OBJECTIVE 1: TO DETERMINE HOW THE KIDNEY HANDLES UREA.
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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.
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).
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.
1. How does the rate of urea excretion vary with the urine flow