Studies in which 15N-labeled precursors of urinary ammonia were infused into the artery of an intact functioning kidney of an acidotic dog have led to the following conclusions: Preformed ammonia and ammonia derived from the amide nitrogen of plasma glutamine are added directly to urine without significant incorporation into amino acid intermediates of renal tissue. Thus, reductive amination of α-ketoglutarate to form glutamate does not occur to an appreciable extent nor is there significant transfer of the amide nitrogen of glutamine to the corresponding keto acids to form glutamate, aspartate, alanine, or glycine. The enzyme system “glutaminase II” may participate to a significant extent in the metabolism of glutamine by forming aspartate and alanine by direct transamination of oxalacetate and pyruvate and liberating the amide nitrogen as ammonia. Renal alanine exists as a well mixed pool derived in roughly equal amounts from filtered and reabsorbed plasma alanine and newly synthesized alanine. The alanine pool of tubular cells does not equilibrate with the alanine of peritubular capillary blood. Transfer of the nitrogen of alanine to α-ketoglutarate and subsequent oxidative demination of the resulting glutamate can account for the ammonia formed from alanine. Glycine is not an important intermediate in renal nitrogen metabolism.
William J. Stone, Robert F. Pitts
Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states.
John W. Jones, Peter Ways
The renal clearance of cystine, lysine, ornithine, arginine, and glycine has been compared with the simultaneously determined glomerular filtration rate in nine cystinuric patients. Five were studied before and after stabilization on penicillamine therapy, two were studied only while taking penicillamine, and two were studied only in the absence of penicillamine administration. The renal clearances of cysteine-penicillamine and of penicillamine disulfide were also determined in the patients who were taking the drug.
J. C. Crawhall, E. F. Scowen, C. J. Thompson, R. W. E. Watts
In previous studies it was found that renal cortical slices from rats with induced metabolic acidosis have an increased capacity to produce glucose, whereas cortical slices from rats with metabolic alkalosis manifest decreased gluconeogenesis. To evaluate the relative influence of extracellular fluid pH, [HCO3-], and carbon dioxide tension on renal gluconeogenesis, we observed glucose production by cortex from rats with induced respiratory acidosis, and by cortex taken from normal animals and incubated in acid and alkaline media.
Donald E. Kamm, Robert E. Fuisz, A. David Goodman, George F. Cahill Jr.
The functional characteristics of the ascending limb of Henle's loop were examined during hypotonic saline infusion by measuring solutefree water clearance (CH2O) at varying rates of solute delivery. The influence of expansion of extracellular volume was studied by comparing CH2O during hypotonic saline diuresis in normal dogs with dogs whose extracellular volume had been expanded acutely by saline infusions or chronically by the administration of deoxycorticosterone acetate and salt.
Garabed Eknoyan, Wadi N. Suki, Floyd C. Rector Jr., Donald W. Seldin
If water and inert solutes are assumed to pass from blood to bile through a fixed population of membrane pores, the changes in clearance produced by dehydrocholate suggest that osmotic filtration rather than diffusion is the predominant mode of transfer for mannitol and erythritol. Bile produced in the canaliculi is modified in the interlobular ducts by the action of secretin. If distal fluid transfer is an important determinant of the choleresis evoked by dehydrocholate, the mechanism appears to effect a net secretion or reabsorption of fluid at a rate roughly proportional to the rate of flow in the canaliculi.
E. L. Forker
The incorporation of extracellular orthophosphate-32P into cellular ATP, 2,3-diphosphoglyceric acid, and inorganic phosphate has been measured over a period of 6 hours in vitro in red blood cells from normal subjects and from patients with hereditary spherocytosis who had undergone splenectomy. The pattern of labeling of the intracellular compounds was found to be the same in both types of red blood cells, as reported by other workers using much shorter periods of incubation. In addition, in the present study it was possible to compare the net flux of extracellular phosphate into ATP between the two groups of erythrocytes. These latter results suggest that the actual turnover rate of ATP was not abnormal in these patients with hereditary spherocytosis.
Claude F. Reed, Lawrence E. Young
We performed studies on dogs under hydrated conditions, utilizing the rate of free water formation (CH2O) as an index of the rate of distal tubular sodium transport. Since CH2O could be progressively increased with no evidence of a maximal rate during loading with hypotonic (2.5%) mannitol, it was concluded that there is no limit on distal tubular sodium transport during mannitol loading. In contrast, during hypotonic (0.45%) saline loading CH2O rose initially, but as urine flow (V) exceeded 25% of the filtered load CH2O attained maximal levels (up to 20% of the filtered load) and remained stable as V increased to 50% of the filtered load. It was concluded that saline loading progressively inhibits proximal sodium reabsorption. Initially, the distal tubule absorbes a large fraction of the proximal rejectate and sodium excretion rises slightly. Eventually, an alteration in distal sodium transport appears which culminates in a maximal rate or transport limit. This distal transport limit provoked by saline loading could not be characterized by a classical Tm as seen with glucose and does not seem to be consequent to high rates of flow through the distal tubule. Regardless of the precise nature of this limit, the major increment in sodium excretion develops during saline loading only after saline alters the capacity of the distal tubule to transport sodium.
Richard M. Stein, Ruth G. Abramson, Thomas Kahn, Marvin F. Levitt
Hamster intrinsic factor (IF) preparations markedly enhanced the uptake of 57cobalt-labeled cyanocobalamin (B12-57Co) by brush borders and microvillous membranes isolated from villous absorptive cells obtained from the distal but not the proximal half of hamster intestine. A similar effect was observed with rat and rabbit IF preparations, but IF preparations obtained from man, dog, and hog were ineffective. After fractionation of hamster IF preparations by gel filtration or ion exchange chromatography, the extent to which each fraction enhanced B12-57Co uptake by brush borders correlated closely with the vitamin B12 binding capacity of the fraction. IF-mediated attachment of B12-57Co to brush borders occurred rapidly, was not diminished by removal of glucose or oxygen from the incubation medium, and was not significantly altered when incubation temperatures were reduced from 37° C to 7° C. Marked reduction in uptake occurred, however, in the absence of divalent cations.
Robert M. Donaldson Jr., Iain L. Mackenzie, Jerry S. Trier
Anesthetized dogs receiving an infusion of chlorothiazide and ethacrynic acid were given 600-ml infusions of distilled water or dilute dextrose solutions. The absolute rate of tubular sodium reabsorption was depressed, and the glomerular filtration rate was increased during the water loading, despite the associated decreases in plasma sodium concentration and decreases in the filtered load of sodium. The extent to which fractional sodium reabsorption decreased and the excretion of sodium increased was inversely related to the degree to which the filtered load of sodium was depressed as a result of the decreased plasma sodium concentration. We conclude that, in the presence of the diuretic blockade of distal tubular sodium reabsorption, infusion of water depresses proximal tubular reabsorption of sodium and that these changes are qualitatively similar to those previously observed during infusions of saline. Similar depression of tubular reabsorption of sodium and increased excretion of sodium occurred during water loading in the absence of diuretics in dogs undergoing saline diuresis, which presumably provided a high rate of distal sodium reabsorption before water loading.
Joseph A. Martino, Laurence E. Earley
Serial measurements of intrarenal distribution of blood flow have been recorded in anesthetized dogs with the 133xenon “washout” technique. The results showed that normal kidneys redistributed their blood flow after laparotomy and mobilization of the kidney. This alteration consisted of a diminution in percentage of total renal blood flow supplied to the fastest flowing component, and a diminution of renal mass supplied by that component. This effect lasted for as long as 7 days. Thereafter, the blood flow distribution remained stable.
Stanley M. Rosen, Bruno P. Truniger, Hans R. Kriek, Joseph E. Murray, John P. Merrill
Acute infusions of isotonic saline in the rat cause an increase in glomerular filtration rate and in the excretion of salt and water. The kidney swells, due to expansion of tubular and interstitial volume. Despite the increase in tubular diameter, transit time through the proximal tubules and loops of Henle is decreased, presumably owing to a greatly accelerated rate of tubular flow. Proximal tubular reabsorption, measured in blocked tubules, is inhibited in a way that cannot be ascribed to changes in tubular diameter. The prolongation of proximal reabsorptive half-time is not affected by the administration of aldosterone. It occurs equally in rats chronically loaded with or deprived of salt, and it is therefore not likely that it is influenced by the renal content of renin. In contrast, reabsorption from the distal convoluted tubule is enhanced by saline infusion. This change is observed in segments of tubules blocked with oil and isolated from their glomeruli and thus appears to occur independently of changes in glomerular filtration or tubular flow.
John P. Hayslett, Michael Kashgarian, Franklin H. Epstein
Materials indistinguishable from authentic mono- and diiodotyrosines were identified in extracts of normal human serum as well as in extracts of purified human serum albumin. These materials were not found in association with the other serum proteins. Identification of MIT and DIT was made by a technique using rechromatography to constant specific activity, as well as by the Barker wet ash distillation method, which established the compounds in question as being iodinated ones. By two different extraction and chromatographic methods we estimated the amounts of both MIT and DIT present in normal human serum or albumin; the estimates were in good agreement. These compounds together constituted between 19% and 25% of the extractable serum iodine.
Henry Weinert, Hideo Masui, Ildiko Radichevich, Sidney C. Werner