Transcript 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
SE Radius
Sieving Coefficient
Charge
References
nAlbumin
35.5
0.0330
0
228
nAlbumin
35.5
0.0260
0
19
Kappa-dimer
28.4
0.1490
0
179
nHRP
nHRP
nMyoglobin
cMyoglobin
32.0
32.0
19.6
17.5
0.0700
0.1100
0.7700
0.7400
0
0
0
2
348
302
179
348
IgG
LDH-5
Anionic proteins
54.0
46.0
0.0023
0.0056
0
2
18
176
Albumin
Albumin
Albumin
Albumin
Ovalbumin
35.5
35.5
35.5
35.5
27.4
0.0021
0.0015
0.0006
0.0007
0.0770
–23
–23
–23
–23
–13
176
214
19
179
301
Orosomucoid
40.5
0.0036
–24
301
aHRP
aHRP
aHRP
aHRP
aMyoglobin
32.0
32.0
32.0
32.0
17.5
0.0690
0.0450
0.0170
0.0100
0.5100
–6
–11
–11
–14
–6
301
302
224
348
348
LDH-1
46.0
0.0011
–19
176
Neutral or slightly
cationic proteins
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
Haraldsson B et al. Physiol Rev 2008;88:451-487
©2008 by American Physiological Society
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+
.
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., Goodpasture’s
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