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Thread: The Ways That substance (including water) Cross Cell Membrane

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    PharmD Year 1 TomHsiung's Avatar
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    Default The Ways That substance (including water) Cross Cell Membrane

    Channels

    1.Mechanosensitive channels
    2.Voltage-sensitive channels
    3.Chemosensitive channels
    4.Others (e.g., channels that usually stay open that maintain resting potential, water channels, cell-cell channels that connect the cytoplasm of one cell with the cytoplasm of another)

    Pumps

    1.Na/K pump
    2.Ca pump
    3.H/K pump
    4.F-type H pumps
    5.V-type H pumps

    Transporters

    1.Uniporters
    2.Symporters/Cotransporters
    3.Antiporters/Exchangers
    4.ABC transporters (active transport)
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    PharmD Year 1 TomHsiung's Avatar
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    Default Re: The Ways That substance (including water) Cross Cell Membrane

    Water permeability of different tubule segments


    Proximal tubule
    Tight junctions (significantly permeable) and luminal membranes (highly permeable)


    Early parts of the descending thin limb
    Tight junctions (-) and luminal membranes (very high water permeability)


    Ascending limbs of Henle's loop (both thin and thick)
    Tight junctions (relatively water impermeable) and luminal membranes (relatively water impermeable)


    Distal convoluted tubule
    Tight junctions (relatively water impermeable) and luminal membranes (relatively water impermeable)


    Collecting-duct system
    Tight junctions (-) and luminal membranes (intrinsically low but can be regulated so that it increases substantially)
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    PharmD Year 1 TomHsiung's Avatar
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    Default Renal Reabsorption Mechanisms

    How the kidney reabsorb substances including water?

    • Sodium reabsorbed at proximal tubule: 65%
    • Chloride reabsorbed at proximal tubule: 63%
    • Bicarbonate reabsorbed at proximal tubule: 90%
    • Glucose reabsorbed at proximal tubule: 100%
    • Water reabsorbed at proximal tubule: 65%
    • Urea reabsorbed at proximal tubule: 50%



    Proximal tubule
    Sodium
    Sodium enters proximal tubule cells by several luminal entry steps. In the early portion, a large fraction of the tubular sodium enters the cells across the luminal membrane via antiport with protons from within the cells. The large amount of protons needed to exchange the large amount of sodium is provided by two proton generating recycles.

    The first recycle is the "carbon dioxide - bicarbonate" cycle, in which the at the cytoplasm carbon dioxide combines with water and produces protons and bicarbonate. The protons exit the cell across the luminal membrane in exchange for sodium entry, while bicarbonate exits the cell across the basolateral membrane in symport with sodium. On the other hand, at the luminal space many of the secreted protons combine with filtered bicarbonate to form carbon dioxide and water and CO2 diffuse into the tubule cells and the carbon dioxide - bicarbonate cycle happens once again. This mechanism is by which the sodium and bicarbonate in the proximal tubule are reabsorbed.

    The second recycle is the "organic acid - organic base" cycle, in which the organic acid in the tubule cells, particularly formate and oxalate, dissociates into a proton and the base. Simultaneously, the protons generated within the cell by the dissociation of the organic acids are actively transported into the lumen by the Na-H antiporters described above. On the other hand, in the lumen, the protons and organic bases (secreted into the lumen via Cl-base antiporters) recombine to form the acid, which is a neutral molecule. This non polar neutral acid then diffuses across the luminal membrane back into the tubule cell, where the entire process is repeated.

    The Ways That substance (including water) Cross Cell Membrane-screen-shot-2016-06-17-at-2-53-18-pm-png

    Chloride

    A major percentage of chloride reabsorption in the proximal tubule occurs via paracellular diffusion. The concentration of chloride in Bowman's capsule is, of course, essentially the same as in plasma (approximately 110 mEq/L). Along the early, proximal tubule, however, the reabsorption of water, driven by the osmotic gradient created by the reabsorption of sodium plus its cotransported solutes and bicarbonate, causes the chloride concentration in the tubular lumen to increase somewhat above that in the peritubular capillaries. Then, as the fluid flows through the middle and late proximal tubule, this concentration gradient, maintained by continued water reabsorption, provides the driving force for paracellular chloride reabsorption by diffusion.

    There is also an important component of active chloride transport from lumen to cell in the later proximal tubule. It uses parallel Na-H (despite Na-H exchange does not involved the reabsorption of Cl directly, the efflux protons recombine the bases in the lumen fluid so improve the cycle) and Cl-base antiporters ("organic acid - organic base" cycle). Chloride transport into the cell is powered by the downhill efflux of organic bases, particularly formate and oxalate.

    Water
    The proximal tubule has a very high permeability to water. This means that very small differences in osmolality (less than 1 most/kg H2O) suffice to drive the reabsorption of very large quantities of water, normally approximately 65% of the filtered water. This osmolality difference is created by the reabsorption of solute.

    The osmolality of the freshly filtered tubular fluid at the very beginning of the proximal tubule is, of course, essentially the same as that of plasma and interstitial fluid. Then, as solute is reabsorbed from the proximal tubule the luminal osmolality falls slightly. Simultaneously, the reabsorbed solute tends to raise the interstitial fluid osmolality. However, interstitial osmolality rises only a small amount because the high perfusion through peritubular capillaries keeps the interstitial osmolality close to the plasma value.
    Last edited by TomHsiung; Thu 7th July '16 at 11:59am.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    PharmD Year 1 TomHsiung's Avatar
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    Default Re: The Ways That substance (including water) Cross Cell Membrane



    The Loop of Henle


    Henle's loop as a whole reabsorbs proportionally more sodium and chloride (approximately 25% of the filtered loads) than water (10% of the filtered water). The result is that the sodium concentration in the tubular fluid is reduced to the range of ~50 mEq/L and the fluid delivered to the distal nephron (distal tubule and beyond) is hypo-osmotic relative to plasma.

    The reabsorption of sodium chloride and reabsorption of water occurs in different place. The descending limbs reabsorb water, but not sodium or chloride. The remaining portions of Henle's loop do not express luminal aquaporins and are water impermeable. There are fewer long-looped nephrons with thin limbs extending pass the border into the inner medulla. Because of this anatomical feature the vast majority of the water reabsorbed by the loop of Henle occurs in the outer medulla only.

    The ascending limbs (both thin and thick) reabsorb sodium and chloride but not water. Water reabsorption in the descending limb concentrates luminal sodium and chloride, creating a favorable gradient for passive reabsorption. The thin ascending limb cells express chloride channels in both luminal and basolateral membranes though which passive chloride reabsorption occurs. They tight junctions are somewhat leaky to sodium, and so sodium follows the chloride.

    As tubular fluid enters the thick ascending limb (at the junction between inner and outer medulla), the transport properties of the epithelium change again, and active processes become dominant. And because most nephrons are short-looped and do not have thin ascending limbs, the vast majority of sodium and chloride reabsorbed by the loop of Henle occurs in the thick ascending limbs in the outer medulla. The major luminal entry step for the sodium and chloride in thick ascending limbs is via the Na-K-2Cl symporter. This symporter is the target for a major class of diuretics collectively known as the loop diuretics, which include the drugs furosemide and bumetanide.

    The Ways That substance (including water) Cross Cell Membrane-screen-shot-2016-06-17-at-2-50-08-pm-png

    The stoichiometry of the Na-K-2Cl symporter has several important consequences. First, it requires that equal amounts of potassium and sodium be transported into the cell. However, there is far less potassium in the lumen than sodium, and it seems that the lumen would be depleted of potassium long before very much sodium was reabsorbed. Interestingly, the luminal membrane has a large number of potassium channels that allow much of the potassium to leak back, that is, potassium recycles between the cytosol and lumen.

    The Na-K-2Cl symporter moves twice as much chloride as sodium into the cell; therefore, twice as much chloride must also exit the cell across the basolateral membrane. The chloride leaves by a combination of chloride channels and chloride-potassium symporters, while sodium leaves primarily via the Na-K-ATPase. But, as there are 2 chloride ions leaving the cell for every 1 sodium, where does the rest of the sodium come from to balance this flux of chloride? It moves paracellularly. The movement of chloride sets up a lumen-posivite potential. This drives luminal cations, specifically including sodium, paracellularly through the tight junctions. Thus, about half the sodium moves through the cells and half moves by paracellular diffusion.

    Summary

    The net of the loop as a whole is reabsorption of more salt than water. The ascending limb is called a diluting segment, because the fluid leaving the loop to enter the distal convoluted tubule is hypo-osmotic compared with plasma.
    Last edited by TomHsiung; Fri 17th June '16 at 4:20pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    Default Re: The Ways That substance (including water) Cross Cell Membrane

    Distal Convoluted Tubule

    The distal convoluted tubule lies entirely within the cortex, beginning just after the macula dense. It parallels the activity of the thick ascending limb by reabsorbing salt without water, and therefore is also a diluting segment, although it uses different transport mechanisms.

    The major luminal entry step in the active reabsorption of sodium and chloride by the distal convoluted tubule is via the Na-Cl symporter. It is sensitive to different drugs. In particular, the Na-Cl symporter is blocked by the thiazide diuretics, which makes it a major site for pharmacological intervention. Sodium exits the cell by the Na-K-ATPase, while chloride leaves via channels and K-Cl symporter.

    The Ways That substance (including water) Cross Cell Membrane-screen-shot-2016-06-17-at-3-41-03-pm-png
    Last edited by TomHsiung; Fri 17th June '16 at 3:46pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    Default Re: The Ways That substance (including water) Cross Cell Membrane

    Connecting Tubule and Collecting-Duct System

    Elements beyond the distal tubule begin an entirely new set of tasks. It is here that water is reabsorbed in highly variable amounts depending on body conditions. These elements continue to reabsorb additional sodium and chloride and have major mechanisms to control potassium and acid/base excretion.

    Anatomically, the tubular elements beyond the distal tubule can be divided into the connecting tubule (9), cortical collecting duct (10), outer medullary collecting duct (11), and inner medullary collecting duct (12). As the tubule epithelial cells reabsorb sodium, the luminal entry step is via epithelial sodium channels (ENaC). The handling of chloride in the distal nephron is rather complex because the handling of solutes other than sodium makes up a significant component of ion transport. Chloride moves through several types of transporters in the intercalated cells that are key players in potassium and acid/base transport. As in all nephron segments, net anion flux must equal net cation flux. Thus chloride flux must match the net of sodium, potassium, and acid-base transport.

    As tubular fluid leaves the diluting segments and enters the collecting duct system the luminal osmolality is low, typically a little above 100 most/kg. Therefore, there is an osmotic gradient favoring water reabsorption. Water permeability in the tubule epithelial cells of the collecting duct system is finely regulated by ADH.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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