Systems analysis of the renal function

Abstract

A previous model of the renal function and compartmented whole body, which incorporated actions of antidiuretic hormone on urine flow and composition, is extended to include the influences of additional phenomena, many exogenous to the kidney. The phenomena incorporated were selected by orderly trial from among those mechanisms suggested in the literature and found by operation of the model to be important for adequately representing renal responses to various stresses. Specifically, these phenomena are: the intrinsic-osmotic effect of water; details of the body's antidiuretic hormone cycle; gastrointestinal exchanges; changes in glomerular filtration caused by alteration in blood volume and pressure; and resistance to flow across kidney tubular walls. Most of these phenomena involve non-steady-state, irreversible processes. The modeled renal function was found not to be sensitive to certain mechanisms sometimes associated with its operation. The most important is volume sensing, whereby extracellular volume changes are postulated to impose control on antidiuretic hormone production through stretch receptors in the circulatory system or through other volume sensors. Model investigations show that blood volume changes that alter blood pressure during stress can operate to affect kidney tubular-fluid flow in a manner which, when combined with other modeled kidney processes, yields correct urinary and other responses. No additional control on the antidiuretic hormone cycle through special volume receptors is required. The stresses to which the present model was exposed and responds correctly are: water loading through ingestion; hypertonic saline infusion; hypertonic urea solution ingestion; antidiuretic hormone dysfunction, as in diabetes insipidus; controlled rehydration after dehydration; and two combined stresses—hypertonic saline solution ingestion followed by water ingestion and the converse experiment. Most of these stresses involve transients in which the body becomes far removed from steady state. Different aspects of the total renal function, depending upon the specific stress, become more or less important in aiding the body to return to its original state.