Novel hemodynamic structures in the human glomerulus

Abstract

To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton and electron microscope imaging. Afferent and efferent arterioles (21.5±1.2µm and 15.9±1.2µm diameter), recognised from vascular origins, lead into previously undescribed wider regions (43.2±2.8 µm and 38.4±4.9 µm diameter) we have termed vascular chambers (VCs) embedded in the mesangium of the vascular pole. Afferent VC(AVC) volume was 1.6 fold greater than Efferent VC(EVC) volume. From the AVC long non-branching high capacity conduit vessels (n=7) (Con; 15.9±0.7µm diameter) led to the glomerular edge where branching was more frequent. Conduit vessels have fewer podocytes than filtration capillaries. VCs were confirmed in fixed and unfixed specimens with a layer of banded collagen identified in AVC walls by multiphoton and electron microscopy. Thirteen highly branched efferent first order vessels (E1;9.9±0.4µm diam.) converge on the EVC draining into the efferent arteriole (15.9±1.2µm diam.). Banded collagen was scarce around EVC. This previously undescribed branching topology does not conform to the branching of minimum energy expenditure (Murray's law), suggesting even distribution of pressure/flow to the filtration capillaries is more important than maintaining the minimum work required for blood flow. We propose that AVCs act as plenum manifolds possibly aided by vortical flow in distributing and balancing blood flow/pressure to conduit vessels supplying glomerular lobules. These major adaptations to glomerular capillary structure could regulate haemodynamic pressure and flow in human glomerular capillaries.

Analysis of the three dimensional structure of the kidney glomerulus capillary network

“…A number of studies have therefore been devoted to obtaining reconstructions (Shea, 1979;Shea and Raskova, 1984;Winkler et al, 1991;Remuzzi et al, 1992). Most recently, careful partial reconstructions of human glomeruli have been made (Neal et al, 2018). Advances in computer capabilities facilitate making reconstructions, and network theory is well suited for analyzing the connectivity (Wahl et al, 2004).…”

Mathematical models for kidney function focusing on clinical interest

“…• on the urine concentrating mechanism, see Stephenson [49] for a thorough, technically detailed history starting with Hargitay & Kuhn [21,22], and see Pannabecker and colleagues for more recent developments that take advantage of imaging studies and 3D reconstruction of medullary nephron-vascular anatomy [8,43,48]; • for reviews and models of tubular function and tubule-specific transporters, see…”

Why until just now? Undiscovered uniqueness of the human glomerulus!

“…Because the glomerular density is less in human kidneys than in experimental animals generally used (6), human afferent arterioles have a higher conductivity than those of rats and dogs, and they supply a disproportionately larger glomerular volume (7). It should not be surprising, although it has not been factually demonstrated, that the human glomerulus would employ an alternative mechanism to distribute flow throughout the glomerular capillary network.…”

“…It should not be surprising, although it has not been factually demonstrated, that the human glomerulus would employ an alternative mechanism to distribute flow throughout the glomerular capillary network. Neal et al (7) investigated this issue in human glomeruli by perfusion fixation at physiological hydrostatic pressures using an oncotically appropriate solution to effectively fill the glomerular capillaries to their functional volume. Although confirmed in fresh tissue, the employment of perfusion fixation with an oncotically balanced solution was necessary for this study because the elastic vascular structures might collapse in the absence of physiological perfusion (10).…”

“…Several novel hemodynamic structures in the human glomerulus were discovered, including a vascular chamber-like manifold arising from the afferent arteriole as it entered the renal corpuscle. Using electron microscopy, Neal et al (7) determined that the chamber walls are rich in collagen I and III, which, in addition to mesangial support, allow the chamber to be resistant to collapse. This chamber in turn gives rise to approximately seven conduit vessels, each with quite similar diameter.…”