CHAPTER 38Renal Function & Micturition 657
RELATION OF URINE
CONCENTRATION TO GFR
The magnitude of the osmotic gradient along the medullary
pyramids is increased when the rate of flow of fluid through
the loops of Henle is decreased. A reduction in GFR such as
that caused by dehydration produces a decrease in the volume
of fluid presented to the countercurrent mechanism, so that
the rate of flow in the loops declines and the urine becomes
more concentrated. When the GFR is low, the urine can be-
come quite concentrated in the absence of vasopressin. If one
renal artery is constricted in an animal with diabetes insipidus,
the urine excreted on the side of the constriction becomes hy-
pertonic because of the reduction in GFR, whereas that excret-
ed on the opposite side remains hypotonic.
"FREE WATER CLEARANCE"
In order to quantitate the gain or loss of water by excretion of
a concentrated or dilute urine, the "free water clearance"
(CH 2 O) is sometimes calculated. This is the difference between
the urine volume and the clearance of osmoles (COsm):
CH 2 O = V
UOsm V
POsm
where V
- is the urine flow rate and UOsm and POsm the urine
and plasma osmolality, respectively. COsm is the amount of
water necessary to excrete the osmotic load in a urine that is
isotonic with plasma. Therefore, CH 2 O is negative when the
urine is hypertonic and positive when the urine is hypotonic.
For example, using the data in Table 38–7, the values for
CH 2 O are –1.3 mL/min (–1.9 L/d) during maximal antidiure-
sis and 14.5 mL/min (20.9 L/d) in the absence of vasopressin.
REGULATION OF Na
+
EXCRETION
Na+ is filtered in large amounts, but it is actively transported out
of all portions of the tubule except the descending thin limb of
Henle’s loop. Normally, 96% to well over 99% of the filtered Na+
is reabsorbed. Because Na+ is the most abundant cation in ECF
and because Na+ salts account for over 90% of the osmotically
active solute in the plasma and interstitial fluid, the amount of
Na+ in the body is a prime determinant of the ECF volume.
Therefore, it is not surprising that multiple regulatory mecha-
nisms have evolved in terrestrial animals to control the excre-
tion of this ion. Through the operation of these regulatory
mechanisms, the amount of Na+ excreted is adjusted to equal
the amount ingested over a wide range of dietary intakes, and
the individual stays in Na+ balance. Thus, urinary Na+ output
ranges from less than 1 mEq/d on a low-salt diet to 400 mEq/d
or more when the dietary Na+ intake is high. In addition, there
is a natriuresis when saline is infused intravenously and a de-
crease in Na+ excretion when ECF volume is reduced.
MECHANISMS
Variations in Na+ excretion are brought about by changes in
GFR (Table 38–9) and changes in tubular reabsorption, pri-
marily in the 3% of filtered Na+ that reaches the collecting ducts.
The factors affecting the GFR, including tubuloglomerular
feedback, have been discussed previously. Factors affecting Na+
reabsorption include the circulating level of aldosterone and
other adrenocortical hormones, the circulating level of ANP
and other natriuretic hormones, and the rate of tubular secre-
tion of H+ and K+.
EFFECTS OF
ADRENOCORTICAL STEROIDS
Adrenal mineralocorticoids such as aldosterone increase tu-
bular reabsorption of Na+ in association with secretion of K+
and H+ and also Na+ reabsorption with Cl–. When these hor-
mones are injected into adrenalectomized animals, a latent
FIGURE 38–18 Approximate relationship between urine
concentration and urine flow in osmotic diuresis in humans. The
dashed line in the lower diagram indicates the concentration at which
the urine is isosmotic with plasma. (Reproduced with permission from
Berliner RW, Giebisch G in: Best and Taylor’s Physiological Basis of Medical Practice, 9th
ed. Brobeck JR [editor]. Williams & Wilkins, 1979.)
Urine flow (mL/min)
Isosmotic
Diabetes
insipidus
Solute load (mosm/min)
Maximal
vasopressin
21
18
15
12
9
6
3
0
0.9 1.8 2.7 4.5 6.3
Urine osmolality (mosm/L)
Isosmotic
Diabetes insipidus
Urine flow (mL/min)
Maximal
vasopressin
1400
1200
1000
800
600
400
200
0
3 6 9 12 15 18 21