Proximal Tubular Reabsorption
Normally, about 65 per cent of the filtered load of sodium and water and a slightly lower percentage of filtered chloride are reabsorbed by the proximal tubule before the filtrate reaches the loops of Henle. These percentages can be increased or decreased in different physiologic conditions, as discussed later.
Proximal Tubules Have a High Capacity for Active and Passive Reabsorption. The high capacity of the proximal tubulefor reabsorption results from its special cellular char-acteristics, as shown in Figure 27–6. The proximal tubule epithelial cells are highly metabolic and have large numbers of mitochondria to support potent active transport processes. In addition, the proximal
tubular cells have an extensive brush border on the luminal (apical) side of the membrane as well as an extensive labyrinth of intercellular and basal channels, all of which together provide an extensive membrane surface area on the luminal and basolateral sides of the epithelium for rapid transport of sodium ions and other substances.
The extensive membrane surface of the epithelial brush border is also loaded with protein carrier mole-cules that transport a large fraction of the sodium ions across the luminal membrane linked by way of the co-transport mechanism with multiple organic nutrientssuch as amino acids and glucose. The remainder of the sodium is transported from the tubular lumen into the cell by counter-transport mechanisms, which reabsorb sodium while secreting other substances into the tubular lumen, especially hydrogen ions. As discussed, the secretion of hydrogen ions into the tubular lumen is an important step in the removal of bicarbonate ions from the tubule (by combining H+ with the HCO3_ to form H2CO3, which then dissociates into H2O and CO2).
Although the sodium-potassium ATPase pump pro-vides the major force for reabsorption of sodium, chloride, and water throughout the proximal tubule, there are some differences in the mechanisms by which sodium and chloride are transported through the luminal side of the early and late portions of the proximal tubular membrane.
In the first half of the proximal tubule, sodium is reabsorbed by co-transport along with glucose, amino acids, and other solutes. But in the second half of the proximal tubule, little glucose and amino acids remain to be reabsorbed. Instead, sodium is now reabsorbed mainly with chloride ions.
The second half of the prox-imal tubule has a relatively high concentration of chloride (around 140 mEq/L) compared with the early proximal tubule (about 105 mEq/L) because when sodium is reabsorbed, it preferentially carries with it glucose, bicarbonate, and organic ions in the early proximal tubule, leaving behind a solution that has a higher concentration of chloride. In the second half of the proximal tubule, the higher chloride concentration favors the diffusion of this ion from the tubule lumen through the intercellular junctions into the renal inter-stitial fluid.
Concentrations of Solutes Along the Proximal Tubule. Figure27–7 summarizes the changes in concentrations of various solutes along the proximal tubule. Although the amount of sodium in the tubular fluid decreases markedly along the proximal tubule, the concentrationof sodium (and the total osmolarity) remains relatively constant because water permeability of the proximal tubules is so great that water reabsorption keeps pace with sodium reabsorption. Certain organic solutes, such as glucose, amino acids, and bicarbonate, are much more avidly reabsorbed than water, so that their concentrations decrease markedly along the length of the proximal tubule. Other organic solutes that are less permeant and not actively reabsorbed, such as creati-nine, increase their concentration along the proximal tubule. The total solute concentration, as reflected by osmolarity, remains essentially the same all along the proximal tubule because of the extremely high per-meability of this part of the nephron to water.
Secretion of Organic Acids and Bases by the Proximal Tubule.
The proximal tubule is also an important site for secre-tion of organic acids and bases such as bile salts, oxalate, urate, andcatecholamines. Many of these sub-stances are the end products of metabolism and must be rapidly removed from the body. Thesecretion of these substances into the proximal tubule plus filtra-tion into the proximal tubule by the glomerular capil-laries and the almost total lack of reabsorption by the tubules, all combined, contribute to rapid excretion in the urine.
In addition to the waste products of metabolism, the kidneys secrete many potentially harmful drugs or toxins directly through the tubular cells into the tubules and rapidly clear these substances from the blood. In the case of certain drugs, such as penicillin and salicylates, the rapid clearance by the kidneys creates a problem in maintaining a therapeutically effective drug concentration.
Another compound that is rapidly secreted by the proximal tubule is para-aminohippuric acid (PAH). PAH is secreted so rapidly that the average person can clear about 90 per cent of the PAH from the plasma flowing through the kidneys and excrete it in the urine. For this reason, the rate of PAH clearance can be used to estimate the renal plasma flow, as dis-cussed later.
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