This article reviews the role of the kidneys in the regulation of acid-base balance. It is intended as a guide for those who teach this aspect of renal physiology to health professions students. An approach is described, which begins with an overview of acid-base balance and then proceeds to describe the details of renal H1 transport and the important role the production and excretion of NH 4 plays in the ability of the kidneys to generate new HCO 3 . In the overview, the role of the kidneys in acid-base balance is placed in context for the student by examining the impact of diet and cellular metabolism on acid-base balance. Also, the interactions between the kidneys and lungs to maintain extracellular HCO 3 concentration within a narrow range are described. This is followed by a detailed look at the cellular mechanisms of H1 secretion along the nephron, how these mechanisms are regulated, and how they result in the reabsorption of the filtered load of HCO 3 . Finally, the important role of NH 4 production and excretion in the generation of new HCO 3 is reviewed and highlighted.
APS REFRESHER COURSE REPORTREGULATION OF CALCIUM AND PHOSPHATE HOMEOSTASISLinda S. CostanzoLinda S. CostanzoPublished Online:15 Dec 1998https://doi.org/10.1152/advances.1998.275.6.S206MoreFiguresReferencesRelatedInformationPDF (321 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationSee PDF Cited ByHereditary Dentin Defects20 November 2016 | Journal of Dental Research, Vol. 86, No. 5 More from this issue > Volume 275Issue 6December 1998Pages S206-216 https://doi.org/10.1152/advances.1998.275.6.S206History Published online 15 December 1998 Published in print 15 December 1998 Metrics Downloaded 6,794 times 5 CITATIONS 5 Total citations 0 Recent citations n/a Field Citation Ratio n/a Relative Citation Ratio publications12supporting0mentioning12contrasting0Smart Citations120120Citing PublicationsSupportingMentioningContrastingView CitationsSee how this article has been cited at scite.aiscite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
An understanding of the physiology of body fluids is essential when considering appropriate fluid resuscitation and fluid replacement therapy in critically-ill patients. In healthy humans, the body is composed of approximately 60% water, distributed between intracellular and an extracellular compartments. The extracellular compartment is divided into intravascular, interstitial and transcellular compartments. The movement of fluids between the intravascular and interstitial compartments, is classically described as being governed by Starling forces, leading to a small net efflux of fluid from the intravascular to the interstitial compartment. More recent evidence suggests that a model incorporating the effect of the endothelial glycoclayx layer, a web of glycoproteins and proteoglycans that are bound on the luminal side of the vascular endothelium, better explains the observed distribution of fluids. The movement of fluid to and from the intracellular compartment and the interstitial fluid compartment, is governed by the relative osmolarities of the two compartments. Body fluid status is governed by the difference between fluid inputs and outputs; fluid input is regulated by the thirst mechanism, with fluid outputs consisting of gastrointestinal, renal, and insensible losses. The regulation of intracellular fluid status is largely governed by the regulation of the interstitial fluid osmolarity, which is regulated by the secretion of antidiuretic hormone from the posterior pituitary gland. The regulation of extracellular volume status is regulated by a complex neuro-endocrine mechanism, designed to regulate sodium in the extracellular fluid.
Since the discovery of the steroid hormone aldosterone nearly 35 years ago, our knowledge on the cellular actions of aldosterone is still incomplete. Most of the present physiological and biochemical knowledge about the antinatriuretic action was revealed by investigations on amphibian tight epithelia, in particular the toad urinary bladder. Less biochemical information was obtained from mammalian tissue such as microdissected renal tubules and cultured cells. In our opinion, it is questionable whether de novo synthesis of cell proteins-induced by aldosterone-can explain all of the hormonal effects to increase the Na+ transport. In the present paper we try to analyze the wide and contradictory field of biochemical data about the action of aldosterone on the increase in Na+ transport in renal cells in an attempt to incorporate this information into an extended working hypothesis. We suggest distinguishing principally between an early and a late biochemical response phase. We speculate that aldosterone may act by a two-step mechanism: the early and late aldosterone-induced proteins.
In previous intravital microscopic studies of the hydronephrotic split kidney a narrow segment in the efferent arteriole at its origin from the glomerulus was observed. In the present study in vivo techniques were combined with transmission electron microscopy of thin sections to investigate the structural basis for the luminal narrowing. At the point where the efferent arteriole leaves Bowman's capsule prominent endothelial cells were found to bulge into the lumen of the vessel. These cells participate in the overall narrowing of the lumen at this site and appear to be responsible for the in vivo picture. However, the principal basis for the narrowing seems to be an extrinsic constriction of the vessel, possibly by extraglomerular mesangial cells located at the exit level. It is suggested that the outflow portion of the efferent arteriole may be an important site of control of glomerular blood flow.
The effect of varying concentrations of substrate-free albumin (SFA) in the absence of exogenous substrate was investigated in the isolated perfused rat kidney. Consistent with starling relationship, there was a progressive decrease in glomerular filtration rate (GFR), from 778 +/- 36 to 41 +/- 17 microliters/min.g, and a progressive increase in fractional sodium reabsorption (%TNa+), from 31.1 +/- 0.9 to 82.6 +/- 2.3%, when the mean SFA concentration in the perfusate was increased from 3 to 10 g/dl. Perfusate flow rate (PFR) remained constant at 30 ml/min.g as the GFR decreased. When the mean perfusate SFA concentration was decreased from 3 g/dl to 0, the anticipated decrease in %TNa+ occurred but the increase in GFR did not. PFR was also reduced by one half when SFA was not present in the perfusion medium. The reason for the anomalous behavior of GFR and PFR when SFA was omitted from the perfusion medium is not clear.
To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg · kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 ± 3 to 48 ± 6 µmol·min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the ‘trapped-label’ method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg·min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg·kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg·min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-β-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.
The effect of three aminoglycosides--gentamicin, netilmicin and amikacin--on renal acid excretion was studied in male rats treated with doses equivalent to those clinically used. The amikacin and netilmicin groups showed no important changes in the values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and U/P inulin ratio during normal and acidotic conditions. The gentamicin group, however, showed a clear tendency to decreases in these functional parameters even in normal conditions, a finding that reinforces the concept that gentamicin is more nephrotoxic than other aminoglycosides. During normal conditions net acid excretion (BH) did not change with any of the three tested drugs. However, after an acute acid load BH markedly fell regardless of the antibiotic used. The capacity to elevate the urine-blood pCO2 was preserved after an alcaline overload, suggesting that the distal tubule was not significantly affected by aminoglycoside treatment. These data suggest that the clinical use of aminoglycosides during metabolic acidosis deserves close attention due to the possible deleterious effect that can emerge as the result of an inappropriate retention of acid loads.
The intrarenal kallikrein-kinin system was studied during the acute phase of renovascular hypertension induced by renal artery constriction and during teprotide inhibition of kininase II in the dog. Kallikrein-like activity measured by both kininogenase and esterolytic assays, was increased during renal artery constriction (p less than 0.5) and (p less than 0.01). The administration of teprotide resulted in a further increase of renal cortical kallikrein-like activity and inhibited kininase II activity (p less than 0.01). Following the inhibition of kininase II, the plasma concentration of kininogen was also significantly decreased (p less than 0.01). These results suggest that kininase II inhibition may increase levels of intrarenal and plasma kinins and that decreased degradation of kinin peptides may contribute significantly to the acute hypertensive effect of teprotide.
The nephrotoxic effect of cisplatin (5 mg/kg i.v.) was evaluated in 8 dogs 48-72 h after administration. The lithium clearance method was used for assessing the absolute and fractional reabsorption rates of sodium and water in proximal as well as in more distal segments of the total nephron population, before and during saline loading (infusion of 5 ml/kg of isotonic saline i.v.). Histological examinations of the kidney biopsies were used to evaluate the degree of renal tissue injury. During 48-72 h after administration of cisplatin blood urea nitrogen and plasma creatinine increased significantly from 3.9 +/- 0.2 to 11.7 +/- 1.4 mmol/l and 96 +/- 3 to 178 +/- 10 mumol/l, respectively. Mean values of renal blood flow, glomerular filtration rate, filtration fraction and lithium clearance in cisplatin-treated animals (143 +/- 14 ml/min, 10.7 +/- 1.1. ml/min, 0.14 +/- 0.01 and 6.3 +/- 0.6 ml/min, respectively) were significantly lower than in 6 control animals (212 +/- 8 ml/min, 49.0 +/- 2.0 ml/min, 0.36 +/- 0.001 and 10.1 +/- 1.3 ml/min, respectively). In contrast, urinary excretion rates of sodium, potassium and water were significantly higher, while fractional as well as absolute proximal and distal reabsorption rates were significantly lower in cisplatin-treated animals compared to controls. Saline loading caused an increase in the output of tubular fluid from the proximal tubules (lithium clearance) in the cisplatin-treated animals, while the fractional distal reabsorption rate of sodium decreased significantly. The histological changes are in agreement with the physiological data which point to the proximal tubules as the more severely damaged segment. In conclusion, the depressed renal function 48-72 h after administration of cisplatin can be attributed to impairment of proximal as well as distal tubular reabsorptive capacities associated with increased renal vascular resistance. The polyuria seems to be due to impaired reabsorption rates in the distal nephron segments, which will affect the concentration mechanism.
The effects of administered thromboxanes on the intact, normal rat kidney were studied. Euvolemic male rats received intraarterial infusions of thromboxane B2 (TXB2) and the stable thromboxane A2 analog (U46619) and the effects on renal function were investigated, using glomerular micropuncture and whole-kidney clearance techniques. Both TXB2 and U46619 were renal vasoconstrictors and lowered GFR by reducing renal plasma flow rate; U46619 was much more potent that TXB2. Neither agent caused any marked change in the glomerular capillary ultrafiltration coefficient (Kf). Thus in the rat, the thromboxanes reduce filtration rate by increasing renal vascular resistance and without exerting a marked influence on Kf.
