Abstract:The air blood barrier phenotype can be reasonably described by the ratio of lung capillary blood volume to the diffusion capacity of the alveolar membrane (Vc/Dm), which can be determined at rest in normoxia. The distribution of the Vc/Dm ratio in the population is normal; Vc/Dm shifts from ∼1, reflecting a higher number of alveoli of smaller radius, providing a high alveolar surface and a limited extension of the capillary network, to just opposite features on increasing Vc/Dm up to ∼6. We studied the kinetic… Show more
“… Fig. 10 Time course of 1 − L eq (index of alveolar-capillary equilibration) in normoxia at rest (continuous line) and on exposure to severe hypoxia (3840 m, P I O 2 90 mmHg, dashed line) in two representative subjects having a high ( A ) or a low ( B ) V c /D m ratio at sea level in resting condition (from Miserocchi et al 2022 ) …”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Figure 11 B allows to estimate the correlation between L eq and 1/ Tt . We consider that 1/Tt is proportional to blood velocity and hypothesize that its increase causes an increase in shear, an important factor leading to an increase in microvascular permeability (Miserocchi et al 2022 ): in fact, on comparing the two subjects, L eq increases remarkably in the red subject (higher blood velocity and shear) compared to the blue subject. Fig.…”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Red and blue dots refer to the two subjects shown in Fig. 10 A, B, respectively (from Miserocchi et al 2022 ) …”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Based on physiological parameters, at present, two approaches have been proposed. One relies on the determination of the Vc/Dm ratio at rest and after a subthreshold work-load in normoxia and in hypoxia (Miserocchi et al 2022 ). A second method aimed at establishing the proneness to develop high acute mountain sickness relies on the estimate of the score value SHAI (severe high-altitude illness), a practical indirect method, after a work-load in hypoxia (30% of maximal power, Richalet et al 2021 ).…”
Section: Proposals To Drive Possible Future Researchmentioning
Purpose
This review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema.
Method
Data from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by “safety factors” in physiological conditions, (2) consider how waning of “safety factors” inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans.
Results
Exercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema.
Conclusion
Data from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air–blood barrier.
“… Fig. 10 Time course of 1 − L eq (index of alveolar-capillary equilibration) in normoxia at rest (continuous line) and on exposure to severe hypoxia (3840 m, P I O 2 90 mmHg, dashed line) in two representative subjects having a high ( A ) or a low ( B ) V c /D m ratio at sea level in resting condition (from Miserocchi et al 2022 ) …”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Figure 11 B allows to estimate the correlation between L eq and 1/ Tt . We consider that 1/Tt is proportional to blood velocity and hypothesize that its increase causes an increase in shear, an important factor leading to an increase in microvascular permeability (Miserocchi et al 2022 ): in fact, on comparing the two subjects, L eq increases remarkably in the red subject (higher blood velocity and shear) compared to the blue subject. Fig.…”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Red and blue dots refer to the two subjects shown in Fig. 10 A, B, respectively (from Miserocchi et al 2022 ) …”
Section: The Kinetics Of Alveolar-capillary Oxygen Equilibrationmentioning
confidence: 99%
“…Based on physiological parameters, at present, two approaches have been proposed. One relies on the determination of the Vc/Dm ratio at rest and after a subthreshold work-load in normoxia and in hypoxia (Miserocchi et al 2022 ). A second method aimed at establishing the proneness to develop high acute mountain sickness relies on the estimate of the score value SHAI (severe high-altitude illness), a practical indirect method, after a work-load in hypoxia (30% of maximal power, Richalet et al 2021 ).…”
Section: Proposals To Drive Possible Future Researchmentioning
Purpose
This review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema.
Method
Data from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by “safety factors” in physiological conditions, (2) consider how waning of “safety factors” inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans.
Results
Exercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema.
Conclusion
Data from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air–blood barrier.
“…This occurs in physiological conditions despite the existence of morphological and mechanical heterogeneities of the terminal lung units. This review will explore how the heterogeneity in the morphology and perfusion of the terminal respiratory units come into play when the lung is facing edemagenic conditions that notably impact on the control of extravascular water and, in parallel, on the efficiency of the oxygen diffusion-transport at the level of the alveolar-capillary unit (Miserocchi et al, 2022). Further, evidence is provided concerning inter-individual differences in humans justifying the proneness to develop lung edema.…”
The architecture of the air-blood barrier is effective in optimizing the gas exchange as long as it retains its specific feature of extreme thinness reflecting, in turn, a strict control on the extravascular water to be kept at minimum. Edemagenic conditions may perturb this equilibrium by increasing microvascular filtration; this characteristically occurs when cardiac output increases to balance the oxygen uptake with the oxygen requirement such as in exercise and hypoxia (either due to low ambient pressure or reflecting a pathological condition). In general, the lung is well equipped to counteract an increase in microvascular filtration rate. The loss of control on fluid balance is the consequence of disruption of the integrity of the macromolecular structure of lung tissue. This review, merging data from experimental approaches and evidence in humans, will explore how the heterogeneity in morphology, mechanical features and perfusion of the terminal respiratory units might impact on lung fluid balance and its control. Evidence is also provided that heterogeneities may be inborn and they could actually get worse as a consequence of a developing pathological process. Further, data are presented how in humans inter-individual heterogeneities in morphology of the terminal respiratory hinder the control of fluid balance and, in turn, hamper the efficiency of the oxygen diffusion-transport function.
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