Effects of Posture on Renal Excretion of

Sodium and Chloride in OrthostaticHypotension

By DANIEL MI. BACHMAN, M.S., M.D., AND WILLIAM B. YOUMANS, PH.D., M.D.

Large decreases in the rates of sodium excretion, chloride excretion, and glomerular filtration were

observed in patients with orthostatic hypotension when they assumed the upright posture followinga period of recumbency. When they returned to the recumbent position, sodium excretion typicallywas not restored immediately in spite of immediate restoration of filtered sodium load. The de-creased sodium excretion found to occur in patients with orthostatic hypotension when they are inthe upright posture is considered to be due in part to the decreased filtered sodium load and in partto changes in tubular reabsorption that are independent of filtered sodium load.

WV THEN the normal human subjectchanges from the recumbent to theerect position, arterial blood pressure

is maintained,' and there is either no changeor only a moderate decrease in renal sodiumexcretion.2-6 When the patient with orthostatichypotension changes from the recumbent tothe upright posture a marked fall in arterialblood pressure occurs7-"; therefore, it mightbe anticipated that the decreased arterialblood pressure in the upright posture wouldbe reflected by a decreased intraglomerularpressure, decreased glomerular filtration rate,and decreased sodium excretion.The effect of posture upon the renal excre-

tion of sodium in human subjects with ortho-static hypotension has not been reportedpreviously. Studies of renal function in ortho-static hypotension have demonstrated a de-creased rate of urine flow when such patientschange from the recumbent to the uprightposition,13" while at the same time, phenol-sulfonphthalein exeretion1"-"5 and uric acidclearance'6 remain unchanged. Corcoran andassociates have demonstrated decreased inulinand Diodrast clearances in patients withorthostatic hypotension who were tipped bymeans of a tilt-table to the 60 degree head-uppassive erect posture."

In the present study it has been demon-strated that in orthostatic hypotension large

From the Department of Physiology, Universityof Oregon Medical School, Portland, Oregon.

changes in the renal excretion of sodium resultfrom changes in body posture. Filtered sodiumloads have been measured, afid the changes insodium excretion have' been interpreted interms of alterations in the glomerular filtrationand tubular reabsorption of sodium.

METHODS1. Clinical Methods. Studies of renal function

were performed upon three patients with orthostatichypotension and upon one hypertensive patientunder the influence of Dibenamine. Changes inrenal function were obtained simply by requestingthe patient either to assume a position of recumbencyor to sit, stand quietly, or walk. In general, a periodof erect posture was interposed between two periodsof recumbent posture. Arterial blood pressures, pulserates, fluid intake, and urine output were recorded.Diets were unrestricted except in experiment 6, inwhich case the patient was fasting, and in experi-ment 7, in which instance the patient was on a dietcontaining about 1.5 Gm. of sodium chloride perday. To assure an adequate urine output for urinevolume measurements the patients drank varyingquantities of water at the beginning of each studyand throughout the course of the study. No intra-venous infusions were employed. Urine samples wereobtained without employment of catheterization.Blood samples were withdrawn from an antecubitalvein either at the midpoint of the urine collectionperiod or at the beginning and end of the urinecollection period.The endogenous creatinine clearance was em-

ployed as a measure of glomerular filtration rate.Although endogenous creatinine clearance is notalways equal to inulin clearance, evidence is ac-cumulating that this function is a reliable measureof changes in glomerular filtration rate.'9-2' In some

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POSTURE ON SODIUM AND CHLORIDE EXCRETION

experiments urinary creatinine excretion was meas-ured instead of endogenous creatinine clearance.

2. Analytic Methods. Sodium and potassium ionswere determined by means of a Barclay Flame

samples were determined by an aeration methoddescribed by West and Todd.24

Creatinine was determined in urine and plasmasamples by a modification of the method of Hare.25

TABLE 1.-Summary of Fluid Intake and Urine Output for All Experiments

Time Position Water Drunk Urine Output Urine Specific Gravity(m.) (ml.) UineSeii rvt

Experiment 1

10:30 p.m. to 7:30 a.m. Recumbent Unrestricted 715 1.0157:30 a.m. to 3:30 p.m. Upright Unrestricted 163 1.025

Experiment 2

10:00 p.m. to 6:00 a.m. Recumbent Unrestricted 1510 1.0086:00 a.m. to 2:00 p.m. Upright Unrestricted 44 1.0282:00 p.m. to 10:00 p.m. Upright Unrestricted 302 1.031

Experiment S

7:15 p.m. to 10:05 p.m. Standing 800 175 1.01010:05 p.m. to 11:05 p.m. Recumbent 385 1.00111:05 p.m. to 3:05 a.m. Recumbent 1206 1.0033:05 a.m. to 7.05 a.m. Recumbent 285 1.0137:05 a.m. to 8:05 a.m. Standing 500 228:05 a.m. to 11:05 a.m. Standing 2511:05 a.m. to 3:17 p.m. Standing 500 45 1.0253:17 p.m. to 7:00 p.m. Standing 800 85 1.027

Experiment 4

7:45 p.m. to 6:30 a.m. Recumbent Unrestricted 1010 1.0157:45 a.m. to 4:00 p.m. Upright Unrestricted 310 1.035

Experiment 5

8:15 a.m. to 12:53 p.m. Recumbent 500 1860 1.00812:53 p.m. to 5:14 p.m. Standing and walking 1000 94 1.0215:14 p.m. to 6:17 p.m. Recumbent 250 192 1.0076:17 p.m. to 8:00 p.m. Recumbent 940 1.003

Experiment 6

2:55 p.m. to 5:50 p.m. Recumbent 1040 76 1.0355:50 p.m. to 8.55 p.m. Sitting 800 167 1.0158:55 p.m. to 9:50 p.m. Head-down 27 min.; recumbent 500 277 1.005

18 min.9:50 p.m. to 12:06 a.m. Recumbent 450 632 1.0038:35 a.m. to 11:29 a.m. Recumbent 400 402 1.00211:29 a.m. to 2:30 p.m. Sitting and walking 350 160 1.0042:30 p.m. to 5:30 p.m. Recumbent 350 440 1.001

Photometer with lithium ion employed as the in-ternal standard.22 The average deviation of thesodium determinations was about 5 per cent.

Chlorides were determined by the method ofVolhard.23Ammonia nitrogen and urea nitrogen in urine

This method allows for determination of "truecreatinine" and not "total creatinine chromogen."

RESULTSData concerning fluid intake, urine output,

and urine specific gravity are listed in table 1

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BACHMAN AND YOUMANS

In figures 1 to 7 the postural variations inurinary sodium excretion are shown graphicallywith the simultaneous variations in eitherendogenous creatinine clearance* or in urinarycreatinine excretion. In those cases in whichserum sodium was measured, the filtered

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FIG. 1. Effects of posture upon sodium excretionand creatinine excretion in patient, R. N., experiment1. Patient R. N. was diagnosed as having orthostatichypotension. From 10:30 p.m., June 8, 1950 to 7:30a.m., June 9, 1950 the patient was recumbent, asleepmost of the time. From 7:30 a.m. to 3:30 p.m., June9, 1950, the patient was in either the sitting or stand-ing posture.

sodium load, which is equal to the product ofthe endogenous creatinine clearance and theserum sodium,t is also shown. Protocols of

* Endogenous creatinine clearances are uncor-rected for body surface area.

t Correction for the Donnan equilibrium and forplasma water content is not applied.

the individual experiments are presented asthe legends of figures 1 to 7. In figure 8 thesimultaneous excretion rates of potassium,ammonia nitrogen, and urea nitrogen aregraphed with the postural changes in thecreatinine and sodium excretion rates. Therate of urinary chloride excretion was deter-mined in all cases and found to approximateclosely the rate of sodium excretion. Anexample of this correlation is presented infigure 9.

k 1.20

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6 8 10 12 14 16 18 20 22 24TIME (HRS.)

A,............

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FIG. 2. Effects of posture upon sodium excretionand creatinine excretion in patient, S. B., experiment2. Patient S. B. had idiopathic orthostatic hypo-tension. He remained recumbent from 10:00 p.m.,Dec. 4, 1950 until 6:00 a.m., Dec. 5, 1950. For the next16 hours the patient was in either the sitting or stand-ing position, occasionally walking.

The renal excretion of sodium was found todecrease greatly in the patients with ortho-static hypotension when they assumed theupright posture after a period during whichthey were recumbent. The rate of sodiumexcretion of the patient in the upright posturewas found to be one-third to one-hundredthof the rate in the recumbent posture. A largepercentage decrease in sodium excretion whilethe patient was in the upright posture occurredeven in experiment 7. in which the patientwas on a "salt-free" diet and excreting onlyminute quantities of sodium during the controlperiod.The decreased sodium excretion rate in-

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POSTURE ON SODIUM AND CHLORIDE EXCRETION

duced by the upright posture was observedto be accompanied by decreases in glomerularfiltration rate and filtered sodium load. Rela-tively small percentage decreases in glomerularfiltration rate or filtered sodium load were

accompanied by relatively large decreases insodium excretion rate. In three experiments,3, 5, and 6, filtered sodium load and urinary

125

50

ST. CLU~ STANDING

25

2 4 6 8 10 12 14 16 18 20 22 24TIME (HRS.)

20

16

7 ~12

ST. ~ STANDING

2 4 6 8 10 12 14 16 18 20 22 24TIME (HRS.)

a 0.16

0.08

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2 4 6 8 10 12 14 16 18 20 22 24

TIME (HRS.)

FIG. 3. Effects of posture upon endogenous cre-

atinine clearance, filtered sodium load, and sodiumexcretion in patient, S. B., experiment 3. The patient,S. B., the same as in experiment 2, was hospitalizedfrom Jan. 23, 1951 to Jan. 24, 1951. Average bloodpressure during this experiment when the patientwas in the recumbent position was 130/80; pulse, 64;average blood pressure while the patient was standingwas 95/80; pulse, 90.

sodium excretion were found to change simul-taneously in opposite directions.

In experiment 5 restoration of the glomerularfiltration rate and filtered sodium load to thelevels obtained while the patient was in therecumbent position occurred without restora-tion of urinary sodium excretion. In experi-ment 3, the initial rise in filtered sodium load isaccompanied by a delayed increase in sodium

excretion. The trend is also seen in experiment2, in which urinary creatinine excretion re-

turned to the value obtained during the periodof recumbency, while urinary sodium excretionremained depressed. On the other hand, inexperiment 7, urinary sodium excretion re-

turned to the value obtained while the patientwas recumbent in spite of the failure of thefiltered sodium load to return to the levelobserved during recumbency.

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FIG. 4. Effects of posture upon sodium excretionand creatinine excretion in patient, S. B., experiment4. This study of patient, S. B., was made about one

year after experiments 2 and 3. Blood pressure was

110/70 in the recumbent position and 60/40 in thestanding position. The patient was not hospitalizedbut was instructed carefully in the collection of urinesamples at home. Diet and fluid intake were un-

restricted. The patient remained recumbent from7:45 p.m., Dec. 15, 1951 to 6:30 a.m., Dec. 16, 1951.He then arose and remained in the upright position,either sitting or standing. from 6:30 a.m. until 4:00p.m., Dec. 16, 1951.

In experiment 3, figure 3, during hour 12, a

decrease in sodium excretion is seen to ac-

company a decrease in the endogenous creat-inine clearance. During hour 13 a furtherdecrease in sodium excretion occurs in the faceof an unchanged glomerular filtration rate andfiltered sodium load. While it is possible thatthe urine sample of hour 12 may have beencontaminated with sodium from the urine ofhours 8 to 12, inspection of figure 8, concerningthe same experiment, reveals no corresponding

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BACHMAN AND YOUMANS

trend in the excretion of ammonia nitrogen orpotassium.

DISCUSSION

In patients with orthostatic hypotensionthe renal excretion of sodium decreases mark-edly when the subject assumes the standingposture. The decreased sodium excretion in thepatient in the upright posture is accompanied

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FIG. 5. Effects of posture upon endogenous crea-

tinine clearance, filtered sodium load, and sodiumexcretion in patient, S. B., experiment 5. Averageblood pressure in the recumbent position was 160/90,pulse, 64; and in the standing position, 100/75, pulse,80.

by large decreases in glomerular filtration rateand filtered sodium load. This is in contrastto the situation in the normal individual whois up and about in whom, at most, relativelyminor decreases in sodium excretion26 andglomerular filtration rate2' 26 occur.

In recent years the relative importance ofthe glomerular filtration and the tubularreabsorption of sodium upon sodium excretionby the kidney has been the subject of many

1.12 .

1.08

.06i-

.04SITTING

1 2 3 4 5 6 7 8 9TIME (HRS.)

FIG. 6. Effect of posture upon endogenous creati-nine clearance, filtered sodium load, and sodiumexcretion in patient, D. R., experiment 6. D. R., a

hypertensive, tuberculous patient, was studied whileunder the influence of Dibenamine, administered as a

diagnostic test for possible pheochromocytoma. Nofood was allowed for 12 hours prior to the test and forthe duration of the urine collection periods. Renalfunction studies were performed with the patient inthe recumbent position and in the partial sittingposture with the head, neck, and trunk elevated 30degrees to 45 degrees from the horizontal by means ofpillows. The foot of the bed was elevated on shockblocks for a brief period (table 1, experiment 7,"Head-down 27 minutes"). The patient's blood pres-

sure averaged 195/125 in the recumbent position;160/110 in the partial sitting position.

investigations in both man and in experimentalanimals. Some workers have demonstratedthat changes in renal sodium excretion are

0$ t

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POSTURE ON SODIUM AND CHLORIDE EXCRETION

t:zi 5C

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I4 5 6TIME (HRS.)

FIG. 7. Effects of posture upon endogenous cre-

atinine clearance, filtered sodium load, and sodiumexcretion in patient, S. D., experiment 7. S. D. washospitalized with the diagnoses of pernicious anemiaand orthostatic hypotension. In the outpatient de-partment, prior to her hospital admission, herblood pressure in the recumbent position was110/70 and in the standing position, 60/40. The pa-tient had been on a "salt-free" diet (1.5 Gm. NaCIper day) for at least 10 days prior to the renal func-tion studies and was maintained on the same diet forthe duration of the studies. She drank 200 ml. of waterat the beginning of the experiment and then 100 ml.of water hourly until its conclusion. During the up-right period the patient sat in a wheelchair mostof the time. Two periods of ambulation, each of 20minutes duration, were included in the uprightperiod. Blood pressure while the patient was re-

cumbent averaged 100/70; pulse, 56. Systolic bloodpressure, taken while the patient was in the sittingposition, was 90 mm. Hg and diastolic pressure couldnot be determined by the indirect method. Pulsewas 72. Hemoglobin, 13.3 Gm.; red cell count, 4.7million per cubic millimeter.

frequently associated with, and possibly are

caused by, somewhat parallel changes inglomerular filtration rate.27 28 Others havereported changes in sodium excretion occurringindependently of changes in glomerular filtra-tion rate.29-33That alterations in amount of sodium fil-

tered play a role in the decreased sodium

1.00

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x 50 S STANDINGST.

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TIME (HRS.)

1.50-

1.00

0.50 WS9

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, 0.005

2 4

1l

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0.00 15-0.030003

8 10 12 14 16 18 20 22 24TIME (HRS.)

FIG. 8. Effects of posture upon urinary excretionof ammonia nitrogen, potassium, creatinine, urea

nitrogen, and sodium, experiment 3. The data de-picted here were recorded simultaneously with thoseshown in figure 3. For further explanations see text.

excretion which occurs in subjects with ortho-static hypotension when they assume the erectposture is indicated by the results of experi-ment 3 shown in figures 3 and 8. Ammonianitrogen and potassium, substances excretedby tubular secretion, are little affected by thedecrease in glomerular filtration rate occurringduring the second period of standing. Creati-nine, a substance which is considered to beexcreted only by glomerular filtration, underthe conditions of the experiment, is decreased

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BACHMIAN AND YOUMANS

proportionately to the decrease in glomerularfiltration rate. In the case of urea, a substancenot reabsorbed by an active process, the de-crease in urea excretion results from the de-creased glomerular filtration rate. Since thepercentage decrease in urea excretion is greaterthan the percentage decrease in creatinineexcretion, the decreased glomerular filtrationof urea must secondarily result in more com-plete tubular reabsorption of urea by simplephysical processes. Sodium resembles ureainsofar as it is also a freely-diffusible substance.By analogy, the decreased filtered sodium loadoccurring when the subject is in the uprightposture may also allow for more completetubular reabsorption of sodium by simplephysical processes. The greater percentagedecrease in the excretion of sodium as com-pared with the percentage decrease in theexcretion of urea is evidence that in addition tosimple physical processes, an active tubulartransport mechanism may be operating toeffect reabsorption of sodium.To prove the occurrence of changes in the

active tubular reabsorption of sodium it isnecessary to demonstrate different rates ofsodium excretion at the same filtered load34 35or to show that sodium excretion and filteredsodium load are changing simultaneously inopposite directions. Many of the investigatorsclaiming to have demonstrated altered tubularreabsorption of sodium have not measuredfiltered sodium loads. They determined glo-merular filtration rates and assumed that theplasma sodium level remained unchanged.Ill the present work serum sodium levels havebeen determined and the filtered sodium loadscalculated. Evidence has been obtained thatsodium excretion may vary independently offiltered sodium load. In experiment 3, figure 3,during the recumbent period, sodium excretionis seen to increase while filtered sodium load isdecreasing. During the early part of the secondperiod of standing, a marked decrease insodium excretion occurs ill the face of an

unchanged filtered sodium load. During thelast period of standing, sodium load tends tobe restored towards control values withoutan accompanying increase in. sodium excretion.In experiment (i, duiring hour 6, sodium excre-

tion increased in spite of a decreasing filteredsodium load. In experiment 7, figure 7, filteredsodium load remains below the level observedduring the last recumbent period, while sodiumexcretion returns to above the control level.The results indicate that changes in sodium

excretion which are due to altered filteredsodium load occur rapidly, whereas the adjust-ments in tubular reabsorption occurring in-

EXP. 30.160.12

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STANDING

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TI ME (HRS)

FIG. 9. Comparison of the changes in urinarysodium excretion and chloride excretion resultingfrom changes of posture in experiments 3, 5, and 7.The sodium excretion is indicated by the solid hori-zontal lines, while the chloride excretion is indicatedbv the broken horizontal lines. When the two wereequal, a single solid horizontal line is employed.

dependently of changes in filtered sodiumload occur more slowly. During the recumbentperiod in experiment 3, figure 3, an immediaterise in filtered sodium load is accompanied bya gradual increase in sodium excretion. In thesame experiment a sudden decrease in filteredsodium load is accompanied by a simultaneousdecrease in sodium excretion; however, afurther decrease ill sodium excretion occurswith the passage of time, in spite of no furtherchange inl filtered sodium load. Ini experiment 5,figure 5, an immediate restoration of filtered

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sodium load to the previous value for therecumbent posture is seen to be accompaniedby a more gradual rise in sodium excretion rate.From these studies it appears that a sudden

large decrease in glomerular filtration rateand filtered sodium load may cause a suddensevere decrease in sodium excretion. Lateradjustments in tubular reabsorption, occurringindependently of glomerular filtration rateand filtered sodium load, may tend to altersodium excretion further, depending uponvariables not yet clearly identified.

SUMMARY

The changes in renal sodium excretion re-sulting from changes of posture in patientswith orthostatic hypotension have been meas-ured and the results interpreted in terms ofalterations in the glomerular filtration and thetubular reabsorption of sodium. The endog-enous creatinine clearance was employed as ameasure of the glomerular filtration rate, andfiltered sodium loads were calculated as theproducts of the glomerular filtration rates andthe serum sodium concentrations.

Large decreases in the rate of urinarysodium excretion and in glomerular filtrationrate occurred when subjects with orthostatichypotension changed from the recumbent tothe upright posture. Typically, when theyreturned to the recumbent posture sodiumexcretion was not restored immediately inspite of the immediate increases in filteredsodium loads. Other examples of sodium ex-cretion varying independently of filtered so-dium load were observed; thus proof wasobtained of altered tubular reabsorption ofsodium. Changes in chloride excretion resultingfrom postural changes in patients with ortho-static hypotension were parallel and approxi-mately equal to the changes in sodium excre-tion.

It is concluded that the decreased sodiumexcretion found to occur in patients withorthostatic hypotension when they were inthe upright position is partly due to the de-creased load of sodium filtered and partly dueto changes in tubular reabsorption that areindependent of filtered sodium load.

SUMARIO ESPAROLGran diminucion en la velocidad de excrecio'n

del sodio y cloruro, y la filtracion glomerularfueron observados en pacientes con hipotensi6nortostatica al asumir la posicion vertical luegode un perifodo de reclinacion. Cuando volvierona la posicion reclinada, la excrecion de sodiotipicamente no fue restaurada inmediatamentea pesar de inmediata restauracion de la cargade sodio filtrado. La diminuci6n de excreci6nde sodio encontrada en pacientes con hipo-tension ortostatica cuando en la posici6n verti-cal es considerada como causada en parte a ladiminuci6n de carga de sodio filtrado y en partea cambios en la reabsorcion tubular que sonindependientes a la carga de sodio filtrado.

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2 KATTUS, A. A., SINCLAIR-SMITH, B., GENEST, J.,AND NEWMAN, E. V.: The effect of exercise onthe renal mechanism of electrolyte excretionin normal subjects. Bull. Johns Hopkins Hosp.84: 344, 1949.

3 EPSTEIN, F. H., GOODYER, A. V. N., LAWRASON,F. D,, AND RELMAN, A. S.: Studies of the anti-diuresis of quiet standing; the importance ofchanges in plasma volume and glomerular filtra-tion rate. J. Clin. Investigation 30: 63, 1951.

4 LEWIS, J. M., JR., BUIE, R. M., SEVIER, S. M.,AND HARRISON, T. R.: The effects of postureand of congestion of the head on sodium excre-tion in normal subjects. Circulation 2: 822, 1950.

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DANIEL M. BACHMAN and WILLIAM B. YOUMANSHypotension

Effects of Posture on Renal Excretion of Sodium and Chloride in Orthostatic

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