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represents a pathological situation, results in glucose being passed on to the loop of Henle Tm systems are perhaps like snow shovelers keeping a driveway clear during a snowstorm With an ordinary snowfall, they can remove snow as it falls and keep a driveway clear However, during a blizzard, snow falls faster than it can be shoveled and accumulates (Although we are discussing Tm systems in terms of reabsorption, the same concept applies to secretion For some secreted substances, there is a Tm limit to how fast they are secreted, and a rise in plasma concentration does not increase the secretion rate above the Tm) Gradient-limited systems are more complicated than Tm systems The key to gradient-limited systems is that the epithelium has a significant passive permeability to the substance, usually through the tight junctions, such that the establishment of a large concentration gradient between the interstitium and lumen results in a large passive back-leak Consider the case of sodium In the proximal tubule, the tight junctions are quite permeable to sodium Any significant lowering of the concentration in the lumen as sodium is reabsorbed results in a large passive flux from the interstitium back into the lumen Sodium is freely filtered and present in the luminal fluid at a concentration of about 140 mEq/L, the same as in plasma It is reabsorbed by a variety of pathways described previously (ie, symporters and antiporters in the apical membrane and the Na-K-ATPase across the basolateral membrane into the interstitium) As sodium is transported into the interstitium, the interstitial concentration begins to rise and the luminal concentration falls The rise in interstitial concentration not only drives a flux of sodium into the peritubular capillaries, but also back through the tight junctions into the lumen Most of the sodium moves into the blood, accomplishing the goal of reabsorption, but some does leak back into the lumen When the concentration of sodium reaches a sufficiently low level in the lumen, the concentration gradient between the interstitium and the lumen drives sodium back across the tight junctions as fast as it can be transported through the transcellular pathway from lumen to interstitium At this point, transport through paracellular and transcellular pathways is large, but net transport is zero: The system has established the largest gradient possible, its gradient limit The leakier the epithelium, the lower is the gradient limit (in the proximal tubule, the gradient limit is about 2 millimolar sodium) In normal conditions the reabsorption of sodium is accompanied by a proportional reabsorption of water, so that the luminal sodium concentration actually falls very little, ie, it does not reach its limiting gradient The main factor governing sodium reabsorption is the activity of its transporters (particularly, the NHE-3 sodium-hydrogen antiporters) However, if there is an unusually large amount of poorly reabsorbed solute in the lumen (eg, infused mannitol), this restrains reabsorption of water because nonreabsorbed osmoles remain in the lumen In turn, less water accompanies reabsorbed sodium Then as sodium is reabsorbed, its luminal sodium concentration falls and reaches the gradient limit This reduces the amount of sodium that is reabsorbed and leads to an osmotic diuresis (see 6) Technically, back-leak of sodium is a secretion, and net sodium reabsorption is the difference between reabsorption from lumen to interstitium and secretion from interstitium to lumen Because the net transport is indeed reabsorption, we. devexpress winforms barcode control BarcodeLib .com - Download .com
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