CHAPTER 38
Renal Function & Micturition 645maintaining the glomerular filtration rate. This is believed to
be the explanation of the renal failure that sometimes develops
in patients with poor renal perfusion who are treated with
drugs that inhibit angiotensin-converting enzyme.
REGIONAL BLOOD FLOW &
OXYGEN CONSUMPTION
The main function of the renal cortex is filtration of large vol-
umes of blood through the glomeruli, so it is not surprising that
the renal cortical blood flow is relatively great and little oxygen
is extracted from the blood. Cortical blood flow is about 5 mL/g
of kidney tissue/min (compared with 0.5 mL/g/min in the
brain), and the arteriovenous oxygen difference for the whole
kidney is only 14 mL/L of blood, compared with 62 mL/L for the
brain and 114 mL/L for the heart (see Table 34–1). The P
O 2
of
the cortex is about 50 mm Hg. On the other hand, maintenance
of the osmotic gradient in the medulla requires a relatively low
blood flow. It is not surprising, therefore, that the blood flow is
about 2.5 mL/g/min in the outer medulla and 0.6 mL/g/min in
the inner medulla. However, metabolic work is being done, par-
ticularly to reabsorb Na
- in the thick ascending limb of Henle,
so relatively large amounts of O
2
are extracted from the blood in
the medulla. The P
O 2
of the medulla is about 15 mm Hg. This
makes the medulla vulnerable to hypoxia if flow is reduced fur-
ther. NO, prostaglandins, and many cardiovascular peptides in
this region function in a paracrine fashion to maintain the bal-
ance between low blood flow and metabolic needs.
GLOMERULAR FILTRATION
MEASURING GFR
The
glomerular filtration rate (GFR)
can be measured in in-
tact experimental animals and humans by measuring the ex-
cretion and plasma level of a substance that is freely filtered
through the glomeruli and neither secreted nor reabsorbed by
the tubules. The amount of such a substance in the urine per
unit of time must have been provided by filtering exactly the
number of milliliters of plasma that contained this amount.
Therefore, if the substance is designated by the letter X, the
GFR is equal to the concentration of X in urine (U
X
) times the
urine flow
per unit of time (V- ) divided by the
arterial plasma
level
of X (P
X
), or U
X
V
/P
X
. This value is called the clearance
of X (C
X
). P
X
is, of course, the same in all parts of the arterial
circulation, and if X is not metabolized to any extent in the tis-
sues, the level of X in peripheral venous plasma can be substi-
tuted for the arterial plasma level.
SUBSTANCES USED TO MEASURE GFR
In addition to the requirement that it be freely filtered and nei-
ther reabsorbed nor secreted in the tubules, a substance suit-
able for measuring the GFR should be nontoxic and not
metabolized by the body. Inulin, a polymer of fructose with a
molecular weight of 5200 that is found in Jerusalem artichokes
(Helianthus tuberosus), meets these criteria in humans and
most animals and is extensively used to measure GFR. In prac-
tice, a loading dose of inulin is administered intravenously,
followed by a sustaining infusion to keep the arterial plasma
level constant. After the inulin has equilibrated with body flu-
ids, an accurately timed urine specimen is collected and a plas-
ma sample obtained halfway through the collection. Plasma
and urinary inulin concentrations are determined and the
clearance calculated:
U
IN
= 35 mg/mL
V- = 0.9 mL/min
P
IN
= 0.25 mg/mL
C
IN(^) =
U
IN
V
- =
35
×
0.9
P
IN
0.25
C
IN
= 126 mL/min
In dogs, cats, rabbits, and a number of other mammalian spe-
cies, clearance of creatinine (CCr) can also be used to determine
the precise GFR, but in primates, including humans, some crea-
tinine is secreted by the tubules and some may be reabsorbed. In
addition, plasma creatinine determinations are inaccurate at low
creatinine levels because the method for determining creatinine
measures small amounts of other plasma constituents. In spite of
this, the clearance of endogenous creatinine is frequently mea-
sured in patients. The values agree quite well with the GFR val-
ues measured with inulin because, although the value for UCrVis high as a result of tubular secretion, the value for PCr is also
high as a result of nonspecific chromogens, and the errors thus
tend to cancel. Endogenous creatinine clearance is easy to meas-
ure and is a worthwhile index of renal function, but when pre-
cise measurements of GFR are needed it seems unwise to rely on
a method that owes what accuracy it has to compensating errors.FIGURE 38–4 Autoregulation in the kidneys.
8006004002000
70 140 210
Arterial pressure (mm Hg)Glomerular filtrationRenal blood flowmL/min