The structural basis of kidney oxygenation

2017-03-05T23:00:13Z (GMT) by Ngo, Jennifer Principal
The kidneys receive ~25% of the cardiac output but weigh ~1% of total body weight. Yet the kidney is susceptible to hypoxia. One mechanism that may contribute to this susceptibility is the countercurrent shunting of oxygen, both in the cortex between arteries and veins and in the medulla between descending and ascending vasa recta. The susceptibility of the kidney, and in particular the renal medulla, to hypoxia may contribute to the pathogenesis of acute kidney injury. The physiology of renal oxygenation is further complicated by the arrangement of the renal circulation. That is, arterial blood destined for the medulla travels with blood destined for the cortex, to the level of the proximal interlobular arteries, where the afferent arterioles of juxtamedullary glomeruli originate. Thus, arterial-to-venous (AV) oxygen shunting in the renal cortex could reduce oxygen delivery to both the cortex and medulla. This proposition is consistent with experimental findings suggesting that oxygenation of the renal medulla is dependent on cortical perfusion and oxygenation. This PhD project was aimed towards developing a better understanding of the impact of renal vascular architecture and structure on kidney oxygenation. Both light microscopy and micro-computed tomography were used to characterize the radial geometry of individual artery-vein pairs in the renal cortex of the rat. We determined the separation distance between artery-vein pairs and the proportion of the arterial wall surrounded by the wall of a vein (wrapping). We observed that there are both wrapped and non-wrapped arteries in the renal cortical circulation. However, the proportion of wrapped arteries was found to change along the course of the cortical circulation. Larger arteries were more often wrapped than were smaller arteries. Consequently, the mean proportion of the arterial wall surrounded by its paired vein gradually decreased, while mean diffusion distance increased, along the course of the preglomerular circulation. Thus our data indicate that AV oxygen shunting should be favored in larger vessels, such as interlobar and arcuate vessels. However, because of the branching nature of the renal circulation, there are many more smaller vessels than larger vessels. When this was taken into account in an analysis of the preglomerular circulation as a network, AV oxygen shunting was found to be most significant between paired interlobular arteries and veins. We then showed that synchrotron-based micro-computed tomography is a valid approach for analysis of the geometry of the preglomerular vasculature. We also developed an automated method for performing such analyses. However, in its current form this method does not generate valid information regarding the geometry of artery-vein pairs. In conclusion, using light microscopy and synchrotron-based micro-computed tomography, we were able to demonstrate that the architecture of the renal cortical circulation is arranged in such a way that likely favors the diffusional shunting of oxygen (and perhaps other gases) in the interlobular vessels of the preglomerular circulation. The data presented in this thesis can be incorporated into computational models of oxygen transport in the kidney. Our approach could also be applied to models of renal disease and various species.