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Fluid Dynamics in the human glomerulus: the formation of ultrafiltrate and possible counter-current enhancement of solute diffusion


Mechanical Engineering

, Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

Contact: Dr Chris Neal Bristol Medical School, or Dr Alberto Gambaruto Department of Mechanical Engineering, University of Bristol

The renal glomeruli form primary urine through filtration as the first stage in urine production and are susceptible to changes in disease. The current concept of glomerular physiology involves afferent arterioles branching from a vascular pole into smaller and smaller vessels until filtration capillaries are reached, these are in a random orientation relative to the network of urinary spaces ending at the urinary pole. From these filtration capillaries convergent branching ends at the vascular pole and the efferent arteriole. In 2018 (Neal et al), we showed human afferent arterioles (21µm, AA) flowed into vascular chambers more than twice their diameter (45-50µm) rather than branching. Wide long conduit vessels (16µm diameter) emerge from these chambers (see figure) on average 7 conduits per glomerulus (3 shown). These conduits do not branch much until they reach a point distant from the vascular pole and close to the glomerular periphery.

Conduit vessels are conserved in diameter with the majority of the surface showing filtration ultrastructure but only half the number of podocyte cell bodies occlude the surface (compared to filtration capillaries) displaying a lot of conduit filtration surface. Since the hydrostatic pressure difference across the conduit filtration barrier should be at its highest and the colloid osmotic pressure at its lowest filtration should be optimal and might even force a wider Bowman’s space adjacent to these peripheral conduits (Figure). This high volume, dilute conduit ultrafiltrate (U1) (dashed lines following the conduit vessels) will be con-current with blood flow and mostly peripheral (Figure: dashed line and solid lines running together).

At the conduit branch point on the glomerular periphery the filtration capillaries proceed from the glomerular periphery back to the vascular pole and efferent vascular chamber to the efferent arteriole (EA). Filtration capillary blood will flow from the periphery TOWARDS the vascular pole, the filtrate in the adjacent urinary spaces must travel AWAY from the vascular pole in the opposite direction to reach the urinary pole. With blood moving one way and filtrate the other there should be a counter-current concentrating mechanism. This second concentrated, counter-current exchange, filtration capillary ultrafiltrate (U2) will be centrally derived in the glomerulus. (Figure: dashed line and solid lines in opposite directions).

We will use mathematical modelling of blood and urinary flows through the glomerulus to reveal the extent of conduit filtration and establish whether counter-current enhanced filtration of solutes occurs in the filtration capillaries. Both U1 and U2 will be modelled with the usual factors affecting filtration pressure and glomerular blood flow in the production of primary urine. We will further investigate how this might compare with other animals and how hypertension or the changes associated with diabetes affect U1 and U2 production? Prospective candidates should have a maths/engineering background or be a numerate biological scientist with an interest in mathematical modelling of biological processes.

References

Neal et al AJP Renal 2018 315(5):F1370-F1384.

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