8  The macromolecular components of ISF may greatly influence the resistance to bulk flow as emphasized for peripheral extracellular fluid by Guyton and associates [609]. Quantitatively macromolecules in peripheral extracellular fluid can increase resistance to flow by orders of magnitude [138, 610, 611] while having much less effect on diffusion of small molecules [76, 81, 612]. A well-known illustration of a closely related effect is the reduced flow with maintained diffusion when agar is added to solutions.