5. Excretion of Organic Molecules

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A. Urea, a waste product of protein catabolism, is present in the plasma at a concentration of 18 to 36 mg/dl, averaging about 27 mg/dl or 4.5 mM. Clinically, however, its concentration is usually expressed as the concentration of "urea nitrogen" the normal range being 9 to 18 mg/dl (blood urea nitrogen, BUN).

B. Urea is freely filtered by the glomerulus, but its rate of clearance from plasma is less than that of inulin since it is reabsorbed to some extent. Reabsorption of urea occurs primarily by diffusion. The gradient for that reabsorption is established by water reabsorption. Thus, urea reabsorption varies with the rate of water reabsorption. To state it differently, the rate of excretion of urea varies with the urine flow rate (Fig. 5-1).

Fig. 5-1. The effect changes in urine flow rate on the fractional excretion of urea.

C. The various segments of the nephron vary in their permeability to urea. Most of the urea is reabsorbed in the proximal tubule and the inner medullary segment of the collecting tubule. In between, in the Loop of Henle, urea is added to the tubular fluid.

1. Water reabsorption in the proximal tubule increases the concentration of urea in the tubular fluid, creating the gradient for passive diffusion of urea. The reabsorption of urea does not quite keep pace with the rate of water reabsorption so the tubular fluid concentration of urea increases somewhat (Fig.3-2).

2. Urea is secreted into the the descending segment of the loop of Henle. This segment of the nephron is surrounded by the medullary interstitial fluid which contains a high concentration of urea. Thus as the tubular fluid flows through this area, the direction of urea diffusion is reversed and urea is secreted into the tubular fluid (Fig. 6-11). In subsequent segments the reabsorption of water with little urea increases the concentration of urea in the tubular fluid greatly.

3. Urea is reabsorbed via a carrier (facilitated diffusion) by the inner medullary segment of the collecting tubule. Tubular fluid reaching the last segment of tubule contains a high concentration of urea,so that a large gradient may exist to drive reabsorption. Antidiuretic hormone stimulates that reabsorption. The reabsorbed urea is concentrated within the medullary interstitium by the countercurrent mechanism and plays a role in water reabsorption there (See Section VI).

D. In patients with renal failure, glomerular filtration is greatly reduced and urea accumulates in the plasma to high levels (100 to 200 mg/dl). It was one of the first chemicals identified in the plasma of patients who were desperately ill due to renal failure, and clinicians still refer to this condition as "uremia". However urea is not especially toxic and the clinical syndrome of uremia is due to other substances inadequately excreted by failing kidneys.

How does the rate of urea excretion vary with the urine flow rate? Why?

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