Glomerular Anatomy and Physiology

Glomerular Anatomy and Physiology

Glomerular Anatomy and Physiology Renal Physiology 6 10/10/2011 Charles J. Foulks, M.D. . (Endothelial cell surface layer) Fenestrations

Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society . Fenestrated endothelium Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society Podocyte foot processes

. Fenestrations Cupromeronic Blue (charged) Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society Lanthanum In steady state production/removal

In steady state production/removal Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society . Produced by podocytes and influence endothelial cells Cultured human podocytes

Foot process buds: white arrows Actin filaments . Normal endothelial cell culture Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society Endothelial cell-specific antigen stain

Endothelial cell specific lectin stain Human podocyte culture . Perlecan antibody stain Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society

Perlecan (green) and actin are labeled red using phalloidin Properties of the Glomerular Barrier and Mechanisms of Proteinuria TABLE 1.Reported sieving coefficients for albumin in studies with "controlled" tubular modification Species Albumin Sieving Coefficient

Technique Reference Nos. Rat 0.00033 In vivo + lysine 310 Rat

Rat Rat 0.00066 0.00060 0.00080 Tissue uptake Tissue uptake Micropuncture 179 18

317 Humans, Fanconi 0.00008 Urine proteomics 208 Rat 0.0015

cIPK 123, 213, 214, 301, 302 Mouse Rat Rat 0.0023 0.0029 0.0080

134 19 228 Rat Rat 0.0087 0.0450 cIPK Tissue uptake IPK no tubular cell

inhibitor Fixed kidney IPK after tubular cell inhibitor Rat 0.0800 IPK after tubular cell inhibitor 228

53 225 Properties of the Glomerular Barrier and Mechanisms of Proteinuria TABLE 2.Sieving coefficients for various proteins in selected studies Type of Protein Neutral or slightly cationic proteins nAlbumin nAlbumin Kappa-dimer

nHRP nHRP nMyoglobin cMyoglobin IgG LDH-5 Anionic proteins Albumin Albumin Albumin Albumin Ovalbumin Orosomucoid

aHRP aHRP aHRP aHRP aMyoglobin LDH-1 SE Radius Sieving Coefficient Charge

References 35.5 35.5 28.4 32.0 32.0 19.6 17.5 54.0 46.0 0.0330

0.0260 0.1490 0.0700 0.1100 0.7700 0.7400 0.0023 0.0056 0 0 0 0

0 0 2 0 2 228 19 179 348 302 179 348

18 176 35.5 35.5 35.5 35.5 27.4 40.5 32.0 32.0 32.0 32.0

17.5 46.0 0.0021 0.0015 0.0006 0.0007 0.0770 0.0036 0.0690 0.0450 0.0170 0.0100

0.5100 0.0011 23 23 23 23 13 24 6 11 11 14

6 19 176 214 19 179 301 301 301 302 224 348

348 176 alb Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society =CB/CP .

alb =CB/CP Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society . - alb

=CB/CP Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society --- + .

alb =CB/CP Pore size increase from 5nm to 6nm. Decreased FR by 50% (Pore radius) Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society

. alb =CB/CP Haraldsson B et al. Physiol Rev 2008;88:451-487 2008 by American Physiological Society 1= subepithelial, MN 2=subepithelial humps,

post-infectiours GN 3=Subendothelial 4=Mesangial 5=GMB-Ab complex e.g., Goodpastures 6=effacement, foot process NORMAL GBM. LEFT - a single glomerulus. There are one million of these in each kidney. RIGHT - a close up of the GBM (G) around part of one tiny blood vessel in a glomerulus (red circle in left hand diagram)

Diagram of a blood vessel with a normal GBM in a glomerulus (compare with the diagram above) A blood vessel with a thin GBM Thin Glomerular Membrane Disease Lipid Accumulation Patients 1&2,

In tubular Epithelial cells. Overwhelms beta-oxidation High Alb filtration Luminal or apical side Entry of free non-esterified fatty acids into proximal tubule cells and the role of albumin as Trojan horse Competes with glutamine

Normal Glomerulus Minimal Change Disease Normal glomerulus FSGS Membranous Nephropathy: note EDD in subepithelial area. Slides courtesy of UNC Kidney Center

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