EDEMAGENIC GAIN AND INTERSTITIAL FLUID REGULATION

Under physiological conditions, interstitial fluid volume is very tightly controlled by balancing microvascular filtration (affected by the filtration coefficient, K f ) with lymphatic return (affected by the effective lymphatic resistance, R L ). Interstitial pressure (affected by interstitial compliance, C ) provides feedback that inhibits filtration and enhances lymphatic return. Resulting changes in interstitial volume are characterized by a differential equation requiring a numerical solution, which limits both the generality of the results and its practical application. To reduce this complexity, we made linear approximations and developed an analytical solution to the standard fluid balance equations. Formulating the solution in terms of a classical feedback system, we could identify an “Edemagenic Gain” ( G e ), characterizing the capacity of the system to alter volume for given changes in driving pressures. G e is related to parameters of the system R L , K f and C . By considering two extreme cases, two types of edema can be identified. When open loop gain ( R L K f ) is large, G e = C. However, when the open loop gain is small, G e = R L K f C . Reformulation of these classical fluid balance relationships in terms of classical control theory thus provides a simple and elegant solution that is transparent to physiologists and clinicians, and provides new insight into a poorly understood condition.