Architecture Guided Fluid Propulsion in a Simulated Nephron
Computational Fluid Dynamics has long been used to solve problems of fluid velocity, shear, and strain in biologic systems. The objective of this study is to underscore the unique architectural features of the renal papilla including the Venturi effect as it pertains to the thick and thin segments of the loop of Henle, and the effect that the length of the thin loop of Henle has on fluid flow.
Using computer aided design software (ANSYS SpaceClaim 18.2), three nephrons were designed based on published dimensions (Fig I). The effect of thin limb length was assessed by comparing a descending limb with a length ratio of 1:4, from thick to thin (Fig. Ia) to a nephron with a limb-length ratio 2:1 (Fig. Ib). The diameter ratio from thick to thin was 8:3. The effect of narrowing was assessed in a nephron with no thin limb (Fig. Ic). ANSYS Fluent 18.2 was used to simulate flow and velocity profiles.
The presence of a thick to thin limb transition in a nephron results in an increase in particle velocity by over ten-fold within the thin limb (Fig. Ia, Ib, Id lines a & b), compared to a nephron without a thin limb (Fig. Ic, Id line c). Regardless of the diameter, particle velocity at the center of the nephron was more than at the wall of the nephron (Fig IIc, IId). The position of the transition from descending thick to thin limbs did not significantly change the pattern of fluid flow, except that it delayed the increase in fluid velocity (Fig Id a vs. b).
The form and function of the nephron are intimately linked. A longer thin limb, relative to the thick limbs, decreases the amount of time a particle will spend in transit. Consistent with laminar flow, particles at the tubule wall are significantly slower compared to particles at the center of a tubule cross-section. Variations in nephron diameter, particularly at the junction of thin and thick limbs of the loop of Henle, may alter flow dynamics in the human papilla. The Venturi effect caused as the thick descending limb joins the thin limb is a critical architectural component that enhances fluid transit within nephrons regardless of the length of the thin limb of the loop of Henle. These findings are likely relevant from a microfluidics perspective to pathologic processes that result in particulate deposition, resulting in mineralization within the proximal papilla, and provide insight into the study of Randall&[prime]s plaque formation.
Funding: NIH/NIDCR R01DE022032 (SPH), NIH/NCRR S10RR026645 (SPH), Department of Preventive and Restorative Dental Sciences, School of Dentistry; NIH/NIDDK R21 DK109912 (SPH, MLS), NIDDK/P20DK100863 (MLS), Department of Urology, School of Medicine, UCSF.