Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation

2013 ◽  
Vol 304 (3) ◽  
pp. R171-R176 ◽  
Author(s):  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Complete Separation ◽  
Blood Gas ◽  
Gas Barrier ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Resolution Electron ◽  
Two Factors ◽  
Key Factor ◽  
Capillary Pressures

In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

scholarly journals Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution

2009 ◽  
Vol 297 (6) ◽  
pp. R1625-R1634 ◽  
Author(s):  
John B. West
Keyword(s):  
Gas Exchange ◽  
Complete Separation ◽  
External Support ◽  
Blood Gas ◽  
Large Area ◽  
Gas Barrier ◽  
Type Iv ◽  
Pulmonary Capillaries ◽  
The Face ◽  
Flow Through

Two opposing selective pressures have shaped the evolution of the structure of the blood-gas barrier in air breathing vertebrates. The first pressure, which has been recognized for 100 years, is to facilitate diffusive gas exchange. This requires the barrier to be extremely thin and have a large area. The second pressure, which has only recently been appreciated, is to maintain the mechanical integrity of the barrier in the face of its extreme thinness. The most important tensile stress comes from the pressure within the pulmonary capillaries, which results in a hoop stress. The strength of the barrier can be attributed to the type IV collagen in the extracellular matrix. In addition, the stress is minimized in mammals and birds by complete separation of the pulmonary and systemic circulations. Remarkably, the avian barrier is about 2.5 times thinner than that in mammals and also is much more uniform in thickness. These advantages for gas exchange come about because the avian pulmonary capillaries are unique among air breathers in being mechanically supported externally in addition to the strength that comes from the structure of their walls. This external support comes from epithelial plates that are part of the air capillaries, and the support is available because the terminal air spaces in the avian lung are extremely small due to the flow-through nature of ventilation in contrast to the reciprocating pattern in mammals.

Thickness of the blood-gas barrier in premature and 1-day-old newborn rabbit lungs

2003 ◽  
Vol 285 (1) ◽  
pp. L130-L136 ◽  
Author(s):  
Zhenxing Fu ◽  
Gregory P. Heldt ◽  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Gas Barrier ◽  
Newborn Rabbit ◽  
Pulmonary Capillaries ◽  
Normal Gestation ◽  
Neonatal Lungs ◽  
Extensive Pilot

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We studied the ultrastructure of the blood-gas barrier (BGB) in premature and 1-day-old rabbit lungs and compared it with the ultrastructure of adult lungs. Normal gestation of rabbits is 30 days. After extensive pilot measurements, three premature (27 days gestation) and three newborn (1 day old) rabbit lungs were perfusion-fixed at arterial, venous, and airway pressures of 25, 0, and 10 cmH2O, respectively, and the measurements were compared with those of three adult lungs. The thickness of the capillary endothelium, alveolar epithelium, and interstitium of the BGB was measured at right angles to the barrier at random points. A striking finding was the large number of measurements of the interstitial thickness in 1-day-old lungs that were very thin (0–0.1 μm). The percentages of occurrence of very thin interstitium in premature, 1-day-old, and adult lungs were 35.3 ± 9.4, 71.7 ± 5.2, and 43.0 ± 2.6, respectively ( P < 0.02 for 1 day old vs. premature and adult). Given the previously found relationship between stress failure and interstitial thickness, this large proportion of very thin interstitial layers in the capillaries of 1-day-old lungs is a reasonable explanation for their previously demonstrated vulnerability to stress failure.

Computer simulation of neutrophil transit through the pulmonary capillary bed

1993 ◽  
Vol 74 (4) ◽  
pp. 1647-1652 ◽  
Author(s):  
C. C. Hanger ◽  
W. W. Wagner ◽  
S. J. Janke ◽  
T. C. Lloyd ◽  
R. L. Capen
Keyword(s):  
Computer Simulation ◽  
Computer Model ◽  
Pulmonary Circulation ◽  
Cell Deformation ◽  
In Vivo Microscopy ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
Diameter Distributions

One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one-half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one-half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed.

Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits

1995 ◽  
Vol 79 (3) ◽  
pp. 908-917 ◽  
Author(s):  
O. Mathieu-Costello ◽  
D. C. Willford ◽  
Z. Fu ◽  
R. M. Garden ◽  
J. B. West
Keyword(s):  
Autologous Blood ◽  
Transmural Pressure ◽  
Blood Gas ◽  
Barrier Thickness ◽  
Rabbit Lung ◽  
Gas Barrier ◽  
Athletic Ability ◽  
Pulmonary Capillaries ◽  
Glutaraldehyde Solution

We previously showed that stress failure of pulmonary capillaries occurs at transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit lung. In this study, we examined whether pulmonary capillaries are more resistant to failure in dogs than in rabbits. This might be expected because of the greater athletic ability of dogs and therefore their presumably greater tolerance to large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12 anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution (10 min), all three perfusions at the same preset transmural pressure of 32.5, 72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break number per millimeter of epithelium and endothelium were right shifted by approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits, neither total nor interstitial thickness increased significantly with increasing pressure. These results indicate that pulmonary capillaries are more resistant to stress failure in dogs than rabbits.

Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung

1993 ◽  
Vol 74 (6) ◽  
pp. 3040-3045 ◽  
Author(s):  
C. M. Doerschuk ◽  
N. Beyers ◽  
H. O. Coxson ◽  
B. Wiggs ◽  
J. C. Hogg
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Polymorphonuclear Leukocytes ◽  
Neutrophil Sequestration ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
The Mean ◽  
Pass Through ◽  
Capillary Size

Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation.

Morphometry of the extremely thin pulmonary blood-gas barrier in the chicken lung

2007 ◽  
Vol 292 (3) ◽  
pp. L769-L777 ◽  
Author(s):  
Rebecca R. Watson ◽  
Zhenxing Fu ◽  
John B. West
Keyword(s):  
Type I Collagen ◽  
Arithmetic Mean ◽  
Type I ◽  
Blood Gas ◽  
Gas Barrier ◽  
Structural Support ◽  
Pulmonary Capillaries ◽  
Mammalian Lung ◽  
Avian Lung ◽  
To Come

The gas exchanging region in the avian lung, although proportionally smaller than that of the mammalian lung, efficiently manages respiration to meet the high energetic requirements of flapping flight. Gas exchange in the bird lung is enhanced, in part, by an extremely thin blood-gas barrier (BGB). We measured the arithmetic mean thickness of the different components (endothelium, interstitium, and epithelium) of the BGB in the domestic chicken lung and compared the results with three mammals. Morphometric analysis showed that the total BGB of the chicken lung was significantly thinner than that of the rabbit, dog, and horse (54, 66, and 70% thinner, respectively) and that all layers of the BGB were significantly thinner in the chicken compared with the mammals. The interstitial layer was strikingly thin in the chicken lung (∼86% thinner than the dog and horse, and 75% thinner than rabbit) which is a paradox because the strength of the BGB is believed to come from the interstitium. In addition, the thickness of the interstitium was remarkably uniform, unlike the mammalian interstitium. The uniformity of the interstitial layer in the chicken is attributable to a lack of the supportive type I collagen cable that is found in mammalian alveolar lungs. We propose that the surrounding air capillaries provide additional structural support for the pulmonary capillaries in the bird lung, thus allowing the barrier to be both very thin and extremely uniform. The net result is to improve gas exchanging efficiency.

Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs

1994 ◽  
Vol 77 (1) ◽  
pp. 463-470 ◽  
Author(s):  
B. R. Wiggs ◽  
D. English ◽  
W. M. Quinlan ◽  
N. A. Doyle ◽  
J. C. Hogg ◽  
...  
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Random Distribution ◽  
Large Fraction ◽  
Pulmonary Capillaries ◽  
Transit Times ◽  
Pulmonary Capillary ◽  
Time Required ◽  
Rapid Deformation

Neutrophil margination within the pulmonary capillary is due to a delay in their transit compared with that of red blood cells (RBC). This delay has been attributed to the large fraction of capillary segments that are narrower than spherical neutrophils and differences between the time required for deformation of neutrophils and that required for deformation of RBC. This study investigated the characteristics of neutrophil deformation in vivo and the perfusion patterns of segments within capillary pathways. Studies comparing the extraction of neutrophils with that of nondeformable microspheres in one transit through the pulmonary circulation suggest that neutrophils can undergo a rapid deformation from 6.4 to 5.0–5.1 microns, whereas larger deformations require a delay. Effective diameters of the perfused capillary pathways were larger than expected for a random distribution of capillary segment diameters within these pathways. The longer transit times of neutrophils in the upper regions of the lung were associated with a greater fraction of pathways containing narrow segments. These studies suggest that neutrophil deformability and capillary pathway diameters are important in determining the size of the marginated pool of neutrophils within the pulmonary capillaries.

Thoughts on the pulmonary blood-gas barrier

2003 ◽  
Vol 285 (3) ◽  
pp. L501-L513 ◽  
Author(s):  
John B. West
Keyword(s):  
Wall Stress ◽  
Complete Separation ◽  
South American ◽  
Blood Gas ◽  
Gas Barrier ◽  
Physiological Conditions ◽  
Type Iv ◽  
Thoroughbred Racehorses ◽  
Bony Fishes ◽  
Essential Components

The pulmonary blood-gas barrier is an extraordinary structure because of its extreme thinness, immense strength, and enormous area. The essential components of the barrier were determined early in evolution and have been highly conserved. For example, the barriers of the African, Australian, and South American lungfish that date from as much as 400 million years ago have essentially the same structure as in the modern mammal or bird. In the evolution of vertebrates from bony fishes through amphibia, reptiles, and ultimately mammals and birds, changes in the pulmonary circulation occurred to limit the stresses in the blood-gas barrier. Only in mammals and birds is there a complete separation of the pulmonary and systemic circulations, which is essential to protect the extremely thin barrier from the necessary high-vascular pressures. To provide the blood-gas barrier with its required strength, evolution has exploited the high ultimate tensile strength of type IV collagen in basement membrane. Nevertheless, stress failure of the barrier occurs under physiological conditions in galloping Thoroughbred racehorses and also apparently in elite human athletes at maximal exercise. The human blood-gas barrier maintains its integrity during all but the most extreme physiological conditions. However, many pathological conditions cause stress failure. The structure of the blood-gas barrier is apparently continually regulated in response to wall stress, and this regulation is essential to maintain the extreme thinness but adequate strength. The mechanisms of this regulation remain to be elucidated and constitute one of the fundamental problems in lung biology.

Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses

2001 ◽  
Vol 90 (6) ◽  
pp. 2371-2377 ◽  
Author(s):  
Murli Manohar ◽  
Thomas E. Goetz ◽  
Aslam S. Hassan
Keyword(s):  
High Intensity ◽  
Structural Changes ◽  
Pulmonary Hemorrhage ◽  
Exercise Bout ◽  
Blood Gas ◽  
Gas Barrier ◽  
Arterial Hypoxemia ◽  
Pulmonary Capillaries ◽  
Thoroughbred Horses ◽  
Exercise Induced

Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pulmonary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was carried out to examine whether the structural changes in the blood-gas barrier caused by a prior bout of high-intensity short-term exercise capable of inducing EIPH would affect the arterial hypoxemia induced during a successive bout of exercise performed at the same workload. Two sets of experiments, double- and single-exercise-bout experiments, were carried out on seven healthy, sound Thoroughbred horses. Experiments were carried out in random order, 7 days apart. In the double-exercise experiments, horses performed two successive bouts (each lasting 120 s) of galloping at 14 m/s on a 3.5% uphill grade, separated by an interval of 6 min. Exertion at this workload induced arterial hypoxemia within 30 s of the onset of galloping as well as desaturation of Hb, a progressive rise in arterial Pco 2, and acidosis as exercise duration increased from 30 to 120 s. In the single-exercise-bout experiments, blood-gas/pH data resembled those from the first run of the double-exercise experiments, and all horses experienced EIPH. Thus, in the double-exercise experiments, before the horses performed the second bout of galloping at 14 m/s on a 3.5% uphill grade, stress failure of pulmonary capillaries had occurred. Although arterial hypoxemia developed during the second run, arterial Po 2 values were significantly ( P < 0.01) higher than in the first run. Thus prior exercise not only failed to accentuate the severity of arterial hypoxemia, it actually diminished the magnitude of exercise-induced arterial hypoxemia. The decreased severity of exercise-induced arterial hypoxemia in the second run was due to an associated increase in alveolar Po 2, as arterial Pco 2 was significantly lower than in the first run. Thus our data do not support a role for structural changes in the blood-gas barrier related to the stress failure of pulmonary capillaries in causing the exercise-induced arterial hypoxemia in horses.

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