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Lung Parenchymal Mechanics

Béla Suki, Dimitrije Stamenović, Rolf Hubmayr

10.1002/cphy.c100033

Source: Volume 1, Issue 3, July 2011

Published online: July 2011

Full Article on Wiley Online Library



Abstract

The lung parenchyma comprises a large number of thin‐walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This chapter focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. © 2011 American Physiological Society. Compr Physiol 1:1317‐1351, 2011.

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Figure 1. Figure 1.

(A) Stress‐strain curves of parenchymal tissue strips from a normal rat and a rat that had been treated with elastase‐mimicking pulmonary emphysema. (B) Pressure‐volume curves measured by injecting 2 ml of air starting from functional residual capacity in a normal and an elastase‐treated rat. Adapted from Ref. 138 with permission.
Figure 2. Figure 2.

Mean and SD of dynamic lung elastance coefficient (H) as a function of positive end‐expiratory pressure (PEEP) in groups of normal and tight skin mice. *denotes significance. Adapted from Ref. 126 with permission.
Figure 3. Figure 3.

Structure and complexity of the parenchyma at three length scales. The top panel shows a terminal bronchiole (TB) leading to an alveolar duct (AD). The bottom left is a zoom into a single air‐filled alveolus (A) with type I (E1) and type II (E2) alveolar epithelial cells covered by a thin liquid layer. The dots represent surfactant (S) molecules at the air‐liquid interface. Secretion of lamellar bodies (LB) by the E2 cell is also shown. The right panel is a schematic representation of the extracellular matrix of the alveolar septal wall with various components including amorphous elastin (El), wavy collagen (C), complex proteoglycans (PG), basement membrane (BM) and fibroblast cells (F). (Drawing by E. Bartolák‐Suki).
Figure 4. Figure 4.

(A) Structure of collagen. Top left: single alpha helix; bottom left: collagen molecule comprising a triple helix; top right: cross‐linked collagen; bottom right: schematic view of 5 molecules; with permission from Ref. 117. (B) Collagen network in the rat lung is wavy at low transpulmonary pressure (left) but significantly straighter at a medium inflation level (right). AE denotes alveolar entrance. Scale bar is 10 μm. Adapted from Ref. 261 with permission.
Figure 5. Figure 5.

(A) Longitudinal sections of elastin‐rich extracellular matrix sheets stained with acid Orcein at 0% strain (top) and 30% uniaxial strain in the horizontal direction (bottom). Note the straightening and thinning of the elastin fibers with increased strain. The scale bar denotes 10 μm. With permission from Ref. 29. (B) Structure of elastin in the parenchyma. V, AS, and AD denote vessel, alveolar sack, and alveolar duct, respectively. The scale bar is 200 μm. Adapted with permission from Ref. 261.
Figure 6. Figure 6.

Proteoglycan structure on a larger scale (A) and at a smaller scale zoom‐in (B). Different colors represent various groups; for example, blue is chondroitin sulfate, red is keratan sulfate, pink spheres are hyaluronan‐binding sites. From Ref. 209 with permission.
Figure 7. Figure 7.

Double‐label immunohistochemistry of mouse lung tissue. The blue labels type I collagen, the brown corresponds to type III collagen, and the pink is cell nucleus. It can be seen that some fibers are comprised of almost exclusively type I or type III collagen (black arrows), whereas at several locations, the two collagen types also appear to co‐localize suggesting that they mix and form composite fibers (red arrow) where the color is intermediate between blue and brown. Green arrow shows a round nucleus, whereas the blue arrow points to an elongated nucleus suggesting that the nucleus is under mechanical tension. From Ref. 249 with permission.
Figure 8. Figure 8.

Stress‐strain curve of collagen in tendon. Nonlinearity characterized by the heel region originates from the crimp (a) unfolding with stretching. From Ref. 72 with permission.
Figure 9. Figure 9.

Electron microscope images of ECM sheets containing both collagen and elastin at 0% (A) and 30% (B) uniaxial strain. Images were taken at 12,500×. Arrows denote collagen fibers and the white regions are elastin. Scale bar represents 0.5 μm. From Ref. 28 with permission.
Figure 10. Figure 10.

Fluorescent images of the same alveolar region labeled for collagen in a normal rat lung. Left: before deformation; Right after 30% uniaxial stretching vertically. The black lines show alveolar walls and the red lines are their new length and orientation after stretching. The yellow arrow points to the same septal wall junction. Note the significant change in angle between the two septal walls. Scale bar denotes 100 μm. From Ref. 31 with permission.
Figure 11. Figure 11.

Effects of the bond‐bending parameter q on the configuration of the elastic network model at 30% strain in the vertical direction. A: stiff network with bond‐bending constant q = 100. B: soft network with q = 0.01. Color is proportional to energy carried by the springs. The maximum energy values corresponding to dark red on A and B are different. From Ref. 45 with permission.
Figure 12. Figure 12.

Schematic drawing of the connective tissue systems in the parenchyma according to the Wilson and Bachofen model showing the alveolar duct with its axial tissue fibers organized in a helical structure, as well as the septal and peripheral fibers. The heavy arrows indicate the distending action of surface tension that exerts radially outward pull on the axial fibers of the alveolar duct. Adapted from Ref. 281 with permission.
Figure 13. Figure 13.

Images of a region of an isolated lung at successive inflation pressures. The inflation was started from the collapsed state and the bottom, middle, and top images correspond to transpulmonary pressure of approximately 25, 27, and 30 cmH2O. Dark red corresponds to collapsed regions. Notice that as inflation progresses, the pink aerated regions gradually penetrate into the atelectatic region by pulling the underlying alveoli open (Z. Hantos and B. Suki; unpublished data).
Figure 14. Figure 14.

(A) P‐V curve during the inflation of a degassed rat lung. The inset shows a magnification of a region with many local negative elastance patterns. (B) Distributions of negative elastance from 10 inflations at rates of 2.0 ml/s (triangles) and 0.5 ml/s (circles). The regression line fits to the measured distributions are shown by dashed lines. The solid lines correspond to the distributions of negative elastance from 1000 simulated inflations of an 18‐generation symmetric binary tree. (C) An example of the P‐V curve from the inflation of the model. The inset shows a magnification of a region with many local negative elastance patterns similar to those in Fig. 14A. The red line in the inset traces an avalanche shock. Adapted from Ref. 4.
Figure 15. Figure 15.

Fits of a computational model of recruitment and derecruitment in the lung (lines) to experimental measurements of respiratory elastance (symbols) in mice with various degrees of acid‐induced injury ventilated at three different PEEP levels. Elastance was measured as a function of time following a recruitment maneuver. From Ref. 161 with permission.
Figure 16. Figure 16.

Optical sections of a normal (left) and a ventilator‐injured (right) rat lung 20 mm below the pleural surface. Because the injured lung had been perfused with a Fluorescein Dextran, alveolar edema appears white on this image. Note that some alveoli are completely filled with edema fluid, while others retain trapped gas (dark ovals). From Ref. 113 with permission.
Figure 17. Figure 17.

Pressure‐volume curves of a canine caudal lobe containing air only, saline only, and an air‐saline mixture. Note the high initial resistance up to 10 cmH2O when air is injected into a saline‐filled lung. Adapted with permission from Ref. 158.
Figure 18. Figure 18.

Schematic diagram of force transmission from the level of the whole lung to single cells with various feedback mechanisms influencing ECM composition and lung mechanics. Dotted lines show external or internal influences as well as various possible feedback loops in disease states (see text for explanation). Adapted from Ref. 252 with permission.
Figure 19. Figure 19.

Schematic representation of the stress‐strain curve in arbitrary units of a lung tissue strip during uniaxial stretch in tissue bath. The regions labeled 1, 2, and 3 correspond approximately to regions of different mechanisms contributing to the stress (see text for explanation).
Figure 20. Figure 20.

Schematic representation of the P‐V curve of a lung during inflation from the collapsed state (black solid line) to total lung capacity (TLC), deflation (dashed line) to residual volume (RV), and during breathing with tidal volume (VT) from functional residual capacity (FRC). The regions labeled 1, 2, 3, and 4 correspond approximately to regions of different mechanisms contributing to the curve (see text for explanation).


Figure 1.

(A) Stress‐strain curves of parenchymal tissue strips from a normal rat and a rat that had been treated with elastase‐mimicking pulmonary emphysema. (B) Pressure‐volume curves measured by injecting 2 ml of air starting from functional residual capacity in a normal and an elastase‐treated rat. Adapted from Ref. 138 with permission.



Figure 2.

Mean and SD of dynamic lung elastance coefficient (H) as a function of positive end‐expiratory pressure (PEEP) in groups of normal and tight skin mice. *denotes significance. Adapted from Ref. 126 with permission.



Figure 3.

Structure and complexity of the parenchyma at three length scales. The top panel shows a terminal bronchiole (TB) leading to an alveolar duct (AD). The bottom left is a zoom into a single air‐filled alveolus (A) with type I (E1) and type II (E2) alveolar epithelial cells covered by a thin liquid layer. The dots represent surfactant (S) molecules at the air‐liquid interface. Secretion of lamellar bodies (LB) by the E2 cell is also shown. The right panel is a schematic representation of the extracellular matrix of the alveolar septal wall with various components including amorphous elastin (El), wavy collagen (C), complex proteoglycans (PG), basement membrane (BM) and fibroblast cells (F). (Drawing by E. Bartolák‐Suki).



Figure 4.

(A) Structure of collagen. Top left: single alpha helix; bottom left: collagen molecule comprising a triple helix; top right: cross‐linked collagen; bottom right: schematic view of 5 molecules; with permission from Ref. 117. (B) Collagen network in the rat lung is wavy at low transpulmonary pressure (left) but significantly straighter at a medium inflation level (right). AE denotes alveolar entrance. Scale bar is 10 μm. Adapted from Ref. 261 with permission.



Figure 5.

(A) Longitudinal sections of elastin‐rich extracellular matrix sheets stained with acid Orcein at 0% strain (top) and 30% uniaxial strain in the horizontal direction (bottom). Note the straightening and thinning of the elastin fibers with increased strain. The scale bar denotes 10 μm. With permission from Ref. 29. (B) Structure of elastin in the parenchyma. V, AS, and AD denote vessel, alveolar sack, and alveolar duct, respectively. The scale bar is 200 μm. Adapted with permission from Ref. 261.



Figure 6.

Proteoglycan structure on a larger scale (A) and at a smaller scale zoom‐in (B). Different colors represent various groups; for example, blue is chondroitin sulfate, red is keratan sulfate, pink spheres are hyaluronan‐binding sites. From Ref. 209 with permission.



Figure 7.

Double‐label immunohistochemistry of mouse lung tissue. The blue labels type I collagen, the brown corresponds to type III collagen, and the pink is cell nucleus. It can be seen that some fibers are comprised of almost exclusively type I or type III collagen (black arrows), whereas at several locations, the two collagen types also appear to co‐localize suggesting that they mix and form composite fibers (red arrow) where the color is intermediate between blue and brown. Green arrow shows a round nucleus, whereas the blue arrow points to an elongated nucleus suggesting that the nucleus is under mechanical tension. From Ref. 249 with permission.



Figure 8.

Stress‐strain curve of collagen in tendon. Nonlinearity characterized by the heel region originates from the crimp (a) unfolding with stretching. From Ref. 72 with permission.



Figure 9.

Electron microscope images of ECM sheets containing both collagen and elastin at 0% (A) and 30% (B) uniaxial strain. Images were taken at 12,500×. Arrows denote collagen fibers and the white regions are elastin. Scale bar represents 0.5 μm. From Ref. 28 with permission.



Figure 10.

Fluorescent images of the same alveolar region labeled for collagen in a normal rat lung. Left: before deformation; Right after 30% uniaxial stretching vertically. The black lines show alveolar walls and the red lines are their new length and orientation after stretching. The yellow arrow points to the same septal wall junction. Note the significant change in angle between the two septal walls. Scale bar denotes 100 μm. From Ref. 31 with permission.



Figure 11.

Effects of the bond‐bending parameter q on the configuration of the elastic network model at 30% strain in the vertical direction. A: stiff network with bond‐bending constant q = 100. B: soft network with q = 0.01. Color is proportional to energy carried by the springs. The maximum energy values corresponding to dark red on A and B are different. From Ref. 45 with permission.



Figure 12.

Schematic drawing of the connective tissue systems in the parenchyma according to the Wilson and Bachofen model showing the alveolar duct with its axial tissue fibers organized in a helical structure, as well as the septal and peripheral fibers. The heavy arrows indicate the distending action of surface tension that exerts radially outward pull on the axial fibers of the alveolar duct. Adapted from Ref. 281 with permission.



Figure 13.

Images of a region of an isolated lung at successive inflation pressures. The inflation was started from the collapsed state and the bottom, middle, and top images correspond to transpulmonary pressure of approximately 25, 27, and 30 cmH2O. Dark red corresponds to collapsed regions. Notice that as inflation progresses, the pink aerated regions gradually penetrate into the atelectatic region by pulling the underlying alveoli open (Z. Hantos and B. Suki; unpublished data).



Figure 14.

(A) P‐V curve during the inflation of a degassed rat lung. The inset shows a magnification of a region with many local negative elastance patterns. (B) Distributions of negative elastance from 10 inflations at rates of 2.0 ml/s (triangles) and 0.5 ml/s (circles). The regression line fits to the measured distributions are shown by dashed lines. The solid lines correspond to the distributions of negative elastance from 1000 simulated inflations of an 18‐generation symmetric binary tree. (C) An example of the P‐V curve from the inflation of the model. The inset shows a magnification of a region with many local negative elastance patterns similar to those in Fig. 14A. The red line in the inset traces an avalanche shock. Adapted from Ref. 4.



Figure 15.

Fits of a computational model of recruitment and derecruitment in the lung (lines) to experimental measurements of respiratory elastance (symbols) in mice with various degrees of acid‐induced injury ventilated at three different PEEP levels. Elastance was measured as a function of time following a recruitment maneuver. From Ref. 161 with permission.



Figure 16.

Optical sections of a normal (left) and a ventilator‐injured (right) rat lung 20 mm below the pleural surface. Because the injured lung had been perfused with a Fluorescein Dextran, alveolar edema appears white on this image. Note that some alveoli are completely filled with edema fluid, while others retain trapped gas (dark ovals). From Ref. 113 with permission.



Figure 17.

Pressure‐volume curves of a canine caudal lobe containing air only, saline only, and an air‐saline mixture. Note the high initial resistance up to 10 cmH2O when air is injected into a saline‐filled lung. Adapted with permission from Ref. 158.



Figure 18.

Schematic diagram of force transmission from the level of the whole lung to single cells with various feedback mechanisms influencing ECM composition and lung mechanics. Dotted lines show external or internal influences as well as various possible feedback loops in disease states (see text for explanation). Adapted from Ref. 252 with permission.



Figure 19.

Schematic representation of the stress‐strain curve in arbitrary units of a lung tissue strip during uniaxial stretch in tissue bath. The regions labeled 1, 2, and 3 correspond approximately to regions of different mechanisms contributing to the stress (see text for explanation).



Figure 20.

Schematic representation of the P‐V curve of a lung during inflation from the collapsed state (black solid line) to total lung capacity (TLC), deflation (dashed line) to residual volume (RV), and during breathing with tidal volume (VT) from functional residual capacity (FRC). The regions labeled 1, 2, 3, and 4 correspond approximately to regions of different mechanisms contributing to the curve (see text for explanation).

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Article Title: Lung Parenchymal Mechanics
 

How to Cite

Béla Suki, Dimitrije Stamenović, Rolf Hubmayr. Lung Parenchymal Mechanics. Compr Physiol 2011, 1: 1317-1351. doi: 10.1002/cphy.c100033