Edemagenic gain and interstitial fluid volume regulation
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
der physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made
... e thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "edemagenic gain" is a function of microvascular filtration coefficient (K f), effective lymphatic resistance (R L), and interstitial compliance (C). This formulation suggests two types of gain: "multivariate" dependent on C, R L , and Kf , and "compliance-dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema. Starling-Landis equation; mathematical model; edematogenic EDEMA, the accumulation of excess interstitial fluid volume (V), can be both a cause and an effect (9, 12, 61) of major morbidity such as cardiac, renal, and pulmonary failure. The techniques used to determine the "degree" of edema, however, have limited prognostic potential. For instance, different inflammatory agents, such as histamine and endotoxin, can result in similar degrees of edema, although edema secondary to endotoxin is more likely to worsen with increased microvascular pressure (1, 44). Despite a focus on anti-edema mechanisms, investigators have neglected to address this sensitivity of edema formation to edemagenic challenges. Though the concept of a "gain" has been used to characterize whole-body fluid balance (30), it has yet to be applied to interstitial fluid balance. The potential exists to bridge the gap between basic physiology and clinical practice, as the complexity of interstitial fluid balance results from three relatively simple processes: transmicrovascular filtration, lymphatic return, and interstitial fluid storage.