Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 16 Kidney Function and Damage
FIGURE 16-2 Electron micrograph of the glomerular filtration barrier.
1: Footlike processes of the podocytes; arrow shows the slit diaphragm of
a filtration slit. 2: glomerular basement membrane. 3: fenestrated endothelium
of the glomerular capillaries. Reproduced with permission of the
publisher from Poirier et al. (1999) .
FIGURE 16-1 Schematic representation and international nomenclature
of the parts of the nephron. 1: Renal corpuscle including Bowman’s capsule
and the glomerulus (glomerular tuft). 2: Proximal convoluted tubule.
3: Proximal straight tubule. 4: Descending thin limb. 5: Ascending thin
limb. 6: Distal straight tubule (thick ascending limb). 7: Macula densa
located within the final portion of the thick ascending limb. 8: Distal convoluted
tubule. 9: Connecting tubule; 9*: Connecting tubule of the juxtamedullary
nephron that forms an arcade. 10: Cortical collecting duct.
11: Outer medullary collecting duct. 12: Inner medullary collecting duct.
Reproduced with permission of the publisher from Kriz and Bankir (1988) .
The general architecture of the nephrons is identical
in all species ( Fig. 16-1 ) ( Kriz and Bankir, 1988 ), but
their disposition within the kidney differs between species
( Bankir and de Rouffignac, 1985 ).
Blood is supplied to the kidneys by the renal arteries.
These divide into interlobar and arcuate arteries located at
the corticomedullary junction. Branches of the latter supply
blood to the afferent arterioles of the tuft of capillaries
in the glomerulus, from which it is collected by the efferent
arterioles. Depending on the location of the glomeruli, blood
is then supplied to a network perfusing the cortical tubules
or to the vasa recta vessels, which penetrate deep into the
medulla in “ hairpins ” parallel to the loops of Henle. See the
review in Pallone et al. (1998) . The total blood supply to
the kidneys (renal blood flow, RBF) is very high, about 20%
of the cardiac output, and most of it goes to the cortex. Only
a fraction of the plasma flow (renal plasma flow, RPF) is
filtered resulting in the glomerular filtration rate (GFR). This
is the filtration fraction (FF), which generally amounts to
20% to 30% of RPF: GFR RPF FF.
The RBF remains quite stable, because of autoregulation,
even with variations in systemic blood pressure.
The precise mechanism of autoregulation is unknown but
results from vasoconstriction/dilation of the afferent and
efferent glomerular arterioles, which maintains an almost
constant hydrostatic pressure within the glomerulus.
Autoregulation is efficient in healthy dogs between 70 to
180 mmHg and may be altered in disease, especially during
CRF ( Brown et al. , 1995 ).
B . Glomerulus and Filtration
Each glomerulus consists of a tuft of anastomosed capillaries
within the Bowman’s capsule, which collects the primitive
urine formed by plasma filtration and opens into the tubule
conducting urine to the renal pelvis. The filter between
the plasma and urine consists of three layers ( Fig. 16-2 )
(see reviews in Deen et al. [2001] , and Rennke and
Venkatachalam [1977] ):
● The fenestrated endothelium of the capillaries, allowing
direct contact between the plasma and the basal membrane
via large pores and fenestrae ( 50 to 100 nm); the
luminal face is coated with sulfated glycosaminoglycans
and glycoproteins.
● The basement membrane made of a gel containing
approximately 90% water and negatively charged sulfated
glycosaminoglycans.
● The filtration slits ( 25 nm) between the footlike
processes of the podocytes (i.e., the visceral epithelial cells
covering the external surface of the capillaries) ( Gubler,
2003 ). The slits are made porous by the slit diaphragm in
which proteins, consisting mainly of the extracellular part
of the nephrin molecule anchored in the membrane of the