Salt reabsorption

Because water is reabsorbed in direct proportion to salt reabsorption in the proximal tubule, luminal fluid osmolality remains nearly constant along its length, and an impermeant solute like inulin rises in concentration as water is reabsorbed. If large amounts of an impermeant solute such as mannitol (an osmotic diuretic) are present in the tubular fluid, water reabsorption causes the concentration of the solute and osmolality of tubular fluid to rise, eventually preventing further water reabsorption. 

The thick ascending limb (TAL) of the loop of Henle actively reabsorbs NaCI from the lumen (about 25% of the filtered sodium), but unlike the proximal tubule and the thin descending limb of Henle s loop, it is nearly impermeable to water. Salt reabsorption in the TAL therefore dilutes the tubular fluid, and it is called a diluting segment. Medullary portions of the TAL contribute to medullary hypertonicity and thereby also play an important role in concentration of urine by the collecting duct. 

By inhibiting salt reabsorption in the TAL, loop diuretics increase delivery to the collecting duct. Increased delivery leads to increased secretion of K+ and H+ by the duct, causing hypokalemic metabolic alkalosis (Table 15-2). This toxicity is a function of the magnitude of the diuresis and can be reversed by K+ replacement and correction of hypovolemia. 

First, salt reabsorption in either the TAL or the DCT can increase when the other is blocked. Inhibition of both can therefore produce more than an additive diuretic response. Second, thiazide diuretics often produce a mild natriuresis in the proximal tubule that is usually masked by increased reabsorption in the TAL. The combination of loop diuretics and thiazides can therefore block Na + reabsorption, to some extent, from all three segments. 

The reabsorption of bile is impeded by oral administration of positively charged polymers, such as cholestyramine, that bind negatively charged bile salts and are not themselves absorbed. Cholesterol synthesis can be effectively blocked by a class of compounds called statins (e.g., lovastatin, which is also called mevacor Figure 26.22). These compounds are potent competitive inhibitors (AT j < 1 nM) of HMG-CoA reductase, the essential control point in the biosynthetic pathway. Plasma cholesterol levels decrease by 50% in many patients given both lovastatin and inhibitors of bile-salt reabsorption. Lovastatin and other inhibitors of HMG-CoA reductase are widely used to lower the plasma cholesterol level in people who have atherosclerosis, which is the leading cause of death in industrialized societies. 

Salty tastants are not detected by 7TM receptors. Rather, they are detected directly by their passage through ion channels expressed on the surface of cells in the tongue. Evidence for the role of these ion channels comes from examining known properties of sodium channels characterized in other biological contexts. One class of channels, characterized first for their role in salt reabsorption, are thought to be important in salt taste detection because they are sensitive to the compound amiloride, which mutes the taste of salt and significantly lowers sensory neuron activation in response to sodium. 

The general properties of the methylxanthines (theophylline, caffeine) are discussed elsewhere (see p. 194). Their mild diuretic action probably depends in part on smooth muscle relaxation in the afferent arteriolar bed increasing renal blood flow, and in part on a direct inhibitory effect on salt reabsorption in the proximal tubule. Their uses in medicine depend on other properties. 

Depending upon their severity, liver diseases may impair bile salt reabsorption, interfere with bile salt conjugation, or both. Detailed discussion of the changes in bile salt concentration in feces, urine, and bile is not necessary it suffices to remark that the concentration of biliary bile salts in serum depends on the rate of production and on intestinal and hepatic reabsorption. The ability of the liver cells to reabsorb bile salts is believed to be the most critical factor therefore, measurements of the bile salt levels in serum can be helpful for diagnosing certain liver diseases. The concentration of primary bile salts in the serum is significant, whereas that of secondary bile salts is too low to influence distribution changes markedly. 

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