Physiology Topics
Cells lining the renal tubules (like other cells) have low cytosolic Na+ concentration due to the activity Na+/K+ ATPases which pump Na+ into the interstitial fluid. The absence of Na+/K+ATPases in the apical membrane ensures the one-way re-absorption of Na+. About 90% of the water re-absorption occurs by osmosis in the proximal tubule and descending loop of Henle, as it moves after reabsorbed solutes like Na+, Cl‾ and glucose. The other 10% of water re-absorption is regulated by ADH and occurs in the later part of the distal convoluted tubule and collecting ducts.
Two different types of Na+ transporters are located in the proximal convoluted tubule: several different symporters that transport Na+ with various other solutes, and Na+/H+ antiporters. The proximal tubule symporters reabsorbs:
For example, the Na+/glucose symporter transports 2 Na+ and one glucose from the tubular fluid into the cell. The glucose the exits via facilitated diffusion through the basolateral membrane, and diffuses into peritubular capillaries.
The Na+/H+ antiporters carry filtered Na+ down its concentration gradient into proximal tubule cells in exchange for H+, thus excreting H+. The H+ comes from dissociation of H2CO3 formed from CO2 diffusing into cells or generated in the cytosol:
carbonic
anhydrase
CO2 + H2O
H2CO3
H+ + HCO3‾
HCO3‾ is reabsorbed by facilitated diffusion from the cytosol to the interstitial fluid. Ammonium ions may substitute for H+ in the Na+/H+ antiporter in order to secrete ammonia. NH4+ secretion increases during acidosis, resulting in increased HCO3‾ intake that helps raise blood pH. The opposite happens during alkalosis.
In the second half of the tubule, electrochemical gradients promote the passage of ions by passive diffusion into the peritubular capillaries. Diffusion of Cl- (present at high concentrations) via paracellular leakage between cells into the interstitial fluid, makes that fluid more negative than tubular fluid. This promotes passive paracellular movement of filtered cations into the interstitial fluid, thus reabsorbing Na+, K+, Ca2+ and Mg2+. Water follows due to the osmolarity differential, via both paracellular and transcellular routes. Cells lining the proximal tubule and descending loop of Henle are especially permeable to water because they contain aquaporin-1 water channels.
The apical membrane of cells in the ascending loop of Henle have Na+/K+/2Cl triplicate symporters. Reclaimed Na+ is actively pumped into the interstitial fluid while Cl- diffuses through leak channels in the basolateral membrane. K+ returns to the tubular fluid through leak channels in the apical membrane.
Although about 15% of water is reabsorbed in the descending loop of Henle, almost none is reabsorbed in the ascending limb since the apical membrane is virtually impermeable. Since ions are reabsorbed, the osmolarity of the tubular fluid progressively decreases as fluid flows up the ascending limb. At the same time, a gradient of decreasing osmolarity is formed in the surrounding interstitial fluid (from about 750 OsM at the beginning of the ascending loop, to about 300 OsM at the distal tubule).
As fluid flows along the distal convoluted tubule, re-absorption of Na+ and Cl- continues by means of Na+/Cl- symporters in the apical membrane and Na+/K+ ATPases and Cl- leak channels in the basolateral membrane. There is little water absorption at the distal tubule since cells are not very permeable. The distal tubule is also the major site of parathyroid action to stimulate Ca2+ re-absorption.
The apical membranes of some intercalated cells in the distal tubule have H+ ATPases that secrete H+ into the tubular fluid. HCO3‾ produced by dissociation of H2CO3 inside the same cells cross the baslateral membrane via Cl-/HCO3‾ antiporters. A second tipe of intercalated cells has H+ ATPases in the basolateral membrane and Cl-/HCO3‾ antiporters in the apical membrane, thus secreting HCO3‾ and reabsorbing H+.
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Advance Topics: Renal Pharmacology (Medical Pharmacology)
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