Renal Excretion of Lactic Acid in Exercise

Renal Excretion of Lactic Acid in Exercise
A. T. MILLER, JR. AND J. 0. MILLER, JR., From the Laboratory
of
Applied Physiology
and the Department
of Physiology,
School of Me&tine, University
of North Carolina,
Chapel Hill, North Carolina
T
METHODS
The experimental subjects were 2 distance runners on the University track team. The
experiments were performed during the season of competition, so that the subjects were in
excellent training and able to push themselves to high blood lactate levels. The exercise
consisted in running on a motor-driven treadmill for 2 to 15 minutes, at zero grade and at
speeds of IO to 16 miles/hr.
A total of 72 experiments was performed, in which the maximal
Received for publication
614
September
IO,
x948.
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HE EXCRETION OF LACTIC ACID in the urine following muscular exercise
was reported by Spiro (I) in 1877-78.
With the demonstration
by Fletcher
and Hopkins (2) that lactic acid accumulates in contracting muscles, attention
was directed to its role in the contraction process. The changes in blood
lactate concentration
accompanying
exercise have been extensively investigated, but quantitative
studies on the renal excretion of lactate have been few.
Liljestrand
and Wilson (3), Jervell (4) and Johnson and Edwards (5) reported
that the amount of lactate recovered in the urine after exercise accounts for
not more than 2 per cent of the amount which disappears from the blood, but
their data shed little light on the mechanism of the renal excretion of lactate.
Jervell’s suggestion (4) that lactate is actively secreted by the renal tubules is
not consistent with the small amount of lactate which he recovered in the urine.
Hewlett, Barnett and Lewis (6) reported that urine lactate concentration rises
only when blood lactate concentration
exceeds 30 to 40 mg. per cent, which
suggests that lactate is a threshold substance, similar to glucose. Craig (7)
determined the renal clearance of lactate in dogs given large amounts of sodium
lactate by mouth or intravenously.
He reported nearly complete tubular reabsorption of lactate at plasma levels below IOO mg. per cent.
In spite of the paucity of information
concerning the mechanism of the
renal excretion of lactate, urine lactate is frequently used as an index of lactic
the present study was undertaken
acid production in exercise. Accordingly,
in an attempt to provide data on the following points: I) the renal threshold
for lactate, 2) the relation between maximal blood lactate concentrations and
total urine lactate over a wide range of blood lactate concentrations and 3) the
accuracy with which urine lactate reflects total lactate production in exercise.
February
1949
LACTATE
EXCRETION
IN
EXERCISE
615
blood lactate concentration ranged from 25 to 116 mg. per cent. Resting lactate excretion
was measured on urine samples collected before exercise. The bladder was emptied just
before the exercise began and urine samples were collected at intervals of IO, 20, 40 and 60
minutes from the beginning of exercise. The water intake of the subjects was adjusted to
insure adequate urine volumes; in a number of experiments the exercise was performed
during water diuresis in order to obtain a wide range of urine flow rates. Lactic acid was
determined by the method of Barker and Summerson (8) on the urine samples and on fingerprick blood samples timed to coincide with the urine samples.
RESULTS
(Subject A) B = .09 L +
54.2
(Subject B) B =
.IO
L +
47.5
where B = post-exercise blood lactate in mg. per cent and L = milligrams of
lactate in a one-hour post-exercise urine sample.
The lactate clearance was calculated from the blood and urine data in a
number of experiments.
The resting clearance is I to 2 ml/min.
In exercise
the maximal clearance rate rises as the blood lactate concentration rises. In
moderate exercise with a blood lactate concentration of approximately
50 mg.
per cent, the clearance is 6 to 8 ml/min .; in exhausting exercise with blood
lactate concentrations of IOO to I 15 mg. per cent, the lactate clearance is 8 to
I 2 ml/min.
during the exercise period and it may rise to 15 to 20 ml/min. in the
early part of the recovery period.
These data must be interpreted with caution
in view of the known decrease in renal blood flow which accompanies exercise.
Thus, White and Rolf (9) reported a decrease in renal blood flow to 20 or 25
per cent of the control level in short periods of exhausting exercise. If Trueta’s
concept (IO) of the diversion of some of the renal blood flow into noneffective
channels in exercise is accepted, the effective renal blood flow would be even
less. Since the filtration fraction was not greatly altered in White and Rolf’s
experiments, it may be assumed that the excretion of lactate in our experiments
is reduced in proportion to the decrease in renal blood flow. Thus a clearance
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The relation between post-exercise blood lactate concentration and total
urine lactate in a one-hour post-exercise period is shown in figure I. In each
case the line drawn through the plotted points was derived from the class
interval averages and the point of intersection with the abscissa is the theoretical lactate threshold.
It is apparent that urine lactate is proportional
to
blood lactate concentration
when the latter exceeds the threshold value of
approximately
60 mg. per cent. There is no sharp break in renal excretion rate
at the threshold blood lactate concentration.
A small amount of lactate is
present in resting urine samples and the excretion rate increases hyperbolically
with increasing blood lactate concentration, becoming linear at a blood concentration of approximately
70 mg. per cent.
The regression equations for prediction
of blood lactate from urine
lactate are :
A. T. MILLER,
616
JR. AND J. 0. MILLER,
JR.
vozwnc
I
rate of IO ml/min.
during severe exercise would be equivalent to a rate of
approximately
50 ml/min.
with the same blood lactate concentration
and
normal resting renal blood flow rate. This agrees well with a calculated renal
000
;3
3
g 700
SUB3ECT
A
om NON-
DIURESIS
0
0
a
t
600
93
.
E
so0
X. DIURESIS
20
30
40
BLOOD
-
600
z
g
SU63ECG
SO
60
LAGTATE
TO
SO
(MO.
PER
100
110
120
100
110
I20
CENT)
0
omNON-DIURESIS
too
x~DIURE$lS
= 600
Q8
d
r
800
5 400
t0
4 300
WI
i
200
3
=
100
IO
20
30
40
8LOOD
50
60
LACTATE
10
00
(MO.PER
90
CENT)
Fig. I. RELATION
BETWEEN
POST-EXERCISE
BLOOD LACTATE
CONCENTRATION
and total lactate
recovered in the urine in a one-hour post-exercise period. In non-diuresis experiments subjects were
normally hydrated; in diuresis experiments subjects drank one liter of water 60 to go minutes before
exercise. The line drawn through experimental points is the best fitting line for the class interval
averages.
threshold of 60 mg. per cent in which approximately
would be reabsorbed when the blood concentration
It is apparent from the data shown in figure
I
one-half the filtered lactate
is IOO to I 15 mg. per cent.
that the renal excretion of
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IO
0
11/
Fdwzwy 1949
LACTATE
EXCRETION
IN
EXERCISE
617
lactate is also influenced
by the urine flow rate. With the large urine volumes
obtained when exercise was performed during water diuresis, the excretion of
lactate was also increased. This is seen especially clearly in the data of Szcbject B.
Finally, it should be pointed out that the calculation of lactate clearance
in these experiments is approximate, since the blood lactate concentration was
changing during the observation period.
However, in the more exhausting
exercise experiments, the blood lactate concentration changed very little during
the first IO minutes of recovery, so that clearances based on this period are
reasonably accurate.
DISCUSSION
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The data presented above support the concept that lactate is filtered in
the glomeruli and variably reabsorbed in the tubules.
The apparent renal
threshold is approximately
60 mg. per cent, but small amounts of lactate appear
in the urine at blood concentrations below this threshold.
Since the renal
excretion of glucose has the same general features (I I, I 2) it is a plausible
assumption that glucose and lactate are handled by the kidney in the same
general manner.
This would place the site of reabsorption of lactate in the
proximal tubule.
It may also be presumed that the threshold for lactate, like
that for glucose, is variable both in different individuals and at different times
in the same individual.
This would account for some of the scatter of individual points about the line relating lactate excretion and blood lactate concentration.
The fact that renal excretion accounts for a very small proportion of the
lactate which disappears from the blood in a post-exercise period is now understandable. I) The amount of lactate filtered in the glomeruli is reduced by
the drastic curtailment
of renal blood flow which accompanies severe exercise.
2) With a threshold value of approximately
60 mg. per cent, fully one-half the
lactate filtered in the glomeruli is reabsorbed in the tubules even in exhausting
exercise. In moderate exercise the reabsorption
fraction increases. The
quantitative
implication
of these facts is made clear by a sample calculation.
If one assumes a blood lactate concentration of IOO mg. per cent, a normal renal
blood flow and no tubular reabsorption of lactate, the lactate clearance would
be about 120 ml/min.
If, however, the renal blood flow is reduced to 25 per
cent of normal and the lactate threshold is 60 mg. per cent, the lactate clearance
becomes 0.4 x 0.25 x 120 = 12 ml/min.,
the approximate value obtained in
severe exercise in our experiments.
The accuracy with which urine lactate reflects total lactate production in
exercise is limited by the variability
in renal threshold and in the changes in
renal blood flow in different individuals and even in the same individual
at
different times. At best it is a rough index of the severity of exertion.
618
A. T.
MILLER,
JR.
AND
J. 0. MILLER,
JR.
Volme
I
SUMMARY
REFERENCES
P. 2. physiol.Chem.I : III, 1877-78.
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8. BARKER,
S. B. AND W. H. SUMMERSON.
J. B&L Chem 138: 5351941.
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R. J. FRANKLIN
AND M. M. L. PRICHARD.
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SHANNON, J. A. AND S. FISHER. Am. J. Physiol. 122: 765, 1938.
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I.
2.
SPIRO,
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Blood lactate concentration and total urine lactate during exercise and
recovery were determined in 72 experiments on 2 subjects. The experiments
covered a wide range of blood lactate concentrations and urine flow rates. The
data support the concept that lactate is filtered in the glomeruli and variably
reabsorbed in the tubules.
The apparent renal threshold is approximately
60
mg. per cent, but small amounts of lactate appear in the urine at blood concentrations below this threshold.
The lactate clearance is I to 2 ml/min. at rest
and rises to 15 to 20 ml/min. in exhausting exercise. The clearance is increased
during water diuresis.
Urine lactate is only an approximate index of total lactate production in
exercise, due probably to variability
in the renal threshold and in the renal
blood flow changes in exercise in different subjects and in the same subject at
different times.