Chaos and synchronization in nephron dynamics

Niels-Henrik Holstein-Rathlou

Department of Medical Physiology, The Panum Institute,
University of Copenhagen, Denmark

Abstract: The tubuloglomerular feedback (TGF) is an intrarenal mechanism that stabilizes renal blood flow, GFR, and the tubular flow rate. The anatomical basis for TGF is the return of the tubule (the ascending limb of the loop of Henle (ALH)) to its own glomerulus. The macula densa, which is the sensor mechanism for the TGF, is a plaque of specialized epithelial cells in the wall of the ALH. It is localized at the site where the tubule establishes contact with the glomerulus. Because of a flow dependency of NaCl reabsorption in the ALH, a change in tubular flow rate, elicited for example by a change in the arterial pressure, will lead to a change in the NaCl concentration of the tubular fluid. This is sensed by the macula densa, and through unknown mechanisms results in a change in the hemodynamic resistance of the afferent arteriole. The dynamic properties of the TGF system has been characterized in experimental studies in both normo-and hypertensive rats. In normotensive rats, TGF displays autonomous self-sustained regular oscillations, whereas in spontaneously hypertensive rats (SHR) highly irregular, "chaotic" fluctuations are present. Experimental studies has shown that the TGF systems of neighboring nephrons interact so that the oscillations and the irregular fluctuations of the respective nephrons becomes synchronized. We have developed a dynamic model of that includes the major coupling mechanisms between the neighboring nephrons that shares a common interlobular artery. The phase of the synchronized oscillations and irregular fluctuations depend on which coupling mechanism dominates. The hemodynamic coupling leads to out-of-phase synchronization, whereas vascular coupling leads to in-phase synchronization. The two type of synchronization patterns can be found in experimental data from rat kidneys. However, in-phase synchronization is by far the most common, suggesting that under physiological conditions, vascular coupling is the dominating form of coupling between neighboring nephrons.