John Curtis Seely , ... Brad Blankenship , in Boorman's Pathology of the Rat (2nd Edition), 2018
2.3.iii Collecting Duct System
The collecting duct organisation consists of connecting tubules and collecting ducts. The connecting tubules join the distal convoluted tubules to the cortical collecting ducts, forming arcades that bleed several nephrons. An average of vi nephrons drains into a collecting duct. Collecting ducts descend through the cortex and medulla and successively fuse almost the inner medullary region. Toward the papillary tip, converging papillary ducts course approximately 20 large ducts, which empty into the renal pelvis. The collecting ducts are equanimous of 2 cell types: principal and intercalated cells. Main or light cells are the most numerous and are characterized by a pale cytoplasm with sparse organelles. Principal cells increase in size from the cortex to the medulla and are largest in the papillary ducts. The intercalated, or nighttime, cell is characterized by electron-dense cytoplasm, numerous mitochondria, and abundant smooth endoplasmic reticulum. These cells also have an elaborate luminal surface that is covered past modified microvilli or ridge-like extensions of the apical membrane known as microplicae. Intercalated cells gradually disappear in the inner medulla, leaving the principal jail cell every bit the only type in papillary collecting ducts. The renal papilla is lined past a single layer of a low cuboidal epithelium, termed the epithelium of the renal papilla (Figure eleven.11).
Figure 11.11. Single depression cuboidal epithelial lining of the renal papilla.
The upper portion of the renal pelvis has specialized folds, chosen fornices, lined by a unmarried layer of epithelium (Effigy 11.12). Fornices act to further concentrate the urine by increasing the interface between pelvic urine and the renal interstitium. The remaining epithelium of the renal pelvis, becoming continuous with the ureteral lining, is the urothelium and consists of cells from three to four layers thick. Smooth musculus cells line the distal one-third of the renal pelvis. Occasionally, urothelial cells containing variable numbers of eosinophilic droplets may be seen as a spontaneous background finding in both male person and female rats (Figure eleven.thirteen). The nature of the eosinophilic droplets is not known but appear to have no known pathological significance.
Figure 11.12. In this image, the fornices are represented as vault-like spaces (asterisks).
Figure eleven.xiii. Intracytoplasmic eosinophilic aerosol in the pelvic urothelium (arrow).
Jill W. Verlander , in Cunningham's Textbook of Veterinarian Physiology (Sixth Edition), 2020
The Collecting Duct Reabsorbs Sodium Chloride
The collecting duct system begins with the connecting segment, which follows the DCT. The tubules of individual nephrons brainstorm merging in the connecting segment and the downstream initial collecting tubule. Depending on the species, the connecting segment contains several distinct epithelial cell types, including DCT cells, connecting segment cells, intercalated cells, and principal cells. Each of these structurally distinct cell types has specific physiological functions.
The initial collecting tubules merge into the collecting duct, which traverses the cortex and medulla to the papillary tip, where the tubule fluid (urine) discharges into the renal pelvis. In nearly of the collecting duct, there are two main prison cell types: the intercalated prison cell, which has many intracytoplasmic vesicles, mitochondria, and a relatively circuitous upmost surface, and the principal cell, which has fewer intracytoplasmic vesicles and mitochondria and a relatively smooth apical surface but generally more extensive basolateral plasma membrane infoldings (Fig. 42.thirteen). The master cell is the major cell type in the initial collecting tubule and the cortical and outer medullary collecting ducts, accounting for approximately ii-thirds of the cells in well-nigh regions. Intercalated cells account for the residuum of the cortical and outer medullary collecting duct cells.
Sodium reabsorption in the collecting duct is primarily a part of principal cells and is driven by basolateral Na+,K+-ATPase. As in other tubule segments, Na+ is actively transported by this pump into the interstitial fluid, establishing an electrochemical gradient that promotes Na+ uptake through apical epithelial Na+ channels (ENaC). The resulting lumen-negative electrical potential drives Cl− absorption through the paracellular pathway, through channels in the tight junctions formed by claudins; approximately lxx% of collecting duct Cl− reabsorption is through the paracellular pathway. A subpopulation of intercalated cells, type B intercalated cells, too contribute to NaCl reabsorption in the collecting duct. Type B intercalated cells mediate Cl− reabsorption via an apical Cl−/HCOthree− exchanger, pendrin, and the basolateral ClC-Kb/ii Cl− channel. In addition to transporting Cl− from the lumen, pendrin action in type B intercalated cells enhances ENaC abundance, open probability, and activity in primary cells. The molecular mechanisms by which pendrin activity in type B intercalated cells alters ENaC activity in chief cells accept not been fully determined. In that location also is evidence that pendrin activeness coordinates with the Na-dependent Cl−/ HCO3− exchanger (NDCBE) in the apical plasma membrane of the blazon B intercalated cells. Thus enhanced pendrin action promotes not only Cl− reabsorption, only also Na+ reabsorption via ENaC and possibly NDCBE.
S. Akilesh , in Pathobiology of Human Disease, 2014
Collecting Duct
A distal convoluted tubule connects to the collecting duct arrangement that fine-tunes salt and water reabsorption and plays a major function in acrid–base of operations rest. The initial segment of the collecting duct, the cortical collecting duct, takes off from the distal convoluted tubule in the cortex. The 2 master jail cell types of the cortical collecting duct are principal cells and intercalated cells. Principal cells are paler than intercalated cells, a difference that is best seen on toluidine blue-stained sections. The chief cells are responsible for sodium reabsorption via the amiloride-sensitive sodium channel ENaC. Chief cells likewise secrete potassium via the ROMK potassium aqueduct. The ability of the cortical collecting duct to absorb water is controlled by antidiuretic hormone (ADH). In the presence of ADH, AQP2-containing vesicles fuse with the apical membrane assuasive water to enter the cell. Water exits from the basolateral aspect via AQP3 and AQP4 channels. The activeness of ADH on the cortical collecting duct allows for the production of concentrated urine and protects against dehydration. In contrast to master cells, intercalated cells express high levels of carbonic anhydrase and are involved in acid–base regulation. At least two types of intercalated cells can exist distinguished based on their ultrastructural advent. Type A intercalated cells accept apical projections and numerous cytoplasmic vesicles close to the upmost surface. Type A intercalated cells use cytoplasmic carbonic anhydrase to produce H+ and HCO3– ions. H+ is secreted into the lumen by an upmost H+ ATPase pump and HCO3– is pumped out of the basolateral surface via a HCO3–/Cl– exchanger. Type B intercalated cells take prominent basolateral interdigitations, numerous cytoplasmic vesicles that are distributed through their cytoplasm, and more mitochondria than type A intercalated cells. Type B intercalated cells take an inverse orientation of pumps and channels as compared to type A intercalated cells. In type B intercalated cells, the HCO3–/Cl– exchanger is located in the upmost membrane and the H+ ATPase pump is located in the basolateral membrane domain. Through the action of cytoplasmic carbonic anhydrase, blazon B intercalated cells secrete HCO3– and reabsorb H+.
The cortical collecting duct continues into the outer medulla equally the outer medullary collecting duct. This tubular segment is lined past principal cells that are involved in sodium reabsorption and by type A intercalated cells. Type B intercalated cells are rarely found in the outer medullary collecting duct. Several outer medullary collecting ducts contribute tributaries to the inner medullary collecting ducts that have correspondingly larger luminal diameters. The epithelial cells lining these ducts accept stake cytoplasm and sharply demarcated lateral prison cell borders. The terminal portions of the inner medullary collecting duct (ducts of Bellini) are lined by taller columnar cells that open into the papillae. The inner medullary collecting duct epithelium expresses urea transporters that play an of import office in maintaining the loftier medullary interstitial concentration of urea. It is this hypertonic interstitium that facilitates urine concentration by the countercurrent multiplication mechanism of the loops of Henle and the thick ascending limb of the distal tubule.
James Southward. Lowe BMedSci, BMBS, DM, FRCPath , Peter G. Anderson DVM, PhD , in Stevens & Lowe's Human being Histology (4th Edition), 2015
Abnormalities of Tubular Function
The renal tubular and duct system is virtually entirely dependent for its oxygen supply on the integrity of the glomerular capillary network and the arterial vessels supplying the glomeruli, as they receive oxygen from the peritubular capillary networks, which are branches of the efferent arterioles leaving the glomeruli (see Fig. fifteen.4).
Thus, the tubular epithelial cells can go significantly hypoxic if at that place is arterial or glomerular affliction that reduces the blood flow into the efferent arterioles. For case, obliteration of the glomerular capillary lumina by proliferation of the lining endothelial cells (see Fig. 15.9) leads to impaired oxygenation of the tubular epithelial cells. The clinical and biochemical moving picture is, however, usually dominated by features resulting from retention of nitrogenous waste products and the increase in peripheral vascular resistance (acute nephritic syndrome, see p. 294).
If such impairment to the glomeruli persists, so the tubular epithelial cells become so starved for oxygen that their enzyme systems and various pumping mechanisms are unable to function, and biochemical abnormalities develop every bit a result of the loss of the sensitive homeostatic mechanisms.
The most of import biochemical abnormalities resulting from dumb tubular function are due to failure of excretion of H+ and K+ ions. The blood therefore contains a loftier concentration of H+ ions (acidosis) and K+ ions (hyperkalaemia). These, along with the retention of nitrogenous waste cloth due to failure of glomerular function, are features of renal failure (see p. 309).
The collecting tubules and ducts start after the distal tubule
The convoluted segment of the distal tubule opens into the collecting arrangement of tubules and ducts. This transition is not sharp, as there is a variable segment (sometimes called the 'connecting segment'), where the epithelial lining contains both distal tubule and collecting tubule cell types in an apparently random fashion.
The collecting tubules are lined past ii cell types
The collecting tubule (Fig. fifteen.23) is lined by two types of cell: clear cells (the bulk) and intercalated dark cells.
The clear cells are cuboidal or rather flat in the proximal function of the collecting arrangement; they have light, poorly-staining cytoplasm, which contains few cytoplasmic organelles (mainly randomly arranged small round mitochondria). Basal membrane infoldings are present in the proximal role of the collecting system but become less apparent further along, but microvilli are short and sparse.
The intercalated or nighttime cells are richer in cytoplasmic organelles, possessing numerous mitochondria. Their luminal surface has a well-developed microvillus system, with vesicles in the cytoplasm at the base of the microvilli. Normally, there are no basal infoldings.
The collecting tubules in the cortex pass towards the medullary rays and open into collecting ducts
The collecting ducts run vertically within the rays into the medulla. All of the medullary collecting ducts merge virtually the papilla to form big straight papillary ducts that run to the tip of papilla, where they open out into the pelvicalyceal system.
The collecting ducts are lined initially by epithelium that is identical in blazon to that of the collecting tubules. As they pass downwardly the medullary rays and into the medulla, still, the number of intercalated dark cells decreases and the clear cells become progressively taller and more than prominent, and then that, as the papilla is approached, the ducts are lined by regular straight-sided columnar clear cells (Fig. 15.24).
In humans, the basement membrane of the collecting duct arrangement becomes progressively thicker as it nearsthe papillary tip. This feature becomes exaggerated with age.
Clinical Case
Acute Tubular Necrosis
Failure of tubular function due to poor oxygenation can also occur in the absence of any significant disease of arteries or glomeruli. The well-nigh mutual cause is a central failure of blood circulation owing to poor cardiac output, which in turn is normally due either to low claret book (hypovolaemia), for example following massive claret loss through bleeding, or to low blood pressure (hypotension), for example following a myocardial infarction.
Poor perfusion through the peritubular capillary network leads to inadequate oxygen supplies for the tubular epithelial cells, and this leads to failure of enzyme systems and pump mechanisms, with consequent biochemical abnormalities, particularly acidosis and hyperkalaemia. Because the glomeruli are not being perfused with arterial blood at an adequate pressure, little filtration takes place, so the production of urine falls or may even cease. The syndrome of acute renal failure comprises:
•
Oliguria or anuria (partial or full cessation of urine production)
•
Hyperkalaemia (elevated Grand+ level in the claret)
•
Acidosis (elevated H+ level in the blood).
When the tubular failure is due to a primal cause such every bit hypovolaemia or hypotension, the tubular epithelial cells degenerate (Fig. 15.25). Their histological appearance is due to aggregating of h2o within the cytosol.
If hypovolaemia or hypotension are treated promptly, tubular epithelial cells tin can recover normal construction and function; otherwise, the tubular epithelial cells die (acute tubular necrosis). If adequate oxygenation is re-established the tubules tin can go repopulated with epithelial cells.
In renal grafting, the tubular epithelial cells of the donor kidney die after the kidney is removed. When the kidney is transplanted (usually many hours after its removal) and its arterial supply is re-established, the tubules are somewhen repopulated with functioning epithelial cells and normal homeostatic control is established.
Key Facts
Tubular and Collecting Duct System Functions
•
Proximal convoluted tubule – reabsorption of water, glucose and amino acid by Na+/K+/ATPase pump, whereas larger molecules are reabsorbed past endocytosis
•
Thin loop of Henle – creates gradient of hypertonicity to allow concentration of urine in collecting duct system
•
Distal tubule – Na+ and HCOiii− ions reabsorbed from urine in exchange for G+ and H+, which are excreted, dependent on aldosterone
•
Collecting tubules and ducts – control concluding concentration of urine by regulated reabsorption of water from urine nether influence of hypertonicity gradient and antidiuretic hormone.
The collecting tubules and ducts play an important office in the final concentration of urine
The collecting tubules and ducts are not solely conduits for the transfer of urine into the pelvicalyceal organization only are instrumental in concentrating urine to a degree appropriate to the level of blood hydration. This is achieved past interplay between the collecting tubules and ducts, the interstitium and the vasa recta, to produce a countercurrent exchanger system (Fig. 15.26). Controlled water ship is made possible past the variable permeability of the collecting duct under the influence of ADH (meet p. 302). The amount of ADH released depends on the body's requirement for water excretion or retentivity.
In the presence of high levels of ADH, water is lost from the collecting duct lumen into the interstitium, from where it passes into the blood circulation via the ascending vasa recta. This results in the product of a pocket-sized amount of highly full-bodied urine. When depression levels of ADH are present, water remains within the collecting duct lumen and is lost in the form of copious dilute urine.
The vascular networks of the vasa recta as well play a role in the concentration of urine in the medulla
On the descending (arterial) side of the looped vessels, the walls are permeable to h2o and salts; water passes out into the interstitium and sodium and chloride ions pass in. Thus, claret in the vasa recta is more or less in equilibrium with the hypertonic medullary interstitium.
On the ascending (venous) side of the vascular loop, sodium and chloride ions pass from the vessel lumen to the interstitium and water is reabsorbed into the venous blood from the interstitium.
Dilute urine in the collecting tubule and duct system is progressively full-bodied by the osmotic transfer of h2o from the lumen into the hypertonic medullary interstitial tissue, whence it is reabsorbed into the vasa recta. The hypertonicity is due to the high concentration of Na+ and Cl− ions in the medulla, resulting from the countercurrent multiplier activity of the loops of Henle. Thus, an increasingly concentrated urine is produced.
L.R. Aronson , in Feline Soft Tissue and Full general Surgery, 2014
Nephrotomy and pyelolithotomy
A nephrotomy (Box 36-3) provides the greatest exposure of the renal pelvis and collecting duct organization, merely entails temporary interruption of the afflicted kidney's blood supply. Alternatively, pyelolithotomy (Box 36-3) may exist performed if the renal calculi have created dilation of the renal pelvis. This approach does not provide as adept an exposure of the pelvis as a nephrotomy, but does non necessitate occlusion of the renal vasculature.
2 split studies have evaluated the effect of nephrotomy on renal function in clinically normal cats. In the first study, bisection nephrotomy did not adversely affect renal function during the 12 week written report flow.87 In the 2d study, nephrotomy resulted in a 10–20% reduction in mean unmarried kidney glomerular filtration charge per unit (GFR) compared with the contralateral command kidney, simply no significant departure from cats that underwent a sham surgical procedure. This difference may reflect the power of the non-operated contralateral kidney to undergo compensatory hypertrophy in response to the decrease in GFR in the kidney that had the nephrotomy performed.88
Scott R. Manson , ... Katelynn H. Moore , in Vitamins & Hormones, 2015
five.three Functions of BMP-7 in the Ureteric Bud
The importance of BMP signaling during renal organogenesis as well extends to the regulation of jail cell populations derived from the UB and the development of the collecting duct system. This is notable as the UB plays a cardinal office in patterning the kidney and reciprocal interactions betwixt the UB and MM significantly impact nephrogenesis. The morphogenesis of the collecting duct arrangement is largely driven by 3 processes: budding of the UB from the nephric duct, elongation/growth of the UB stalk, and branching at the UB tips. While the underlying mechanisms of regulation are extremely complex, the prevailing model is that the opposing deportment of positive and negative regulatory factors control the timing and localization of these morphogenic processes (Michos, 2009).
BMP signaling has been implicated in the budding, elongation, and branching of the UB, primarily as a negative regulatory factor. This is evident in the phenotypes of mice with genetic alterations that increase BMP signaling. Mice with a germline deletion of the BMP adversary Gremlin1 exhibit bilateral renal agenesis due to a complete block in UB budding and outgrowth (Michos et al., 2004). This phenotype is due to excessive BMP signaling, equally demonstrated by the finding that UB budding and outgrowth and normal kidney development are restored in Grem1−/−; Bmp4+/− mice (Michos et al., 2007). Similarly, mice engineered to express a constitutively active version of the BMP receptor ALK3 under control of the UB-specific HoxB7 promoter develop renal dysplasia characterized by decreased branching of the UB and maldevelopment of the collecting duct system (Hu, Piscione, & Rosenblum, 2003).
While elevated BMP signaling has adverse consequences, BMP signaling is notwithstanding required for the normal development of the collecting duct system. Conditional knockout of ALK3 in lineages derived from the UB results in renal dysplasia. At early developmental time points, there is an increase in the number of primary and secondary UB branches including aberrant structures with iii or more branches. This, in turn, leads to impairment of higher order UB branching and maldevelopment of the collecting duct system (Hartwig et al., 2008). Similarly, Bmp4+/− have a wide spectrum of defects related to abnormal UB budding and branching. Well-nigh prominently, ectopic ureteral budding results in duplication of the collecting duct system and ureterovesical junctions (Miyazaki et al., 2000). Together, these findings propose a model where BMP signaling ensures the proper timing of morphogenic events and localization of developing structures in the collecting duct system by inhibiting UB budding and branching.
While these inhibitory functions likely extend to BMP-seven, examining the role of BMP-7 in the collecting duct system presents technical challenges. Bmp7−/− mice exhibit reduced branching of the ureter and collecting duct system, but it is hard to discern whether this phenotype is secondary to the premature abeyance of nephrogenesis in Bmp7−/− mice given the numerous reciprocal interactions between the UB and MM. However, the importance of BMP-7 in the UB is strongly suggested by findings that the defects in UB budding and outgrowth in Grem1−/− mice are reversed in a Bmp7−/− background (Goncalves & Zeller, 2011).
A role for BMP-7 in the collecting duct organization is farther supported past in vitro studies. Treatment with BMP-seven inhibits UB branching morphogenesis in whole kidney explants in vitro (Piscione et al., 1997). Although these explants also contain MM, this phenomenon tin also be reproduced in inner medullary collecting duct cells where BMP-vii inhibits branching morphogenesis and tubule formation in a Smad-dependent manner (Piscione, Phan, & Rosenblum, 2001). Interestingly, in both of these in vitro models, low doses of BMP-7 tin can instead stimulate branching morphogenesis, suggesting a circuitous arrangement that depends upon the context and magnitude of the BMP-7 betoken (Piscione et al., 1997, 2001).
While these findings demonstrate the importance of BMP-vii in the developing collecting duct arrangement, its specific roles remain poorly defined. The loftier levels of BMP-vii expression in UB lineages and wide importance of BMP signaling in collecting duct morphogenesis, nevertheless, abet the need for additional studies in this expanse. Our understanding of the roles of BMP-seven in the collecting duct arrangement volition likely go on to evolve equally improved methods for examining UB morphogenesis are developed and applied to the written report of BMP-7.
Xiao-Tong Su , ... David H. Ellison , in Methods in Jail cell Biological science, 2019
1 Introduction
An efficient method to decide 3-dimensional construction and to quantify microanatomy has long been sought. The functional units in the kidney are glomeruli, nephrons, and the collecting duct organization; each of these structures comprises unique sets of defining cells. The distribution, size, number, and appearance of nephrons and cells reverberate the function and organization of the kidney. Traditional approaches to microanatomical analysis involve the apply of microtomes to generate in thin sections. Inferences in three dimensions are often made by analyzing a sample of such sections and, for instance, counting glomeruli or cells within glomeruli (White & Bilous, 2004). To provide more rigorous quantitative information well-nigh renal structures, based on sparse sections, stereological methods accept been; these have been used to estimate the length of nephrons, the number and size of glomeruli, and the number of cells within structures, and are based on systemic sampling of structures within thin sections (Grimm, Coleman, Delpire, & Welling, 2017; Grimm et al., 2012; Kaissling, Bachmann, & Kriz, 1985; Nyengaard, 1999; Zhai et al., 2006). However, stereological methods require advanced grooming and are time-consuming, which limits their application and utility for kidney research. Another approach is to image the surface of the tissue and and so sequentially shave off the surface to get the paradigm of the unabridged tissue (Toga, Ambach, & Schluender, 1994; Tsai et al., 2009). Although this method eliminates the issues with respect to tissue alignment, its biggest drawback is that once each department is imaged, the surface of the tissue is destroyed to reveal the next section.
The ability to return tissue transparent has been bachelor for more than a century, having been investigated by the High german anatomist Werner Spalteholz (Spalteholz, 1911). Nonetheless it was the introduction of newer approaches, combined with genetically encoded fluorescent proteins that has popularized this approach, especially for neuroanatomical studies (Chung et al., 2013). With the structurally complex nature of the kidney and the ongoing need for three-dimensional data for both physiological and pathophysiological studies, kidneys are ideal structures for this approach.
There are ii major obstacles facing the investigators. The get-go problem is that data from the regions in a higher place and beneath the focus plane interferes with imaging of any plane in focus. With the awarding of optical sectioning techniques, including confocal microscopy, two-photon microscopy, light-sheet microscopy, and computational paradigm deconvolution methods, information from unmarried planes of a book can be acquired without physical sectioning (Denk, Strickler, & Webb, 1990; Mertz, 2011; Minsky, 1988). These methods minimize contributions from out-of-focus regions of the thick tissue and permit access to virtual thin sections from within a thick sample. Past computational three-dimensional rendering from the optically sectioned images, the reconstruction of tissue volume can exist made.
The other problem in volumetric imaging is the translucency of the biological tissues caused by lite scattering (Stelzer, 2015). Light rays deviate many times as low-cal is reflected by membranes, organelles, and cells equally it travels through the tissue (Richardson & Lichtman, 2015). Virtually of the light will exist scattered and reduce velocity with depth. The velocity reduction is the basis of the refractive index of the medium, which is the ratio of the light speed in a vacuum to that in the medium. Short-wavelength light is more than greatly scattered, which makes information technology advantageous to utilize long-wavelength infrared-based excitation fluorophores. Considering of the low-cal handful, techniques that alter the scattering property of the tissue cellular components are critical to making full use of the current microscopic techniques. A comprehensive review of both approaches can be institute in Richardson and Lichtman (2015).
Matteo Tardelli , Thomas M. Stulnig , in Vitamins and Hormones, 2020
4 Aquaporins regulation in kidney
Water and solute trafficking/reabsorption are pivotal kidney functions. AQP1 and -7 are expressed in the proximal tubules and AQP2, -iii, -4 localize to the collecting duct system (Agarwal & Gupta, 2008). AQP2 is the most studied AQP in kidney with several studies showing its regulation by vasopressin (Bouley et al., 2006; Deen et al., 1994; Wilson, Miranda, & Knepper, 2013). AQP2 KO mice practise non survive to adulthood considering of excessive fluid loss (Rojek, Fuchtbauer, Kwon, Frokiaer, & Nielsen, 2006). AQP2 knockout restricted to kidney connecting tubule evidenced its essential role in regulation of trunk h2o residue that cannot be compensated for by other mechanisms (Kortenoeven, Pedersen, Miller, Rojek, & Fenton, 2013; Rojek et al., 2006). In another report, authors studied -F204V mutation in mice (which is due to thymine to guanine (T–Yard) transversion, leading to a substitution of a valine with phenylalanine at amino acid 204 of the poly peptide) and showed improper AQP2 translocation in connectedness to the pathogenesis of nephrogenic diabetes insipidus (Lloyd, Hall, Tarantino, & Gekakis, 2005). AQP6 is expressed in collecting ducts, however, localizing on the intracellular vesicles but non the plasma membrane (Yasui et al., 1999). AQP7 and -eight localize to the proximal tubule castor edge, whereas AQP9 is institute only at gene just not protein level in the kidney (Nielsen et al., 2002). Notably, AQP7 is non involved in water reabsorption, however it plays an of import role in glycerol reabsorption in the kidney. Consequently, AQP7 KO mice suffer marked loss of glycerol in the urine (glyceroluria) (Sohara et al., 2005; Sohara, Rai, Sasaki, & Uchida, 2006). AQP11 is localized intracellularly in the endoplasmic reticulum of proximal tubule cells. Its importance is highlighted past the fact that AQP11 KO mice develop polycystic kidney disease (Okada et al., 2008).
Bruce M. Carlson Dr., PhD , in The Human being Trunk, 2019
Collecting Tubules and Ducts
Like tributaries to a stream, the individual collecting tubules in the cortex merge into a larger straight collecting duct that drops through the medullary pyramid and leaves through its apex equally the duct of Bellini. Virtually of the collecting duct organization is lined by a cuboidal epithelium containing two types of cells—principal cells and intercalated cells (see Fig. 13.7). In addition to a basolateral membrane adapted for Na+,1000+ commutation, the apical surface of a master cell contains a master cilium, which acts as a mechanosensor of fluid menstruum. Principal cells are as well heavily involved in G+ secretion into the lumen. Intercalated cells take apical microvilli and contain many mitochondria. They engage in Yard+ and secretion out of and H+ secretion into the collecting duct.
An important feature of the epithelium of the collecting duct is that its secretory activity is heavily influenced by the adrenal cortical hormone aldosterone. Aldosterone, which acts through the nucleus of the cells, increases K+ secretion and Na+ reabsorption by the chief cells and H+ secretion into the lumen by the intercalated cells. Overall, aldosterone serves to protect the composition of body fluids, and under conditions of aridity the adrenal gland secretes more aldosterone, which causes the cells of the collecting ducts to secrete more K+ into the forming urine. Because of their responsiveness to external agents, such as aldosterone, the collecting duct is also the target of diuretic medications.
The collecting duct arrangement is likewise the region where urine is acidified. This is accomplished past the secretion of H+ by the intercalated cells into the collecting duct.
One important process in the final production of urine is a last phase of removal of water in the deep medullary part of the collecting duct organisation. This is accomplished by the principal cells, operating under the influence of antidiuretic hormone (ADH), produced by the posterior pituitary gland (Box 13.iii). In improver to maintaining bodily homeostasis through the selective resorption and secretion of many disquisitional solutes, the kidney serves the vital part of regulating the vast majority of water that is retained by or lost from the body. Agreement the ins and outs of water menstruation in the kidney requires a knowledge of the osmotic gradient found in the medullary pyramid and the footing for information technology.
Box 13.3
ADH and Diabetes Insipidus
The basolateral surfaces of the principal cells within the collecting ducts contain aquaporin-based h2o channels and are always permeable to water. Permeability of the apical surfaces, however, depends upon the presence or absence of ADH. In the absence of ADH, the upmost surfaces of the principal cells of the collecting ducts are impermeable to water. When ADH is present, aquaporin-2-based water channels that have been stored in vesicles close to the apical membrane are inserted into the membrane. This allows h2o to menstruum from the urine into the cells. The h2o then flows through the basolateral h2o channels and into the medulla of the kidney because of the loftier osmotic pressure of the interstitial fluids of the medulla. Upon removal of ADH, the h2o channels are taken upwards by the sub-membrane vesicles and are stored in them until needed. In addition to its outcome on water uptake, ADH also increases the removal of urea from the tubular fluid deep in the medulla. The removed urea becomes concentrated in the deep renal medulla.
If ADH is absent or is secreted at less than 80% of normal levels, water removal from the collecting ducts fails, and the body excretes massive amounts of urine—typically more than iv 50/day. This condition is called diabetes insipidus and is accompanied past great thirst and aridity in the absence of increased fluid intake. Less mutual causes of diabetes insipidus are genetic defects affecting the h2o channels in the collecting ducts. In these cases the patients may have normal levels of circulating ADH, simply in the absence of receptors or with defective water channel genes, the hormone is without effect on the kidneys.
Bruce Grand. Koeppen Md, PhD , Bruce A. Stanton PhD , in Renal Physiology (Fifth Edition), 2013
Ultrastructure of the Nephron
The functional unit of the kidneys is the nephron. Each human kidney contains approximately ane.2 million nephrons, which are hollow tubes composed of a single jail cell layer. The nephron consists of a renal corpuscle, proximal tubule, loop of Henle, distal tubule, and collecting duct system (Figure 2-2).∗ The renal corpuscle consists of glomerular capillaries and Bowman'due south sheathing.† The proximal tubule initially forms several coils, followed by a directly piece that descends toward the medulla. The adjacent segment is the loop of Henle, which is composed of the directly part of the proximal tubule, the descending thin limb (which ends in a hairpin turn), the ascending thin limb (just in nephrons with long loops of Henle), and the thick ascending limb. Near the end of the thick ascending limb, the nephron passes betwixt the afferent and efferent arterioles of the same nephron. This short segment of the thick ascending limb that touches the glomerulus is called the macula densa (encounter Figure 2-two). The distal tubule begins a curt distance beyond the macula densa and extends to the point in the cortex where two or more nephrons join to form a cortical collecting duct. The cortical collecting duct enters the medulla and becomes the outer medullary collecting duct and then the inner medullary collecting duct.
Each nephron segment is made up of cells that are uniquely suited to perform specific transport functions. Proximal tubule cells have an extensively amplified upmost membrane (the urine side of the cell) called the brush border, which is present simply in the proximal tubule of the nephron. The basolateral membrane (the claret side of the cell) is highly invaginated. These invaginations incorporate many mitochondria. In contrast, the descending and ascending thin limbs of Henle's loop have poorly developed upmost and basolateral surfaces and few mitochondria. The cells of the thick ascending limb and the distal tubule accept abundant mitochondria and extensive infoldings of the basolateral membrane.
The collecting duct is composed of two cell types: chief cells and intercalated cells. Principal cells have a moderately invaginated basolateral membrane and comprise few mitochondria. Principal cells play an important role in sodium chloride (NaCl) reabsorption (meet Capacity 4 and half-dozenChapter fourAffiliate 6) and Grand+ secretion (see Chapter 7). Intercalated cells, which play an important role in regulating acid-base of operations balance, have a high density of mitochondria. I population of intercalated cells secretes H+ (i.e., reabsorbs bicarbonate []) and a 2d population of intercalated cells secretes (see Chapter viii). The final segment of the nephron, the inner medullary collecting duct, is composed of inner medullary collecting duct cells. Cells of the inner medullary collecting duct have poorly developed upmost and basolateral surfaces and few mitochondria.
Except for intercalated cells, all cells in the nephron have in the apical plasma membrane a single nonmotile principal cilium that protrudes into tubule fluid (Figure ii-3). Primary cilia are mechanosensors (i.e., they sense changes in the menstruum rate of tubule fluid) and chemosensors (i.e., they sense or respond to compounds in the surrounding fluid), and they initiate Ca++-dependent signaling pathways, including those that control kidney jail cell function, proliferation, differentiation, and apoptosis (i.e., programmed prison cell expiry).
AT THE CELLULAR LEVEL
Polycystin one (encoded by the PKD1 gene) and polycystin 2 (encoded by the PKD2 gene) are expressed in the membrane of primary cilia, and the PKD1/PKD2 complex mediates the entry of Ca++ into cells. PKD1 and PKD2 are thought to play an of import part in catamenia-dependent K+ secretion by master cells of the collecting duct (encounter Chapter 7). As described in more item in Chapter 7, increased menstruum of tubule fluid in the collecting duct is a potent stimulus for Grand+ secretion. Increased catamenia bends the chief cilium in principal cells, which activates the PKD1/PKD2 Ca++ conducting aqueduct circuitous, allowing Ca++ to enter the jail cell and increase intracellular [Ca++]. The increase in [Ca++] activates Yard+ channels in the upmost plasma membrane, which enhances One thousand+ secretion from the cell into the tubule fluid.
IN THE Clinic
Autosomal dominant polycystic kidney affliction (ADPKD), which is the most common inherited kidney affliction, occurs in 1 in grand people. Approximately 12.5 meg people worldwide have ADPKD, which is caused primarily by mutations in the genes PKD1 (85% of cases) and PKD2 (~15% of cases). The major phenotype of ADPKD is enlargement of the kidneys related to the presence of hundreds to thousands of renal cysts that can exist as big as 20 cm in diameter. Cysts also are seen in the liver and other organs. About fifty% of patients with ADPKD progress to renal failure by the age of 60 years. Although information technology is not clear how mutations in PKD1 and PKD2 cause ADPKD, renal cyst germination results from defects in Ca++ uptake that atomic number 82 to alterations in Ca++-dependent signaling pathways, including those that command kidney jail cell proliferation, differentiation, and apoptosis.
Nephrons may be subdivided into superficial and juxtamedullary types (see Figure two-2). The glomerulus of each superficial nephron is located in the outer region of the cortex. Its loop of Henle is brusk, and its efferent arteriole branches into peritubular capillaries that surround the nephron segments of its own and adjacent nephrons. This capillary network conveys oxygen and important nutrients to the nephron segments in the cortex, delivers substances to the nephron for secretion (i.eastward., the movement of a substance from the claret into the tubular fluid), and serves as a pathway for the render of reabsorbed water and solutes to the circulatory organization. A few species, including humans, too possess very curt superficial nephrons whose Henle's loops never enter the medulla.
The glomerulus of each juxtamedullary nephron is located in the region of the cortex side by side to the medulla (see Figure 2-2). In comparison with the superficial nephrons, the juxtamedullary nephrons differ anatomically in two important ways: the loop of Henle is longer and extends deeper into the medulla, and the efferent arteriole forms non merely a network of peritubular capillaries only also a serial of vascular loops called the vasa recta.
As shown in Figure two-i, B, the vasa recta descend into the medulla, where they grade capillary networks that surround the collecting ducts and ascending limbs of the loop of Henle. The blood returns to the cortex in the ascending vasa recta. Although less than 0.7% of the blood enters the vasa recta, these vessels subserve important functions in the renal medulla, including (1) conveying oxygen and important nutrients to nephron segments, (2) delivering substances to the nephron for secretion, (3) serving equally a pathway for the return of reabsorbed water and solutes to the circulatory system, and (4) concentrating and diluting the urine (urine concentration and dilution are discussed in more particular in Chapter 5).
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