Excretion of Inulin, Creatinine, Xylose and Urea in the Normal Rabbit

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 ...

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

“…The question arises as to what may be the mechan'ism regulating the filtration. Renal ischemia is a possibility reviewed by Kaplan and Smith (11) in discussing variations in glomerular filtration in the rabbit. Another possibility lies in the differential contraction of the afferent and efferent glomerular vessels, which would produce changes in glomerular pressure.…”

Section: Resultsmentioning

confidence: 99%

Renal Excretion at Low Urine Volumes and the Mechanism of Oliguria

Chesley¹

1938

In previous papers (1, 2) it was shown that when the urine volume output falls below about 0.35 ml. per minute, the urine becomes " maximally" concentrated with respect to urea. The urea concentration of the urine is constant below this critical volume, and thus the urea clearance (U V/B) varies directly and quantitatively with the urine volume (V).In an effort to analyze the mechanism of renal excretion at low urine volumes, the plasma clearance of endogenous creatinine, and the excretions of phosphorus, total nitrogen, and total solids have been studied in a series of oliguric subjects. These findings are the basis for this report. MATERIAL AND METHODSSeries of excretion studies were carried out, using four normal non-pregnant adults, one normal pregnant woman at term, six patients with preeclamptic toxemia, one patient with terminal malignant nephrosclerosis and cardiac decompensation, one with Bright's disease, and one unclassified cardiac patient. In the normals, a thirty to sixty hour food and water fast was necessary to get the urine volume down to the desired level. In the toxemia patients, a twelve hour fast sufficed, while the patient with renal disease required no preparation. Most of the urines were taken at hourly intervals, though some were for longer periods up to three hours. When the completeness of collection was controlled by washing out the bladder, specimens were taken at intervals of twenty to thirty minutes. In the first two normals, voided specimens were used; in all other cases the urines were obtained by catheter. In the later experiments the urine was first collected, and then the bladder washed out twice with saline at the end of each collection. The washings were separately analyzed. The observed urine volume was corrected by adding the volume of urine calculated, from the creatinine, to be in the saline washings.The apparent plasma creatinine was determined in a modified Folin-Wu filtrate of the plasma, by the method of Folin and Wu (3). Urinary creatinine was determined by Folin's (3) method.For the determination of urinary nitrogen, 1 ml. of urine was diluted to volume in a 200 ml. volumetric flask. From this were taken 2, 3, and 5 ml. samples which were digested by the Wong persulphate method (4). After cooling, they were nesslerized and read against a standard containing 0.15 or 025 mgm. of nitrogen. Correction was made for protein whenever present.Inorganic phosphorus was determined in 1, 2, and 5 ml. samples of the urine diluted 1:200. Youngburg's method (3) was used.Total solids were determined indirectly, because of the small amounts of urine available. Using calibrated pipettes, 10, or when necessary, 5 ml. of urine were weighed to a tenth of a milligram. The specific gravity was then calculated and corrected for protein (for each 10 grams of protein per liter 0.0030 was subtracted from the specific gravity). The significant figures in the specific gravity were then multiplied by Long's coefficient, 2.6, to get the approximate total solid content (3).All data were fitted to...

“…It is to be noted especially that the mean value quoted from Goldring, et (17,18) has shown that all analyzable, diffusible solutes in the plasma are passed in unchanged proportions into the capsular space of the Amphibia, the most noteworthy instance being the simultaneous passage of water and inulin molecules, as referred to above. An equally strong argument can be based upon the identity of the inulin and creatinine clearances in the dog, frog and rabbit (7,11,19,20,22,39), which identity is preserved under all conditions of filtration so far examined in normal animals. So far as man is concerned, more immediate evidence is available in the identity of the creatinine and inulin clearances in phlorizinized subjects (21), and the identity of the xylose and inulin clearances during hyperglycemia in dog and man (Shannon and Fisher,24, and unpublished observations by these authors).…”

mentioning

confidence: 99%

Glomerular Dynamics in the Normal Human Kidney 1

Smith¹,

Chasis²,

Goldring³

et al. 1940

Self Cite

One of the most interesting facts about the renal circulation is that during marked changes in renal blood flow (adrenalin ischemia and pyrogenic hyperemia) the rate of glomerular filtration typically remains unchanged. This fact has been attributed to the circumstance that the changes in renal blood flow are mediated primarily by changes in the tonus of the efferent arterioles; consequently, any increase or decrease in blood flow is accompanied by a reciprocal change in glomerular filtration pressure, with the result that the filtration rate remains unchanged (3).Beyond the fact that this emphasis upon the efferent arteriole is to some extent contrary to the importance which has hitherto, chiefly for anatomical reasons, been attached to the afferent vessel, this description of the glomerular circulation presents several interesting implications. It assumes that the rate of glomerular filtration is determined solely by glomerular pressure factors, exclusive of any limitation imposed by the permeability of the glomerular membranes. There logically issues from this assumption the question whether or not filtration pressure equilibrium is normally reached in the glomerulus. The answer to this question is of practical importance in two respects. If filtration equilibrium is reached in the glomerular circulation, then this fact must set the upper limit to the hydrostatic pressure available to propel blood through the efferent arterioles and the postglomerular circulation. And in the face of a demonstration of filtration equilibrium in the normal kidney, a decrease in filtration rate in renal disease cannot logically be attributed to reduced permeability of the glomerular capillaries, in contradistinction to a decrease in filtration pressure or in total filtering 1This investigation has been supported in part by aid from the William Gibbs Memorial Prize Fund, granted especially for the study of renal hyperemia, and in part by the Commonwealth Fund.surface, without evidence that glomerular permeability is actually reduced.These and other considerations lead us to a further analysis of this problem. It has recently been shown that the inulin and diodrast clearances in different subjects are closely correlated with differences in the tubular excretory mass (diodrast Tm), it being presumed that the last term varies with the total quantity of renal parenchyma (8). It is advantageous to utilize this correlation in examining the relations which exist in various subjects between the inulin and diodrast clearances; i.e., to make this comparison in terms of the ratios, CINITmD and CDITmD (where CIN and CD are the inulin and diodrast clearances, respectively, and TmD is diodrast Tm). Such an analysis is, in the first approximation, equivalent to comparing the filtration rate and renal plasma flow of various subjects on the basis of their actual renal weights.Furthermore, we now have in our records numerous data, not available when the previous paper was published, on the diodrast and inulin clearances in normal subjects under va...