Excretion tubular reabsorption, passive

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

Salicylate and its metabolites are rapidly and almost completely excreted in the urine by glomerular filtration and by renal tubular secretion. Passive reabsorption of salicylate occurs in the distal tubules. Salicylate elimination is saturable and characterized by Michaelis-Menton kinetics where the elimination half-life is dependent on the dose. Since the pRa of salicylic acid is 3, its renal clearance is greatly influenced by changes in urinary pH. Increasing urinary pH can significantly increase the overall salicylate elimination rate via ion trapping. 

RENAL EXCRETION Excretion of drugs and metabolites in the urine involves three distinct processes glomerular filtration, active tubular secretion, and passive tubular reabsorption. Changes in overall renal function generally affect aU three processes to a similar extent. In neonates, renal function is low compared with body mass but matures rapidly within the first few months after birth. During adulthood, there is a slow decline in renal function, 1% per year, so that in elderly patients a substantial degree of functional impairment may be present. 

Any drug known to be largely excreted by the kidney that has a body half-life of less than 2 hours is probably eliminated, at least in part, by tubular secretion. Some drugs can be secreted and have long half-lives, however, because of extensive passive reabsorption in distal segments of the nephron (see Passive Diffusion, earlier in the chapter). Several pharmacologically active drugs, both anions and cations, known to be secreted are listed in Table 4.5. 

Mineralocorticoids are believed to increase sodium reabsorption by affecting sodium channels and sodium pumps on the epithelial cells lining the renal tubules.18,58 Mineralocorticoids ability to increase the expression of sodium channels is illustrated in Figure 29-5. These hormones enter the tubular epithelial cell, bind to receptors in the cell, and create an activated hormone-receptor complex.18 This complex then travels to the nucleus to initiate transcription of messenger RNA units, which are translated into specific membrane-related proteins.27,58 These proteins in some way either create or help open sodium pores on the cell membrane, thus allowing sodium to leave the tubule and enter the epithelial cell by passive diffusion.27,83 Sodium is then actively transported out of the cell and reabsorbed into the bloodstream. Water reabsorption is increased as water follows the sodium movement back into the bloodstream. As sodium is reabsorbed, potassium is secreted by a sodium-potassium exchange, thus increasing potassium excretion (see Fig. 29-5). 

Figure 10.4 (a) A highly simplified diagram of a kidney tubule to illustrate the filtration and secretion of drugs from the blood into the tubular filtrate, and their subsequent reabsorption or loss in the urine, (b) Schematic representation of the influence of urinary pH on the passive reabsorption of a weak acid and a weak base from the urine in the renal tubules at a high pH the passive reabsorption of the weak base and the excretion of the weak acid are enhanced, while at a low pH values the reabsorption of the weak acid and the excretion of the weak base ore enhanced. 

The major effect is on the distal tubules of nephrons, where aldosterone promotes sodium retention and potassium excretion. Under the influence of aldosterone, sodium ions are actively transported out of the distal tubular cell into blood, and this transport is coupled to passive potassium flux in the opposite direction. Consequently, intracellular [Na" ] is diminished and intracellular [K+] is elevated. This intracellular diminution of [Na+] promotes the diffusion of sodium from the filtrate into the cell, and potassium diffuses into the filtrate. Aldosterone also stimulates sodium reabsorption from salivary fluid in the salivary gland and from luminal fluid in the intestines, but these sodium-conserving actions are of minor importance. 

For example, at low and high rates of urine flow, the minimal and maximal values of the may vary from 30% to 60% of the glomerular filtration rate. This occurs because various tubular segments are permeable to urea and allow passive reabsorption to occur under conditions of antidiuresis. The fractional excretion of urea (FE ,pa) is calculated as [(urine urea/ plasma urea)/(urine creatinine/plasma creatinine) x... 

The major processes involved in renal excretion are glomerular filtration, active tubular secretion, and passive reabsorption. Overall, renal excretion results from the net contributions of these three processes ... 

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