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Ganong's Review of Medical Physiology, 23rd Edition

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Urine flow (mL/min)<br />

Urine osmolality (mosm/L)<br />

21<br />

18<br />

15<br />

12<br />

9<br />

6<br />

3<br />

0<br />

1400<br />

1200<br />

1000<br />

800<br />

600<br />

400<br />

200<br />

0<br />

Diabetes<br />

insipidus<br />

Isosmotic<br />

0.9 1.8 2.7 4.5 6.3<br />

Solute load (mosm/min)<br />

Maximal<br />

vasopressin<br />

Isosmotic<br />

FIGURE 38–18 Approximate relationship between urine<br />

concentration and urine flow in osmotic diuresis in humans. The<br />

dashed line in the lower diagram indicates the concentration at which<br />

the urine is isosmotic with plasma. (Reproduced with permission from<br />

Berliner RW, Giebisch G in: Best and Taylor’s Physiological Basis <strong>of</strong> <strong>Medical</strong> Practice, 9th<br />

ed. Brobeck JR [editor]. Williams & Wilkins, 1979.)<br />

RELATION OF URINE<br />

CONCENTRATION TO GFR<br />

The magnitude <strong>of</strong> the osmotic gradient along the medullary<br />

pyramids is increased when the rate <strong>of</strong> flow <strong>of</strong> fluid through<br />

the loops <strong>of</strong> Henle is decreased. A reduction in GFR such as<br />

that caused by dehydration produces a decrease in the volume<br />

<strong>of</strong> fluid presented to the countercurrent mechanism, so that<br />

the rate <strong>of</strong> flow in the loops declines and the urine becomes<br />

more concentrated. When the GFR is low, the urine can become<br />

quite concentrated in the absence <strong>of</strong> vasopressin. If one<br />

renal artery is constricted in an animal with diabetes insipidus,<br />

the urine excreted on the side <strong>of</strong> the constriction becomes hypertonic<br />

because <strong>of</strong> the reduction in GFR, whereas that excreted<br />

on the opposite side remains hypotonic.<br />

"FREE WATER CLEARANCE"<br />

Maximal<br />

vasopressin<br />

Diabetes insipidus<br />

3 6 9 12 15 18 21<br />

Urine flow (mL/min)<br />

In order to quantitate the gain or loss <strong>of</strong> water by excretion <strong>of</strong><br />

a concentrated or dilute urine, the "free water clearance"<br />

CHAPTER 38 Renal Function & Micturition 657<br />

(C H2O ) is sometimes calculated. This is the difference between<br />

the urine volume and the clearance <strong>of</strong> osmoles (C Osm ):<br />

CH2O = V •<br />

– UOsm V•<br />

POsm where V •<br />

is the urine flow rate and UOsm and POsm the urine<br />

and plasma osmolality, respectively. COsm is the amount <strong>of</strong><br />

water necessary to excrete the osmotic load in a urine that is<br />

isotonic with plasma. Therefore, CH2O is negative when the<br />

urine is hypertonic and positive when the urine is hypotonic.<br />

For example, using the data in Table 38–7, the values for<br />

CH2O are –1.3 mL/min (–1.9 L/d) during maximal antidiuresis<br />

and 14.5 mL/min (20.9 L/d) in the absence <strong>of</strong> vasopressin.<br />

REGULATION OF Na + EXCRETION<br />

Na + is filtered in large amounts, but it is actively transported out<br />

<strong>of</strong> all portions <strong>of</strong> the tubule except the descending thin limb <strong>of</strong><br />

Henle’s loop. Normally, 96% to well over 99% <strong>of</strong> the filtered Na +<br />

is reabsorbed. Because Na + is the most abundant cation in ECF<br />

and because Na + salts account for over 90% <strong>of</strong> the osmotically<br />

active solute in the plasma and interstitial fluid, the amount <strong>of</strong><br />

Na + in the body is a prime determinant <strong>of</strong> the ECF volume.<br />

Therefore, it is not surprising that multiple regulatory mechanisms<br />

have evolved in terrestrial animals to control the excretion<br />

<strong>of</strong> this ion. Through the operation <strong>of</strong> these regulatory<br />

mechanisms, the amount <strong>of</strong> Na + excreted is adjusted to equal<br />

the amount ingested over a wide range <strong>of</strong> dietary intakes, and<br />

the individual stays in Na + balance. Thus, urinary Na + output<br />

ranges from less than 1 mEq/d on a low-salt diet to 400 mEq/d<br />

or more when the dietary Na + intake is high. In addition, there<br />

is a natriuresis when saline is infused intravenously and a decrease<br />

in Na + excretion when ECF volume is reduced.<br />

MECHANISMS<br />

Variations in Na + excretion are brought about by changes in<br />

GFR (Table 38–9) and changes in tubular reabsorption, primarily<br />

in the 3% <strong>of</strong> filtered Na + that reaches the collecting ducts.<br />

The factors affecting the GFR, including tubuloglomerular<br />

feedback, have been discussed previously. Factors affecting Na +<br />

reabsorption include the circulating level <strong>of</strong> aldosterone and<br />

other adrenocortical hormones, the circulating level <strong>of</strong> ANP<br />

and other natriuretic hormones, and the rate <strong>of</strong> tubular secretion<br />

<strong>of</strong> H + and K + .<br />

EFFECTS OF<br />

ADRENOCORTICAL STEROIDS<br />

Adrenal mineralocorticoids such as aldosterone increase tubular<br />

reabsorption <strong>of</strong> Na + in association with secretion <strong>of</strong> K +<br />

and H + and also Na + reabsorption with Cl – . When these hormones<br />

are injected into adrenalectomized animals, a latent

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