Comprehensive Physiology Wiley Online Library

Development and Growth of the Human Lung

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Lung Morphology
1.1 Gas‐Exchange Region
1.2 Airways
1.3 Blood Vessels
2 Structural Development of the Human Lung
2.1 Embryonic Development
2.2 Fetal Period
2.3 Postnatal Development of Respiratory Tissue—Alveolar Stage
3 Growth of the Lung
3.1 Normal Growth
3.2 Adaptive Growth of Gas‐Exchange Apparatus
4 Final Dimensions of the Human Lung
5 Development of Pulmonary Surfactant System
5.1 Historical Background and Function of Pulmonary Surfactant
5.2 Biochemistry of Pulmonary Surfactant
5.3 Type II Cells and Regulation of Surfactant Production
Figure 1. Figure 1.

Lung with 3 zones: conductive, transitional, and respiratory. A, airways; PA, pulmonary artery; PV, pulmonary vein.

Figure 2. Figure 2.

Light micrograph of gas‐exchanging parenchyma of adult human lung. Delicate tissue framework delineates air spaces; alveoli (x) open into alveolar ducts (da). Note sporadically thickened entrance rings (arrows). Scale, 200 μm; × 41.

Figure 3. Figure 3.

Scanning electron micrograph of alveoli (a) arrangement around alveolar duct (da) of adult human lung. Capillary relief of interalveolar septa clearly visible due to fixation by instillation of glutaraldehyde into airways. Note alveolar entrance ring (arrows). Scale, 100 μm; × 150.

Figure 4. Figure 4.

Electron micrograph of portion of interalveolar septum of adult human lung. Pulmonary capillary (cap) containing plasma and erythrocytes interlaced with connective tissue fibers (cf). a, Alveolar space; epI, nucleus of epithelial type I cell; en, nucleus of endothelial cell; ma, alveolar macrophage. Scale, 5 μm; × 2,550.

Figure 5. Figure 5.

Electron micrograph of fibroblast (f) in human interalveolar septum. Cell contains rough endoplasmic reticulum (er) as sign of active protein synthesis. In a bay elastic fibers (e) and collagen fibrils have been deposited. Note intracytoplasmic filaments anchoring epithelium (arrow), ep, Epithelial type I cell; en, endothelial cell; ma, macrophage. Scale, 1 μm; × 10,000.

Figure 6. Figure 6.

Electron micrograph of thin portion of air‐blood barrier of human lung showing 3‐layered structure with epithelium (ep), basement membrane (bm), and endothelium (en), a, Alveolar space; ec, erythrocyte. Scale, 1 μm; × 16,000.

Figure 7. Figure 7.

A: electron micrograph of alveolar epithelial type I cell (epI) in human lung. Cell body consists merely of nucleus enclosed in very narrow cytoplasmic rim. Cell possesses long and thin cytoplasmic extensions, en, Endothelium; f, cytoplasmic process of fibroblast; p, process of pericyte. Scale, 2 μm; × 7,200. B: electron micrograph of alveolar epithelial type II cell (epII) in human lung. Cell edges are covered by type I cell extensions; free surface shows short microvilli. In cytoplasm, prominent Golgi apparatus (g), few small mitochondria (m), and characteristic lamellar bodies (lb). Scale, 1 μm; × 9,300. C: electron micrograph of alveolar macrophage (ma) attached to underlying epithelium of type I cell (epI) in human lung. In septum, capillaries with erythrocytes (ec) and a leukocyte (lc). Scale, 2 μm; × 4,500. D: electron micrograph of capillary endothelial cell (en) in human lung. As in epithelial type I cells, nucleus is enclosed in thin cytoplasmic rim with very few organelles. On one side, cell body connects neighboring cell with junction; on the other side it tapers into thin cytoplasmic process. f, Cytoplasmic process of fibroblast; p, pericytic process; ma, pseudopodium of macrophage. Scale, 1 μm; × 10,000.

Figure 8. Figure 8.

Scanning electron micrograph of brush cell (br) in distal portion of rat terminal bronchiole. Numerous short microvilli are arranged like a bunch of flowers at top of cell. Neighboring cells are ciliated (c) or Clara cells (arrows). Scale, 2 μm; × 7,200.

Micrograph courtesy of G. Wandel
Figure 9. Figure 9.

Scanning electron micrograph of human alveolar macrophage (ma) close to edge of alveolar entrance ring (▴) and extending numerous filopodia. Note cell borders of epithelial type I cells (arrows). Scale, 1 μm; × 1,400.

Figure 10. Figure 10.

Airway tree with subdivision in conducting, transitional, and respiratory zones. Z, branching order.

From Weibel
Figure 11. Figure 11.

Wall structure of large and small conducting airways (A) and their epithelial lining (B). B: basal cells, ciliated cells, goblet cells, and brush cell in trachea and bronchus. In bronchiole, goblet cells are replaced by Clara cells. Mucous blanket carrying particles lies on top of epithelium.

Figure 12. Figure 12.

Early development of human lung in side view (A, B) and ventral view (C‐E); fetal age is indicated by crown‐rump lengths. A: appearance of prospective lung as protrusion in foregut. B: formation of lung bud by distal‐to‐proximal segregation of prospective trachea from foregut by deepening of laryngotracheal grooves (arrows). C: dichotomous branching of lung bud, forming prospective main bronchi. D: prospective main bronchi growing into surrounding mesenchyme. E: left and right lungs formed with their lobar and partly segmental bronchi, u, Upper lobes; m, middle lobe; l, lower lobes.

Figure 13. Figure 13.

Origin and development of pulmonary arteries. A: paired ventral (va) and dorsal (da) aortae interconnected by 6 pairs of aortic arches (I‐VI). Pulmonary arteries (pa) branch off from 6th pair of aortic arches and connect to pulmonary mesenchyme. Diagram is simplified in the sense that the 6 aortic arches are never present simultaneously. B: further development of blood vessels. Some segments of arterial pathway regress and disappear (white areas), others develop further and show preferential growth (dotted areas), a, Aorta; du, ductus arteriosus; eca, external carotid artery; ica, internal carotid artery; pt, pulmonary trunk; sa, subclavian artery.

Figure 14. Figure 14.

Light micrograph of pseudoglandular stage of human fetal lung, gestational age ∼15 wk. Airway tubes are embedded in loose mesenchyme and represent roughly the prospective conductive airways. From mesenchyme underlying the pleura, septa penetrate into pulmonary tissue (arrows); they contain venous vessels and delineate mostly prospective lobules. A broader layer of mesenchyme ensheathes larger aiways (a) and accompanying branches of pulmonary arteries (pa). Scale, 200 μm; × 35.

Figure 15. Figure 15.

Timetable for development of the airway tree, its generations, and typical wall structures. Generation numbers are fitted to the averaged airway tree of Weibel's dichotomous branching model [; see also Fig. ]. Dotted area, respiratory portion of airway tree. Most of these respiratory airway generations develop between wk 16 and birth by peripheral branching and growth; a few may develop by centripetal transformation of nonrespiratory into respiratory bronchioles.

Adapted from Bucher and Reid
Figure 16. Figure 16.

Phases of epithelial transformation. Pseudoglandular stage: high columnar epithelium, cells rich in glycogen. Canalicular stage: epithelium begins to differentiate into 2 cell types, secretory cells and prospective lining cells, labeled by low position of junctional complex with neighboring cells and close contact with capillaries. Terminal sac stage: differentiation of type I and type II cells; increasing portions of air‐blood barrier are thin.

Adapted from Burri and Weibel
Figure 17. Figure 17.

Early saccular stage of human lung. Bronchiole (br) generates 2 transitory airways (ta). Upper branch produces at least 2 transitory saccules (arrows) that are lined by caps of cuboidal epithelium (c) that appear in transections either as tubules or cell clusters. Transitory airways are lined partly by cuboidal and partly by flat epithelium; the latter is present where capillaries (ca and dotted areas) are closely apposed to epithelial lining, p, Pleura with subpleural embryonal connective tissue; a, arteries; v, veins.

Figure 18. Figure 18.

Electron micrograph of interstitial cell (ic) in interalveolar septum of human lung. Cell is actively secreting collagen and elastin into extracellular bays (arrows), er, Rough endoplasmic reticulum; li, lipid droplet; epI, epithelial type I cell; ma, alveolar macrophage. Scale, 0.5 μm; × 16,000.

Figure 19. Figure 19.

Growth of intraluminal arterial diameters of human lung during fetal life and childhood. Data from measurements on arteriograms of lower lobe at hilum and at 75% distance from hilum to periphery.

From Hislop and Reid
Figure 20. Figure 20.

Muscular structure of a pulmonary artery toward its distal end. Muscle coat ends in the form of a muscle spiral. In this segment the vessel appears as partially muscular in cross sections.

From Hislop and Reid
Figure 21. Figure 21.

A: light micrograph of paraffin section of rat lung 1 day old. Terminal bronchiole (tb) branches into smooth‐walled channels (transitory ducts, td) opening into terminal saccules (ts). Air spaces are smoothly contoured; septa are thick. These terminal airways have often been mistaken as alveoli; direct comparison with an older lung (B), however, reveals their nature. B: light micrograph of paraffin section of rat lung 21 days old. Terminal bronchiole and its branches at the same magnification as in A. Terminal saccules have been partitioned by newly formed septa (secondary septa, arrows) and now represent alveolar sacs (sa). By the same process transitory ducts have been transformed into alveolar ducts (da). Scale, 100 μm; × 160.

Figure 22. Figure 22.

Electron micrograph of ultrastructure of immature primary septum during early postnatal days. Capillary network (cap) is present on both sides of a highly cellular interstitial layer, ic, Nuclei of interstitial cells; epI, nucleus of epithelial type I cell; en, nucleus of endothelial cell; ec, erythrocytes. Scale, 5 μm; × 3,000.

Figure 23. Figure 23.

Quantitative findings in growing rat lung showing volume changes of pulmonary parenchyma and its compartments. Note that increase in parenchymal volume between days 1 and 4 is brought about by the air‐space compartment, the increase between days 4 and 7 by the tissue and blood compartments. The latter period corresponds to phase of most active septal outgrowth.

Data from Burri et al.
Figure 24. Figure 24.

A: scanning electron micrograph of gas‐exchange tissue of rat lung 4 days old. Transitory ducts (td) and air spaces in general are rounded; septa are smooth, bv, Blood vessel. B: scanning electron micrograph of pulmonary parenchyma of rat lung 8 days old. Numerous secondary septa have appeared (arrows), dividing air spaces into alveoli (a) and transforming transitory ducts into alveolar ducts (da). Scale, 50 μm; × 280.

Figure 25. Figure 25.

Double logarithmic plot of alveolar (Sa) and capillary (Sc) surface areas against lung volume (VL) in growing rat lung. Triphasic growth pattern with most intense increase in surface area between day 4 and wk 3. r, Correlation coefficient.

Data from Burri et al.
Figure 26. Figure 26.

Electron micrograph of secondary crest of rat lung 7 days old with capillaries (cap) on both sides. Central interstitial layer contains interstitial cells (ic) of 2 types: at base, interstitial cells contain lipid droplets (li); toward tip they contain no lipid but form slender cytoplasmic extensions enfolding connective tissue (e, elastin). Capillary walls form closed extensions toward tip of crest (arrows). Scale, 2 μm; × 5,200.

Figure 27. Figure 27.

Formation and capillarization of secondary septa. Capillary meshes are folded up from primary septum present at birth (A) and form secondary septum (B). This increases in height as new capillary segments are formed by sprouting (C, D). At tip of crests increasing amounts of elastic tissue are present. Quadratic lattice, septal tissue; white spaces, capillary lumina; fine dots, closed capillary segments; coarse dots, elastic fibers; black spaces, cells of unknown origin, which seem to participate in lengthening and sprouting of capillaries.

From Burri
Figure 28. Figure 28.

Model for structural transformation and maturation of immature interalveolar septum (dotted area, interstitial tissue). Through thinning of interstitium and lengthening of septum with expansion of capillary meshes (arrows), immature structure (left) is transformed into mature form (right). Capillary fusion may complete the picture so that blood flows, e.g., from a to d over b and c.

From Burri
Figure 29. Figure 29.

Development of pulmonary capillaries. A: pseudoglandular stage, capillaries are randomly distributed in mesenchyme. B: beginning of canalicular stage, capillaries start to arrange around epithelial tubes, which enlarge to canaliculi. C: canalicular stage, capillaries establish close contact to lining epithelium, which flattens to form thin air‐blood barriers. Widening of canaliculi reduces intervening interstitium so that capillary layers of adjacent air spaces lie closer to each other. D: end of saccular stage, epithelium differentiated in type I and type II cells, intersaccular walls with 2 capillary networks. E: alveolar stage, formation of secondary septa; all septa contain 2 capillary networks; further reduction of interstitial tissue. F: mature lung, capillary layers in primary and secondary septa have fused; at a few places double row may stay; septa have lengthened and narrowed.

Figure 30. Figure 30.

Light micrographs of postnatal structure of gas‐exchange tissue in human and rat, illustrating similarity of alveolization process in both species. A: lung of normal boy 1 mo old who died from sudden infant death. Alveolar ducts (da) show numerous secondary septa (arrows) defining alveoli (a). Secondary and rather thick primary septa possess 2 capillary networks (arrowheads). Epon section 1 μm thick; scale, 50 μm; × 260. B: parenchyma of rat lung 1 wk old. Alveolar ducts much smaller than in human lung (note different magnification) but show same structural pattern. Secondary septa (arrows) demarcating alveoli and double capillary networks (arrowheads) are also visible. Epon section 1 μm thick; scale, 50 μm; × 415.

Micrographs courtesy of A. M. Steiner
Figure 31. Figure 31.

Electron micrographs of secondary septa in infant lung of Fig. A. A: relatively low septum with capillary loop passing over edge of crest, cap, Capillaries; en, endothelial cells; ic, interstitial cells. Scale, 2 μm; × 5,200. B: higher secondary septum with double capillary networks (cap). Interstitial layer (int and arrows) swollen and not well preserved due to delay between death and fixation of lung. Scale, 2 μm; × 4,000.

Micrographs courtesy of A. Keller
Figure 32. Figure 32.

Progressive extension with age of muscle coat in arterial walls. Within acinus, muscle is not found before birth. With increasing age muscle coat extends into parenchymal region.

From Hislop and Reid
Figure 33. Figure 33.

Quantitative adaptation of rat parenchymal lung structures to altered Po2 Morphometrically determined specific diffusing capacity (DL) of rats in 3 groups: raised for 3 wk at high altitude (JJ), in room air as controls (C), and in O2 chamber with 40% O2 (OC).

From Burri and Weibel
Figure 34. Figure 34.

Adaptation of growing mouse lung to increased /body weight (W). Drug‐induced waltzing mice [imino‐ββ′‐dipropionitrile (IDPN)] show a 50% increase in specific /W when compared to their nonwaltzing littermates (C). Specific morphometrically determined pulmonary diffusing capacity (DL/W) was correspondingly increased 3.5 mo after induction of the permanent waltzing syndrome.

From Hugonnaud, Burri, et al.
Figure 35. Figure 35.

The per 100 g body wt (shaded bars) and corresponding alveolar surface area (Sa) per 100 g body wt (open bars) in 4 groups of hamsters under different treatments from postnatal wk 6 to 10. T3, triiodothyronine.

Adapted from Thompson
Figure 36. Figure 36.

Synthesis of DNA in left lung and right lower lobe of rats subjected to resection of upper and medium lobes of right lung at 3 wk of age. Incorporation of [3H]thymidine into lung DNA expressed as disintegrations per min (or counts) per mg DNA by liquid‐scintillation counting. Note high peaks in lobectomy group and quicker response in right lung. (P. H. Burri, unpublished data.)

Figure 37. Figure 37.

Structure of the 2 most important phospholipids of pulmonary surfactant. A: dipalmitoyl phosphatidylcholine. B: dipalmitoyl phosphatidylglycerol.

Figure 38. Figure 38.

Pathways of phosphatidylcholine and phosphatidylglycerol biosynthesis.

From Perelman et al.
Figure 39. Figure 39.

Concentrations of disaturated phosphatidylcholine in lung tissue and alveoli plotted against relative gestational age for rat, rabbit, lamb, monkey, and human. Values are averaged over intervals of 10%–20% of gestation.

From Clements and Tooley , by courtesy of Marcel Dekker, Inc
Figure 40. Figure 40.

Effect of cortisol on [1‐14C]palmitate incorporation into lecithin by primary mixed cultures of fetal rabbit lung prepared at gestation days 20–28. Solid line, cultures grown in the presence of cortisol at 5.5 μmol.

From Smith et al. , by copyright permission of The American Society for Clinical Investigation
Figure 41. Figure 41.

Effect of cortisol on DNA content of primary fetal rabbit lung cell cultures prepared at gestation days 20–28. Bars, means; brackets, ± 1 SD.

From Smith et al. . by copyright permission of The American Society for Clinical Investigation


Figure 1.

Lung with 3 zones: conductive, transitional, and respiratory. A, airways; PA, pulmonary artery; PV, pulmonary vein.



Figure 2.

Light micrograph of gas‐exchanging parenchyma of adult human lung. Delicate tissue framework delineates air spaces; alveoli (x) open into alveolar ducts (da). Note sporadically thickened entrance rings (arrows). Scale, 200 μm; × 41.



Figure 3.

Scanning electron micrograph of alveoli (a) arrangement around alveolar duct (da) of adult human lung. Capillary relief of interalveolar septa clearly visible due to fixation by instillation of glutaraldehyde into airways. Note alveolar entrance ring (arrows). Scale, 100 μm; × 150.



Figure 4.

Electron micrograph of portion of interalveolar septum of adult human lung. Pulmonary capillary (cap) containing plasma and erythrocytes interlaced with connective tissue fibers (cf). a, Alveolar space; epI, nucleus of epithelial type I cell; en, nucleus of endothelial cell; ma, alveolar macrophage. Scale, 5 μm; × 2,550.



Figure 5.

Electron micrograph of fibroblast (f) in human interalveolar septum. Cell contains rough endoplasmic reticulum (er) as sign of active protein synthesis. In a bay elastic fibers (e) and collagen fibrils have been deposited. Note intracytoplasmic filaments anchoring epithelium (arrow), ep, Epithelial type I cell; en, endothelial cell; ma, macrophage. Scale, 1 μm; × 10,000.



Figure 6.

Electron micrograph of thin portion of air‐blood barrier of human lung showing 3‐layered structure with epithelium (ep), basement membrane (bm), and endothelium (en), a, Alveolar space; ec, erythrocyte. Scale, 1 μm; × 16,000.



Figure 7.

A: electron micrograph of alveolar epithelial type I cell (epI) in human lung. Cell body consists merely of nucleus enclosed in very narrow cytoplasmic rim. Cell possesses long and thin cytoplasmic extensions, en, Endothelium; f, cytoplasmic process of fibroblast; p, process of pericyte. Scale, 2 μm; × 7,200. B: electron micrograph of alveolar epithelial type II cell (epII) in human lung. Cell edges are covered by type I cell extensions; free surface shows short microvilli. In cytoplasm, prominent Golgi apparatus (g), few small mitochondria (m), and characteristic lamellar bodies (lb). Scale, 1 μm; × 9,300. C: electron micrograph of alveolar macrophage (ma) attached to underlying epithelium of type I cell (epI) in human lung. In septum, capillaries with erythrocytes (ec) and a leukocyte (lc). Scale, 2 μm; × 4,500. D: electron micrograph of capillary endothelial cell (en) in human lung. As in epithelial type I cells, nucleus is enclosed in thin cytoplasmic rim with very few organelles. On one side, cell body connects neighboring cell with junction; on the other side it tapers into thin cytoplasmic process. f, Cytoplasmic process of fibroblast; p, pericytic process; ma, pseudopodium of macrophage. Scale, 1 μm; × 10,000.



Figure 8.

Scanning electron micrograph of brush cell (br) in distal portion of rat terminal bronchiole. Numerous short microvilli are arranged like a bunch of flowers at top of cell. Neighboring cells are ciliated (c) or Clara cells (arrows). Scale, 2 μm; × 7,200.

Micrograph courtesy of G. Wandel


Figure 9.

Scanning electron micrograph of human alveolar macrophage (ma) close to edge of alveolar entrance ring (▴) and extending numerous filopodia. Note cell borders of epithelial type I cells (arrows). Scale, 1 μm; × 1,400.



Figure 10.

Airway tree with subdivision in conducting, transitional, and respiratory zones. Z, branching order.

From Weibel


Figure 11.

Wall structure of large and small conducting airways (A) and their epithelial lining (B). B: basal cells, ciliated cells, goblet cells, and brush cell in trachea and bronchus. In bronchiole, goblet cells are replaced by Clara cells. Mucous blanket carrying particles lies on top of epithelium.



Figure 12.

Early development of human lung in side view (A, B) and ventral view (C‐E); fetal age is indicated by crown‐rump lengths. A: appearance of prospective lung as protrusion in foregut. B: formation of lung bud by distal‐to‐proximal segregation of prospective trachea from foregut by deepening of laryngotracheal grooves (arrows). C: dichotomous branching of lung bud, forming prospective main bronchi. D: prospective main bronchi growing into surrounding mesenchyme. E: left and right lungs formed with their lobar and partly segmental bronchi, u, Upper lobes; m, middle lobe; l, lower lobes.



Figure 13.

Origin and development of pulmonary arteries. A: paired ventral (va) and dorsal (da) aortae interconnected by 6 pairs of aortic arches (I‐VI). Pulmonary arteries (pa) branch off from 6th pair of aortic arches and connect to pulmonary mesenchyme. Diagram is simplified in the sense that the 6 aortic arches are never present simultaneously. B: further development of blood vessels. Some segments of arterial pathway regress and disappear (white areas), others develop further and show preferential growth (dotted areas), a, Aorta; du, ductus arteriosus; eca, external carotid artery; ica, internal carotid artery; pt, pulmonary trunk; sa, subclavian artery.



Figure 14.

Light micrograph of pseudoglandular stage of human fetal lung, gestational age ∼15 wk. Airway tubes are embedded in loose mesenchyme and represent roughly the prospective conductive airways. From mesenchyme underlying the pleura, septa penetrate into pulmonary tissue (arrows); they contain venous vessels and delineate mostly prospective lobules. A broader layer of mesenchyme ensheathes larger aiways (a) and accompanying branches of pulmonary arteries (pa). Scale, 200 μm; × 35.



Figure 15.

Timetable for development of the airway tree, its generations, and typical wall structures. Generation numbers are fitted to the averaged airway tree of Weibel's dichotomous branching model [; see also Fig. ]. Dotted area, respiratory portion of airway tree. Most of these respiratory airway generations develop between wk 16 and birth by peripheral branching and growth; a few may develop by centripetal transformation of nonrespiratory into respiratory bronchioles.

Adapted from Bucher and Reid


Figure 16.

Phases of epithelial transformation. Pseudoglandular stage: high columnar epithelium, cells rich in glycogen. Canalicular stage: epithelium begins to differentiate into 2 cell types, secretory cells and prospective lining cells, labeled by low position of junctional complex with neighboring cells and close contact with capillaries. Terminal sac stage: differentiation of type I and type II cells; increasing portions of air‐blood barrier are thin.

Adapted from Burri and Weibel


Figure 17.

Early saccular stage of human lung. Bronchiole (br) generates 2 transitory airways (ta). Upper branch produces at least 2 transitory saccules (arrows) that are lined by caps of cuboidal epithelium (c) that appear in transections either as tubules or cell clusters. Transitory airways are lined partly by cuboidal and partly by flat epithelium; the latter is present where capillaries (ca and dotted areas) are closely apposed to epithelial lining, p, Pleura with subpleural embryonal connective tissue; a, arteries; v, veins.



Figure 18.

Electron micrograph of interstitial cell (ic) in interalveolar septum of human lung. Cell is actively secreting collagen and elastin into extracellular bays (arrows), er, Rough endoplasmic reticulum; li, lipid droplet; epI, epithelial type I cell; ma, alveolar macrophage. Scale, 0.5 μm; × 16,000.



Figure 19.

Growth of intraluminal arterial diameters of human lung during fetal life and childhood. Data from measurements on arteriograms of lower lobe at hilum and at 75% distance from hilum to periphery.

From Hislop and Reid


Figure 20.

Muscular structure of a pulmonary artery toward its distal end. Muscle coat ends in the form of a muscle spiral. In this segment the vessel appears as partially muscular in cross sections.

From Hislop and Reid


Figure 21.

A: light micrograph of paraffin section of rat lung 1 day old. Terminal bronchiole (tb) branches into smooth‐walled channels (transitory ducts, td) opening into terminal saccules (ts). Air spaces are smoothly contoured; septa are thick. These terminal airways have often been mistaken as alveoli; direct comparison with an older lung (B), however, reveals their nature. B: light micrograph of paraffin section of rat lung 21 days old. Terminal bronchiole and its branches at the same magnification as in A. Terminal saccules have been partitioned by newly formed septa (secondary septa, arrows) and now represent alveolar sacs (sa). By the same process transitory ducts have been transformed into alveolar ducts (da). Scale, 100 μm; × 160.



Figure 22.

Electron micrograph of ultrastructure of immature primary septum during early postnatal days. Capillary network (cap) is present on both sides of a highly cellular interstitial layer, ic, Nuclei of interstitial cells; epI, nucleus of epithelial type I cell; en, nucleus of endothelial cell; ec, erythrocytes. Scale, 5 μm; × 3,000.



Figure 23.

Quantitative findings in growing rat lung showing volume changes of pulmonary parenchyma and its compartments. Note that increase in parenchymal volume between days 1 and 4 is brought about by the air‐space compartment, the increase between days 4 and 7 by the tissue and blood compartments. The latter period corresponds to phase of most active septal outgrowth.

Data from Burri et al.


Figure 24.

A: scanning electron micrograph of gas‐exchange tissue of rat lung 4 days old. Transitory ducts (td) and air spaces in general are rounded; septa are smooth, bv, Blood vessel. B: scanning electron micrograph of pulmonary parenchyma of rat lung 8 days old. Numerous secondary septa have appeared (arrows), dividing air spaces into alveoli (a) and transforming transitory ducts into alveolar ducts (da). Scale, 50 μm; × 280.



Figure 25.

Double logarithmic plot of alveolar (Sa) and capillary (Sc) surface areas against lung volume (VL) in growing rat lung. Triphasic growth pattern with most intense increase in surface area between day 4 and wk 3. r, Correlation coefficient.

Data from Burri et al.


Figure 26.

Electron micrograph of secondary crest of rat lung 7 days old with capillaries (cap) on both sides. Central interstitial layer contains interstitial cells (ic) of 2 types: at base, interstitial cells contain lipid droplets (li); toward tip they contain no lipid but form slender cytoplasmic extensions enfolding connective tissue (e, elastin). Capillary walls form closed extensions toward tip of crest (arrows). Scale, 2 μm; × 5,200.



Figure 27.

Formation and capillarization of secondary septa. Capillary meshes are folded up from primary septum present at birth (A) and form secondary septum (B). This increases in height as new capillary segments are formed by sprouting (C, D). At tip of crests increasing amounts of elastic tissue are present. Quadratic lattice, septal tissue; white spaces, capillary lumina; fine dots, closed capillary segments; coarse dots, elastic fibers; black spaces, cells of unknown origin, which seem to participate in lengthening and sprouting of capillaries.

From Burri


Figure 28.

Model for structural transformation and maturation of immature interalveolar septum (dotted area, interstitial tissue). Through thinning of interstitium and lengthening of septum with expansion of capillary meshes (arrows), immature structure (left) is transformed into mature form (right). Capillary fusion may complete the picture so that blood flows, e.g., from a to d over b and c.

From Burri


Figure 29.

Development of pulmonary capillaries. A: pseudoglandular stage, capillaries are randomly distributed in mesenchyme. B: beginning of canalicular stage, capillaries start to arrange around epithelial tubes, which enlarge to canaliculi. C: canalicular stage, capillaries establish close contact to lining epithelium, which flattens to form thin air‐blood barriers. Widening of canaliculi reduces intervening interstitium so that capillary layers of adjacent air spaces lie closer to each other. D: end of saccular stage, epithelium differentiated in type I and type II cells, intersaccular walls with 2 capillary networks. E: alveolar stage, formation of secondary septa; all septa contain 2 capillary networks; further reduction of interstitial tissue. F: mature lung, capillary layers in primary and secondary septa have fused; at a few places double row may stay; septa have lengthened and narrowed.



Figure 30.

Light micrographs of postnatal structure of gas‐exchange tissue in human and rat, illustrating similarity of alveolization process in both species. A: lung of normal boy 1 mo old who died from sudden infant death. Alveolar ducts (da) show numerous secondary septa (arrows) defining alveoli (a). Secondary and rather thick primary septa possess 2 capillary networks (arrowheads). Epon section 1 μm thick; scale, 50 μm; × 260. B: parenchyma of rat lung 1 wk old. Alveolar ducts much smaller than in human lung (note different magnification) but show same structural pattern. Secondary septa (arrows) demarcating alveoli and double capillary networks (arrowheads) are also visible. Epon section 1 μm thick; scale, 50 μm; × 415.

Micrographs courtesy of A. M. Steiner


Figure 31.

Electron micrographs of secondary septa in infant lung of Fig. A. A: relatively low septum with capillary loop passing over edge of crest, cap, Capillaries; en, endothelial cells; ic, interstitial cells. Scale, 2 μm; × 5,200. B: higher secondary septum with double capillary networks (cap). Interstitial layer (int and arrows) swollen and not well preserved due to delay between death and fixation of lung. Scale, 2 μm; × 4,000.

Micrographs courtesy of A. Keller


Figure 32.

Progressive extension with age of muscle coat in arterial walls. Within acinus, muscle is not found before birth. With increasing age muscle coat extends into parenchymal region.

From Hislop and Reid


Figure 33.

Quantitative adaptation of rat parenchymal lung structures to altered Po2 Morphometrically determined specific diffusing capacity (DL) of rats in 3 groups: raised for 3 wk at high altitude (JJ), in room air as controls (C), and in O2 chamber with 40% O2 (OC).

From Burri and Weibel


Figure 34.

Adaptation of growing mouse lung to increased /body weight (W). Drug‐induced waltzing mice [imino‐ββ′‐dipropionitrile (IDPN)] show a 50% increase in specific /W when compared to their nonwaltzing littermates (C). Specific morphometrically determined pulmonary diffusing capacity (DL/W) was correspondingly increased 3.5 mo after induction of the permanent waltzing syndrome.

From Hugonnaud, Burri, et al.


Figure 35.

The per 100 g body wt (shaded bars) and corresponding alveolar surface area (Sa) per 100 g body wt (open bars) in 4 groups of hamsters under different treatments from postnatal wk 6 to 10. T3, triiodothyronine.

Adapted from Thompson


Figure 36.

Synthesis of DNA in left lung and right lower lobe of rats subjected to resection of upper and medium lobes of right lung at 3 wk of age. Incorporation of [3H]thymidine into lung DNA expressed as disintegrations per min (or counts) per mg DNA by liquid‐scintillation counting. Note high peaks in lobectomy group and quicker response in right lung. (P. H. Burri, unpublished data.)



Figure 37.

Structure of the 2 most important phospholipids of pulmonary surfactant. A: dipalmitoyl phosphatidylcholine. B: dipalmitoyl phosphatidylglycerol.



Figure 38.

Pathways of phosphatidylcholine and phosphatidylglycerol biosynthesis.

From Perelman et al.


Figure 39.

Concentrations of disaturated phosphatidylcholine in lung tissue and alveoli plotted against relative gestational age for rat, rabbit, lamb, monkey, and human. Values are averaged over intervals of 10%–20% of gestation.

From Clements and Tooley , by courtesy of Marcel Dekker, Inc


Figure 40.

Effect of cortisol on [1‐14C]palmitate incorporation into lecithin by primary mixed cultures of fetal rabbit lung prepared at gestation days 20–28. Solid line, cultures grown in the presence of cortisol at 5.5 μmol.

From Smith et al. , by copyright permission of The American Society for Clinical Investigation


Figure 41.

Effect of cortisol on DNA content of primary fetal rabbit lung cell cultures prepared at gestation days 20–28. Bars, means; brackets, ± 1 SD.

From Smith et al. . by copyright permission of The American Society for Clinical Investigation
References
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Peter H. Burri. Development and Growth of the Human Lung. Compr Physiol 2011, Supplement 10: Handbook of Physiology, The Respiratory System, Circulation and Nonrespiratory Functions: 1-46. First published in print 1985. doi: 10.1002/cphy.cp030101