The Effects of Quiet Standing on Solute Diuresis 1

Mannitol, when given intravenously to normal human subjects or animals, shares with a number of other substances the property of promoting an increased rate of renal excretion of sodium, chloride, and water. The generally accepted hypothesis concerning the mechanism of this action is that mannitol exerts its effect directly on the renal tubules. The osmotic pressure of the mannitol within the tubular lumen is considered to interfere with the reabsorption of water. Sodium excretion is thought to be increased in the presence of the increased amounts of water in the tubule per unit time, either because reabsorption of sodium is limited by a maximum concentration difference for sodium which can be achieved between the tubular urine and the extracellular fluid (1)(2)(3) or because the contact of the sodium with the tubule cells is so brief that reabsorption is incomplete (4, 5). Evidence for a direct effect of mannitol on the renal excretion of salt and water is afforded by the experiments of Goodyer and Glenn (5). They injected large mannitol loads directly into one renal artery of dogs and produced prompt increases in salt and water excretion on the injected side. However another mechanism of action of mannitol in the intact animal is not excluded by these observations. Seldin and Tarail (6) have suggested that mannitol infusions may exert their effects outside the kidney by producing an expansion of extracellular volume and, when given in hypertonic solution, a contraction of intracellular volume, and thus indirectly altering some regulatory mechanism which increases the renal excretion of salt. This hypothesis has not thus far been excluded, and indeed was suggested as the probable mechanism of ac-1 Present address: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carol'a tion of sodium chloride infusions in increasing renal sodium excretion by Green and Farah (7). They believe that the increased sodium intake influences sodium excretion primarily by establishing an osmotic pressure difference between extraand intracellular fluids.In most studies (1,4,6,8,9) hypertonic mannitol solutions (usually 25 per cent) have been injected. Such solutions would be expected, and have been calculated, to expand extracellular volume and contract intracellular volume. West, Kaplan, Fomon, and Rapoport (10) gave hypotonic mannitol solutions to hydrated dogs and found increased salt excretion. Here extracellular volume was expanded and although under such circumstances an absolute contraction of intracellular volume would appear unlikely, the calculated osmolarity of the plasma did rise during the mannitol infusion and therefore a relative decrease in intracellular water cannot be excluded.Goodyer and Seldin ( 11 ) gave hypertonic mannitol solutions to two subjects during quiet standing and found less increase in salt excretion than normally occurs; to one standing, hydrated subject they gave a small amount (one liter) of hypotonic mannitol and found no increase in salt excretion.2 Recent...

Section: Resultsmentioning

confidence: 61%

mentioning

confidence: 99%

Mechanism of Increased Renal Sodium Excretion Following Mannitol Infusion in Man

Williams¹,

Hollander²,

Strauss³

et al. 1955

“…In a previous communication (4) the literature has been summarized to indicate that a) most workers find a fall in filtration rate on changing from the horizontal to a head-up tilt or to standing, b) all workers find falls in water and sodium excretion on changing from the horizontal to a head-up tilt or to standing. Additional relevant reports have since been published (5,(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Postural Effects on Renal Tubular Activity 1

Surtshin¹,

White²

1956

A nunber of observers have reported that acute reduction of glomerular filtration rate (GFR) in experimental animals induces a considerable fall in renal excretion of sodium and water. Chronic constriction of one renal artery is followed by persistent fall in salt and water excretion by that kidney (1). In man, change from the recumbent to the erect position is followed by a considerable fall in urinary flow and sodium excretion and by small decrease in inulin and exogenous or endogenous creatinine clearances (2-4). The above findings were on subjects not in maximal water diuresis. In human subjects with a large water load who had been sitting for four to eight hours, change to recumbency was followed by increase in urine flow, sodium excretion and sodium urinary concentration while creatinine U/P ratios fell and endogenous creatinine clearance rose slightly (5).Whether more nearly complete reabsorption of sodium and water following maneuvers reducing GFR is accomplished in the proximal or the distal segment of the tubule is not certain. Pitts and Duggan (6, 7) inferred that organic mercurial diuretics depress the distal reabsorption of sodium, and after observing that aortic constriction produced marked fall in sodium excretion even after administration of a large dose of Mercuhydrin®: in dogs they concluded that the increased sodium and water reabsorption resulting from fall in GFR takes place in the proximal segment. The inference that mercurial diuretics act solely distally has been supported (8) and rejected (9,10) and the loci of the more complete reabsorption remain unidentified.As has been reviewed previously (4) most workers have found a fall in GFR with postural change from the horizontal to a head-up tilt or standing.We here report the effects of postural change on the excretion of water, sodium, creatinine and os- motically active solutes in normal human subjects in maximum water diuresis. We have attempted to localize within the nephron some of the changes observed, using the following assumptions: 1) Distal water reabsorption is abolished in maximum water diuresis with the subject at ease, recumbent or standing (11). 2) Proximal reabsorption is isotonic (12-15). Evidence for the first assumption is that urine flow in maximal water diuresis or in complete diabetes insipidus about equals the volume of fluid leaving the proximal tubules, as estimated by observations on proximal fluid samples obtained by micropuncture (13).If it should be found that the percentage fall in water excretion on changing from recumbency to standing with subjects in maximal water diuresis is significantly greater than the percentage fall in GFR it would follow that the percentage of filtered water reabsorbed proximally is increased on standing. Since proximal reabsorption is considered as isotonic, the percentage of filtered sodium reabsorbed proximally is also increased. If it should further be found that urine and plasma osmolarity remain unchanged, free water clearance also shows a greater percentage fall than does GFR. T...

“…The consequent retention of sodium is not accompanied by an increase in the rates of excretion of potassium and ammonium when quiet standing is superimposed upon a diuresis induced by water ingestion (16,17), infusion of physiological saline (4, 17), (4). The fact that urinary out-tion which postulate an inverse relationship between puts of potassium, ammonium and hydrogen ions the rates of secretion of potassium and hydrogen were simultaneously increased when sodium reten-ions (19), it is of interest that increases in the tion was provoked during the infusion of a non-production of ammonium and marked falls in urireabsorbable anion suggests alterations in tubular nary pH were promoted acutely by quiet standing activity since this cannot be explained by the hy-with a simultaneous increase in the excretion of pothesis of a lowered rate of glomerular filtration potassium.…”

Section: Discussionmentioning

confidence: 99%

Studies of the Antidiuresis of Quiet Standing: Observations Upon Electrolyte and Acid-Base Excretion During Sulfate Diuresis 1

Epstein¹,

Kleeman²,

Lamdin³

et al. 1956

It is well established that when blood is pooled in the limbs, either by the use of congesting tourniquets or by standing erect and motionless, there is an immediate and marked decrease in urinary flow and in the excretion of sodium and chloride (1,2). This is usually accompanied by a slight diminution in glomerular filtration rate and by little or no change in the excretion of potassium and ammonium or in urinary pH (24). The mechanisms by which sodium excretion is diminished remain unclear, although considerable evidence suggests that the rates of urinary excretion of sodium and other strong electrolytes are interrelated through a process of ionic exchange in the renal tubules (5). It was thought that these relationships might be illuminated by measuring changes in the excretion of K+ and H+, when reabsorption of Na+ was acutely increased but total cation reabsorption limited, by assuming the upright posture during the course of a sodium sulfate diuresis. METHODSExperiments were carried out on normal young men, in the morning after a light breakfast. An isotonic solution of sodium sulfate (248 mEq. per L., 296 mOsm. per L.)2 was infused intravenously at 4 to 5 cc. per min. over a period of six hours in all experiments. Four kinds of experiments were performed. In Group I (control) the subject remained supine for the duration of the procedure. In Group II he stood upright and motionless during the fifth hour of the infusion. In Groups III and IV the latter procedure was repeated while an effort was (12) in the earlier experiments and later by a modified colorimetric method using benzidine (13,14). pH of blood and urine was determined with a Cambridge pH meter. Urine was analyzed for ammonia (15) and in most cases for titratable acidity. RESULTSI. Continuous infusion of sodium sulfate in the supine position (Table I, Figure 1) The rates of excretion of sodium and sulfate increased rapidly during the first three hours but continued to rise only very slowly during the fourth, fifth and sixth hours, as equilibrium between the intake and output of sulfate was approached. During the last three hours the clearance of sulfate progressively approached the clearance of endogenous creatinine. Although the excretion of potassium invariably increased from the first to the second hour, this was not true of ammonium, and during the final three hours the excretion of K+ and NH4+ was fairly constant.The excretion of chloride at first increased slightly but then progressively declined to very low levels. The normal diurnal variation in urinary pH was unaltered. Urinary flow and the clearance of endogenous creatinine changed little during the six hours of infusion. 308