Skip to main content
Log in

Lung morphometry: the link between structure and function

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this “machine lung” structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

References

  • Bachofen H, Schurch S (2001) Alveolar surface forces and lung architecture. Comp Biochem Physiol A Mol Integr Physiol 129:183–193

    Article  CAS  PubMed  Google Scholar 

  • Bachofen H, Ammann A, Wangensteen D, Weibel ER (1982) Perfusion fixation of lungs for structure-function analysis: credits and limitations. J Appl Physiol Respir Environ Exerc Physiol 53:528–533

    CAS  PubMed  Google Scholar 

  • Baddeley A, Jensen EBV (2005) Stereology for statisticians. Chapman and Hall/CRC, Boca Raton

  • Bohr C (1909) Über die spezifische Tätigkeit der Lungen bei der respiratorischen Gasaufnahme und ihr Verhalten zu der durch die Alveolarwand stattfindenden Gasdiffusion. Skand Arch Physiol 22:221–280

  • Borok Z, Whitsett JA, Bitterman PB, Thannickal VJ, Kotton DN, Reynolds SD, Krasnow MA, Bianchi DW, Morrisey EE, Hogan BL, Kurie JM, Walker DC, Radisky DC, Nishimura SL, Violette SM, Noble PW, Shapiro SD, Blaisdell CJ, Chapman HA, Kiley J, Gail D, Hoshizaki D (2011) Cell plasticity in lung injury and repair: report from an NHLBI workshop, April 19-20, 2010. Proc Am Thorac Soc 8:215–222

    Article  PubMed  PubMed Central  Google Scholar 

  • Burri PH (2006) Structural aspects of postnatal lung development—alveolar formation and growth. Biol Neonate 89:313–322

    Article  PubMed  Google Scholar 

  • Burri PH, Dbaly J, Weibel ER (1974) The postnatal growth of the rat lung. I. Morphometry. Anat Rec 178:711–730

    Article  CAS  PubMed  Google Scholar 

  • Campbell H, Tomkeieff SI (1952) Calculation of the internal surface of a lung. Nature 170:116–117

    Article  CAS  PubMed  Google Scholar 

  • Carlin JI, Hsia CC, Cassidy SS, Ramanathan M, Clifford PS, Johnson RL (1991) Recruitment of lung diffusing capacity with exercise before and after pneumonectomy in dogs. J Appl Physiol 70:135–142

    Article  CAS  PubMed  Google Scholar 

  • Crapo JD, Barry BE, Gehr P, Bachofen M, Weibel ER (1982) Cell number and cell characteristics of the normal human lung. Am Rev Respir Dis 126:332–337

    CAS  PubMed  Google Scholar 

  • Cruz-Orive LM, Weibel ER (1981) Sampling designs for stereology. J Microsc 122:235–257

    Article  CAS  PubMed  Google Scholar 

  • Eberth CJ (1862) Ueber den feineren Bau der Lunge. Z Wiss Zool 12:1–32

    Google Scholar 

  • Elze C, Hennig A (1956) Inspiratory enlargement of volume and inner surface of the human lung. Z Anat Entwicklungsgesch 119:457–469

    Article  CAS  PubMed  Google Scholar 

  • Evans MJ, Cabral LJ, Stephens RJ, Freeman G (1975) Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2. Exp Mol Pathol 22:142–150

    Article  CAS  PubMed  Google Scholar 

  • Federspiel WJ (1989) Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries. Respir Physiol 77:119–134

    Article  CAS  PubMed  Google Scholar 

  • Fritts HW Jr, Harris P, Chidsey CA 3rd, Clauss RH, Cournand A (1961) Estimation of flow through bronchial-pulmonary vascular anastomoses with use of T-1824 dye. Circulation 23:390–398

    Article  PubMed  Google Scholar 

  • Fuchs A, Weibel ER (1966) Morphometric study of the distribution of a specific cytoplasmatic organoid in the rat’s endothelial cells. Z Zellforsch Mikrosk Anat 73:1–9

    Article  CAS  PubMed  Google Scholar 

  • Gehr P, Bachofen M, Weibel ER (1978) The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol 32:121–140

    Article  CAS  PubMed  Google Scholar 

  • Gehr P, Sehovic S, Burri PH, Claassen H, Weibel ER (1980) The lung of shrews: morphometric estimation of diffusion capacity. Respir Physiol 40:33–47

    Article  CAS  PubMed  Google Scholar 

  • Gomez DM (1963) A mathematical treatment of the distribution of tidal volume throughout the lung. Proc Natl Acad Sci U S A 49:312–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haldane JS, Smith JL (1897) The absorption of oxygen by the lungs. J Physiol (Lond) 22:231–258

    Article  CAS  Google Scholar 

  • Hammond MD, Hempleman SC (1987) Oxygen diffusing capacity estimates derived from measured VA/Q distributions in man. Respir Physiol 69:129–147

    Article  CAS  PubMed  Google Scholar 

  • Holland RA, Hezewikj W van, Zubzanda J (1977) Velocity of oxygen uptake by partly saturated adult and fetal human red cells. Respir Physiol 29:303–314

  • Holland RA, Shibata H, Scheid P, Piiper J (1985) Kinetics of O2 uptake and release by red cells in stopped-flow apparatus: effects of unstirred layer. Respir Physiol 59:71–91

    Article  CAS  PubMed  Google Scholar 

  • Hsia CCW (2006) Quantitative morphology of compensatory lung growth. Eur Respir Rev 15:148–156

    Article  Google Scholar 

  • Hsia CC, Fryder-Doffey F, Stalder-Nayarro V, Johnson RL Jr, Reynolds RC, Weibel ER (1993) Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs. J Clin Invest 92:758–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsia CC, Hyde DM, Ochs M, Weibel ER (2010) An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 181:394–418

    Article  PubMed  Google Scholar 

  • Hsia CC, Hyde DM, Weibel ER (2016) Lung structure and the intrinsic challenges of gas exchange. Compr Physiol 6:827–895

    Article  PubMed  PubMed Central  Google Scholar 

  • Kapanci Y, Weibel ER, Kaplan HP, Robinson FR (1969) Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies. Lab Invest 20:101–118

    CAS  PubMed  Google Scholar 

  • Kapanci Y, Assimacopoulos A, Irle C, Zwahlen A, Gabbiani G (1974) “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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kauffman SL, Burri PH, Weibel ER (1974) The postnatal growth of the rat lung. II. Autoradiography. Anat Rec 180:63–76

    Article  CAS  PubMed  Google Scholar 

  • Kölliker A (1881) Zur Kenntnis des Baues der Lunge des Menschen. Verh physik-med Ges Würzburg NF 16:1–24

    Google Scholar 

  • Krogh A, Krogh M (1910) On the rate of diffusion of carbonic oxide into the lungs of man. Skand Arch Physiol 23:236–247

    Article  Google Scholar 

  • Loring WE, Liebow AA (1954) Effects of bronchial collateral circulation on heart and blood volume. Lab Invest 3:175–196

    CAS  PubMed  Google Scholar 

  • Low FN (1953) The pulmonary alveolar epithelium of laboratory mammals and man. Anat Rec 117:241–263

    Article  CAS  PubMed  Google Scholar 

  • Lucocq JM, Mayhew TM, Schwab Y, Steyer AM, Hacker C (2015) Systems biology in 3D space—enter the morphome. Trends Cell Biol 25:59–64

    Article  CAS  PubMed  Google Scholar 

  • Mason RJ, Shannon JM (1997) Alveolar type II cells. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) The lung: scientific foundations, vol 1, 3, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 543–555

  • Mayhew TM, Lucocq JM (2015) From gross anatomy to the nanomorphome: stereological tools provide a paradigm for advancing research in quantitative morphomics. J Anat 226:309–321

    Article  PubMed  Google Scholar 

  • Metcalf DJ, Nightingale TD, Zenner HL, Lui-Roberts WW, Cutler DF (2008) Formation and function of Weibel-Palade bodies. J Cell Sci 121:19–27

    Article  CAS  PubMed  Google Scholar 

  • Ochs M (2006) A brief update on lung stereology. J Microsc 222:188–200

    Article  PubMed  Google Scholar 

  • Ochs M (2010) The closer we look the more we see? Quantitative microscopic analysis of the pulmonary surfactant system. Cell Physiol Biochem 25:27–40

    Article  CAS  PubMed  Google Scholar 

  • Ochs M, Johnen G, Muller KM, Wahlers T, Hawgood S, Richter J, Brasch F (2002) Intracellular and intraalveolar localization of surfactant protein A (SP-A) in the parenchymal region of the human lung. Am J Respir Cell Mol Biol 26:91–98

    Article  CAS  PubMed  Google Scholar 

  • Ochs M, Nyengaard JR, Jung A, Knudsen L, Voigt M, Wahlers T, Richter J, Gundersen HJ (2004) The number of alveoli in the human lung. Am J Respir Crit Care Med 169:120–124

    Article  PubMed  Google Scholar 

  • Ochs M, Knudsen L, Hegermann J, Wrede C, Grothausmann R, Muhlfeld C (2016) Using electron microscopes to look into the lung. Histochem Cell Biol 146:695–707

    Article  CAS  PubMed  Google Scholar 

  • Pakkenberg B, Gundersen HJ (1995) Solutions to old problems in the quantitation of the central nervous system. J Neurol Sci 129 Suppl:65–67

    Article  CAS  PubMed  Google Scholar 

  • Policard A (1929) Les nouvelles idées sur la disposition de la surface respiratoire pulmonaire. Presse Med 80:1–20

    Google Scholar 

  • Policard A, Collet A, Pregermain S (1959) Research with the electron microscope on the parietal alveolar cells of the lung of mammals. Z Zellforsch Mikrosk Anat 50:561–587

    Article  CAS  PubMed  Google Scholar 

  • Ren X, Moser PT, Gilpin SE, Okamoto T, Wu T, Tapias LF, Mercier FE, Xiong L, Ghawi R, Scadden DT, Mathisen DJ, Ott HC (2015) Engineering pulmonary vasculature in decellularized rat and human lungs. Nat Biotechnol 33:1097–1102

    Article  CAS  PubMed  Google Scholar 

  • Richards DW (1957) Right heart catheterization; its contributions to physiology and medicine. Science 125:1181–1185

    Article  CAS  PubMed  Google Scholar 

  • Rock JR, Hogan BL (2011) Epithelial progenitor cells in lung development, maintenance, repair, and disease. Annu Rev Cell Dev Biol 27:493–512

    Article  CAS  PubMed  Google Scholar 

  • Roughton FJ, Forster RE (1957) Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J Appl Physiol 11:290–302

    CAS  PubMed  Google Scholar 

  • Sterio DC (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134:127–136

    Article  CAS  PubMed  Google Scholar 

  • Stone KC, Mercer RR, Gehr P, Stockstill B, Crapo JD (1992) Allometric relationships of cell numbers and size in the mammalian lung. Am J Respir Cell Mol Biol 6:235–243

    Article  CAS  PubMed  Google Scholar 

  • Vanhecke D, Studer D, Ochs M (2007) Stereology meets electron tomography: towards quantitative 3D electron microscopy. J Struct Biol 159:443–450

    Article  PubMed  Google Scholar 

  • Vock R, Weibel ER (1993) Massive hemorrhage causes changes in morphometric parameters of lung capillaries and concentration of leukocytes in microvasculature. Exp Lung Res 19:559–577

    Article  CAS  PubMed  Google Scholar 

  • Wagner DD, Frenette PS (2008) The vessel wall and its interactions. Blood 111:5271–5281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weibel E (1958) Origination of longitudinal muscles in branches of the bronchial artery. Z Zellforsch Mikrosk Anat 47:440–468

    Article  CAS  PubMed  Google Scholar 

  • Weibel E (1959) Blood vessel anastomoses in the human lungs. Z Zellforsch Mikrosk Anat 50:653–692

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (1963) Morphometry of the human lung. Springer, Berlin

    Book  Google Scholar 

  • Weibel ER (1970) Morphometric estimation of pulmonary diffusion capacity. I. Model and method. Respir Physiol 11:54–75

    Article  PubMed  Google Scholar 

  • Weibel ER (1971) The mystery of “non-nucleated plates” in the alveolar epithelium of the lung explained. Acta Anat (Basel) 78:425–443

    Article  CAS  Google Scholar 

  • Weibel ER (1979) Stereological methods. Academic Press, London

    Google Scholar 

  • Weibel ER (1984) The pathways of oxygen. Harvard University Press, Cambridge, Mass.

    Google Scholar 

  • Weibel ER (1991) Fractal geometry: a design principle for living organisms. Am J Physiol 261:L361–L369

    CAS  PubMed  Google Scholar 

  • Weibel ER (2009) What makes a good lung? Swiss Med Wkly 139:375–386

    PubMed  Google Scholar 

  • Weibel ER (2012) Fifty years of Weibel-Palade bodies: the discovery and early history of an enigmatic organelle of endothelial cells. J Thromb Haemost 10:979–984

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (2013a) It takes more than cells to make a good lung. Am J Respir Crit Care Med 187:342–346

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (2013b) A retrospective of lung morphometry: from 1963 to present. Am J Physiol Lung Cell Mol Physiol 305:L405–L408

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (2015) On the tricks alveolar epithelial cells play to make a good lung. Am J Respir Crit Care Med 191:504–513

    Article  PubMed  Google Scholar 

  • Weibel ER, Elias H (1967) Quantitative methods in morphology. Springer, Berlin

    Google Scholar 

  • Weibel ER, Gil J (1968) Electron microscopic demonstration of an extracellular duplex lining layer of alveoli. Respir Physiol 4:42–57

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER, Gomez DM (1962a) Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137:577–585

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER, Gomez DM (1962b) A principle for counting tissue structures on random sections. J Appl Physiol 17:343–348

    CAS  PubMed  Google Scholar 

  • Weibel ER, Knight BW (1964) A morphometric study on the thickness of the pulmonary air-blood barrier. J Cell Biol 21:367–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weibel ER, Vidone RA (1961) Fixation of the lung by formalin steam in a controlled state of air inflation. Am Rev Respir Dis 84:856–861

    CAS  PubMed  Google Scholar 

  • Weibel ER, Federspiel WJ, Fryder-Doffey F, Hsia CC, Konig M, Stalder-Navarro V, Vock R (1993) Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity. Respir Physiol 93:125–149

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER, Hsia CC, Ochs M (2007) How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol 102:459–467

  • Yamaguchi K, Nguyen-Phu D, Scheid P, Piiper J (1985) Kinetics of O2 uptake and release by human erythrocytes studied by a stopped-flow technique. J Appl Physiol 58:1215–1224

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ewald R. Weibel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weibel, E.R. Lung morphometry: the link between structure and function. Cell Tissue Res 367, 413–426 (2017). https://doi.org/10.1007/s00441-016-2541-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-016-2541-4

Keywords

Navigation