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Gas Exchange in the Respiratory Distress Syndromes

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Abstract

This article describes the gas exchange abnormalities occurring in the acute respiratory distress syndrome seen in adults and children and in the respiratory distress syndrome that occurs in neonates. Evidence is presented indicating that the major gas exchange abnormality accounting for the hypoxemia in both conditions is shunt, and that approximately 50% of patients also have lungs regions in which low ventilation‐to‐perfusion ratios contribute to the venous admixture. The various mechanisms by which hypercarbia may develop and by which positive end‐expiratory pressure improves gas exchange are reviewed, as are the effects of vascular tone and airway narrowing. The mechanisms by which surfactant abnormalities occur in the two conditions are described, as are the histological findings that have been associated with shunt and low ventilation‐to‐perfusion. © 2012 American Physiological Society. Compr Physiol 2:1585‐1617, 2012.

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Figure 1. Figure 1.

Distributions of shunt, VA/Q and dead space in patients with acute respiratory distress syndrome not receiving positive end‐expiratory pressure (from Dantzker et al. ).

Figure 2. Figure 2.

Effect of oleic acid on end‐expiratory lung volume and tidal oscillations (data recorded supine and prone, and marker beads located in dorsal lung regions) (from Martynowicz, ).

Figure 3. Figure 3.

Effect of positive end‐expiratory pressure on end‐expiratory lung volume and ventilatory oscillations after oleic acid. (Modified from Martynowicz et al. ).

Figure 4. Figure 4.

Regional distribution of lung density quantified by CT scan in normal subjects and patients with acute respiratory distress syndrome (Modified from Pelosi et al. ).

Figure 5. Figure 5.

Lobar end‐expiratory lung volumes and functional residual capacities in normal subjects and patients with acute respiratory distress syndrome. (Modified from Puybasset et al. ().

Figure 6. Figure 6.

The electron microscopic image of alveolar surface film of the guinea pig lung. (Modified from Schurch et al. ).

Figure 7. Figure 7.

(A) Pressure‐volume curves with air and saline for a normal rat lung, and (B) the surface pressure to surface area relationship for an extract of this rat lung measured on a surface balance. (Modified from Clements et al. ).

Figure 8. Figure 8.

Pressure‐volume curves of human lungs. Volume is expressed as ml/g tissue for a normal infant, a stillborn, and infants who died of RDS. (Modified from Gribetz et al. ).

Figure 9. Figure 9.

Schematic illustration of the effect of surface tension at the meniscus of fluid filling progressively smaller airways ending in a fluid‐filled and collapsed alveolus (A‐C). The pressure needed to open the alveolus may exceed the pressure that will stress the more primoral airway (D). (Modified from Amato et al. ).

Figure 10. Figure 10.

Stresses on cells lining a collapsed compliant airway (A) or a fluid occluded airway (B) as a fluid meniscus passes over the cells. (Modified from Bilek et al. ).

Figure 11. Figure 11.

Tantalum bronchograms of a normal rat lung at end expiration or end inspiration using a high tidal volume of 2.5 ml/kg with no positive end‐expiratory pressure (PEEP) (ZEEP) or 10 cmH2O PEEP. The marker Do indicates bronchus diameter at end expiration with Zeep, and the airway diameter increased with tidal volume and PEEP (from Sinclair et al. ).

Figure 12. Figure 12.

Conditional expression of SP‐B regulated by doxacillin in transgenic mice. Adult mice have normal SP‐B levels in surfactant (A), normal minimal surface tensions (Min ST) (B), low protein in BALF (C), low inflammatory cells in BALF (D), and low IL‐1 protein in lung tissue. (E) Withdrawal of Dox results in a progressive fall in SP‐B, an increase in Min ST, and increases in indicators of lung injury, which revert to normal when Dox is reintroduced (from Ikegami et al. ). * P < 0.05 vs. C

Figure 13. Figure 13.

Withdrawal of doxacillin (Dox0 resulted in a fall in oxygen saturation (A), a loss of vascular protrusions into alveoli (B), and increased trapping of microspheres in the microvasculature of the lungs (C) of transgenic mice. In frame D, the shape of a vesicle in SP‐B sufficient mouse (D and A) flattens with a decreased diameter with (D and B) SP‐B deficiency (from Ikegami, M, Weaver, TE, Grant, SN, Whitsett, A. Am J Respir Cell Mol Biol 41: 433‐439, 2009)

.

Figure 14. Figure 14.

Light micrographs of normal rabbit lungs fixed at 40% (A), 80% (B), and 100% (C) of total lung capacity on the inflation limb of the pressure‐volume curve (from Bachofen et al. ).

Figure 15. Figure 15.

Alveolar appearances of the lungs of preterm sheep that were not ventilated fetal lungs) frame A of upper and frame A of lower panel. Lungs of lambs ventilated for 24 h without surfactant treatment, frame B in upper and lower panels show overinflation of alveolar ducts. In contrast, the lung of a lamb that was surfactant treated and ventilated for 24 h is more uniformly inflated (from Pinkerton, KE, Lewis JF, Rider ED, Peake J, Chen W, Madl AK, Luu RH, Ikegami M, Jobe AH. J. Appl. Physiol 77: 1953‐1960, 1994).

Figure 16. Figure 16.

Changes in PaO2 and minimum surface tensions of airway samples from preterm ventilated lambs following treatment with surfactant (from Ikegami M, Jobe A, Glatz T. J Appl Physiol 51: L306‐L312, 1981).

Figure 17. Figure 17.

Infants with RDS on high frequency oscillation had mean airway pressures increased until the lungs opened (defined as adequate oxygenation on an FIO2 <0.25), lined bar, and then mean airway pressures were decreased until oxygenation deteriorated (closed). Optimal pressure was the pressure sufficient to maintain oxygenation during continued ventilation. Pressures for the recruitment maneuver were lower after surfactant treatment (Modified from de Jaegere, ).

Figure 18. Figure 18.

RDS with respiratory failure is associated with high minimum surface tensions. Airway samples taken at intubation of infants with RDS and progressive respiratory failure have high minimum surface tensions in contrast to samples from infants without RDS, left frame. However, surfactant with low surface tensions can be isolated from those airway samples. The supernatant fluid contains proteins that inhibit surfactant function, right frame, and the proteins in airway samples are more potent inhibitors than proteins from infants without RDS (Modified from Ikegami M, Jacobs H, Jobe AH. J Pediatr 102: 443‐447, 1982).

Figure 19. Figure 19.

Posterior view of dog lung after inhaling blue vapor for 2 h 50 min after 3 h and 45 min supine under Nembutal anesthesia (Modified from Drinker and Harenbergh ).

Figure 20. Figure 20.

Effect of spontaneous and mechanical ventilation on respiratory system compliance (Modified from Mead and Collier ).

Figure 21. Figure 21.

Dorsal‐caudal atelectasis in supine dogs ventilated for 3 h without periodic hyperinflations. With successive inflations re‐expansion occurred (Modified from Mead and Collier ).



Figure 1.

Distributions of shunt, VA/Q and dead space in patients with acute respiratory distress syndrome not receiving positive end‐expiratory pressure (from Dantzker et al. ).



Figure 2.

Effect of oleic acid on end‐expiratory lung volume and tidal oscillations (data recorded supine and prone, and marker beads located in dorsal lung regions) (from Martynowicz, ).



Figure 3.

Effect of positive end‐expiratory pressure on end‐expiratory lung volume and ventilatory oscillations after oleic acid. (Modified from Martynowicz et al. ).



Figure 4.

Regional distribution of lung density quantified by CT scan in normal subjects and patients with acute respiratory distress syndrome (Modified from Pelosi et al. ).



Figure 5.

Lobar end‐expiratory lung volumes and functional residual capacities in normal subjects and patients with acute respiratory distress syndrome. (Modified from Puybasset et al. ().



Figure 6.

The electron microscopic image of alveolar surface film of the guinea pig lung. (Modified from Schurch et al. ).



Figure 7.

(A) Pressure‐volume curves with air and saline for a normal rat lung, and (B) the surface pressure to surface area relationship for an extract of this rat lung measured on a surface balance. (Modified from Clements et al. ).



Figure 8.

Pressure‐volume curves of human lungs. Volume is expressed as ml/g tissue for a normal infant, a stillborn, and infants who died of RDS. (Modified from Gribetz et al. ).



Figure 9.

Schematic illustration of the effect of surface tension at the meniscus of fluid filling progressively smaller airways ending in a fluid‐filled and collapsed alveolus (A‐C). The pressure needed to open the alveolus may exceed the pressure that will stress the more primoral airway (D). (Modified from Amato et al. ).



Figure 10.

Stresses on cells lining a collapsed compliant airway (A) or a fluid occluded airway (B) as a fluid meniscus passes over the cells. (Modified from Bilek et al. ).



Figure 11.

Tantalum bronchograms of a normal rat lung at end expiration or end inspiration using a high tidal volume of 2.5 ml/kg with no positive end‐expiratory pressure (PEEP) (ZEEP) or 10 cmH2O PEEP. The marker Do indicates bronchus diameter at end expiration with Zeep, and the airway diameter increased with tidal volume and PEEP (from Sinclair et al. ).



Figure 12.

Conditional expression of SP‐B regulated by doxacillin in transgenic mice. Adult mice have normal SP‐B levels in surfactant (A), normal minimal surface tensions (Min ST) (B), low protein in BALF (C), low inflammatory cells in BALF (D), and low IL‐1 protein in lung tissue. (E) Withdrawal of Dox results in a progressive fall in SP‐B, an increase in Min ST, and increases in indicators of lung injury, which revert to normal when Dox is reintroduced (from Ikegami et al. ). * P < 0.05 vs. C



Figure 13.

Withdrawal of doxacillin (Dox0 resulted in a fall in oxygen saturation (A), a loss of vascular protrusions into alveoli (B), and increased trapping of microspheres in the microvasculature of the lungs (C) of transgenic mice. In frame D, the shape of a vesicle in SP‐B sufficient mouse (D and A) flattens with a decreased diameter with (D and B) SP‐B deficiency (from Ikegami, M, Weaver, TE, Grant, SN, Whitsett, A. Am J Respir Cell Mol Biol 41: 433‐439, 2009)

.



Figure 14.

Light micrographs of normal rabbit lungs fixed at 40% (A), 80% (B), and 100% (C) of total lung capacity on the inflation limb of the pressure‐volume curve (from Bachofen et al. ).



Figure 15.

Alveolar appearances of the lungs of preterm sheep that were not ventilated fetal lungs) frame A of upper and frame A of lower panel. Lungs of lambs ventilated for 24 h without surfactant treatment, frame B in upper and lower panels show overinflation of alveolar ducts. In contrast, the lung of a lamb that was surfactant treated and ventilated for 24 h is more uniformly inflated (from Pinkerton, KE, Lewis JF, Rider ED, Peake J, Chen W, Madl AK, Luu RH, Ikegami M, Jobe AH. J. Appl. Physiol 77: 1953‐1960, 1994).



Figure 16.

Changes in PaO2 and minimum surface tensions of airway samples from preterm ventilated lambs following treatment with surfactant (from Ikegami M, Jobe A, Glatz T. J Appl Physiol 51: L306‐L312, 1981).



Figure 17.

Infants with RDS on high frequency oscillation had mean airway pressures increased until the lungs opened (defined as adequate oxygenation on an FIO2 <0.25), lined bar, and then mean airway pressures were decreased until oxygenation deteriorated (closed). Optimal pressure was the pressure sufficient to maintain oxygenation during continued ventilation. Pressures for the recruitment maneuver were lower after surfactant treatment (Modified from de Jaegere, ).



Figure 18.

RDS with respiratory failure is associated with high minimum surface tensions. Airway samples taken at intubation of infants with RDS and progressive respiratory failure have high minimum surface tensions in contrast to samples from infants without RDS, left frame. However, surfactant with low surface tensions can be isolated from those airway samples. The supernatant fluid contains proteins that inhibit surfactant function, right frame, and the proteins in airway samples are more potent inhibitors than proteins from infants without RDS (Modified from Ikegami M, Jacobs H, Jobe AH. J Pediatr 102: 443‐447, 1982).



Figure 19.

Posterior view of dog lung after inhaling blue vapor for 2 h 50 min after 3 h and 45 min supine under Nembutal anesthesia (Modified from Drinker and Harenbergh ).



Figure 20.

Effect of spontaneous and mechanical ventilation on respiratory system compliance (Modified from Mead and Collier ).



Figure 21.

Dorsal‐caudal atelectasis in supine dogs ventilated for 3 h without periodic hyperinflations. With successive inflations re‐expansion occurred (Modified from Mead and Collier ).

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Richard K. Albert, Alan Jobe. Gas Exchange in the Respiratory Distress Syndromes. Compr Physiol 2012, 2: 1585-1617. doi: 10.1002/cphy.c090019