These IgA-molecules, however, are unable to directly induce podocyte changes in culture. Instead when medium from mesangial cells cultured in the presence of polymeric IgA is added to podocyte culture, it caused decreased expression of podocyte differentiation markers. Together, these examples of mesangio-podocyte interaction could help devise a therapeutic strategy in these diseases centered around the mesangial cell.
In summary, we have attempted to highlight the interdependence among the principal components of the glomerular filtration apparatus that is vital to its integrity. Injury to these individual components or disruption of intercomponent relationships seems to bring out both specific and common disease phenotypes often characterized by glomerular proteinuria. Menon et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Menon, 1 Peter Y. Academic Editor: Omran Bakoush. Received 22 Mar Revised 02 Jun Accepted 05 Jun Published 14 Aug Abstract The glomerular filtration barrier is a highly specialized blood filtration interface that displays a high conductance to small and midsized solutes in plasma but retains relative impermeability to macromolecules.
Glomerular Filtration Slit Diaphragm: A Multicomponent Apparatus The filtration apparatus is complex; its integrity is maintained by an interplay of all participating cell types and constituents [ 9 ].
Table 1. Figure 1. Components of the Glomerular filtration barrier with examples of crosstalk. This figure summarizes important signaling interactions between the 3 key components of the GFB and their putative involvement in human disease models dotted arrows.
References J. Peterson, S. Adler, J. Burkart et al. View at: Google Scholar C. Chronic Kidney Disease Prognosis, K. Matsushita, M. View at: Google Scholar M. Carroll and J. View at: Google Scholar J. Barratt and P. Russo, R. Sandoval, M. McKee et al. F—F, Tojo and H. View at: Google Scholar H. Kriz, and M. View at: Google Scholar V. D'Agati, F.
Kaskel, and R. Hudson, K. Tryggvason, M. Sundaramoorthy, and E. Noris and G. Ambrus Jr. View at: Google Scholar D. Kerjaschki, D. Sharkey, and M. View at: Google Scholar E. Schnabel, J. Anderson, and M. Reiser, W. Kriz, M. Kretzler, and P. Ruotsalainen, P. Ljungberg, J. Wartiovaara et al. Wartiovaara, L. Khoshnoodi et al. Liu, B. Kaw, J. Kurfis, S. Rahmanuddin, Y. Kanwar, and S. Kaplan, S. Kim, K. North et al. Brown, J. Becker et al. Ma, A. Togawa, K. Soda et al. Branten, J. Van den Born, J.
Jansen, K. Assmann, J. Wetzels, and H. Macconi, M. Ghilardi, M. Bonassi et al. View at: Google Scholar S. Karumanchi, S. Maynard, I. Stillman, F. Epstein, and V. Wharram, M. Goyal, P. Gillespie et al. Weening, and S. Seiler, M. Venkatachalam, and R. View at: Google Scholar P. Garg, R. Verma, L. Cook et al. Kim, H. Wu, G. Green et al. Wei and J. Garg and T. Reiser, J. Oh, I. Shirato et al. Adler and X. El-Aouni, N. Herbach, S.
Blattner et al. Kang, Y. Li, C. Dai, L. Kiss, C. Wu, and Y. Blasi and P. Smith and C. Wei, C. Moller, M. Altintas, " et al. Wei, S. These features comprise the filtration membrane. The filtration membrane prevents passage of blood cells, large proteins, and most negatively charged particles but allows most other constituents through.
These substances cross readily if they are less than 4 nm in size and most pass freely up to 8 nm in size. Negatively charged particles have difficulty leaving the blood because the proteins associated with the filtration membrane are negatively charged, so they tend to repel negatively charged substances and allow positively charged substances to pass more readily. There are also mesangial cells in the filtration membrane that can contract to help regulate the rate of filtration of the glomerulus.
The result is the creation of a filtrate that does not contain cells or large proteins, and has a slight predominance of positively charged substances. Simple cuboidal cells form this tubule with prominent microvilli on the luminal surface, forming a brush border.
These cells actively transport ions across their membranes, so they possess a high concentration of mitochondria in order to produce sufficient ATP. The descending and ascending portions of the loop of Henle sometimes referred to as the nephron loop are continuations of the same tubule. They run adjacent and parallel to each other after having made a hairpin turn at the deepest point of their descent.
The descending loop of Henle consists of an initial short, thick portion and long, thin portion, whereas the ascending loop consists of an initial short, thin portion followed by a long, thick portion. The descending thick portion consists of simple cuboidal epithelium similar to that of the PCT. The descending and ascending thin portions consists of simple squamous epithelium. As you will see later, these are important differences, since different portions of the loop have different permeabilities for solutes and water.
The ascending thick portion consists of simple cuboidal epithelium similar to the DCT. These cells are not as active as those in the PCT and there are fewer microvilli on the apical surface. However, these cells must also pump ions against their concentration gradient, so you will find of large numbers of mitochondria, although fewer than in the PCT. The collecting ducts are continuous with the nephron but not technically part of it. In fact, each duct collects filtrate from several nephrons for final modification.
Collecting ducts merge as they descend deeper in the medulla to form about 30 terminal ducts, which empty at a papilla. They are lined with simple cuboidal epithelium to facilitate water transport. Net fluid movement will be in the direction of the lower pressure. Osmosis is the movement of solvent water across a membrane that is impermeable to a solute in the solution. This creates a pressure, osmotic pressure, which will exist until the solute concentration is the same on both sides of a semipermeable membrane.
As long as the concentration differs, water will move. There is also an opposing force, the osmotic pressure, which is typically higher in the glomerular capillary. To understand why this is so, look more closely at the microenvironment on either side of the filtration membrane. Recall that cells and the medium-to-large proteins cannot pass between the podocyte processes or through the fenestrations of the capillary endothelial cells.
This means that red and white blood cells, platelets, albumins, and other proteins too large to pass through the filter remain in the capillary, creating an average colloid osmotic pressure of 30 mm Hg within the capillary.
Hydrostatic fluid pressure is sufficient to push water through the membrane despite the osmotic pressure working against it. The sum of all of the influences, both osmotic and hydrostatic, results in a net filtration pressure NFP of about 10 mm Hg.
A proper concentration of solutes in the blood is important in maintaining osmotic pressure both in the glomerulus and systemically. There are disorders in which too much protein passes through the filtration slits into the kidney filtrate. This excess protein in the filtrate leads to a deficiency of circulating plasma proteins. In turn, the presence of protein in the urine increases its osmolarity; this holds more water in the filtrate and results in an increase in urine volume.
Because there is less circulating protein, principally albumin, the osmotic pressure of the blood falls. Less osmotic pressure pulling water into the capillaries tips the balance towards hydrostatic pressure, which tends to push it out of the capillaries. The net effect is that water is lost from the circulation to interstitial tissues and cells.
As you can see, there is a low net pressure across the filtration membrane. Intuitively, you should realize that minor changes in osmolarity of the blood or changes in capillary blood pressure result in major changes in the amount of filtrate formed at any given point in time. The kidney is able to cope with a wide range of blood pressures.
In large part, this is due to the autoregulatory nature of smooth muscle. When you stretch it, it contracts. Thus, when blood pressure goes up, smooth muscle in the afferent capillaries contracts to limit any increase in blood flow and filtration rate.
0コメント