Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH2O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the “safety factor” opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D > 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening.

Measurement of extravascular lung water in the ICU

The accumulation of fluid in the interstitium and alveolar space is known as extravascular lung water (EVLW). EVLW is associated with increased morbidity and mortality in critically ill patients and is elevated in patients with cardiogenic pulmonary oedema, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). Pulmonary oedema is a consequence of increased pulmonary capillary hydrostatic pressure and/or an increased capillary permeability. The quantity of pulmonary oedema fluid is dependent on the balance of fluid formation and clearance, and this contributes to the overall dynamic net lung fluid balance. Measurement of EVLW is therefore an indirect surrogate measurement of the alveolar epithelial and endothelial damage in ALI/ARDS. The single indicator transpulmonary thermodilution technique is an available bedside technique to measure EVLW.