Sensitivity functions in the estimation of parameters of cellular exchange.

The estimation of unidirectional rates of transport into the cells of intact organs is complex. The transport process cannot be isolated so that its kinetics can be assessed only as a part of a larger system that includes the flow (and its heterogeneity), transport across capillary membranes, diffusion and distribution throughout the interstitial and cellular spaces, and perhaps intracellular consumption. The analysis therefore depends on defining a mathematical analog of the system, acquiring as much data on the system as is possible within a short time while the system is stable, and then analyzing the data by fitting the mathematical model to all of the data at once. The formulation of the model that best fits the data is considered then to provide estimates of the kinetic parameters governing each of the processes involved. In the presence of some variability in the data, and some imperfections or inadequacies in the model compared to reality, one has to question the reliability and accuracy of the parameter estimates. The answer depends on a number of features of experimentation, data collection, and model design as well as model fitting. Sensitivity analysis plays a role in experiment design as well as in analysis, but its contribution depends on accurate data collection and good model design, to neither of which can sensitivity analysis contribute.