Superficial nephron tubular-vascular relationships in the rat kidney

Silicone rubber injections of methyl salicylate-cleared rat kidneys were performed. In 50 of 56 injections of superficial nephrons with their accompanying blood supply, the efferent vessel and early proximal tubule were closely approximated. In 18 of 21 tubular injections filling through the pars recta, the proximal tubule folded upon itself with early and late proximal segments, in close contact, located over their parent glomerulus, and the midproximal segments separate and located over their parent interlobular artery. The distribution of blood was serially through the early-late proximal region above the glomerulus via a long unbranched efferent vessel, via branches over the capsular surface, via capillaries down through the midproximal region, then into the interlobular vein. The observed anatomical pattern of the superficial nephron appears to permit direct functional interactions between the juxtaposed early and late proximal tubule, and in turn may effect midproximal function via the distribution of blood (modified by early proximal) from the efferent vessel to midproximal convolutions. In addition, the relationship between specific segments of the proximal tubule and specific portions of the postglomerular peritubular blood supply may be important in determining the distribution of peritubular physical forces to these nephrons.     

Effects of parathyroid hormone on electrolyte transport in the hamster nephron.

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.     

Cellular heterogeneity of the distal nephron and its relation to function

Summary The distal segments beyond the macula densa — distal convoluted tubule, connecting tubule, cortical collecting duct — display cellular heterogeneity. The four different cell types, namely the DCT cell, CNT cell, the principal cell and intercalated cell differ mainly by the pattern of membrane amplification and they reveal also qualitative differences as to some cytoplasmic proteins.Each of the four cell types adapts to chronic changes in electrolyte metabolism with structural alteration, concerning essentially the membrane area over which the active transport step of the cell proceeds, in DCT-, CNT- and P-cells the basolateral cell membrane with the Na-K-ATPase, in intercalated cells the luminal cell membrane with a H⁺ ATPase. Since each cell type responds only to specific conditions with changes in membrane area and associated transcellular transport activity, morphological studies can help to determine the specific role of each cell type in the regulation of renal electrolyte excretion. Such investigations demonstrated that besides mineralocorticoid hormones the transport capacity of certain cells should depend on the solute composition of tubular fluid. Thus, changes in the transport pattern specifically induced in only one segment alters also the transport patterns of segments downstream. Cellular heterogeneity seems to guarantee the optimal regulation of renal electrolyte excretion.     

Effects of certain diuretics on the electrophysiological characteristics of the nephron in the rat kidney

Electrophysiological micropuncture techniques were used to study the effect of certain diuretics on transtubular transport of electrolytes in the rat kidney. The mercurial diuretic novurite caused a reduction of active sodium transport in the proximal tubule, measured by short-circuit current and increased permeability of the tubular wall to ions which led to a considerable drop in transtubular potential and transepithelial resistance. Ethacrynic acid decreased the short-circuit current in the proximal tubule, without changing the permeability characteristics of the nephron. Xanthine diuretic euphylline did not reduce the short-circuit current in the proximal segment of the nephron; however, it increased the transepithelial potential of the renal tubule. In the distal tubule, euphylline and ethacrynic acid increased the difference in transtubular potential, whereas novurite reduced the transtubular potential. An increase in the electrical gradient of the distal tubule as a result of euphylline and ethacrynic acid action may be responsible for increasing potassium excretion. A decrease of the transtubular potential in the potassium excretion under mercurial diuretic action. The reduction of tubular reabsorption as a result of diuretic action is due to drug effect on different levels of the transtubular-ion transport system.     

A mathematical model of fluid transport in the kidney

A mathematical model of the rat kidney is developed from glomerular and tubular submodels. It is assumed that all nephrons are identical, that the hydraulic pressure in the tubules obeys Hagen-Poiseuille's law, that the rate of fluid reabsorption depends on the flow rate of tubular fluid, and that the tubules are distensible. The independent variables of the model are selected to comply with experimental measurements in the hydropenic rat. The model is used to evaluate the mechanism of glomerulotubular balance: changing the mean ultrafiltration pressure in the glomerular capillaries has a substantial influence on glomerular filtration rate (GFR). A change in the rate of fluid reabsorption in the proximal tubules has a strong influence on GFR notwithstanding that the change in GFR is smaller than that in the rate of fluid reabsorption. The calculated values for the hydraulic pressure profile in the tubular system and the interstitial pressure during ureteral obstruction are in close agreement with experimental measurements. Increasing the arterial haematocrit above normal causes a substantial decrease in GFR, whilst reducing it below normal has only a small effect on GFR.     

Renal potassium transport: contributions of individual nephron segments and populations.

General features of the processes that contribute to renal potassium excretion are understood from clearance, stop-flow, micropuncture, and in vitro microperfusion experiments. However, the complex architecture of the kidney has made it difficult to examine individual nephron segments in all parts of the kidney. Accordingly, the extent to which distinguishable nephron populations, such as superficial and deep, may differ in their contributions to overall potassium excretion are not known. Also, the nature of transport processes across the successive segments of the nephrons (including not only the underlying cellular mechanisms, but even the direction of transport) is not known for all segments in any one nephron population. Excreted potassium is derived both from filtered potassium that escapes reabsorption and from secreted potassium. The filtered portion is large in amphibians and may be larger than generally recognized in mammals. The remainder is secreted primarily by distal nephron segments (distal tubule and cortical collecting duct). Potassium is also secreted into descending limbs of Henle loops; apparently this fraction is recycled from collecting ducts, and so does not represent an additional quantity of potassium transferred from blood to tubule fluid. Systemic factors that affect potassium excretion (potassium intake, sodium chloride intake, mineralocorticoid hormone levels, acid-base balance, and diuretic treatments) do so by modifying the net uptake of potassium from blood to cell and by altering the rate of fluid flow through the distal nephron. Under most circumstances, the distal nephron in the cortex appears to secrete potassium and the medullary collecting duct reabsorbs potassium. Although it is clear that successive nephron segments transport potassium in different ways, evidence to date does not indicate that potassium is handled differently by superficial nephrons compared to nephrons whose glomeruli lie in the deeper levels of the cortex.     

Effects of inhibition of chloride transport on intracellular sodium activity in distal Amphibian nephron

Previous experiments had demonstrated that cell chloride activities in early distal tubule cells of Amphiuma are above equilibrium distribution. Chloride activities fell sharply towards electrochemical equilibrium following perfusion of the tubular lumen with furosemide or with sodium-free solutions. These results suggested a furosemide-sensitive sodium chloride cotransport system in the luminal cell membrane. The present experiments were carried out to evaluate directly the electrochemical driving forces acting on sodium ions under similar experimental conditions. Intracellular sodium activity measurements were performed in the doublyperfused kidney of Amphiuma by means of single-barreled liquid ion-exchange microelectrodes. Basolateral cell membrane potential and resistance ratio measurements of tubular cell membranes were also carried out under control conditions and after inhibition of chloride transport by luminal application of furosemide (5 · 10^–5 mol/l) or by omission of chloride.Control conditions were characterized by a steep downhill electrochemical gradient for sodium ions from lumen to cell. Inhibition of chloride transport led to a sharp decrease of intracellular sodium activity and to hyperpolarization of the peritubular membrane potential while the resistance ratio of the tubular cell membranes did not change significantly. These results demonstrate the presence of low cellular sodium activities in early distal tubule cells. The sharp decline of cell sodium after furosemide and after luminal chloride removal is consistent with inhibition of a sodium chloride cotransport system and continued peritubular sodium extrusion. The latter can increase the electrochemical gradient of sodium ions beyond that observed under control conditions.This work was supported by NIH Grant PHS AM 17433 and by Österreichischem Forschungs-Proj. No.: 4366.Part of the data has been presented at the 55th meeting of the Deutsche Physiologische Gesellschaft, Innsbruck 1981 an at the International Symposium on Molecular Basis of Tubular Transport and Action of Diuretics, Bonn 1981.     

Reverse engineering the kidney: modelling calcium oxalate monohydrate crystallization in the nephron

Crystallization of calcium oxalate monohydrate in a section of a single kidney nephron (distal convoluted tubule) is simulated using a model adapted from industrial crystallization. The nephron fluid dynamics is represented as a crystallizer/separator series with changing volume to allow for water removal along the tubule. The model integrates crystallization kinetics and crystal size distribution and allows the prediction of the calcium oxalate concentration profile and the nucleation and growth rates. The critical supersaturation ratio for the nucleation of calcium oxalate crystals has been estimated as 2 and the mean crystal size as 1 μm. The crystal growth order, determined as 2.2, indicates a surface integration mechanism of crystal growth and crystal growth dispersion. The model allows the exploration of the effect of varying the input calcium oxalate concentration and the rate of water extraction, simulating real life stressors for stone formation such as dietary loading and dehydration.     

Autoregulation of superficial nephron function in the alloperfused dog kidney

Isolated dog kidneys were each pumpperfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i. e. 160, 130, 95, and 60 mm Hg). At the 3 highest PP values, the total kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were perfectly autoregulated while at the lowest value both values were significantly lowered. No significant difference was observed between the single nephron GFR (SNGFR) of periods 1 and 2; in period 3 (PP=13 kPa) a lower value was observed (P<0.05). Free flow pressure in proximal convolution (FFP), stop-flow pressure (SFP), and peritubular capillary pressure (PCP) were not different in period 2 than in period 1, but were significantly lower in period 3 (P=0.02–0.05). Effective filatration pressure (EFP) was the highest in period 1, decreasing significantly with decreasing PP. Filtration pressure equilibrium was observed in period 4 at PP 8 kPa. Total blood flow resistance (R_T) fell with decreasing PP, the drop being due to a steep decline in afferent resistance (R_A). Efferent resistance (R_E) increased as PP decreased. Ultrafiltration coefficient (K_f) rose with declining PP both within and outside the autoregulatory range. The results indicate that the lower limit of autoregulation is higher in superficial nephrons than in the whole kidney.     

The ultrastructural development of distal nephron segments in the human fetal kidney

Summary The ultrastructural development of the human distal nephron was studied in fetuses 14–18 weeks of gestational age. The three-dimensional course of the nephrons was traced in serial semi-thin sections. Single semi-thin sections containing defined distal nephron segments were then reembedded, thin-sectioned and analyzed by electron microscopy. In stage I (renal vesicle) and stage II (S-shaped body) epithelial cells were essentially similar in ultrastructure. In stage III there were only minor variations in cell ultrastructure between distal nephron segments, but distinct differences were observed between proximal and distal tubule cells, the former being the most differentiated. The segments which are present in nephrons of adult kidneys could be identified in stage IV and some ultrastructural differences recognized between the cells. However, the amplification of the baso-lateral membrane, which is prominent in iontransporting mature distal segments, was almost absent and the baso-lateral membrane area per unit tubule length was similar in all distal segments. Intercalated cells were present towards the end of the distal convoluted and in the connecting tubule in stage IV but the ampulla of the collecting tubule was composed of cells with a uniform ultrastructure. Cell ultrastructure varied again to some extent in the collecting tubule.The present observations demonstrate that distal nephron segments in the human kidney are structurally undifferentiated in the early fetal development and suggest that they only to a limited extent are capable of modifying the composition of the tubular fluid.