Recent advances in renal morphology.
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Animals↗
Biomedical subjects
D C Dobyan
Publications and source records attributed to D C Dobyan.
Renal carbonic anhydrase.
Carbonic anhydrase is a zinc metalloenzyme widely distributed throughout the tissues of the body. This enzyme exists in a number of isozymic forms in most mammalian species. Significant advances over the past decade have been made in characterizing the nature of renal carbonic anhydrase. In the kidney, this enzyme is thought to play a pivotal role in urinary acidification and bicarbonate reabsorption. Two distinct isozymes of carbonic anhydrase have now been identified in the mammalian kidney. A soluble cytoplasmic form, similar if not identical to human erythrocyte carbonic anhydrase C, accounts for the bulk of the renal carbonic anhydrase activity. In addition, a membrane-bound form constituting only about 2--5% of the renal activity has been found in the brush border and basolateral fractions of kidney homogenates. The histochemical and immunocytochemical localization of these isozymes along the nephron and collecting duct system of various mammalian species suggests that marked heterogeneity exists. The Editorial Review examines the biochemical and morphological approaches that have been used to elucidate the nature of renal carbonic anhydrase and to assess its distribution along the urinary tubule. Possible physiological roles for the renal carbonic anhydrases are considered for the different segments of the nephron and collecting duct system.
Animals↗
Effect of furosemide on sodium and potassium flow at the end of the juxtamedullary descending limb in Psammomys obesus.
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.
Animals↗
Mercuric chloride-induced acute renal failure in the rat. I. Correlation of functional and morphologic changes and their modification by clonidine.
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Acute Kidney Injury↗
Effect of potassium depletion on tubular morphology in gentamicin-induced acute renal failure in dogs.
Potassium deprivation has recently been reported to potentiate the degree of functional impairment in a gentamicin-induced model of acute renal failure. The present study investigated the effects of two different states of potassium homeostasis on the development of cellular injury in the early stage of gentamicin nephrotoxicity in dogs. Gentamicin (15 mg. per kg. intramuscularly twice daily) was administered for 4 and 7 days to potassium-depleted or potassium-supplemented animals. The results show that potassium supplementation markedly lessens the severity of pathologic alterations induced by gentamicin. In both groups of animals, the S1 and S2 segments of the proximal tubule were the most consistently damaged regions of of the nephron. Potassium-supplemented dogs had a significantly higher number of normal proximal tubule cells than did the animals deprived of potassium and viewed 7 days after gentamicin treatment (77.3 versus 36.9 per cent; p less than 0.025). The degree of total injury to the proximal tubule was significantly higher in potassium-depleted animals than in those supplemented with potassium (59.9 versus 21.9 per cent; p less than 0.05). Only those dogs depleted of potassium prior to the administration of gentamicin had a markedly elevated plasma creatinine level of proximal tubular injury and functional impairment (r = 0.81; p less than 0.005). Potassium supplementation appears to lessen the extent of structural alterations seen in this model of gentamicin-induced acute renal failure in dogs.
Acute Kidney Injury↗
The ultrastructure of the thin limbs of Henle in Kidneys of the desert heteromyid (Perognathus penicillatus).
The thin limbs of both long- and short-looped nephrons in Perognathus kidneys were studied with transmission and scanning electron microscopy. The superficial nephrons have a short thin limb located in the vascular bundles of the outer medulla and are characterized by a simple, low-lying epithelium (0.4 +/- 0.1 mu thickness). In contrast, the first descending part of the thin limb of the majority of midcortical and juxtamedullary nephrons has a relatively thick epithelium (1.7 +/- 0.6 mu in thickness) with marked lateral and basal interdigitation and a dense surface covering of microvilli. The remaining part of the long descending thin limb is relatively simple with a low-lying epithelium (0.6 +/- 0.1 mu in thickness), decorated on its surface by sparse microplicae. The bend of the loop and the ascending limb are covered by a very simple low-lying epithelium (0.6 +/- 0.2 mu in thickness) with relatively little surface modification. The extreme urine-concentrating ability of Perognathus does not appear to be due to the development of a unique thin loop epithelium but rather to the extensive length of the inner and outer medulla.
Animals↗
Potassium recycling in the renal medulla: effects of acute potassium chloride administration to rats fed a potassium-free diet.
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.
Amiloride↗
Cyst formation in rat kidney induced by cis-platinum administration.
The long-term pathologic effects of the antitumor drug, cis-diamminedichloroplatinum II (CP) on the structure of the rat kidney were investigated. Light microscopy and transmission and scanning electron microscopy were used to characterize the morphologic changes 2 weeks, 4 weeks, and 6 months after the intraperitoneal injection of CP to rats. At all time intervals examined, the S3 segment of the proximal tubule located in the outer stripe of the medulla showed the most consistent pattern of injury. Two weeks after CP, the proximal tubules located in the outer stripe region as well as in the medullary rays were widely dilated and lined by low-lying epithelial cells, many of which contained large atypical nuclei. Many tubules still showed evidence of necrosis, whereas other tubules appeared to be undergoing atrophic changes. After 4 weeks, proximal tubular dilation continued resulting in the formation of numerous microcysts in the region of the outer stripe. These changes appeared to progress, and after 6 months large cysts (mean diameter 2152 +/- 1241 micrometer) were identified which involved the entire outer stripe, with many of these cysts extending to the subcapsular cortex. The kidneys at this time period showed a pattern of chronic renal injury in the outer stripe, and this damage was now also observed in the cortex. In several animals, small foci of abnormal foam cells surrounded by a basal lamina could be identified. We conclude that CP has a pronounced long-term effect and causes cyst formation in the rat kidney.
Animals↗
Effect of potassium depletion on gentamicin nephrotoxicity.
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Animals↗
Glomerular architectural changes after a two-hour infusion of norepinephrine.
Alterations in glomerular architecture have been suggested to play a role in the pathogenesis of several models of acute renal failure. In this study, mongrel dogs were subjected to an intrarenal infusion of norepinephrine for 2 hours. Light microscopy and scanning and transmission electron microscopy were used to describe glomerular architecture 2 days after the initial norepinephrine infusion. In addition, scanning electron microscopy was used to quantitate the percentage of "abnormal areas" in glomerular capillary-loop morphology in both norepinephrine-infused kidneys and the contralateral control kidneys. Alterations in glomerular structure in these experiments appeared to be much less extensive than previously reported. A variable amount of glomerular pedical shape simplification was seen, which involved about 15% of the capillary loop. Quantitative evaluation revealed abnormal morphology of 15.2% +/- 0.6% of the glomerular capillary loop in the norepinephrine-infused kidneys, compared to 2.9% +/- 0.4 abnormal loop structure in the contralateral control kidneys (P less than 0.001). It is concluded that alterations in glomerular structure are not extensive in this model.
Acute Kidney Injury↗
Terminal papillary collecting duct reabsorption of water, sodium, and potassium in Psammomys obesus.
Micropuncture studies were performed to assess the contribution of the terminal collecting duct to reabsorption of water, sodium, and potassium in the desert rodent, Psammomys obesus. Tubule fluid was collected at base and tip of the exposed papilla before (period I) and after (period II) administration of furosemide. In period I, a significant rise occurred in tubule fluid-to-plasma (TF/P) ratios of inulin, osmolality, and sodium and potassium from base to tip; 2.3 +/- 0.8% of filtered water and 5.1 +/- 1.7% of filtered sodium were reabsorbed by the collecting duct. In period II water, sodium, and potassium delivery to the collecting duct was significantly increased. Although TF/P ratios for inulin, osmolality, and sodium and potassium were lower at base and tip in period II than corresponding values in period I, all ratios increased between base and tip. Approximately 3 times as much water (7.4 +/- 1.8%) and twice as much sodium (10.1 +/- 3.0%) were reabsorbed by the exposed collecting duct in period II. These results reveal a remarkable reabsorptive capacity and suggest that the terminal collecting duct plays an important role in regulation of water and sodium excretion in Psammomys obesus.
Animals↗
Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations.
Light microscopy, transmission electron microscopy and scanning electron microscopy were used to characterize the morphologic alterations and to localize the site of injury within the kidney 1, 2, 3, 5 and 7 days after the intraperitoneal injection of cis-diamminedichloroplatinum. Pathologic alterations were evident 3 days after the injection of the drug and were localized to the S3 segment of the proximal tubule situated in the outer stripe of the outer medulla. A spectrum of changes was seen in this S3 segment which included a thinning or focal loss of brush border, cellular swelling, condensation of the nuclear chromatin and focal areas of necrosis. After 5 days, widespread tubular necrosis of the S3 segment in the outer stripe was the predominant finding. Necrotic tubular epithelial cells could be seen detaching from the basal lamina and being sloughed into the tubular lumen. Only a bare basal lamina remained in many areas. Regeneration of the S3 segment was seen after 7 days and was characterized by tubules with widely dilated lumens which were lined by many low-lying epithelial cells. The observation that cis-diamminedichloroplatinum exerts its nephrotoxic effect on the S3 segment of the proximal tubule located in the outer stripe of the outer medulla demonstrates that the pattern of injury produced by this antitumor drug is similar to that associated with other nephrotoxic and ischemic models of acute renal failure.
Animals↗
Survey of the morphology of the dog kidney.
Dogs are frequent subjects in experimental studies of renal physiology and pathology in spite of the paucity of information on their normal renal morphology. In this study, gross morphology, light microscopy, and scanning and transmission electron microscopy were used to describe dog renal anatomy. The dog has a multilobed kidney with the medulla fused into an elongate crest and a renal pelvis of elaborate shape. The outer zone of the medulla lacks a definitive outer stripe. The proximal tubule consists of four distinct anatomical segments. Dark cells are abundant in the collecting duct of the inner medulla. The majority of the nephron segments demonstrate remarkable similarities to those of the human kidney and less to those of the kidney of the laboratory rat.
Animals↗
Suppression of potassium-recycling in the renal medulla by short-term potassium deprivation.
Recently we proposed that potassium, like urea, normally undergoes medullary recycling from collecting tubule to the pars recta or descending limb of the juxtamedullary nephron and suggested that the extent of recycling is a function of the concentration of potassium in collecting tubule fluid. To test this hypothesis further, we fed young rats a potassium-free diet for 3 days and then prepared them for micropuncture of the left renal papilla. Compared to findings in normally fed animals, potassium deprivation caused a significant fall in plasma potassium and urinary excretion of potassium. There was a striking decrease in the fraction of filtered potassium remaining at the end of the justamedullary descending limb for 94 +/- 11% to 38 +/- 3% (P less than 0.001). The latter value is not significantly different from the fraction of filtered sodium remaining (36 +/- 4%) and suggests that net addition of potassium to the pars recta or descending limb was completely abolished. A correlation was observed between the fraction of filtered potassium remaining at the end of the descending limb and either urinary potassium excretion (P less than 0.001) or urinary potassium concentration(P less than 0.001) in the contralateral unexposed kidney. These results lend further support to the hypothesis of medullary recycling of potassium.
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Effect of chronic potassium loading on potassium secretion by the pars recta or descending limb of the juxtamedullary nephron in the rat.
Recently we demonstrated potassium secretion by the pars recta or by the descending limb of the juxtamedullary nephron. The purpose of this present investigation is to study the effect of a chronic high-potassium intake on this phenomenon. Fractional reabsorption of water and sodium by the juxtamedullary proximal nephron was decreased when compared to that in normal hydropenic rats. There was a striking increase in the fraction of filtered potassium at the end of the juxtamedullary descending limb from 94+/11% to 180+/18%, which was principally a result of enhanced potassium secretion. When the concentration of potassium in the collecting tubule fluid of potassium-loaded rats was reduced after the administration of amiloride, a sharp fall was observed in the amount of potassium which reached the end of the descending limb (64+/8%). A direct correlation was observed between the fraction of filtered potassium at the descending limb and the potassium concentration in the final urine (P less than 0.001). The findings suggest that potassium, like urea, normally undergoes medullary recycling, which is enhanced by chronic potassium loading.
Amiloride↗
Hypovolemic models of acute tubular necrosis in the rat kidney.
Studies were undertaken to determine whether a hypotensive episode under variable conditions is capable of inducing experimental acute renal failure in rats. Animals were subjected to hypovolemic shock by withdrawing volumes of blood necessary to maintain a systolic pressure of 30-40 mm Hg for 105-110 min. The blood was then reinfused and the animal was allowed to recover for 48 h prior to sacrifice. In an attempt to increase the injury, a second group of animals was salt-depleted prior to injury, a third group was volume-depleted by being deprived of H2O for 72 h prior of injury, a fourth group received 7.5 mg/kg indomethacin 30 min prior to injury, and a fifth group had 30% of the blood which was removed to produce shock hemolyzed and returned following the injury. In all groups examined, light microscopy revealed a moderate to severe acute tubular necrosis localized mainly in the outer stripe of the outer zone as defined by Peter (1909). Tubular damage was confined to the medullary pars recta of the proximal tubule and only in the most severe cases did injury involve the cortical pars recta and pars convoluta. Casts were present in the distal tubules and collecting ducts. Despite these significant histologic alterations, BUN values from all experimental groups remained within control levels. These studies clearly show that extensive necrosis of the medullary pars recta can be dissociated from the development of acute renal failure.
Acute Kidney Injury↗
Acute tubular necrosis in the rat kidney following sustained hypotension: Physiologic and morphologic observations.
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Acute Kidney Injury↗