Interstitial-lymphatic mechanisms in the control of extracellular fluid volume

The canonical pre-modern review of interstitial-lymphatic physiology, by two figures of the Bergen-school programme on microvascular and interstitial fluid mechanics. Knut Aukland (1925–2017) was professor of physiology at the University of Bergen for several decades and the senior figure of the Norwegian physiology of microcirculation tradition; Rolf K. Reed, also at Bergen, was the continuing senior figure and Aukland's long-term collaborator (Reed is also the institutional precursor and senior colleague of Wiig).

Published in Physiological Reviews in January 1993 — a 78-page review — the paper is the foundational secondary citation for pre-2000 interstitial physiology. The substance: a systematic treatment of the structural composition of the interstitium (collagen, glycosaminoglycans, hyaluronic acid, the role of negatively-charged matrix in fluid exclusion), the Starling-force balance regulating transcapillary filtration, the autoregulatory mechanisms that adjust interstitial volume in response to perturbation, and the role of the lymphatic system in returning excess interstitial fluid to circulation. The review is the place where the standard pre-2018 understanding of interstitial fluid as a structured, dynamic, mechanically-active compartment is laid out in detail.

The piece sits as the pre-modern foundation underneath the post-2018 interstitium debate. The Mestres- Ventura 2019 critique that the unrecognised framing of Benias 2018 depends on conflating not visualised by standard slide-preparation with not previously known draws much of its force from reviews like this one: the interstitium was extensively characterised by 1993, and what the 2018 imaging added was scale and architecture, not the existence of structured fluid spaces.

The stake is internal to physiology — Aukland and Reed had no commercial position and the review is the kind of slow synthesis that established physiologists produce as a service to the field. The Bergen lineage continued through Reed and into Wiig and Swartz's 2012 follow-up review, which sits in the same venue twenty years later. Read this paper before the 2018 debate; the modern functional claims rest on the kind of physiology this review consolidates.