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. Downloaded from http://jap.physiology.org/ by 10.220.33.6 on July 31, 2017 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 Downloaded from http://jap.physiology.org/ by 10.220.33.6 on July 31, 2017 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 Downloaded from http://jap.physiology.org/ by 10.220.33.6 on July 31, 2017 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 Downloaded from http://jap.physiology.org/ by 10.220.33.6 on July 31, 2017 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. FLETCHER, W. M. AND F. G. HOPKINS. J. Physiol. 35: 247,Igo6-07. 3. LILJESTRAND, S. H. AND D. W. WILSON. J. Biol. Chem.65: 773, 1925. 4. JERVELL, 0. Ada Med. Stand. 24: (Suppl.), 1928. 5. JOHNSON, R. E. AND H. T. EDWARDS. J. Biol. Chew.118: 427,1g37. 6. HEWLETT, A. W., G. D. BARNETT AND J. K. LEWIS. J. Cl&z.Invest. 3 : 317, 1926. 7. CRAIG, F. N. Am. J. Physiol. 146: 146, 1946. 8. BARKER, S. B. AND W. H. SUMMERSON. J. B&L Chem 138: 5351941. 9. WHITE, H. L. AND D. ROLF. Am. J. Physiol. 152: 505,Ig@. IO. TIUIETA, J., A. E. BARCLAY, P. M. DANIEL, R. J. FRANKLIN AND M. M. L. PRICHARD. Studiesof theResaZCirczclatim. Springfield, Ill.: Charles C Thomas, 1947. II. SHANNON, J. A. AND S. FISHER. Am. J. Physiol. 122: 765, 1938. 12. GOVAERTS, P. AND P. MULLER. J. CZin.Invest. 18: 25, 1939. I. 2. SPIRO, Downloaded from http://jap.physiology.org/ by 10.220.33.6 on July 31, 2017 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.
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