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Where's the Leak in Vascular Barriers? A Review

Kottke, Melissa A.; Walters, Thomas J.

doi: 10.1097/SHK.0000000000000666
Review Articles

ABSTRACT Edema is typically presented as a secondary effect from injury, illness, disease, or medication, and its impact on patient wellness is nested within the underlying etiology. Therefore, it is often thought of more as an amplifier to current preexisting conditions. Edema, however, can be an independent risk factor for patient deterioration. Improper management of edema is costly not only to the patient, but also to treatment and care facilities, as mismanagement of edema results in increased lengths of hospital stay. Direct tissue trauma, disease, or inappropriate resuscitation and/or ventilation strategies result in edema formation through physical disruption and chemical messenger-based structural modifications of the microvascular barrier. Derangements in microvascular barrier function limit tissue oxygenation, nutrient flow, and cellular waste removal. Recent studies have sought to elucidate cellular signaling and structural alterations that result in vascular hyperpermeability in a variety of critical care conditions to include hemorrhage, burn trauma, and sepsis. These studies and many others have highlighted how multiple mechanisms alter paracellular and/or transcellular pathways promoting hyperpermeability. Roles for endothelial glycocalyx, extracellular matrix and basement membrane, vesiculo-vacuolar organelles, cellular junction and cytoskeletal proteins, and vascular pericytes have been described, demonstrating the complexity of microvascular barrier regulation. Understanding these basic mechanisms inside and out of microvessels aid in developing better treatment strategies to mitigate the harmful effects of excessive edema formation.

Extremity Trauma and Regenerative Medicine Research Program, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas

Address reprint requests to CPT Melissa A. Kottke, PhD, U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Building 3611, JBSA Fort Sam Houston, TX 78234-6315. E-mail:

Received 29 February, 2016

Revised 23 March, 2016

Accepted 8 June, 2016

Funding support: DoD grants: F_003_2015_USAISR (TJW); W81XWH-14-2-0165 (TJW); W81XWH-14-2-0003 (TJW).

The authors report no conflicts of interest.

© 2016 by the Shock Society