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Surfactant alteration and replacement in acute respiratory distress syndrome.

Günther A, Ruppert C, Schmidt R, Markart P, Grimminger F, Walmrath D, Seeger W - Respir. Res. (2001)

Bottom Line: It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators.There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS.An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Justus-Liebig-University Giessen, Germany. andreas.guenther@innere.med.uni-giessen.de

ABSTRACT
The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occurring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

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Schematic illustration of trigger mechanisms leading to acute respiratory distress syndrome (ARDS). Four key pathophysiological and clinical findings are encountered in ARDS: firstly, noxious agents may attack the alveolar compartment directly or hit the lung via the intravascular compartment (indirect, classical ARDS). Secondly, during the early exudative phase, a self-perpetuating inflammatory process involves the entire gas exchange unit leading to type II cell injury, loss of epithelial (and endothelial) integrity, alveolar edema formation, and severe impairment of surfactant function. Thirdly, as a result a ventilation-perfusion mismatch with extensive shunt flow is observed. Fourthly, aggravating complications including new inflammatory events, such as recurrent or persistent sepsis, or acquisition of secondary (nosocomial) pneumonia may repetitively worsen the state of lung function and then progressively favour proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis. infl., inflammatory, interst., interstitial.
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Figure 1: Schematic illustration of trigger mechanisms leading to acute respiratory distress syndrome (ARDS). Four key pathophysiological and clinical findings are encountered in ARDS: firstly, noxious agents may attack the alveolar compartment directly or hit the lung via the intravascular compartment (indirect, classical ARDS). Secondly, during the early exudative phase, a self-perpetuating inflammatory process involves the entire gas exchange unit leading to type II cell injury, loss of epithelial (and endothelial) integrity, alveolar edema formation, and severe impairment of surfactant function. Thirdly, as a result a ventilation-perfusion mismatch with extensive shunt flow is observed. Fourthly, aggravating complications including new inflammatory events, such as recurrent or persistent sepsis, or acquisition of secondary (nosocomial) pneumonia may repetitively worsen the state of lung function and then progressively favour proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis. infl., inflammatory, interst., interstitial.

Mentions: In the early, exudative, phase of ARDS, the massive, self-perpetuating inflammatory process involves the entire gas exchange unit (see Supplementary Fig. 1). Pathophysiologically, this phase has four characteristics: an increase in capillary endothelial and/or alveolar epithelial permeability; leakage of plasma protein, with flow of edematous fluid into the interstitial and, later, the alveolar spaces; vasoconstriction and microembolism or microthrombosis in the vascular compartment, and thus increased pulmonary vascular resistance, with maldistribution of pulmonary perfusion; and an increase in alveolar surface tension favoring alveolar instability with formation of atelectasis and ventila-tory inhomogeneities. As a consequence, a profound ventilation/perfusion (V/Q) mismatch, with extensive intrapulmonary shunt flow and highly impaired gas exchange, is regularly seen. This exudative phase may persist for about a week, during which full recovery without persistent loss of lung function is very possible [8] (see Supplementary Fig. 1). However, new inflammatory events, such as recurrent sepsis or acquisition of secondary (nosocomial) pneumonia, may repetitively worsen the state of lung function and then progressively favor proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis [9] (see Supplementary Fig. 1). Fibroproliferative events such as increased collagen matrix production occur early in the course of ARDS (about 5 to 7 days after the onset [10]) and may lead to irreversible, restrictive abnormalities of lung function. In addition, the development of pulmonary fibrosis and deposition of extracellular collagen in the alveolar space correlates with an increased risk of death in ARDS [11,12] (see Supplementary Fig. 1).


Surfactant alteration and replacement in acute respiratory distress syndrome.

Günther A, Ruppert C, Schmidt R, Markart P, Grimminger F, Walmrath D, Seeger W - Respir. Res. (2001)

Schematic illustration of trigger mechanisms leading to acute respiratory distress syndrome (ARDS). Four key pathophysiological and clinical findings are encountered in ARDS: firstly, noxious agents may attack the alveolar compartment directly or hit the lung via the intravascular compartment (indirect, classical ARDS). Secondly, during the early exudative phase, a self-perpetuating inflammatory process involves the entire gas exchange unit leading to type II cell injury, loss of epithelial (and endothelial) integrity, alveolar edema formation, and severe impairment of surfactant function. Thirdly, as a result a ventilation-perfusion mismatch with extensive shunt flow is observed. Fourthly, aggravating complications including new inflammatory events, such as recurrent or persistent sepsis, or acquisition of secondary (nosocomial) pneumonia may repetitively worsen the state of lung function and then progressively favour proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis. infl., inflammatory, interst., interstitial.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC64803&req=5

Figure 1: Schematic illustration of trigger mechanisms leading to acute respiratory distress syndrome (ARDS). Four key pathophysiological and clinical findings are encountered in ARDS: firstly, noxious agents may attack the alveolar compartment directly or hit the lung via the intravascular compartment (indirect, classical ARDS). Secondly, during the early exudative phase, a self-perpetuating inflammatory process involves the entire gas exchange unit leading to type II cell injury, loss of epithelial (and endothelial) integrity, alveolar edema formation, and severe impairment of surfactant function. Thirdly, as a result a ventilation-perfusion mismatch with extensive shunt flow is observed. Fourthly, aggravating complications including new inflammatory events, such as recurrent or persistent sepsis, or acquisition of secondary (nosocomial) pneumonia may repetitively worsen the state of lung function and then progressively favour proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis. infl., inflammatory, interst., interstitial.
Mentions: In the early, exudative, phase of ARDS, the massive, self-perpetuating inflammatory process involves the entire gas exchange unit (see Supplementary Fig. 1). Pathophysiologically, this phase has four characteristics: an increase in capillary endothelial and/or alveolar epithelial permeability; leakage of plasma protein, with flow of edematous fluid into the interstitial and, later, the alveolar spaces; vasoconstriction and microembolism or microthrombosis in the vascular compartment, and thus increased pulmonary vascular resistance, with maldistribution of pulmonary perfusion; and an increase in alveolar surface tension favoring alveolar instability with formation of atelectasis and ventila-tory inhomogeneities. As a consequence, a profound ventilation/perfusion (V/Q) mismatch, with extensive intrapulmonary shunt flow and highly impaired gas exchange, is regularly seen. This exudative phase may persist for about a week, during which full recovery without persistent loss of lung function is very possible [8] (see Supplementary Fig. 1). However, new inflammatory events, such as recurrent sepsis or acquisition of secondary (nosocomial) pneumonia, may repetitively worsen the state of lung function and then progressively favor proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis [9] (see Supplementary Fig. 1). Fibroproliferative events such as increased collagen matrix production occur early in the course of ARDS (about 5 to 7 days after the onset [10]) and may lead to irreversible, restrictive abnormalities of lung function. In addition, the development of pulmonary fibrosis and deposition of extracellular collagen in the alveolar space correlates with an increased risk of death in ARDS [11,12] (see Supplementary Fig. 1).

Bottom Line: It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators.There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS.An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Justus-Liebig-University Giessen, Germany. andreas.guenther@innere.med.uni-giessen.de

ABSTRACT
The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occurring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

Show MeSH
Related in: MedlinePlus