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Scientists investigating the specifics of kidney function in humans develop a new technique allowing them to measure the concentration of various compounds along the length of the proximal tubule.  During an experiment, they record the concentrations of several endogenous substances in the fluid traversing the proximal tubule.  Tubular fluid/plasma ultrafiltrate concentration ratios for the measured substances are shown in the image below:

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Which of the following substances are most likely to produce lines 2 and 4, respectively?

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The tubular fluid/plasma ultrafiltrate value is calculated by dividing the tubular fluid concentration of a given substance in the proximal tubule by the initial concentration of that substance within Bowman's capsule.  Therefore, an upward (positive) slope indicates an increasing concentration of that substance as fluid moves toward distal parts of the tubule, which is usually the result of secretion or nonreabsorption of that substance.  A downward slope indicates active reabsorption of that substance in the proximal tubule.

  • Line 1 represents creatinine, which is freely filtered in the glomerulus, as well as actively secreted and not reabsorbed along the proximal tubule, resulting in a rapidly increasing concentration in the tubular fluid.

  • Line 2 represents urea, which is freely filtered from the glomerular capillaries and is poorly reabsorbed from the proximal tubule, resulting in increasing concentrations along the proximal tubule but less so than with creatinine.  Renal handling of urea varies throughout the different tubular systems, but it is ultimately secreted in very high concentrations because it is a waste product of metabolism.

  • Line 3 represents sodium or potassium, which is reabsorbed in concentrations approximately equal with water in the proximal tubule, resulting in no concentration change along the proximal tubule.

  • Line 4 represents bicarbonate, which is actively reabsorbed in the proximal tubule due to the activity of carbonic anhydrase along the brush border.  This reabsorption causes the concentration of bicarbonate to decrease as fluid runs along the proximal tubule.

  • Line 5 represents glucose or amino acids, which are avidly reabsorbed in the proximal tubule.

In summary, the concentrations of creatinine and urea increase along the proximal tubule due to active secretion or poor reabsorption, respectively, whereas the concentrations of bicarbonate, glucose, and amino acids decrease due to active reabsorption.  Sodium and potassium are reabsorbed with water in the proximal tubule, resulting in no concentration change.

Educational objective:
The concentrations of creatinine and urea increase as fluid runs along the proximal tubule, whereas the concentrations of bicarbonate, glucose, and amino acids decrease.  Sodium and potassium are reabsorbed with water in the proximal tubule, resulting in no concentration change.