Edemagenic gain and interstitial fluid volume regulation

Abstract

Under 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 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 K(f), 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.

A mathematical model of intestinal oedema formation

“…Intestinal oedema refers to the excess accumulation of fluid in the interstitium (the spaces between cells) of the intestinal wall tissue (Granger & Barrowman, 1984;Dongaonkar et al, 2008). This condition can arise in patients with gastroschisis, inflammatory bowel disease and cirrhosis (Moore-Olufemi et al, 2009), as well as in patients receiving resuscitative treatments after traumatic injuries .…”

“…The presence of this excess fluid has been shown to cause ileus (oedema-induced intestinal contractile and transit dysfunction) due to a decrease in intestinal smooth muscle contraction (Moore-Olufemi et al, 2005;Cox et al, 2008). The oedema and subsequent delayed intestinal transit can lead to longer patient recovery times and hospital stays, as well as death (Dongaonkar et al, 2008;Moore-Olufemi et al, 2009).…”

“…Significant experimental work has been done in the field of intestinal oedema (Moore-Olufemi et al, 2005;Uray et al, 2006Uray et al, , 2007Cox et al, 2008;Moore-Olufemi et al, 2009). Theoretical work has been done on volume regulation, fluid balance and fluid transport in the interstitium (Taylor et al, 1990;Gyenge et al, 1999;Dongaonkar et al, 2008Dongaonkar et al, , 2009, and some oedema models have been developed for other organs (Wiener et al, 1983;Hempling & Katz, 1989;Nagashima et al, 1990). However, these models neglect one or more factors, that are important for modelling oedema in the intestine.…”

“…However, these models neglect one or more factors, that are important for modelling oedema in the intestine. In Dongaonkar et al (2008Dongaonkar et al ( , 2009, Gyenge et al (1999), Taylor et al (1990), Wiener et al (1983) and Hempling & Katz (1989) changes in the mechanical response (stress tensor) of the tissue that surrounds the interstitium are not explicitly evolved, but are represented with a pressure-volume compliance relationship. To provide a more detailed description of the tissue deformation, a model of oedema formation must include an equation describing the balance of forces from pressure gradients and mechanical stress.…”

“…Under homoeostatic conditions, the fluid volume in the interstitium is kept relatively constant by a balanced fluid exchange between blood capillaries and lymphatics in the interstitium, controlled by hydrostatic and oncotic pressure gradients (Guyton (1995); Reed (1995); Dongaonkar et al (2008)). Fluid tends to flow into the interstitium by filtering through the blood capillaries (Reed, 1995;Dongaonkar et al, 2008). This fluid is removed from the interstitium by the lymphatics via a filling and pumping mechanism (Guyton, 1995).…”