure 9. Figure 9.

Two‐dimensional model explaining hierarchy of interlobular septa as a sequence of shells around the branchings of a fractal airway tree.

Figure 10. Figure 10.

Septal fiber network of human lung. A: alveolar septa are extended between alveolar ducts (AD) marked by axial fibers (ax). per, Peripheral fibers. Scale, 200 μm. B: flat view at higher power of septal fibers extended between axial and peripheral fibers. Scale, 20 μm.

Figure 11. Figure 11.

Structure of human alveolar septum. A: scanning electron micrograph showing capillaries (C) in cross‐sectional and surface view; note free edge of septum toward alveolar duct (AD) and alveolar pores (P). Scale, 10 μm. B: model reconstruction of interweaving between capillaries and septal fiber meshwork.

From Weibel
Figure 12. Figure 12.

Alveolar septum of human lung in thin section. Capillary (C) bounded toward alveoli (A) by tissue barrier made of endothelium (EN) and type I epithelium (EP). On the left side the interstitium contains fibers (F) and fibroblast processes (FB); on the right side it is reduced to the fused basement membranes (minimal barrier). Note pericytes (PC). Scale, 1 μm.

From Weibel
Figure 13. Figure 13.

Surface lining layer (SLL) from perfusion‐fixed rat lung filling crevice in epithelial lining (EP) between 2 capillaries (C). Note osmiophilic surface film, presumably surfactant phospholipids, associated with some tubular myelin (TM). EN, endothelium; A, alveolus. Scale, 0.2 μm. Insets: fine structure of tubular myelin in transverse (A) and longitudinal (B) section. Scale, 0.1 μm.

Insets from Hassett et al.
Figure 14. Figure 14.

Forces interacting in molding structure of alveolar septum.

From Weibel
Figure 15. Figure 15.

Arrangement of alveolar septa in perfusion‐fixed rabbit lungs at 80% TLC (A, C, E) and 40% TLC (B, D, F). A, B: saline‐filled; C, D: normal air‐filled; E, F: detergent‐rinsed, air‐filled lungs. PV, pulmonary venule. Scale, 100 μm.

A, B from Gil et al. ; CF from Bachofen et al.
Figure 16. Figure 16.

Deformation of alveolar septum under the effect of surface forces counteracted by tissue force and capillary distending pressure.

From Weibel
Figure 17. Figure 17.

Smoothing of alveolar surface by pools of surface lining layer (SLL) and folding of barrier (arrows) in perfusion‐fixed human lung. C, capillary. Scale, 2 μm.

From Weibel
Figure 18. Figure 18.

Perfusion‐fixed air‐filled rabbit lung at 80% TLC after detergent rinsing. Capillaries are squashed by high surface tension (arrows). Scale, 20 μm.

From Bachofen et al.
Figure 19. Figure 19.

Crumpling of alveolar surface in perfusion‐fixed air‐filled rabbit lung at 40% TLC. High local curvatures (arrows) are sustained and a thin lamella of lining layer (L) spans across an alveolar pore (A). C, capillaries. Scale, 5 μm.

From Gil et al.
Figure 20. Figure 20.

Deformation of alveolar septum under the effect of surface forces. A: fluid‐filled lung; capillaries weave around a fiber sheet. B: air‐filled lung; capillaries appear arranged as a sheet and fibers weave across the septum. Scale, 10 μm.

Figure 21. Figure 21.

Model, reduced in length, of acinar fiber system under the effect of surface forces (arrows). Septal fibers become folded into corners.

From Weibel
Figure 22. Figure 22.

Surface‐to‐volume ratio of parenchymal air spaces in rabbit lungs as a function of lung volume.

Data from Bachofen et al. and Gil et al.


Figure 1.

A: alveolar septum of dog lung showing delicate fiber bundle in septum and strong bundle at free edge forming the alveolar entrance ring as boundary of alveolar duct. Note collagen (CF) and elastic (EL) fibers, fibroblasts (F), and smooth muscle cell (SM). Capillaries (C) lined by endothelial cells (EN), alveolar surface lined by epithelium made of cuboidal type II (EP2) and squamous type I (EP1) cells. Scale, 2 μm. B: entrance ring at higher power. Scale, 0.5 μm.



Figure 2.

Fine structure of collagen (CF) and elastic (EL) fibers in perivascular sheath. Collagen fibers are bundles of banded fibrils seen in longitudinal and transverse section. Elastic fibers are made of amorphous core surrounded by microfibrils (arrows) that are partly embedded in core in thicker fibers. Scale, 0.5 μm.



Figure 3.

Integral fiber system seen by interference‐contrast microscopy of subcutaneous tissue of rat. Elastic fibers (EL) form network of straight fibers associated with wavy collagen fibers (CF). Scale, 50 μm.



Figure 4.

Section of fetal human lung showing continuity of loose peripheral mesenchymal bed from pleura (PL) to deeper parts of lung, and condensed mesenchyme (arrows) around bronchi (B) and within lobules as anlage of axial fiber system. Note location of pulmonary veins (V) and arteries (A) in loose mesenchyme. Scale, 200 μm.



Figure 5.

Acinar airways of perfusion‐fixed rabbit lung. Note that the wall of alveolar ducts (AD) is formed by network of coarse fiber bundles around alveolar mouths that represent the acinar extension of the axial fiber system from terminal (TB) and respiratory (RB) bronchioles. Peripheral fiber system is represented by pleura (PL) and a small septum with a branch of the pulmonary vein (arrow). Scale, 200 μm.

From Weibel


Figure 6.

Thick section of acinar airways in human lung with elastic fiber stain. Fiber strands in wall of alveolar ducts (AD, heavy arrows) decrease in thickness toward periphery. Light arrows outline peripheral fiber strands that extend from pleura (PL). Scale, 200 μm.

From Weibel


Figure 7.

Subpleural region of human lung with 2 interlobular septa (S) extending from pleura (PL). Gomori fiber stain. AD, alveolar duct. Scale, 200 μm.



Figure 8.

Thick slice of dried human lung showing hierarchy of interlobular septa (arrows). PL, pleura. Scale, 1 mm.



Figure 9.

Two‐dimensional model explaining hierarchy of interlobular septa as a sequence of shells around the branchings of a fractal airway tree.



Figure 10.

Septal fiber network of human lung. A: alveolar septa are extended between alveolar ducts (AD) marked by axial fibers (ax). per, Peripheral fibers. Scale, 200 μm. B: flat view at higher power of septal fibers extended between axial and peripheral fibers. Scale, 20 μm.



Figure 11.

Structure of human alveolar septum. A: scanning electron micrograph showing capillaries (C) in cross‐sectional and surface view; note free edge of septum toward alveolar duct (AD) and alveolar pores (P). Scale, 10 μm. B: model reconstruction of interweaving between capillaries and septal fiber meshwork.

From Weibel


Figure 12.

Alveolar septum of human lung in thin section. Capillary (C) bounded toward alveoli (A) by tissue barrier made of endothelium (EN) and type I epithelium (EP). On the left side the interstitium contains fibers (F) and fibroblast processes (FB); on the right side it is reduced to the fused basement membranes (minimal barrier). Note pericytes (PC). Scale, 1 μm.

From Weibel


Figure 13.

Surface lining layer (SLL) from perfusion‐fixed rat lung filling crevice in epithelial lining (EP) between 2 capillaries (C). Note osmiophilic surface film, presumably surfactant phospholipids, associated with some tubular myelin (TM). EN, endothelium; A, alveolus. Scale, 0.2 μm. Insets: fine structure of tubular myelin in transverse (A) and longitudinal (B) section. Scale, 0.1 μm.

Insets from Hassett et al.


Figure 14.

Forces interacting in molding structure of alveolar septum.

From Weibel


Figure 15.

Arrangement of alveolar septa in perfusion‐fixed rabbit lungs at 80% TLC (A, C, E) and 40% TLC (B, D, F). A, B: saline‐filled; C, D: normal air‐filled; E, F: detergent‐rinsed, air‐filled lungs. PV, pulmonary venule. Scale, 100 μm.

A, B from Gil et al. ; CF from Bachofen et al.


Figure 16.

Deformation of alveolar septum under the effect of surface forces counteracted by tissue force and capillary distending pressure.

From Weibel


Figure 17.

Smoothing of alveolar surface by pools of surface lining layer (SLL) and folding of barrier (arrows) in perfusion‐fixed human lung. C, capillary. Scale, 2 μm.

From Weibel


Figure 18.

Perfusion‐fixed air‐filled rabbit lung at 80% TLC after detergent rinsing. Capillaries are squashed by high surface tension (arrows). Scale, 20 μm.

From Bachofen et al.


Figure 19.

Crumpling of alveolar surface in perfusion‐fixed air‐filled rabbit lung at 40% TLC. High local curvatures (arrows) are sustained and a thin lamella of lining layer (L) spans across an alveolar pore (A). C, capillaries. Scale, 5 μm.

From Gil et al.


Figure 20.

Deformation of alveolar septum under the effect of surface forces. A: fluid‐filled lung; capillaries weave around a fiber sheet. B: air‐filled lung; capillaries appear arranged as a sheet and fibers weave across the septum. Scale, 10 μm.



Figure 21.

Model, reduced in length, of acinar fiber system under the effect of surface forces (arrows). Septal fibers become folded into corners.

From Weibel


Figure 22.

Surface‐to‐volume ratio of parenchymal air spaces in rabbit lungs as a function of lung volume.

Data from Bachofen et al. and Gil et al.
References
 1. Agostoni, E. Mechanics of the pleural space. Physiol. Rev. 52: 57–128, 1972.
 2. Albert, E. N. Developing elastic tissue. An electron microscopic study. Am. J. Pathol. 69: 89–102, 1972.
 3. Askin, F. B., and C. Kuhn. The cellular origin of pulmonary surfactant. Lab. Invest. 25: 260–268, 1971.
 4. Atwal, O. S., and L. M. Brown. Membrane‐bound glycoprotein in the alveolar cells of the caprine lung. Am. J. Anat. 159: 275–283, 1980.
 5. Ayer, J. P. Elastic tissue. Int. Rev. Connect. Tissue Res. 2: 33–100, 1964.
 6. Bachofen, H., P. Gehr, and E. R. Weibel. Alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 47: 1002–1010, 1979.
 7. Bachofen, H., J. Hildebrandt, and M. Bachofen. Pressure‐volume curves of air‐ and liquid‐filled excised lungs—surface tension in situ. J. Appl. Physiol. 29: 422–431, 1970.
 8. Bernstein, J., S. S. Yang, H. S. Hahn, and Y. Kikkawa. Mucopolysaccharide in the pulmonary alveolus. I. Histochemical observations on the development of the alveolar lining layer. Lab. Invest. 21: 420–425, 1969.
 9. Bignon, J., M. C. Jaurand, M. C. Pinchon, C. Sapin, and J. M. Warnet. Immunoelectron microscopic and immunochemical demonstrations of serum proteins in the alveolar lining material of the rat lung. Am. Rev. Respir. Dis. 113: 109–120, 1976.
 10. Buckingham, S., H. O. Heinemann, S. C. Sommers, and W. F. McNary. Phospholipid synthesis in the large pulmonary alveolar cells. Am. J. Pathol. 48: 1027–1041, 1966.
 11. Bull, H. B. Protein structure and elasticity. In: Tissue Elasticity, edited by J. W. Remington. Washington, DC: Am. Physiol. Soc., 1957, p. 33–42.
 12. Burri, P. H. The postnatal growth of the rat lung. III. Morphology. Anat. Rec. 180: 77–98, 1974.
 13. Burri, P. H., and E. R. Weibel. Ultrastructure and morphometry of the developing lung. In: Lung Biology in Health and Disease. Development of the Lung, edited by W. A. Hodson. New York: Dekker, 1977, vol. 6, p. 215–268.
 14. Carton, R. W., J. Dainauskas, and J. W. Clark. Elastic properties of single elastic fibers. J. Appl. Physiol. 17: 547–551, 1962.
 15. Carton, R. W., J. Dainauskas, B. Tews, and C. M. Hass. Isolation and study of the elastic tissue network of the lung in three dimensions. Am. Rev. Respir. Dis. 82: 186–194, 1960.
 16. Clements, J. A. Pulmonary surfactant. Am. Rev. Respir. Dis. 101: 984–990, 1970.
 17. Clements, J. A., R. F. Hustead, R. P. Johnson, and I. Gribetz. Pulmonary surface tension and alveolar stability. J. Appl. Physiol. 16: 444–450, 1961.
 18. Clements, J. A., and R. King. Composition of surface active material. In: Lung Biology in Health and Disease. The Biochemical Basis of Pulmonary Function, edited by R. G. Crystal. New York: Dekker, 1976, vol. 2, p. 363–387.
 19. Crapo, J. D., B. E. Barry, H. A. Foscue, and J. Shelburne. Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am. Rev. Respir. Dis. 122: 123–143, 1980.
 20. Crapo, J. D., J. Marsh‐Salin, P. Ingram, and P. C. Pratt. Tolerance and cross‐tolerance using NO2 and O2. II. Pulmonary morphology and morphometry. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 44: 370–379, 1978.
 21. Crystal, R. G. (editor). Lung Biology in Health and Disease. The Biochemical Basis of Pulmonary Function. New York: Dekker, 1976, vol. 2.
 22. Emery, J. Connective tissue and lymphatics. In: The Anatomy of the Developing Lung, edited by J. Emery. Lavenham, UK: Heinemann, 1969, p. 49–73.
 23. Finley, T. N., S. A. Pratt, A. J. Ladman, L. Brever, and M. B. McKay. Morphological and lipid analysis of the alveolar lining material in dog lung. J. Lipid Res. 9: 357–365, 1968.
 24. Fishman, A. P., and E. M. Renkin (editors). Pulmonary Edema. Bethesda, MD: Am. Physiol. Soc., 1979.
 25. Fulmer, J. D., and R. G. Crystal. The biochemical basis of pulmonary function. In: Lung Biology in Health and Disease. The Biochemical Basis of Pulmonary Function, edited by R. G. Crystal. New York: Dekker, 1976, vol. 2, p. 419–466.
 26. Fung, Y. C. Stress, deformation, and atelectasis in the lung. Circ. Res. 37: 481–496, 1975.
 27. Fung, Y. C., and S. S. Sobin. Theory of sheet flow in lung alveoli. J. Appl. Physiol. 26: 472–488, 1969.
 28. Fung, Y. C., and S. S. Sobin. Elasticity of the pulmonary alveolar sheet. Circ. Res. 30: 451–469, 1972.
 29. Gabbiani, G., B. J. Hirschel, G. B. Ryan, P. R. Statkov, and G. Majno. Granulation tissue as a contractile organ. A study of structure and function. J. Exp. Med. 135: 719–734, 1972.
 30. Gehr, P., M. Bachofen, and E. R. Weibel. The normal human lung ultrastructure and morphometric estimation of diffusion capacity. Respir. Physiol. 32: 121–140, 1978.
 31. Gehr, P., D. K. Mwangi, A. Ammann, G. M. Maloiy, C. R. Taylor, and E. R. Weibel. Design of the mammalian respiratory system. V. Scaling morphometric pulmonary diffusing capacity to body mass: wild and domestic mammals. Respir. Physiol. 44: 61–86, 1981.
 32. Gil, J. Influence of surface forces on pulmonary circulation. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 4, p. 53–64.
 33. Gil, J., H. Bachofen, P. Gehr, and E. R. Weibel. Alveolar volume‐surface area relation in air‐ and saline‐filled lungs fixed by vascular perfusion. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 47: 990–1001, 1979.
 34. Gil, J., and J. M. McNiff. Interstitial cells at the boundary between alveolar and extraalveolar connective tissue in the lung. J. Ultrastruct. Res. 76: 149–157, 1981.
 35. Gil, J., and O. K. Reiss. Isolation and characterization of lamellar bodies and tubular myelin from rat lung homogenates. J. Cell Biol. 58: 152–171, 1973.
 36. Gil, J., and E. R. Weibel. Improvements in demonstration of lining layer of lung alveoli by electron microscopy. Respir. Physiol. 8: 13–36, 1969.
 37. Gil, J., and E. R. Weibel. Extracellular lining of bronchioles after perfusion‐fixation of rat lungs for electron microscopy. Anat. Rec. 169: 185–199, 1971.
 38. Gil, J., and E. R. Weibel. Morphological study of pressure‐volume hysteresis in rat lungs fixed by vascular perfusion. Respir. Physiol. 15: 190–213, 1972.
 39. Glazier, J. B., J. M. B. Hughes, J. E. Maloney, and J. B. West. Vertical gradient of alveolar size in lungs of dogs frozen intact. J. Appl. Physiol. 23: 694–705, 1967.
 40. Glazier, J. B., J. M. B. Hughes, J. E. Maloney, and J. B. West. Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J. Appl. Physiol 26: 65–76, 1969.
 41. Greenlee, T. K., Jr., R. Ross, and J. L. Hartman. The fine structure of elastin fibers. J. Cell Biol 30: 59–71, 1966.
 42. Groniowski, J., and W. Biczykowa. Structure of the alveolar lining film of the lungs. Nature London 204: 745–747, 1964.
 43. Guntheroth, W. G., D. L. Luchtel, and I. Kawabori. Pulmonary microcirculation: tubules rather than sheet and post. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 510–515, 1982.
 44. Haies, D., J. Gil, and E. R. Weibel. Morphometric study of rat lung cells. I. Numerical and dimensional characteristics of parenchymal cell population. Am. Rev. Respir. Dis. 123: 533–541, 1981.
 45. Hance, A. J., and R. G. Crystal. Collagen. In: Lung Biology in Health and Disease. The Biochemical Basis of Pulmonary Function, edited by R. G. Crystal. New York: Dekker, 1976, vol. 2, p. 215–271.
 46. Hassett, R. J., W. Engelman, and C. Kuhn. Extramembranous particles in tubular myelin from rat lung. J. Ultrastruct. Res. 71: 60–67, 1980.
 47. Hayek, H. von. Die menschliche Lunge (2nd ed.). Berlin: Springer‐Verlag, 1970.
 48. Hoppin, F. G., and J. Hildebrandt. Mechanical properties of the lung. In: Lung Biology in Health and Disease. Bioengineering Aspects of the Lung, edited by J. B. West. New York: Dekker, 1977, vol. 3, p. 83–162.
 49. Horsfield, K., G. Dart, D. E. Olson, G. F. Filley, and G. Cumming. Models of the human bronchial tree. J. Appl. Physiol. 31: 207–217, 1971.
 50. Horwitz, A. L., N. A. Elson, and R. G. Crystal. Proteoglycans and elastic fibers. In: Lung Biology in Health and Disease. The Biochemical Basis of Pulmonary Function, edited by R. G. Crystal. New York: Dekker, 1976, vol. 2, p. 273–311.
 51. Hughes, G. M., and E. R. Weibel. Similarity of supporting tissues in fish gills and mammalian reticuloendothelium. J. Ultrastruct. Res. 39: 106–114, 1972.
 52. Kapanci, Y., A. Assimacopoulos, C. Irle, A. Zwahlen, and G. Gabbiani. “Contractile interstitial cells” in pulmonary alveolar septa: a possible regulator of ventilation‐perfusion ratio? Ultrastructural, immunofluorescence, and in vitro studies. J. Cell Biol. 60: 375–392, 1974.
 53. Kapanci, Y., Y. P. M. Costabella, and G. Gabbiani. Location and function of contractile interstitial cells of the lungs. In: Lung Cells in Disease, edited by A. Bouhuys. Amsterdam: North‐Holland, 1976, p. 69–82.
 54. Kikkawa, Y., K. Yoneda, F. Smith, B. Packard, and K. Suzuki. The type II epithelial cells of the lung. II. Chemical composition and phospholipid synthesis. Lab. Invest. 32: 295–302, 1975.
 55. King, R. J., H. Martin, D. Mitts, and F. M. Holmstrom. Metabolism of the apoproteins in pulmonary surfactant. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 483–491, 1977.
 56. Krahl, V. E. Microscopic anatomy of the lungs. Am. Rev. Respir. Dis. 80: 23–44, 1959.
 57. Krahl, V. E. Anatomy of the mammalian lung. In: Handbook of Physiology. Respiration, edited by W. O. Fenn and H. Rahn. Washington, DC: Am. Physiol. Soc., 1964, sect. 3, vol. I, chapt. 6, p. 213–284.
 58. Kuhn, C. A comparison of freeze‐substitution with other methods for preservation of the pulmonary alveolar lining layer. Am. J. Anat. 133: 495–508, 1972.
 59. Lauweryns, J. M. The juxta‐alveolar lymphatics in the human adult lung. Am. Rev. Respir. Dis. 102: 877–885, 1970.
 60. Lauweryns, J. M., and J. H. Baert. Alveolar clearance and the role of pulmonary lymphatics. Am. Rev. Respir. Dis. 115: 625–683, 1977.
 61. Low, F. N. Microfibrils: fine filamentous components of the tissue space. Anat. Rec. 142: 131–137, 1962.
 62. Low, F. N. Extracellular components of the pulmonary alveolar wall. Arch. Intern. Med. 127: 847–852, 1971.
 63. Low, F. N. Lung interstitium. Development, morphology, fluid content. In: Lung Biology in Health and Disease. Lung Water and Solute Exchange, edited by N. C. Staub. New York: Dekker, 1978, vol. 7, p. 17–48.
 64. Majno, G., G. Gabbiani, B. J. Hirschel, G. B. Ryan, and P. R. Statkov. Contraction of granulation tissue in vitro: similarity to smooth muscle. Science 173: 548–550, 1971.
 65. Mandelbrot, B. B. Fractals: Form, Chance and Dimension. San Francisco, CA: Freeman, 1977.
 66. Mazzone, R. W. Influence of vascular and transpulmonary pressures on the functional morphology of the pulmonary microcirculation. Microvasc. Res. 20: 295–306, 1980.
 67. Mazzone, R. W., C. M. Durand, and J. B. West. Electron microscopy of lung rapidly frozen under controlled physiological conditions. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 45: 325–333, 1978.
 68. Mead, J. Mechanical properties of lungs. Physiol. Rev. 41: 281–330, 1961.
 69. Mead, J. Mechanics of respiratory structures. In: Pulmonary Structure and Function, edited by A. V. S. de Reuck and M. O. O'Connor. London: Churchill, 1962, p. 111–138. (Ciba Found. Symp.).
 70. Mead, J., T. Takishima, and D. Leith. Stress distribution in lungs: a model of pulmonary elasticity. J. Appl. Physiol. 28: 596–608, 1970.
 71. Mead, J., J. L. Whittenberger, and E. P. Radford, Jr. Surface tension as a factor in pulmonary volume‐pressure hysteresis. J. Appl. Physiol. 10: 191–196, 1957.
 72. Miller, W. S. The Lung (2nd ed.). Springfield, IL: Thomas, 1947.
 73. Monkhouse, W. S., and W. F. Whimster. An account of the longitudinal mucosal corrugations of the human tracheobronchial tree, with observations on those of some animals. J. Anat. 122: 681–695, 1976.
 74. Neergaard, K. von. Neue Auffassungen über einen Grundbegriff der Atemmechanik. Die Retraktionskraft der Lunge, abhängig von der Oberflächenspannung in den Alveolen. Z. Gesamte Exp. Med. 66: 373–394, 1929.
 75. Orsós, F. Ueber das elastische Gerüst der normalen und der emphysematösen Lunge. Beitr. Pathol. Anat. Allg. Pathol. 41: 95–121, 1907.
 76. Orsós, F. Die Gerüstsysteme der Lunge und deren physiologische und pathologische Bedeutung. I. Normal‐anatomische Verhältnisse. Beitr. Klin. Tuberk. 87: 568–609, 1936.
 77. Pattle, R. E. Properties, function and origin of the alveolar lining layer. Nature London 175: 1125–1126, 1955.
 78. Pattle, R. E. Surface lining of lung alveoli. Physiol. Rev. 45: 48–79, 1965.
 79. Pierce, J. A. The elastic tissue of the lung. In: The Lung, edited by A. A. Liebow and D. E. Smith. Baltimore, MD: Williams & Wilkins, 1968, p. 41–47.
 80. Pierce, J. A., and R. V. Ebert. Fibrous network of the lung and its change with age. Thorax 20: 469–476, 1965.
 81. Pietra, G. G., M. Magno, L. Johns, and A. P. Fishman. Bronchial veins and pulmonary edema. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 14, p. 195–206.
 82. Prockop, D. J. Collagen, elastin, and proteoglycans: matrix for fluid accumulation in the lung. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 9, p. 125–135.
 83. Rambourg, A., and C. P. Leblond. Electron microscope observations on the carbohydrate‐rich cell coat present at the surface of cells in the rat. J. Cell Biol. 32: 27–53, 1967.
 84. Rosenquist, T. H., S. Bernick, S. S. Sobin, and Y. C. Fung. The structure of the pulmonary interalveolar sheet. Microvasc. Res. 5: 199–212, 1973.
 85. Ross, R., and E. P. Benditt. Wound healing and collagen formation. V. Quantitative electron microscope radioautographic observations of proline‐H3 utilization by fibroblasts. J. Cell Biol. 27: 83–106, 1965.
 86. Ross, R., and P. Bornstein. The elastic fiber. I. The separation and partial characterization of its macromolecular components. J. Cell Biol. 40: 366–381, 1969.
 87. Roth, J., H. Winkelmann, and H. W. Meyer. Electron microscopic studies in mammalian lungs by freeze‐etching. IV. Formation of the superficial layer of the surfactant system by lamellar bodies. Exp. Pathol. 8: 354–362, 1973.
 88. Ryan, G. B., W. J. Cliff, G. Gabbiani, C. Irle, P. R. Statkov, and G. Majno. Myofibroblasts in an avascular fibrous tissue. Lab. Invest. 29: 197–206, 1973.
 89. Sanderson, R. J., G. W. Paul, A. E. Vatter, and G. F. Filley. Morphological and physical basis for lung surfactant action. Respir. Physiol. 27: 379–392, 1976.
 90. Schneeberger, E. E. Barrier function of intercellular junctions in adult and fetal lungs. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 2, p. 21–37.
 91. Schneeberger, E. E., and M. J. Karnovsky. The ultra‐structural basis of alveolar‐capillary membrane permeability to peroxidase used as a tracer. J. Cell Biol. 37: 781–793, 1968.
 92. Schneeberger, E. E., and M. J. Karnovsky. The influence of intravascular fluid volume on the permeability of newborn and adult mouse lungs to ultrastructural protein tracers. J. Cell Biol. 49: 319–334, 1971.
 93. Schneeberger, E. E., and M. J. Karnovsky. Substructure of intercellular junctions in freeze‐fractured alveolar‐capillary membranes of mouse lung. Circ. Res. 38: 404–411, 1976.
 94. Schürch, S., J. Goerke, and J. A. Clements. Direct determination of surface tension in the lung. Proc. Natl. Acad. Sci. USA 73: 4693–4702, 1976.
 95. Schürch, S., J. Goerke, and J. A. Clements. Direct determination of volume and time dependence of alveolar surface tension in excised lungs. Proc. Natl. Acad. Sci. USA 75: 3417–3421, 1978.
 96. Siegwart, B., P. Gehr, J. Gil, and E. R. Weibel. Morphometric estimation of pulmonary diffusion capacity. IV. The normal dog lung. Respir. Physiol. 13: 141–159, 1971.
 97. Sleigh, M. A. The nature and action of respiratory tract cilia. In: Lung Biology in Health and Disease. Respiratory Defense Mechanisms, edited by J. D. Brain, D. F. Proctor, and L. M. Reid. New York: Dekker, 1977, vol. 5, pt. 1, p. 247–288.
 98. Staub, N. C. Pulmonary edema. Physiol. Rev. 54: 678–811, 1974.
 99. Staub, N. C. Extravascular forces in lung affecting fluid and protein exchange. Am. Rev. Respir. Dis. 115: 159–163, 1977.
 100. Staub, N. C. Pathways for fluid and solute fluxes in pulmonary edema. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 8, p. 113–124.
 101. Stromberg, D. D., and C. A. Wiederhielm. Viscoelastic description of a collagenous tissue in simple elongation. J. Appl. Physiol. 26: 857–862, 1969.
 102. Untersee, P., J. Gil, and E. R. Weibel. Visualization of extracellular lining layer of lung alveoli by freeze‐etching. Respir. Physiol. 13: 171–185, 1971.
 103. Wangensteen, D., H. Bachofen, and E. R. Weibel. Lung tissue volume changes induced by hypertonic NaCl: morphometric evaluation. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 1443–1450, 1981.
 104. Weibel, E. R. Morphometry of the Human Lung. Heidelberg: Springer‐Verlag, 1963.
 105. Weibel, E. R. The mystery of “non‐nucleated plates” in the alveolar epithelium of the lung explained. Acta Anat. 78: 425–443, 1971.
 106. Weibel, E. R. Morphological basis of alveolar‐capillary gas exchange. Physiol. Rev. 53: 419–495, 1973.
 107. Weibel, E. R. On pericytes, particularly their existence on lung capillaries. Microvasc. Res. 8: 218–235, 1974.
 108. Weibel, E. R. Stereological Methods. Practical Methods for Biological Morphometry. London: Academic, 1979, vol. 1.
 109. Weibel, E. R. Looking into the lung: what can it tell us? Am. J. Roentgenol. 133: 1021–1031, 1979.
 110. Weibel, E. R. Design and structure of the human lung. In: Pulmonary Diseases and Disorders, edited by A. P. Fishman. New York: McGraw‐Hill, 1980, p. 224–271.
 111. Weibel, E. R. The Pathway for Oxygen. Cambridge, MA: Harvard Univ. Press, 1984.
 112. Weibel, E. R. Lung cell biology. In: Handbook of Physiology. The Respiratory System. Circulation and Nonrespiratory Functions, edited by A. P. Fishman and A. B. Fisher. Bethesda, MD: Am. Physiol. Soc., 1985, sect. 3, vol. I, chapt. 2, p. 47–91.
 113. Weibel, E. R., and H. Bachofen. Structural design of the alveolar septum and fluid exchange. In: Pulmonary Edema, edited by A. P. Fishman and E. M. Renkin. Bethesda, MD: Am. Physiol. Soc., 1979, chapt. 1, p. 1–20.
 114. Weibel, E. R., and J. Gil. Electron microscopic demonstration of an extracellular duplex lining layer of alveoli. Respir. Physiol. 4: 42–57, 1968.
 115. Weibel, E. R., and J. Gil. Structure‐function relationships at the alveolar level. In: Lung Biology in Health and Disease. Bioengineering Aspects of the Lung, edited by J. B. West. New York: Dekker, 1977, vol. 3, p. 1–81.
 116. Weibel, E. R., G. S. Kistler, and G. Töndury. A stereologic electron microscope study of “tubular myelin figures” in alveolar fluids of rat lungs. Z. Zellforsch. Mikrosk. Anat. 69: 418–427, 1966.
 117. Weibel, E. R., W. Limacher, and H. Bachofen. Electron microscopy of rapidly frozen lungs: evaluation on the basis of standard criteria. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 53: 516–527, 1982.
 118. Weibel, E. R., P. Untersee, J. Gil, and M. Zulauf. Morphometric estimation of pulmonary diffusion capacity. VI. Effect of varying positive pressure inflation of air spaces. Respir. Physiol. 18: 285–308, 1973.
 119. West, J. B. Stresses. In: Regional Differences in the Lung, edited by J. B. West. New York: Academic, 1977, p. 281–322.
 120. West, J. B., and F. L. Matthews. Stress, strains, and surface pressures in the lung caused by its weight. J. Appl. Physiol. 32: 332–345, 1972.
 121. Whimster, W. F. The microanatomy of the alveolar duct system. Thorax 25: 141–149, 1975.
 122. Williams, M. C. Freeze‐fracture studies of tubular myelin and lamellar bodies in fetal and adult rat lungs. J. Ultrastruct. Res. 64: 352–361, 1978.
 123. Wilson, T. A. Parenchymal mechanics at the alveolar level. Federation Proc. 38: 7–10, 1979.
 124. Wilson, T. A. Relations among recoil pressure, surface area, and surface tension in the lung. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 50: 921–926, 1981.
 125. Wilson, T. A., and H. Bachofen. A model for mechanical structure of the alveolar duct. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 1064–1070, 1982.
 126. Wright, R. R. Elastic tissue of normal and emphysematous lungs. A tridimensional histologic study. Am. J. Pathol. 39: 355–367, 1961.
 127. Young, C. D., G. W. Moore, and G. M. Hutchins. Connective tissue arrangement in respiratory airways. Anat. Rec. 198: 245–254, 1980.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Ewald R. Weibel. Functional Morphology of Lung Parenchyma. Compr Physiol 2011, Supplement 12: Handbook of Physiology, The Respiratory System, Mechanics of Breathing: 89-111. First published in print 1986. doi: 10.1002/cphy.cp030308