Abstract
To investigate human glomerular structure under conditions of physiological perfusion, we have analyzed 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 ± 1.2 µm and 15.9 ± 1.2 µm diameter), recognized 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 nonbranching high-capacity conduit vessels (n = 7) (Con; 15.9 ± 0.7 µm 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 ± 0.4 µm diameter) converge on the EVC, draining into the efferent arteriole (15.9 ± 1.2 µm diameter). Banded collagen was scarce around EVCs. This previously undescribed branching topology does not conform to the branching of minimum energy expenditure (Murray’s law), suggesting that 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 hemodynamic pressure and flow in human glomerular capillaries.
Highlights
The control of glomerular blood flow is crucial for maintaining efficient ultrafiltration across the glomerular filtration barrier (GFB)
We show for the first time in human glomeruli that clearly defined afferent arterioles lead into afferent vascular chambers of ellipsoid shape and structure embedded in the mesangium of the glomerular vascular pole and ensheathed in collagen fibrils
Branching frequency increases at the end of the conduits, leading to filtration capillary networks that lead back to smaller efferent vascular chambers in the mesangium of the vascular pole and the efferent arteriole
Summary
The control of glomerular blood flow is crucial for maintaining efficient ultrafiltration across the glomerular filtration barrier (GFB). A few studies have attempted to reconstruct the human glomerular vascular network; a wax model of a human neonate glomerulus was reconstructed by Johnston in 1899 [21] and in 1956 plastic glomerular vessels were reconstructed from waxmolded outlines [6]. These and later casting techniques render impressions of the glomerular surface capillaries with deeper vessels remaining largely hidden. The human reconstructions were performed on 5-m sections and/or on immersion-fixed sources or only on small glomerular regions, and the few studies of the vascular pole of the human glomerulus have used biopsy or cadaverrecovered material [33, 56]. Only one reconstructive study has been published using perfusion-fixation of a human transplant kidney but at elevated hydrostatic pressure (140 mmHg) where the authors chose a stereological approach for vessel analysis rather than reconstruction [4]
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