A patient with polyuria and hyponatremia.
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Biomedical subjects
Publications and source records attributed to R L Jamison.
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Rats fed a low potassium diet were studied before and after KCl infusion to determine whether potassium recycling in the renal medulla accelerates potassium excretion by increasing delivery of sodium, water, and potassium to the distal tubule. Fluid samples were obtained from the end-proximal and beginning-distal tubule before and at the same sites after KCl loading by re-collection micropuncture and were compared with samples obtained from similarly fed control animals not infused with KCl. Potassium excretion increased in the KCl group from 3 to 48% but remained low in the controls. Fractional sodium and water delivery to end-proximal and beginning-distal tubule increased with time equally in both groups. Potassium reabsorption in Henle's loop fell from 75 to 58% (P less than 0.005) after KCl infusion but not significantly in the controls (from 77 to 75%). Fractional potassium delivery to the distal tubule increased from 12 to 26% (P less than 0.005) in the KCl group, which could account for over half the potassium excreted. The increase in controls from 12 to 17% was significantly less (P less than 0.02). These findings suggest that potassium recycling reduces potassium reabsorption in Henle's loop, enabling the loop to participate with the distal and collecting tubule in accelerating urinary excretion of an acute potassium load.
Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (n = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine gamma-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 +/- 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 +/- 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 microliter/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 microliter/min. The difference between outflow and inflow (6.1 microliter/min) represents an estimate of water by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla.
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Glomerular and tubular function were evaluated in 30 non-oliguric patients with increasing azotemia following open heart surgery. Fractional clearances (theta) of test solutes relative to that of inulin were determined. In 16 patients, theta dextran (radius 22 to 30 A) exceeded unity, a finding attributed to inulin backleak through necrotic tubules. These patients were classified as having acute renal failure; 14 subsequently required dialysis. In the remaining patients (N = 14), theta dextran was normal. These patients were considered to have prerenal failure; all recovered spontaneously. clearance of inulin (Cin) was lower in acute renal failure than in prerenal failure (12 +/- 2 versus 18 +/- 2 ml/min/1.73 m2; p less than 0.025). The apparent difference in glomerular filtration rate when Cin is used as an index was abolished, however, when Cin in acute renal failure was corrected for tubule backleak of inulin. In acute renal failure, fractional clearance of p-aminohippurate (theta PAH) was 7.1 +/- 1.0, and fractional excretion of potassium (FEk) was 160 +/- 18 percent. These findings strongly suggest that secretory ability in both proximal and terminal tubule augments, respectively, is preserved in acute renal failure. Compared with prerenal failure, the urine-to-plasma inulin ratio was lower (U/Pin = 10 +/- 1 versus 25 +/- 4; p less than 0.005) and FENa was higher (FENa = 5.1 +/- 1.5 versus 0.5 +/- 1.0 percent; p less than 0.01) in acute renal failure.
A new approach to the classification of disorders of urinary concentration and dilution is recommended based on recent studies of how the kidney elaborates a urine of widely varying osmolality. The capacity to concentrate urine depends on ft, the fractional reabsorption of solute delivered to the loop of Henle; fu, the excretion of solute relative to the sum of solute excretion and solute delivery to Henle's loop; fw, the fraction of solute loss by vascular outflow from the medulla relative to that reabsorbed by the loop; and finally, collecting duct response to antidiuretic hormone (ADH). A decrease in ft or in increased fu or fw will diminish urinary concentrating ability, as will resistance of the tubule to ADH. Conversely, urinary dilution depends on the delivery of sodium and water to the ascending limb; NaCl reabsorption by the ascending limb; and the absence of ADH. A decrease in sodium and water delivery to the ascending limb or in NaCl reabsorption by the ascending limb will impair urinary diluting ability, as will the presence of ADH. The consequences of disorders in urinary concentrating and diluting ability vary widely. In an alert patient with an intact thirst center, there may be no consequence; in a patient unable to communicate thirst or whose thirst center is deranged, the results may be catastrophic. Keeping in mind the kidney's few basic requirements for formation of concentrated or dilute urine may help the physician avoid these potentially serious dislocations of water balance.
A patient with profound hypokalemia satisfied the criteria for Bartter's syndrome, including hyperreninemia, aldosteronism, normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. Two screening tests of urine and one of plasma for diuretic agents gave negative results. A third urinary sample gave negative results for thiazide but positive for furosemide; the fourth and fifth samples gave negative results for furosemide but positive for thiazide. Urinary prostaglandin excretion was normal. We conclude that this apparent case of Bartter's syndrome was caused by long term surreptitious diuretic ingestion and suggest this may occur more frequently than is generally appreciated.
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This review focuses on the hypothesis that potassium is recycled in the medulla by secretion into the pars recta or descending limb of long-looped nephrons and reabsorption from the ascending limb and/or medullary collecting duct. Evidence supporting the recycling hypothesis is summarized and the process is analyzed quantitatively by an examination of the mass flow of potassium reaching different sites along superficial and juxtamedullary nephrons and collecting tubules. From differences in potassium mass flow between sites, we have estimated the amount of potassium that must be secreted or absorbed by individual segments of the renal tubule. These rates of secretion and absorption are compared with the potassium transport characteristics of the respective segments, as assessed by isolated tubule perfusion in vitro and micropuncture in vivo. It is apparent that potassium secretion can occur passively in the pars recta and descending limb of long-looped nephrons as a consequence of the elevated potassium concentration in the medullary interstitium. At present, no active potassium absorptive mechanism has been demonstrated in any segment of the ascending limb. Due to the very high ionic permeability of the thin ascending segment and the lumen-positive transepithelial voltage in the thick ascending segment, however, considerable passive absorption likely occurs, although net potassium secretion has also been demonstrated in the cortical thick ascending limb. The high potassium concentration in the inner medullary interstitium and the difference in mass flow of potassium between the end of superficial nephrons in the cortex and the collecting ducts in the papilla, at least under certain circumstances, are best accounted for by net potassium reabsorption in the medullary collecting duct.
Effects of acute-base disturbances on fractional delivery of potassium to the juxtamedullary end-descending limb were examined by micropuncture in the rat to test the hypothesis that potassium is reabsorbed from the collecting duct and is secreted in juxtamedullary pars recta or descending limb in the renal medulla. In metabolic acidosis, fractional potassium delivery was only slightly reduced compared with control values and was a function of potassium excretion, as the hypothesis predicts. Fractional potassium delivery was sharply reduced both in respiratory acidosis and metabolic alkalosis and was no longer a function of potassium excretion. Although seemingly inconsistent with the recycling hypothesis, the latter finding may be reconciled by the following observations. In respiratory acidosis, vasa recta blood flow nearly doubled, which would lead to vascular washout of interstitial potassium. In metabolic alkalosis, flow rate in the pars recta or descending limb was reduced by 28%, which would limit transepithelial potassium addition. The results indicate complex effects of acid-base disturbances on fractional potassium delivery to the end-descending limb, which can be unified by postulated changes in transepithelial potassium concentration differences across the juxtamedullary pars recta or descending limb. An unexpected observation emerged--fractional delivery of water to the end-descending limb declined as a function of plasma bicarbonate concentration when all groups were combined.
The effects of acute metabolic and respiratory acidosis and acute metabolic alkalosis on magnesium excretion and on fractional magnesium delivery to the end-accessible proximal tubule of the superficial nephron and the end-descending limb of the juxtamedullary nephron were examined by micropuncture in anesthetized thyroparathyroid-intact rats. Compared with normal control rats, acute metabolic acidosis (HCl infusion) did not produce any significant change. Acute respiratory acidosis (15% CO2 in inspired air) significantly increased the absolute but not the fractional excretion of magnesium and did not alter fractional delivery of magnesium to the end-accessible superficial proximal tubule or juxtamedullary end-descending limb. Acute metabolic alkalosis (NaHCO3 infusion) significantly reduced absolute and fractional magnesium excretion and fractional magnesium delivery to the end-descending limb of the juxtamedullary nephron but did not affect fractional magnesium delivery to the end-accessible proximal tubule of the superficial nephron. Tubule fluid-to-ultrafilterable magnesium ratio was a function of tubule fluid-to-plasma inulin ratio in the end-descending limb when all groups were combined. These results suggest that although acute metabolic or respiratory acidosis has no significant effect, acute metabolic alkalosis enhances magnesium reabsorption in the juxtamedullary proximal nephron--possibly in the pars recta.
To examine the effect of reducing medullary interstitial solute concentration on sodium and potassium flow at the end of the juxtamedullary descending limb in Psammomys obesus, micropuncture was performed on the exposed left renal papilla. After a control period, furosemide was administered to reduce medullary interstitial solute concentration without altering the delivery of sodium, potassium and water from the proximal tubule. The fraction of filtered sodium remaining at the end-descending limb before (52 +/- 4.9%) and after furosemide (55 +/- 4.2%) was not significantly different, despite a fall in tubule-to-plasma osmolality from 4.32 to 2.00 (p less than 0.001). In contrast, the fraction of filtered potassium delivered to the end-descending limb fell from 92 +/- 9.0% to 61 +/- 8.0% (p less than 0.001). As expected, the fraction of filtered sodium and potassium remaining at the end of the accessible proximal tubule of the superficial nephron was not changed after the administration of furosemide. While these findings do not provide additional support for the thesis of transepithelial sodium addition to the juxtamedullary descending limb, they strongly suggest that transepithelial entry (secretion) of potassium normally occurs upstream to the juxtamedullary hairpin turn of Psammomys obesus.
Urine was observed to flow intermittently in the collecting ducts of the extrarenal papilla of antidiuretic rats. The purpose of this investigation was to test Reinking and Schmidt-Nielsen's hypothesis that intermittent flow plays an important role in the production of maximally concentrated urine. Samples of collecting duct fluid were obtained from the base and tip of the papilla by micropuncture through the intact ureter. Fluid osmolality rose sharply from base, 894+/-120 mosmol/kg H(2)O(-1) (mean+/-SE), to tip, 1,667+/-114 (P<0.001), a distance of only 2 mm, and was due exclusively to reabsorption of water. After excision of the ureter, which abolished intermittent flow, osmolality fell modestly at the base to 723+/-82 mosmol/kg H(2)O(-1) (P < 0.02), but strikingly at the tip to 1,012+/-103 (P < 0.001). The pelvic ureter was paralyzed by topical verapamil and dimethylsulfoxide, which abolished intermittent flow. Osmolality of urine at the tip was not changed (1,959+/-184 mosmol/kg H(2)O(-1) before, vs. 1,957+/-126 after paralysis). The ureter was severed just beyond the papillary tip, a maneuver which preserved intermittent flow but abolished urinary reflux over the papilla. Urinary osmolality fell from 1,876+/-134 mosmol/kg H(2)O(-1) to 1,284+/-115 (P < 0.005). These findings demonstrate that when the ureter is intact, over half of the increase in urinary osmolality above isotonicity occurs in the terminal one-fourth of the medullary collecting duct and is due exclusively to water reabsorption (no net solute addition). It is the continuity of the ureter, rather than intermittent flow due to ureteral peristalsis, which is essential for the formation of a maximally concentrated urine.
According to the hypothesis of potassium recycling in the renal medulla, a portion of potassium in fluid in the medullary collecting duct is reabsorbed, trapped in the medullary interstitium by countercurrent exchange, and secreted in either the pars recta or descending limb of the juxtamedullary nephron. To examine the effects of an acute change in potassium balance on recycling, we performed a micropuncture study on the exposed papilla of 8 chloride. A second group of 6 rats was studied under identical conditions and infused with potassium chloride and amiloride. In the first group, the fraction of filtered potassium remaining at the end of the juxtamedullary descending limb increased with time to values over 100% concomitantly with the rise in urinary excretion of potassium. A strong association was found between those two variables (P less than 0.025). In the second group, in which the increase in urinary fractional excretion of potassium was prevented by amiloride, the rise in fractional of filtered potassium remaining at the end of the juxtamedullary nephron was abolished. These findings are interpreted as providing further support for the hypothesis of medullary recycling of potassium.
A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.
Adult Munich Wistar rats undergoing mild salt diuresis (NaCl 20 g x l-1, 0.1 ml x min-1) were injected with tracer doses of 3H-Inulin and 32P-sodium phosphate in thin descending and ascending limbs of Henle's loop, collecting ducts accessible at the surface of the papilla and early distal superficial tubules. Kidneys were prepared for simultaneous papillar microinjection and urinary flow collection. Expressed in percent of the amounts injected, unidirectional phosphate reabsorption fluxes were 5 +/- 1% and 3 +/- 1% for injections into early distal superficial tubules and collecting ducts, respectively. By contrast, the flux was 21.7 +/- 3% for injections into either the descending or ascending thin limbs of juxtamedullary nephrons. We conclude from these results that in the rat, a significant amount of phosphate is reabsorbed by the juxtamedullary distal tubules and/or the subsequent arcades connecting the juxtamedullary distal tubules to the collecting ducts.
To provide an approximate estimate of the need for academic faculty in renal research, 1200 questionnaires were mailed to most departments in all medical schools in the United States. There were 627 completed questionnaires returned from 99 divisions of nephrology, 79 divisions or departments of urology, and 67 divisions of pediatric nephrology or departments of pediatrics in 120 medical schools. Analysis of the responses revealed that in these three departments there are 1057 faculty members engaged in teaching and research related to the kidney and urinary tract, and 131 current vacancies. The responses suggest that from 1979 to 1984 another 483 faculty members will be required to fill projected vacancies in the foregoing three clinical departments, making the total needed 614.