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Fluid Flux and Clearance in Acute Lung Injury

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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. © 2012 American Physiological Society. Compr Physiol 2:2471‐2480, 2012.

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Figure 1. Figure 1.

The physiology of microvascular fluid exchange in the normal lung (Panel A) and the edematous lung (hydrostatic edema in Panel B, permeability edema in Panel C). The Starling equation for filtration of fluid across a semipermeable membrane describes the factors that determine the amount of fluid leaving the vascular space. In the normal lung (Panel A), fluid moves continuously from the vasculature to the interstitial space according to the net difference between hydrostatic and protein osmotic pressures, as well as to the permeability of the capillary membrane. When vascular hydrostatic pressure increases, the rate of transvascular fluid filtration rises and hydrostatic pulmonary edema develops first in the interstitium and later in the alveolus (Panel B). Permeability pulmonary edema (Panel C) occurs when the microvascular membrane permeability increases because of direct or indirect injury, resulting in a net increase in fluid and protein leaving the vascular space and reaching the alveolus. Reproduced with permission from reference 73.

Figure 2. Figure 2.

Illustration of Starling's equation, depicting the balance of forces affecting fluid flux across a semipermeable membrane, as with the alveolocapillary membrane. Pc = capillary hydrostatic pressure, Pi = interstitial hydrostatic pressure, πc = capillary colloid osmotic pressure, πi = interstitial oncotic pressure, Kf = capillary filtration coefficient, QLYMPH = lymphatic flow, and δ = capillary reflection coefficient. Reproduced with permission from reference 19.



Figure 1.

The physiology of microvascular fluid exchange in the normal lung (Panel A) and the edematous lung (hydrostatic edema in Panel B, permeability edema in Panel C). The Starling equation for filtration of fluid across a semipermeable membrane describes the factors that determine the amount of fluid leaving the vascular space. In the normal lung (Panel A), fluid moves continuously from the vasculature to the interstitial space according to the net difference between hydrostatic and protein osmotic pressures, as well as to the permeability of the capillary membrane. When vascular hydrostatic pressure increases, the rate of transvascular fluid filtration rises and hydrostatic pulmonary edema develops first in the interstitium and later in the alveolus (Panel B). Permeability pulmonary edema (Panel C) occurs when the microvascular membrane permeability increases because of direct or indirect injury, resulting in a net increase in fluid and protein leaving the vascular space and reaching the alveolus. Reproduced with permission from reference 73.



Figure 2.

Illustration of Starling's equation, depicting the balance of forces affecting fluid flux across a semipermeable membrane, as with the alveolocapillary membrane. Pc = capillary hydrostatic pressure, Pi = interstitial hydrostatic pressure, πc = capillary colloid osmotic pressure, πi = interstitial oncotic pressure, Kf = capillary filtration coefficient, QLYMPH = lymphatic flow, and δ = capillary reflection coefficient. Reproduced with permission from reference 19.

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How to Cite

Greg S. Martin, Kenneth L. Brigham. Fluid Flux and Clearance in Acute Lung Injury. Compr Physiol 2012, 2: 2471-2480. doi: 10.1002/cphy.c100050