Integrating Microvascular, Interstitial, and Lymphatic Function with a Balance Point Characterization of Interstitial Fluid Volume and Protein Regulation

Objective To develop simple algebraic formulas and an intuitive graphical approach to characterize interstitial fluid volume and protein regulation, and to derive insights that are not available from conventional numerical approaches that are overly complex, conceptually opaque, and lack generality. Methods Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for interstitial fluid pressure and protein concentration as functions of parameters characterizing microvascular, interstitial and lymphatic function. Model results were validated by comparing to reported experimental values. Results Equilibrium values of interstitial fluid pressure and protein concentration arise as balance points from the graphical intersection of transmicrovascular flux and lymph flow (analogous to Guyton's classical cardiac output‐venous return curves). Algebraic solutions reveal that interstitial fluid pressure and protein concentration result from a ratio of the microvascular filtration coefficient and the effective lymphatic resistance, and are independent of interstitial compliance. Model results are consistent with reported measurements. Conclusion The present work presents a simple, transparent, and general balance point approach to predict lymph flow, interstitial fluid pressure and protein concentration that yields new insights concerning the complex interaction of microvascular, interstitial and lymphatic function. Supported by NIH‐K25HL070608 (CMQ), AHA‐0565116Y (CMQ), AHA‐0365127Y (RHS), CDC‐623086 (GAL).