Fluid Flux and Clearance in Acute Lung Injury

Abstract

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), were presciently described nearly two centuries ago by René Laennec, later to be described clinically in the 1950s and 1960s. Substantial advances have been made in understanding the pathogenesis of these forms of permeability pulmonary edema, including Starling forces and cellular transport mechanisms involved in the generation and resolution of this form of lung injury. Functional animal models and clinically applicable case definitions for ALI and ARDS were instrumental in gaining these new insights. Although no specific pharmacological therapies for ALI and ARDS yet exist, outcomes have improved with advancements in respiratory and fluid-based supportive therapies, and methods to prevent the development or exacerbation of lung injury. Newer targeted therapies continue to be tested for efficacy in this condition where mortality rates frequently exceed 30%. In this article, we review the history of the pathophysiology of lung fluid and solute movement and the seminal clinical observations that brought that history to clinical relevance. We review the relevant lung structure and function and the dynamics of edema formation and resolution, and we describe the related clinical syndromes and the current treatment modalities.

Blood cells and endothelial barrier function

“…This is commonly manifested in the lungs as an accumulation of interstitial fluid in the alveolar spaces (pulmonary edema), which results when the alveolar membrane is ruptured due to excessive interstitial fluid accumulation (and an elevated interstitial pressure) secondary to capillary fluid leakage. 163 A similar phenomenon has been described in the intestine, with excessive capillary fluid and protein leakage resulting in mucosal barrier disruption and the movement of interstitial fluid in the gut lumen. 164 However, the response in gut is not as immediately life-threatening as pulmonary edema, which impairs gas exchange and may cause respiratory failure.…”

Lung Circulation

“…In vivo measures of endothelial permeability measure leak of fluid into the interstitial space due to either increase in intravascular pressures or endothelial permeability (478). An important consideration is that the net efflux of fluid from the vascular space is a function of Starling forces, as well as properties of the luminal fluid, permeability state of the endothelium, flooding in the alveolus and lymphatic flow (401), and occurs in both the alveolar and extra-alveolar vessels [reviewed in (478)]. Methods of quantifying endothelial leak in vivo in intact animals include gravimetric methods (e.g., wet/dry ratios), light and electron microscopy, and visual quantification of dye extravasation from the vascular compartment (i.e., Evans Blue Dye).…”

A Physiologically Informed Strategy to Effectively Open, Stabilize, and Protect the Acutely Injured Lung

“…The systemic inflammatory response syndrome (SIRS) secondary to sepsis, trauma, burns, pneumonia, and so on increases pulmonary capillary permeability. Endothelial leakage: increased microvascular permeability allowing pulmonary edema to move into the alveolus (black arrows and tan edema blebs) (Martin and Brigham, 2012). Surfactant deactivation: the continuous layer of pulmonary surfactant molecules is disrupted as the edema blebs expand causing surfactant deactivation (surfactant sluffing off into the alveolar space).…”

“…Edema usurping surfactant from the alveolar surface, the proteins in the edema fluid deactivating the surfactant (Taeusch et al, 2005), and improper mechanical ventilation (Albert, 2012) causing further surfactant disruption all combine to exacerbate surfactant loss. Alveolar edema: increased capillary permeability (Martin and Brigham, 2012) and high alveolar surface tension combine to flood alveoli with edema fluid (tan). Recruitment/derecruitment (R/D): loss of surfactant function results in increased alveolar surface tension causing loss of alveolar stability (i.e., causing alveolar R/D with each breath).…”