Anatomy of the renal pelvis in the hamster

The hamster renal pelvis has been studied by means of low-power light microscopy, scanning electron microscopy and morphometric analyses. The results of this study are highly suggestive that the contact of pelvic urine with the other medulla as well as with the inner medulla may be an important aspect of final urine formation. The outer medulla constituted nearly 50% of the total pelvic surface area, with the inner stripe of the outer medulla more than twice the pelvic surface area of the outer stripe of the outer medulla. The large outer medullary pelvic surface area was accounted for by the elaboration of the upper pelvic walls into peripelvic columns, opercula (“secondary pyramids”), fornices and secondary pouches. A thin simple-squamous to low cuboidal pelvic epithelium separated pelvic urine from outer medullary parenchyma. The inner medulla which constituted about one quarter of the total pelvic surface area was covered by a cuboidal to columnar pelvic epithelium which appeared morphologically similar to the papillary collecting duct epithelium. Tubules and capillaries of the inner medulla did not appear as closely juxtaposed to the pelvic epithelium as did those of the outer medulla. Cortical tissue comprised only 11.7% of the total pelvic surface area and was covered by transitional epithelium similar to that of ureter and bladder. The previously reported impermeability of this epithelium suggests that pelvic urine contact with the cortex is unimportant in final urine formation. The rich layer of smooth muscle under the transitional epithelium probably functions to move urine into and out of the pelvis during pelvic peristalsis, which has been observed in vivo.     

Effect of increased distal sodium delivery on organic osmolytes and cell electrolytes in the renal outer medulla

Sodium absorption in distal tubule segments was stimulated by increasing the distal delivery via infusion of hypertonic saline. In these animals, and in control rats, electrolyte concentrations in thick ascending limb cells, light and dark cells of the collecting duct in the outer and inner stripe of the outer medulla and in cells of the proximal straight tubule (outer stripe only) were studied. The measurements were performed by electron microprobe analysis of freeze-dried cryosections of the outer medulla. In addition, organic osmolytes (glycerophosphorylcholine, betaine and myo-inositol) were measured by high performance liquid chromatography in cortex and outer medulla. Augmented delivery of sodium chloride to the distal tubule was associated with increased sodium concentrations of thick ascending limb cells both in the outer and inner stripe and of medullary collecting duct light and dark cells in the outer stripe. While the sum of organic osmolyte concentrations was 28% higher in the outer medulla of the salt-loaded animals compared with controls, this value was unchanged in the renal cortex. These findings indicate that the primary event underlying stimulation of sodium absorption along the thick ascending limb during increased distal sodium delivery is enhanced entry of sodium across the apical cell membrane. This would be expected to lead to higher cell sodium concentrations and stimulation of basolateral active Na-K-exchange. The enhanced transport activity of outer medullary tubules may be associated with increased interstitial tonicities and intracellular retention of organic osmolytes.     

Early appearance and localization of intranuclear inclusions in the segments of renal proximal tubules of rats following ingestion of lead.

Intranuclear inclusions in epithelial cells lining rat renal proximal tubules were detected by electron microscopy as early as 4 days after the addition of lead (5 mg/ml as lead acetate) to the drinking water. At 9 and 12 weeks pathological changes, but very few intranuclear inclusions, were apparent in the epithelial cells lining the third segment of the proximal tubules in the outer stripe of outer zone of the medulla. On the other hand, morphological changes were less in the epithelial cells lining the first and second segments of the proximal tubules in the cortex, which contained many intranuclear inclusions. These findings suggest that lead incorporated into the epithelial cells in the proximal tubules may exist in an inert chemical form as inclusions, especially in the second segment. These bodies, therefore, may protect the cells from the toxic effect of lead.     

Ultrastructure of the thick ascending limb of henle in the rat kidney

The thick ascending limb of Henle (TAL) in the rat until recently has been considered a morphologically homogeneous structure despite physiologic and biochemical evidence to the contrary. The present study was designed to examine the ultrastructural characteristics of the TAL in the inner cortex and the outer and inner stripes of the outer medulla using qualitative and quantitative transmission electron microscopy. Kidneys of male Sprague-Dawley rats were preserved by in vivo perfusion with glutaraldehyde for light and electron microscopy. The peritubular diameter and cell height were determined by direct measurements on tubule cross sections. Morphometric analyses were performed on montages of tubule cross sections. The peritubular diameter of the TAl was similar in the three regions under investigation, but the TAL cells were taller in the inner stripe than in the inner cortex and outer stripe. Morphometry revealed significant differences between the three regions with respect to the mean tubular cross-sectional area (A_T), the surface density (S_V), and the surface area per mm of tubule (S_T) of apical and basolateral plasma membranes, and the volume density (V_V) of mitochondria. The major morphologic division appeared to be between the inner stripe segment and the remainder of the TAL. These findings document the presence of significant morphologic heterogeneity of the rat TAL.     

Total and regional renal blood flow during complete unilateral ureteral obstruction

Regional renal blood flow was investigated after 1, 2, 12 and 24 h of unilateral ureteral obstruction in rats. Total renal and cortical blood flow rates were determined by the microsphere technique and regional medullary blood flow by the 86-Rb extraction method. The kidneys were microdissected into cortex and medulla, which was further divided into the outer stripe and the inner stripe of the outer zone, and the inner zone. In the obstructed kidneys cortical blood flow increased by 33% after 1 h of obstruction, but was normalized after 2 h. After 12 and 24 h this flow was significantly decreased (55% and 65% of control respectively). The pattern of total renal blood flow was similar to that of cortical blood flow. In the outer stripe there was an initial increase (44%) after 1 h, but later no significant deviations from control values were found. After 1 h of obstruction the blood flows in the inner stripe and the inner zone were not significantly different from control values. A significantly decreased blood flow was seen in the inner stripe after 2 h (57% of control) and in the inner zone after 12 h (58% of control). A significant recovery of the blood flow had occurred in the inner stripe and the inner zone after 24 h of obstruction. In the contralateral, non-obstructed kidney no significant changes were found, besides an increased innerstripe blood flow after 24 h of UUO.     

Renal medullary blood flow studied with the 86-Rb extraction method Methodological considerations

The 86-Rb extraction method was applied for a study of regional renal blood flow. In the cortex, a samling time of 30 s led to an underestimation by about 15% as compared with the microsphere method. This was due to incomplete cortical cellular extraction of rubidium with subsequent rapid wash-out the tracer. In the renal medulla, a sampling of 30–60 s gave valid data with almost complete extraction. A sampling time of only 10 s, i. e. a time similar to the intravascular transit time, gave rise to a 50% underestimation of the inner medullary blood flow. Errors due to transport of rubidium by the tubular fluid were investigated in detail. A theoretical analysis based on equilibrium data revealed a maximal error of about 5%. Studies with micropuncture of distal tubules and studies of the urinary transport showed no or negligible contamination from tubular urine. Under control antidiuretic conditions the blood flow in the cortex was 5.2±0.2 ml-min± g± (mean±SE, n=16), in the outer stripe of the outer zone 2.2±0.1, in the inner stripe 1.5±0.1 and in the inner zone 0.69±0.06.     

The morphologic relationship of light and dark cells of the collecting tubule in potassium-depleted rats.

The luminal surface of collecting tubule cells in the inner stripe of the renal medulla in normal and potassium-depleted rats was studied by scanning electron microscopy. In normal rats the luminal surfaces were of two types. One cell type was sparsely covered with small bulbous microvilli and had either a single or double cilium. This type corresponds to the light cell seen in transmission electron microscopy. The second cell type was covered by prominent microplicae and represents the dark cell observed in transmission electron microscopy. In potassium-depleted animals, numerous cells with a morphologic appearance of intermediate forms were identified. By scanning electron microscopy, the luminal surface of these cells was covered by a mixed population of villi and microplicae in different stages of development and often showed cilia, which were previously considered to exist only on light cells. On the basis of these morphologic findings, we conclude that the dark and light cells are not different cell types but rather represent different forms of a single type of cell.     

Ultrastructural organization of the hamster renal pelvis

The renal pelvis of the hamster has been studied by light microscopy (epoxy resin sections), transmission electron microscopy, and morphometric analysis of electron micrographs. Three morphologically distinct epithelia line the pelvis, and each covers a different zone of the kidney. A thin epithelium covering the outer medulla (OM) consists of two cell types: (1) granular cells are most numerous and have apically positioned granules which stain intensely with toluidine blue, are membrane-bound, and contain a fine particulate matter that stains light grey to black in electron micrographs. (2) Basal cells do not have granules, are confined to the basal lamina region, and do not reach the mucosal epithelial surface. The inner medulla (IM) is covered by a pelvic epithelium morphologically similar to collecting duct epithelium of IM. Some cells in this portion of the pelvic epithelium (IM) stain intensely dark with toluidine blue, osmium tetroxide, lead, and uranyl acetate. Transitional epithelium, which separates cortex (C) from pelvic urine, has an asymmetric luminal plasma membrane and discoid vesicles, each of which is similar to those previously observed in mammalian ureter and urinary bladder epithelia. Based on morphological comparisons with other epithelia, the IM and OM pelvic epithelia would appear permeable to solutes and/or water, while the transitional epithelium covering the C appears relatively impermeable. It would also appear that the exchange of solutes and water between pelvic urine and OM would involve capillaries, primarily, since morphometric analysis showed that both fenestrated and continuous capillaries of the OM were extremely abundant ( > 60% of OM pelvic surface area) just under the thin pelvic epithelium.     

Outer medullary circulatory defect in ischemic acute renal failure.

Changes in medullary circulation may contribute significantly to the pathogenesis of ischemic acute renal failure. The microcirculation of the outer medulla of the rat kidney was studied by morphometry, carbon injection, and scanning electron microscopy of vascular casts after temporary renal ischemia. Morphometry showed a markedly reduced vascular area and an increased tubular epithelial cell area in the outer stripe of the medulla 2 hours after blood reflow. Maximum diminution in vascular area occurred 24-48 hours after reflow, with swollen and later necrotic tubular epithelium compressing the surrounding vascular compartment. Outflow blockade of venous vasa recta in the outer stripe caused congestion of the inner stripe. Carbon injection and scanning electron microscopy of vascular casts confirmed the perfusion defects of the outer stripe. These results suggest that decreased blood reflow to the outer stripe of the medulla secondary to tubular epithelial cell swelling and necrosis plays a significant role in the pathogenesis of ischemic acute renal failure in the rat.     

小鼠短髓襻肾单位在外髓的分布

目的 肾外髓间质渗透梯度形成的机制与髓襻上皮转运功能及其毗邻关系有密切关系,本研究拟建立短髓袢肾单位在外髓的走行规律。方法C57/BL/6J小鼠3只,灌流固定后取肾组织块并树脂812包埋,垂直肾长轴连续半薄切片,从肾被膜到内外髓交界处,共得到1 200张2.5μm厚的连续切片,显微镜下获取数字图像,计算机配准,C语言编程,进而追踪来自皮质浅层和中层的120个短髓襻肾单位。结果 短髓襻肾单位的53%起于肾皮质外1/3,47%起于中间肾皮质。前者髓襻襻曲分布在外髓内带中部同一水平,其襻曲或完全由细段上皮构成,或由髓襻降支细段上皮与升支粗段上皮移行构成;来自中间皮质的短髓襻襻曲位于外髓内带内侧1/2的不同水平,其深度与其肾小球在中间皮质的深度成正比。其襻曲由髓襻升支粗段上皮构成,并在襻曲前构成约50~450μm长的髓襻降支。最深的襻曲在外髓内带弯曲走行。结论髓袢襻曲在外髓的位置及上皮类型不同,提示外髓不同区域的小管对超滤液重吸收的成分也有所区别,对外髓深部渗透梯度增高的形成产生一定的影响;而襻曲的位置和上皮构成与肾小球在皮质的位置相关,提示肾小球的滤过与肾小管的重吸收功能有整体的调节。     

Mathematical model of mass transport throughout the kidney: Effects of nephron heterogeneity and tubular-vascular organization

A model of transport processes throughout the mammalian kidney is presented. Structural features of the model include labyrinth and medullary ray subsystems in the cortex, distinct vasa recta and capillary plexus subsystems in the outer and inner stripes, and an inner zone subsystem. Distinctions are also made between short and long nephrons, juxtamedullary and nonjuxtamedullary nephrons, vasculature, and interstitial spaces. Salt, urea, plasma proteins, and miscellaneous “nonreabsorbable” solutes in tubular and interstitial fluids are chosen as the essential solutes for describing renal mass transport. Geometric and number density data of vessels are taken from anatomical studies. Membrane parameters are evaluated principally from isolated rabbit tubule perfusion and rat micropuncture experiments. By numerical solution of the mass transport equations, the mild antidiuretic, steady state of a rat is simulated. To assess the importance of special structual features of the model, simulations were performed with different values of the anatomical parameters. By distributing more arterial blood toward the inner cortex and medulla, the osmotic gradient in the inner stripe is reduced while the urinary water and solute excretion rates are increased. When the reabsorption of urea from the papillary collecting duct is enhanced, the interstitial osmotic gradient monotonically increases throughout the inner medulla. This work was supported by a grant to GMS (P.I.) from the National Institutes of Health (AM 26073). PSC held a NIH Predoctoral Traineeship (GM-07535).     

Blood supply and drainage of the outer medulla of the rat kidney: scanning electron microscopy of microvascular casts

Blood supply and drainage of the outer medulla of the rat kidney were studied by scanning electron microscopy of vascular casts, using both arterial (n = 10) and venous (n = 10) injections of resin. Both outer and inner stripes of the outer medulla were supplied through different arterial capillary networks arising from efferent arterioles and arterial (descending) vasa recta. In contrast to previous studies using silicone rubber and light microscopy, a rich arterial capillary network supplying the outer stripe was demonstrated. Capillaries in the outer stripe and outer part of the inner stripe drained into venous vasa recta between vascular bundles, while capillaries in the inner part of the inner stripe drained into venous vasa recta within the bundles. The results indicate that each zone in the outer medulla is supplied through separate capillary networks. The demonstration of a rich capillary network in the outer stripe of the outer medulla suggests that the predilection of this zone for tubular necrosis with ischemic or toxic injury is not related to a sparse capillary blood supply.     

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.     

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.     

The kidney of tapirs: a macroscopical study.

The renal cortex of tapirs, water-loving primordial ungulates, was continuous, nonlobed, and about 80% of renal mass in adult and 71% in term-neonate. In the neonates even the peripheral glomeruli were moderately mature. Tapirus bairdi had about 4 million glomeruli per kidney and T. pinchaque about 3 million smaller glomeruli. Number of glomeruli per gm of cortex was 12,444 in T. bairdi and 13,400 in T. pinchaque. Cortical loops were common in the medullary rays. The medulla was the simple crest-type. The terminal collecting ducts (T.C.D.) opened separately at the crest and not into a tubus maximus. The "outer stripe" of the outer medulla apparently was telescoped into the deep cortex. The medullary loops turned at a thick portion and at nearly all levels of the medulla. The medullary crest was lined by urothelium which extended into the ends of the T.C.D. Otherwise the T.C.D. were made of columnar epithelium. The pelvic urothelium was continuous with that of the medullary crest at the dorsal and ventral fornices. The fornices were well within the inner medulla. Hence only inner medulla could be exposed to pelvic urine. The hilar arteries, unlike the other two perissodactyl families (rhinoceri and equids), passed through the cortico-medullary (C-M) border and some large arteries and veins passed through the outer medulla to and from the C-M border without branches or tributaries. Unlike kidneys with a medullary crest in diverse eutherian mammals, tapirs lacked pelvic extensions along the major intrarenal blood vessels and thus lacked pelvic intervascular eminences.     

Histogenesis of the loop of Henle in the rat kidney

Summary The epithelial differentiation of the loop of Henle was investigated in the kidneys of Wistar rats between embryonic day 15 and postnatal day 30. Three stages can be distinguished in the development of the loop of Henle: (1) the primitive loop, (2) the immature loop and (3) the mature loop. The primitive loop of Henle is composed of thick undifferentiated tubule epithelium and is divided into a strongly basophilic proximal tubule anlage that stains dark in the semithin section, and a weakly basophilic, light-staining distal tubule anlage. The two anlages are separated by a cytologically sharp boundary located in the descending limb just before the bend of the loop. The immature loop of Henle is present when differentiation of the tubule epithelium begins. The shorter initial portion of the proximal tubule anlage develops into proximal straight tubule epithelium with brush border, brush border enzymes and lysosomal enzymes, while the longer, more distal portion of the proximal tubule anlage develops into thin undifferentiated epithelium that is a transitory feature of the immature loop stage. The primitive epithelium of the distal tubule anlage develops into distal straight tubule epithelium. The cytologically sharp boundary of the thin undifferentiated epithelium and distal tubule epithelium is located just before the bend of the loop. The loop of Henle matures as the thin undifferentiated epithelium in the medullary ray and outer stripe of the outer medulla becomes transformed into proximal straight tubule epithelium. At the point where this descending differentiation ends, the borderline of the inner and outer stripe of the outer medulla arises. The thin undifferentiated epithelium in the inner stripe and the inner medulla differentiates into the thin epithelium of the descending limb of Henle's loop. In the bend and ascending limb of long loops, the thick distal tubule epithelium is trans-formed by an ascending autophagous process into the thin epithelium of the ascending limb of Henle. The termination of this process marks the borderline between the inner and outer medulla. The thin descending and thin ascending limb of Henle arise from 2 different anlages; between them lies the histogenetic boundary of the proximal and distal renal tubule.Supported by the Deutsche Forschungsgemeinschaft (SFB 105)     

Die Nierenmarkhypoxie: Ein Schlüssel zum Verständnis des akuten Nierenversagens?

Summary The ability to produce a concentrated urine is imposed by a uniquely low ambient oxygen pressure in the renal medulla due to shunt diffusion within the vascular bundles. As the thick ascending limb of Henle's loop (TAL-segment) is able to glycolyse anaerobically, a phase of oxygen deficiency may be bridgespanned. It allows an exceptionally high oxygen extraction of 80% in this area. If oxygen capacity is reduced systematically, which can be effected in the isolated kidney model by using cell free perfusate, a typical pattern of lesions occur in TAL-segments. Segments near vascular bundles remain intact, as they take advantage from a radial oxygen diffusion originating from vascular bundles. The extent of lesions is increasing directed to the inner medulla due to the reduction of oxygen pressure, whereas lesions are not present in the inner medulla itself. Cells of TAL-segments are swelling during oxygen deficiency, when transport work surpasses the available energy necessary due to the luminal fluid inflow. Lesions could be prevented, when oxygen capacity was enhanced by adding erythrocytes or when transport was blocked by furosemide. Swollen cells in TAL-segments however are able to aggravate medullary hypoxia by an outflow block in vivo.Secondly, it can be demonstrated, that oxygen shunt diffusion is not only present in renal medulla but also within renal cortex especially as a preglomerular diffusion shunt for blood gases. Thus PCO₂ has been measured to be 65 mmHg in the outermost cortical zone and thereby some 20 mmHg higher than renal venous blood. Our own measurements of the PO₂ at superficial glomeruli in vivo using MWF-rats demonstrate values as low as 42–46 mmHg at average and a simultaneously measured arterial PO₂ of 90 mmHg in systemic blood. This represents a markedly higher desaturation of hemoglobin than found in renal venous blood. This unexpected high preglomerular shuntdiffusion is likely localized within interlobular vessels, where thinwalled arteries and veins exhibiting the wall structure of capillaries are generally in close contact. Following this concept, PO₂ of the superficial cortical zone is low and the PO₂ of the juxtamedullary cortical zone is not far from arterial PO₂. Plasmaskimming may modify O₂-pressure as well as O₂-capacity within the different cortical zones. These results may explain, why proximal tubules within the renal cortex — which exhibit a low enzymatic activity to glycolyse anaerobically compared to TAL-segments — develop lesions very rapidly under ischemic or hypoxic conditions or when the demand of energy for transport work cannot be produced aerobically. This becomes evident especially within areas of oxygen deficiency at the outer stripe of outer medulla, where predominantly P₃-segments in the interbundle area are involved however much less TAL-segments. This may also explain, that the production of erythropoietin is localized within the renal cortex and outer stripe of outer medulla, as oxygen deficiency can be measured effectively in this area. The common error, that oxygen supply of the kidney is abundant, must be revised: it is at the brink of oxygen deficiency in the case of renal medulla and at shortage also for renal cortex.     

The mammalian renal pelvis: Physiological implications from morphometric analyses

Summary Morphometric analyses have been used to study the renal pelvises of four common rodents: laboratory rat (R), hamster (H), gerbil (M), sand rat (P). Measurements on photographs of serial sections were used to determine the 1) area of the outer kidney surface, 2) surface area of each kidney zone and hilum facing the pelvic space, 3) volume of the pelvic space, 4) volume of each kidney zone.As a standard measure the total pelvic surface area (kidney zones plus hilum) of each species was expressed as a percent of its respective outer kidney surface area: R=25.0%, H=32.6%, M=48.7%, P=97.2%. The medullary tissue formed about 80% of the total pelvic surface area in each species while cortex and hilum formed the remaining 20%. The outer medulla had about twice as much surface area facing the pelvic urine as did the inner medulla. The amount of inner stripe of the outer medulla was greater than the outer stripe of the outer medulla as the following progression of ratios (mm²/mm²) shows: R=1.8, H=2.5, M=2.2, P=4.9.When the volume of the pelvic space and each kidney zone of each species was compared to the total volume of the respective kidney as a standard measure, it was determined that 1) the pelvic space was small being less than 5% of the total kidney volume, 2) the cortex was the largest kidney zone in all species: R=69.6%, H=68.1%, M=69.9%, P=51.6%, 3) the outer medulla was intermediate: R=25.8%, H=27.4%, M=23.1%, P=33.8%, 4) the inner medulla formed the smallest tissue zone in all species but was noticeably larger in P (10.7%) in comparison to the values for R=2.1%, H=2.5% and M=5.2%.The simultaneous increases (from R to H to M to P) in: a) relative inner medullary volume, b) relative pelvic surface area, c) maximum urine concentrating capacity (Schmidt-Nielsen and O'Dell 1961; Munkasci and Miklos 1977) may support earlier hypotheses which suggest that a back diffusion of pelvic urine solutes augments medullary interstitial tonicity and thus is an intergral part of the urine concentrating mechanism.Alexander von Humboldt StipendiatA portion of this work was presented at the Symposium on Animal Research in Nephrology, Hannover Medical School, Federal Republic of Germany, 1978. Dr. Lacy's present address is: Department of Anatomy, Harvard Medical School, Boston, Massachusetts 02115, USA     

A morphological and biochemical study of the effects of L-cysteine on the renal uptake and nephrotoxicity of cadmium.

In JCLR and Wistar-Porton rats renal concentrations of Cd2+ were maximal (21-22 micrograms Cd2+/g wet wt tissue) at 1 and 4 h respectively after the administration of CdCl2 (10 micromol, 1-12 mg Cd2+/kg body wt) together with L-cysteine (5 mmol/kg body wt). Synthesis of metallothionein in the kidney in response to the uptake of Cd2+, which occurred between 2 and 7 h after treatment in the Wistar-Porton rat, affected the distribution of Cd2+ between proteins of the renal soluble fraction, but not between the particulate components and, at both times, about 40% of the total Cd2+ was associated with the heterogeneous nuclei + cell debris fraction. Autoradiographic studies with 109CdCl2 revealed that Cd2+, accumulated by the kidney under these conditions, was not uniformly distributed throughout the renal cortex, but was concentrated unevenly in proximal tubules in the outer stripe of the outer zone of the medulla. Pathological changes, which were correlated with the concentrations of accumulated Cd2+ and were limited to the S3 segments of the proximal tubules, were apparent by light microscopy at 4 h after the administration of Cd2+ + cysteine and progressed with time. Thus by 7 h the lesion had extended to include almost the whole of the outer stripe of the outer zone of the medulla and, by 24 h the cells of the affected epithelia showed extensive necrosis and karyorrhexis. At this, as at earlier times, the cortex appeared to be undamaged. Neither these nor other morphological changes were observed in the kidneys of animals that had been dosed with either Cd2+, or L-cysteine alone. Within 60 min of the administration of Cd2+ + cysteine an increase in the number of endocytotic vesicles in the apical cytoplasm of the proximal tubular epithelium was observed by electron microscopy. Subsequent cytoplasmic vesiculation, which was conspicuous at 2 h, was extensive and widespread in both the apical and basal regions of the cytoplasm at 4 h. In some cells at this time the nuclei were irregular in shape; the mitochondria were swollen and their cristae were disorganized. As, after the administration of either Cd2+ or cadmium-metallothionein, damage is known to occur in the S1 and S2 segments of proximal tubules throughout the cortex, the Cd2+ + cysteine combination does not provide an exact model which reproduces in a short time the effects of long-term, low level exposure to Cd2+. Nevertheless it is suggested that the toxic mechanisms are the same after either treatment with Cd2+ + cysteine or continual exposure to Cd2+, but are limited to different segments of the proximal tubules. Possible mechanisms of toxicity are discussed.     

The structural organization of the kidney of the desert rodent Psammomys obesus.

The architecture of the desert rodent Psammomys obesus has been studied by means of standard histologic procedures and by single nephron injections. As other rodent kidneys (rat, mouse), the Psammomys kidney consists of two types of nephrons, 66% short looped and 34% long looped nephrons. The cortex is composed of 4 to 5 layers of glomeruli, which lie closely put together, the glomeruli often touch each other. The superficial and the midcortical glomeruli give rise to short looped neophrons, the juxtamedullary to long looped nephrons. In the strongly developed medulla the inner stripe shows the most striking pattern. It consists of two distinct compartments, that of the giant vascular bundles and that of the interbundle regions. The giant vascular bundles consist of about 8 to 14% arterial vasa recta and 39 to 47% venous vasa recta; furthermore they include the thin descending limbs of the short loops of Henle which amount to 44 to 51% of the bundle structures. The tubules of the interbundle regions surround the bundles in a regular pattern. The inner zone is almost completely surrounded by the renal pelvis; the long broad papilla protrudes into the ureter. The thin descending limbs of short looped nephrons traverse the inner stripe inside the giant vascular bundles. Leaving the bundles they turn back within the inner stripe; their ascending limbs lie in the interbundle region. Both limbs of the long loops of Henle run in the interbundle region, together with the ascending limbs of the short loops and the collecting ducts. The long loops penetrate deeply the inner zone. Many bends are found near the tip of the papilla. The renal pelvis has a very specialized form. It penetrates the inner stripe with many complexely shaped extensions, which surround the giant vascular bundles. Large parts of the bundles with their thin walled structures are thus separated from the pelvic urine only by a single layer of cuboidal epithelium. The possible functional importance of the described specializations of the Psammomys kidney (giant vascular bundles, large inner zone, special shape of the renal pelvis) for the urine concentrating and urea recyclng mechanisms is discussed.