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Glomerular Anatomy and Physiology Renal Physiology 6 10/10/2011 Charles J. Foulks, M.D.

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Presentation on theme: "Glomerular Anatomy and Physiology Renal Physiology 6 10/10/2011 Charles J. Foulks, M.D."— Presentation transcript:

1 Glomerular Anatomy and Physiology Renal Physiology 6 10/10/2011 Charles J. Foulks, M.D.

2 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society (Endothelial cell surface layer) Fenestrations

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

4 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society Fenestrations Cupromeronic Blue (charged)Lanthanum

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

6 Foot process buds: white arrows Actin filamentsCultured human podocytes

7 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society Normal endothelial cell culture Endothelial cell-specific antigen stain Endothelial cell specific lectin stain

8 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society Human podocyte culture Perlecan antibody stain Perlecan (green) and actin are labeled red using phalloidin

9 Species Albumin Sieving CoefficientTechniqueReference Nos. Rat0.00033In vivo + lysine310 Rat0.00066Tissue uptake179 Rat0.00060Tissue uptake18 Rat0.00080Micropuncture317 Humans, Fanconi0.00008Urine proteomics208 Rat0.0015cIPK123, 213, 214, 301, 302 Mouse0.0023cIPK134 Rat0.0029Tissue uptake19 Rat0.0080IPK no tubular cell inhibitor 228 Rat0.0087Fixed kidney53 Rat0.0450IPK after tubular cell inhibitor 225 Rat0.0800IPK after tubular cell inhibitor 228 Properties of the Glomerular Barrier and Mechanisms of Proteinuria TABLE 1.Reported sieving coefficients for albumin in studies with "controlled" tubular modification

10 Type of ProteinSE RadiusSieving CoefficientChargeReferences Neutral or slightly cationic proteins nAlbumin35.50.03300228 nAlbumin35.50.0260019 Kappa-dimer28.40.14900179 nHRP32.00.07000348 nHRP32.00.11000302 nMyoglobin19.60.77000179 cMyoglobin17.50.74002348 IgG54.00.0023018 LDH-546.00.00562176 Anionic proteins Albumin35.50.0021–23176 Albumin35.50.0015–23214 Albumin35.50.0006–2319 Albumin35.50.0007–23179 Ovalbumin27.40.0770–13301 Orosomucoid40.50.0036–24301 aHRP32.00.0690–6301 aHRP32.00.0450–11302 aHRP32.00.0170–11224 aHRP32.00.0100–14348 aMyoglobin17.50.5100–6348 LDH-146.00.0011–19176 Properties of the Glomerular Barrier and Mechanisms of Proteinuria TABLE 2.Sieving coefficients for various proteins in selected studies

11 Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society alb =C B /C P

12 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society alb =C B /C P

13 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society + - --- alb =C B /C P

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

15 . Haraldsson B et al. Physiol Rev 2008;88:451-487 ©2008 by American Physiological Society alb =C B /C P

16 1= subepithelial, MN 2=subepithelial humps, post-infectiours GN 3=Subendothelial 4=Mesangial 5=GMB-Ab complex e.g., Goodpasture’s 6=effacement, foot process

17 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)

18 Diagram of a blood vessel with a normal GBM in a glomerulus (compare with the diagram above)above A blood vessel with a thin GBM Thin Glomerular Membrane Disease

19 Lipid Accumulation Patients 1&2, In tubular Epithelial cells.

20 Entry of free non-esterified fatty acids into proximal tubule cells and the role of albumin as ‘Trojan horse’ Luminal or apical side High Alb filtration Overwhelms beta-oxidation

21 Competes with glutamine

22 Normal Glomerulus Minimal Change Disease

23 Normal glomerulus FSGS

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26 Membranous Nephropathy: note EDD in subepithelial area.

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34 Slides courtesy of UNC Kidney Center


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