The postnatal development and growth of the human lung. I. Morphometry

doi:10.1016/0034-5687(87)90057-0

Respiration Physiology

Volume 67, Issue 3, March 1987, Pages 247-267

Respiration Physiolo...

https://doi.org/10.1016/0034-5687(87)90057-0 Get rights and content

Abstract

The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproprotionate volume increase in the O₂-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth af all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to adulthood, indicating a steady increase in the air-blood interface complexity during the entire growth period. As a consequence of the differences in growth paces between the various structural lung components in early childhood, the morphometric parameters showed large variations in their overall growth rates between birth and adulthood. Thus, the parenchymal tissue components increased by a factor of 15, lung volume and the gas-exchange surface areas between 20 and 25 times (in parallel to body mass), and, finally, the O₂-transporting media, air and blood, more than 30 times. The morphometrically determined pulmonary diffusing capacity for O₂ (Dl_O2) scaled with body mass to the power of 1.15, a value significantly different from 1. This relative improvement with age of the gas exchange function per unit body mass is due mainly to an overproportionate growth of the capillary blood compartment.

References (34)

P.H. Burri et al.
Morphometric estimation of pulmonary diffusion capacity. II. Effect of P_O2 on the growing lung. Adaption of the growing rat lung to hypoxia and hyperoxia
Respir. Physiol.
(1971)
P. Gehr et al.
The normal human lung: Ultrastructure and morphometric estimation of diffusion capacity
Respir. Physiol.
(1978)
P. Gehr et al.
Design of the mammalian respiratory system. V. Scaling morphometric pulmonary diffusing capacity to body mass: wild and domestic mammals
Respir. Physiol.
(1981)
E.R. Weibel
Morphometric estimation of pulmonary diffusion capacity. I. Model and method
Respir. Physiol.
(1970/1971)
E.R. Weibel et al.
Design of the mammalian respiratory system. IX. Functional and structural limits for oxygen flow
Respir. Physiol.
(1981)
E.R. Weibel et al.
Maximal oxygen consumption and pulmonary diffusing capacity: a direct comparison of physiologic and morphometric measurements in canids
Respir. Physiol.
(1983)
T.B. Zeltner et al.
The postnatal development and growth of the human lung. II. Morphology
Respir. Physiol.
(1987)
R.W.M. Amy et al.
Postnatal growth of the mouse lung
J. Anat.
(1977)
M. Bachofen et al.
Postmortem fixation of human lungs for electron microscopy
Am. Rev. Respir. Dis.
(1975)
P.H. Burri
The postnatal growth of the rat lung. III. Morphology
Anat. Rec.
(1974)

P.H. Burri et al.

The postnatal growth of the rat lung. I. Morphometry

Anatl. Rec.

(1974)

P.H. Burri et al.

Reactive changes in pulmonary parenchyma after bilobectomy: A scanning electron microscopic investigation

Exp. Lung Res.

(1982)

P.H. Burri

Development and growth of the human lung

J.H. Caduff et al.

Scanning electron microscopic study of the developing microvasculature in the postnatal rat lung

Anat. Rec.

(1986)

D.M. Cooper et al.

Aerobic parameters of exercise as a function of body size during growth in children

J. Appl. Physiol.

(1984)

L.M. Cruz-Orive et al.

Stereological estimation of volume ratios by systematic section

J. Microsc.

(1981)

L.M. Cruz-Orive et al.

Sampling designs for stereology

J. Microsc.

(1981)

Cited by (209)

Sox9 is associated with two distinct patterning events during snake lung morphogenesis
2024, Developmental Biology
The evolutionary forces that allowed species adaptation to different terrestrial environments and led to great diversity in body shape and size required acquisition of innovative strategies of pattern formation during organogenesis. An extreme example is the formation of highly elongated viscera in snakes. What developmental patterning strategies allowed to overcome the space constraints of the snake's body to meet physiological demands? Here we show that the corn snake uses a Sox2-Sox9 developmental tool kit common to other species to generate and shape the lung in two phases. Initially Sox9 was found at low levels at the tip of the primary lung bud during outgrowth and elongation of the bronchial bud, without driving branching programs characteristic of mammalian lungs. Later, Sox9 induction is recapitulated in the formation of an extensive network of radial septae emerging along the elongated bronchial bud that generates the respiratory region. We propose that altogether these represent key patterning events for formation of both the respiratory faveolar and non-respiratory posterior compartments of the snake's lung.
The alveolus: Our current knowledge of how the gas exchange unit of the lung is constructed and repaired
2024, Current Topics in Developmental Biology
The mammalian lung completes its last step of development, alveologenesis, to generate sufficient surface area for gas exchange. In this process, multiple cell types that include alveolar epithelial cells, endothelial cells, and fibroblasts undergo coordinated cell proliferation, cell migration and/or contraction, cell shape changes, and cell-cell and cell-matrix interactions to produce the gas exchange unit: the alveolus. Full functioning of alveoli also involves immune cells and the lymphatic and autonomic nervous system. With the advent of lineage tracing, conditional gene inactivation, transcriptome analysis, live imaging, and lung organoids, our molecular understanding of alveologenesis has advanced significantly. In this review, we summarize the current knowledge of the constituents of the alveolus and the molecular pathways that control alveolar formation. We also discuss how insight into alveolar formation may inform us of alveolar repair/regeneration mechanisms following lung injury and the pathogenic processes that lead to loss of alveoli or tissue fibrosis.
The lung surfactant activity probed with molecular dynamics simulations
2022, Advances in Colloid and Interface Science
Citation Excerpt :
Depending on the species, alveolarization can take place either pre- or postnatally [2]. In humans 85% of alveoli develops after birth via secondary septation of alveolar sacs [31]. Alveolar walls are built of connective tissue containing capillary endothelium, fibroblasts and pericytes.
The surface of pulmonary alveolar subphase is covered with a mixture of lipids and proteins. This lung surfactant plays a crucial role in lung functioning. It shows a complex phase behavior which can be altered by the interaction with third molecules such as drugs or pollutants. For studying multicomponent biological systems, it is of interest to couple experimental approach with computational modelling yielding atomic-scale information. Simple two, three, or four-component model systems showed to be useful for getting more insight in the interaction between lipids, lipids and proteins or lipids and proteins with drugs and impurities. These systems were studied theoretically using molecular dynamic simulations and experimentally by means of the Langmuir technique. A better understanding of the structure and behavior of lung surfactants obtained from this research is relevant for developing new synthetic surfactants for efficient therapies, and may contribute to public health protection.
Evaluation of recombinant human SP-D in the rat premature lung model
2021, Annals of Anatomy
Citation Excerpt :
These morphological characteristics were confirmed in the rats used in this study, providing detailed images of the lung histology of 10-day-old rat lungs where the low number of alveoli and enlarged air spaces described in the result section can be observed (Fig. 1A) and compared to the adult rat lung. The changes observed in the early alveolarization phase resemble the development process from saccular to alveolar stage of the human lung in preterm babies (Zeltner et al., 1987; Zoetis and Hurtt, 2003). Ideally, 4 to 6-day-old rats would have been more representative of the saccular morphology of the preterm human lung.
The lungs of premature and term babies are structurally different from the adult lungs. Preterm lungs are underdeveloped, non-compliant in terms of breathing, often need mechanical ventilation and these patients commonly develop syndromes as a consequence of their prematurity, such as bronchopulmonary dysplasia (BPD). Surfactant protein SP-D could be a therapy for BPD. However, there is a need for an animal model that resembles the structural characteristics of premature lungs to test SP-D and future molecules that will target the newborn population. The aim of this study was to develop and validate a pre-clinical model of early alveolarization and structurally premature lungs in 10-day-old rats, and establish the dose safety and distribution of rhSP-D administered intratracheally to premature lungs.
Ten-day-old Sprague Dawley rats were selected to develop the lung model. SP-D was administered intratracheally. Bronchoalveolar lavage fluid and lungs were collected to evaluate inflammation and SP-D distribution.
The 10-day-old rat pup demonstrates early alveolarization features of premature lung development and it tolerates daily intratracheal injections for up to 14 days. The intratracheal administration of rhSP-D, at a dose of 8 mg/kg, does not induce an inflammatory response or histological signs of toxicity in the premature lung, even with a daily administration for 14 days. The pharmacokinetic distribution of rhSP-D in premature lungs has a half-life of ∼9 h, and the incorporation into blood is minimal.
10-day-old rats are a good pre-clinical animal model of premature lungs, and rhSP-D can be intratracheally administered at doses up to 8 mg/kg without expecting adverse reactions.
Sialic acids expression in newborn rat lungs: implications for pulmonary developmental biology
2020, Acta Histochemica
Mammalian lung development proceeds during the postnatal period and continues throughout life. Intricate tubular systems of airways and vessels lined by epithelial cells are developed during this process. All cells, and particularly epithelial cells, carry an array of glycans on their surfaces. N-acetylneuraminic (Neu5Ac) and N-glycolylneuraminic (Neu5Gc) acids, two most frequently-occurring sialic acid residues, are essential determinants during development and in the homeostasis of cells and organisms. However, systematic data about the presence of cell surface sialic acids in the postnatal lung and their content is still scarce. In the present study, we addressed the histochemical localization of Neu5Ac > Neu5Gc in 0-day-old rat lungs. Furthermore, both residues were separated, identified and quantified in lung membranes isolated from 0-day-old rat lungs using high-performance liquid chromatography (HPLC) methodologies. Finally, we compared these results with those previously reported by us for adult rat lungs. The Neu5Ac > Neu5Gc residues were located on the surface of ciliated and non-ciliated cells and the median values for both residues in the purified lung membranes of newborn rats were 5.365 and 1.935 μg/mg prot., respectively. Comparing these results with those reported for the adults, it was possible to observe a significant difference between the levels of Neu5Ac and Neu5Gc (p < 0.001). A more substantial change was found for the case of Neu5Ac. The preponderance of Neu5Ac and its expressive increase during the postnatal development points towards a more prominent role of this residue. Bearing in mind that sialic acids are negatively charged molecules, the high content of Neu5Ac could contribute to the formation of an anion “shield” and have a role in pulmonary development and physiology.
Functional morphometry for the estimation of the alveolar surface area in prematurely-born infants
2018, Respiratory Physiology and Neurobiology
Citation Excerpt :
Some studies have used post-mortem material to morphometrically quantify this reduction in SA in infants with fatal BPD: while a term-born infant without respiratory disease has an SA of 4.7–8.3 m2 (Zeltner et al., 1987), an extremely premature infant (born before 28 weeks of gestation) when measured at a term-corrected age (the age when the infant would have been born had it not been premature) might have a SA as small as 0.6 m2 (Margraf et al., 1991). Of note, using similar measuring methodology this area in adult lungs might range from 97 to 194 m2 (Zeltner et al., 1987). The reduced SA might explain why prematurely-born infants may present later in life with profound exercise limitation as low-intensity everyday activities do not require the recruitment of all the available SA but in conditions of increased cardiorespiratory demand, such as during moderate-high intensity aerobic exercise, the decreased SA becomes a limiting factor (Malleske et al., 2017; Mitchell and Teague, 1998).
Conventionally, the alveolar surface area (S_A) has been measured by using post-mortem morphometry. Such studies have highlighted that S_A in prematurely-born infants is markedly smaller when compared to term-born infants as a result of postnatal impairment or arrest of alveolar development. We herein explore how, non-invasive measurements of the ventilation/perfusion ratio (V_A/Q) can be used to estimate S_A in prematurely-born surviving, convalescent infants. We also compare S_A in prematurely-born infants measured at term-corrected age, to term-born infants using previously published datasets of V_A/Q. Fick’s first law of diffusion is employed for the conversion of V_A/Q measurements to S_A values after correcting for differences in pulmonary perfusion, thickness of the respiratory membrane and alveolar-arterial gradient. We report that S_A is fivefold smaller in prematurely-born compared to term-born infants. We conclude that non-invasive measurements of V_A/Q can be used for the functional estimation of S_A which could, in turn, be used as a future outcome measure in respiratory studies of prematurely-born infants.

View all citing articles on Scopus

^∗: Present address: Department of Environmental Science and Physiology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, U.S.A.

View full text

The postnatal development and growth of the human lung. I. Morphometry

Abstract

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Postnatal growth of the mouse lung

J. Anat.

Postmortem fixation of human lungs for electron microscopy

Am. Rev. Respir. Dis.

The postnatal growth of the rat lung. III. Morphology

Anat. Rec.

The postnatal growth of the rat lung. I. Morphometry

Anatl. Rec.

Reactive changes in pulmonary parenchyma after bilobectomy: A scanning electron microscopic investigation

Exp. Lung Res.

Development and growth of the human lung

Scanning electron microscopic study of the developing microvasculature in the postnatal rat lung

Anat. Rec.

Aerobic parameters of exercise as a function of body size during growth in children

J. Appl. Physiol.

Stereological estimation of volume ratios by systematic section

J. Microsc.

Sampling designs for stereology

J. Microsc.