The Mechanism of Polyuria of Diabetes Insipidus in Man. The Effect of Osmotic Loading

Brodsky, William A.; Rapoport, S.

doi:10.1172/jci102442

Cited by 52 publications

(14 citation statements)

References 20 publications

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“…Changes in urine flow bore no consistent relationship to serum sodium concentration. The clearances and U/P ratios of creatinine in the present study indicate that the variations in urine flow observed cannot be related to changes in glomerular filtration rate, but, unless tubular secretion of water is postulated (21), must be determined by alterations in tubular reabsorption of water. Moreover, the data indicate that these changes in tubular reabsorption are associated with alterations in solute excretion and can be most consistently related to the concomitant rate of sodium excretion.…”

Section: Discussionmentioning

confidence: 47%

“…Nor could an inverse relation between the flow of urine and its total osmolar concentration be demonstrated after urea loading, when osmolarity was calculated either from urinary solutes determined individually or from measurements of freezing point." Moreover, patients and experimental animals with diabetes insipidus exhibit similar variations in urine flow related to the solute load presented for excretion (21,23,(44)(45)(46)(47)(48)(49) The variety of changes observed in the renal excretion of water may thus be related both to alterations in solute load and to slight variations in the level of ADH activity, dependent upon changes in "effective" ECF volume. Parallel alterations in excretion of water and of sodium would be explained if a) volume changes which stimulate ADH excretion also serve as stimuli for sodium retention and b) tubular water is obligated differently by various solutes and the obligation imposed by sodium is usually more important than that of other solutes, such as urea.…”

Section: Discussionmentioning

confidence: 92%

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Variation in the Diuretic Response to Ingested Water Related to the Renal Excretion of Solutes 1

Rosenbaum¹,

Nelson²,

Strauss³

et al. 1953

J. Clin. Invest.

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The administration of a large amount of water to the normal subject results in the copious excretion of a dilute urine. An extensive body of evidence indicates that this response is primarily dependent upon a decrease in the effective osmotic pressure of the plasma and extracellular fluid, with resultant inhibition of the secretion of antidiuretic hormone (ADH) by the neurohypophysis and decreased facultative reabsorption of water by the renal tubules (2-5).Although alterations of this normal response to water loading have been studied in a variety of abnormal conditions, factors which influence the magnitude of water diuresis in normal man have received scant attention, even though Haldane and Priestley in 1916 noted that the initial high rates of urine flow which followed the ingestion of water subsequently underwent a gradual moderate decline despite a continued large fluid intake (6). Depletion of body sodium in man and experimental animals has been shown to diminish the excretion of administered water, but under the conditions of these studies general impairment of renal excretory function was evident (7-9) or was not excluded (10, 11).The present communication describes observations which indicate that in man the maintenance of a large water load evokes a diuresis the magnitude of which is. greatly influenced by factors which evoke concomitant changes in the renal excretion of solutes, particularly sodium. These influences include the dietary intake of sodium, postural effects, and the administration of various solute loads. METHODSThe subjects were three normal men and seven adult male patients, of whom four had neurodermEititis, one psoriasis, one bronchial asthma, and one rheumatoid ar-1A preliminary report (1) thritis. All were free of renal or cardiovascular disease. Dietary intake was controlled only with regard to its sodium content. The regimens employed were: 1) "saltfree" diet providing approximately 15 mEq. of sodium daily; 2) "salt-poor" diet providing 35-70 mEq. of sodium daily; 3) "regular" diet of unrestricted salt content containing approximately 170-250 mEq. of sodium; 4) "high-salt" diet consisting of the "regular" diet with 170 mEq. of added sodium chloride. The same regimen was employed for a minimum of three days before each experiment, except that the "high-salt" diet was given for only one day prior to an experiment in subjects who had previously been taking the regular diet. Repeated studies were performed on the same subjects at intervals which ranged from one week to 10 months. Hence weight changes unrelated to dietary salt intake occurred.The subjects came to the laboratory one to two hours after breakfast, voided, and were weighed on a scale sensitive to + 10 gm. Arterialized venous blood (12) was then obtained and a water load established by the ingestion of tap water at room temperature. In most experiments, 1500 ml. were drunk during a period of 10 to 40 minutes. The subject was again weighed and the water load was maintained throughout the experiment by oral administration ...

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 92%

Variation in the Diuretic Response to Ingested Water Related to the Renal Excretion of Solutes 1

Rosenbaum¹,

Nelson²,

Strauss³

et al. 1953

J. Clin. Invest.

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“…In the experiments by Taylor, Peirce, and Page (3) (21). Their behavior under both loading and non-loading conditions thus appears to correspond closely to that of the hydrated normal subject given Pitressin@ Data on glomerular filtration rate are too scanty in the present study to establish a relationship between this function and urinary concentration.…”

Section: Discussionmentioning

confidence: 54%

A Comparison of the Relative Effectiveness of Hydropenia and of Pitressin® in Producing a Concentrated Urine12

West¹,

Traeger²,

Kaplan³

1955

J. Clin. Invest.

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It is a common assumption that exogenous antidiuretic hormone (Pitressing) is equal to the endogenous anti-diuretic hormone (ADH) in its ability to stimulate the production of a concentrated urine. However, clinical studies of urine formation after the administration of Pitressin'S or Pituitrin@ leave some doubt as to the ability of the exogenous hormone to produce a maximally concentrated urine. Sodeman and Engelhardt (1) found that if urinary specific gravity was low at the time of Pituitrin0 administration, the value attained was not so high as could be produced in the same subject by water deprivation. Similar observations were made by Little, Wallace, Whatley, and Anderson (2). Taylor, Peirce, and Page (3) gave Pituitrin@ at frequent intervals for 12 hours and found the urine to be often more dilute and of larger volume than after a 12-hour period of water deprivation. In every case the amounts of anti-diuretic hormone administered were much greater than are assumed to be normally produced.In the present study the ability of exogenous anti-diuretic hormone, administered as Pitressin@, to concentrate the urine has been reinvestigated in humans and in the dog. Because it is now recognized that the concentration of urine depends not only on the degree of hydropenia, but also on the prevailing rate of solute excretion (4-6), it seemed pertinent to investigate urinary concen- tration after Pitressin® administration during mild solute diuresis as well as under normal conditions of urine formation. To insure absence of circulating endogenous anti-diuretic hormone at the time PitressinD was tested, the subjects were hydrated and having a water diuresis at the start of hormone infusion. In evaluating the results, the urinary concentrations after Pitressins, expressed in milliosmols, have been compared with the urine osmolarity of hydropenic subjects, taking into account the fall in osmolarity normally occurring during solute diuresis.It was found that once water diuresis was inhibited by the administration of PitressinS, urine osmolarity slowly increased to approach, but rarely equal, values observed during hydropenia. Differences in plasma osmolarity in the hydratedPitressin(D and hydropenic groups accounted to some extent for the discrepancy. When urine osmolarity was expressed as a function of plasma osmolarity, either as the osmotic U/P ratio or the urine-plasma osmotic pressure difference, values after a sufficient period of Pitressin@ infusion were often comparable to those of hydropenic subjects providing solute diuresis was present. In the absence of solute diuresis, the results were not as consistent. Prolonged Pitressin® administration in several instances failed to elevate osmotic pressure differentials to values observed in hydropenic subjects. METHODSFor the study 32 experiments were performed, 17 on eight female mongrel dogs and 15 on five male subjects. At least two experiments were usually performed on each subject, one to determine urinary concentration during hydropenia and a second to test the eff...

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“…11 The recognition that, as solute excretion increases, the osmolality of the urine decreases even in the presence of maximal doses of vasopressin has been known since the 1950s from the classic observations made by Brodsky and Rapoport ( Figure 2). 12 This well-established physiologic observation is of therapeutic value in patients with severe syndrome of inappropriate secretion of antidiuretic hormone, 13 and particularly in those in whom almost no degree of water restriction will increase the serum sodium concentration, as elegantly analyzed by Furst et al 14 We use the data from the patient that these authors 14 reported as a failure of water restriction to illustrate how increasing his solute intake would have benefited him. The patient had metastatic lung cancer and a serum sodium concentration of 121 mEq/L.…”

Section: Increasing Solute Intake In the Treatment Of Hyponatremiamentioning

confidence: 99%

Impact of Solute Intake on Urine Flow and Water Excretion

Berl¹

2008

Journal of the American Society of Nephrology

144

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The Mechanism of Polyuria of Diabetes Insipidus in Man. The Effect of Osmotic Loading

Cited by 52 publications

References 20 publications

Variation in the Diuretic Response to Ingested Water Related to the Renal Excretion of Solutes 1

Variation in the Diuretic Response to Ingested Water Related to the Renal Excretion of Solutes 1

A Comparison of the Relative Effectiveness of Hydropenia and of Pitressin® in Producing a Concentrated Urine12

Impact of Solute Intake on Urine Flow and Water Excretion

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