Ganong's Review of Medical Physiology, 23rd Edition

658 SECTION VIII Renal Physiology

period of 10 to 30 min occurs before their effects on Na+ reab-
sorption become manifest, because of the time required for
the steroids to alter protein synthesis via their action on DNA.
Mineralocorticoids may also have more rapid membrane-me-
diated effects, but these are not apparent in terms of Na+ ex-
cretion in the whole animal. The mineralocorticoids act
primarily in the collecting ducts to increase the number of ac-
tive epithelial sodium channels (ENaCs) in this part of the
nephron. The molecular mechanisms believed to be involved
are discussed in Chapter 22 and summarized in Figure 38–19.
In Liddle syndrome, mutations in the genes that code for
the β subunit and less commonly the γ subunit of the ENaCs
cause them to become constitutively active in the kidney. This
leads to Na+ retention and hypertension.

OTHER HUMORAL EFFECTS

Reduction of dietary intake of salt increases aldosterone secre-
tion (see Figure 22-26), producing marked but slowly develop-
ing decreases in Na+ excretion. A variety of other humoral
factors affect Na+ reabsorption. PGE 2 causes a natriuresis,
possibly by inhibiting Na, K ATPase and possibly by increas-
ing intracellular Ca2+, which in turn inhibits Na+ transport via
ENaCs. Endothelin and IL-1 cause natriuresis, probably by in-
creasing the formation of PGE 2. ANP and related molecules
increase intracellular cyclic 3',5'-guanosine monophosphate
(cGMP), and this inhibits transport via the ENaCs. Inhibition
of Na, K^ ATPase by another natriuretic hormone, which ap-
pears to be endogenously produced ouabain, also increases
Na+ excretion. Angiotensin II increases reabsorption of Na+
and HCO 3 – by an action on the proximal tubules. There is an
appreciable amount of angiotensin-converting enzyme in the
kidneys, and the kidneys convert 20% of the circulating angio-
tensin I reaching them to angiotensin II. In addition, angio-
tensin I is generated in the kidneys.
Prolonged exposure to high levels of circulating mineralo-
corticoids does not cause edema in otherwise normal individ-
uals because eventually the kidneys escape from the effects of
the steroids. This escape phenomenon, which may be due to
increased secretion of ANP, is discussed in Chapter 22. It
appears to be reduced or absent in nephrosis, cirrhosis, and
heart failure, and patients with these diseases continue to

retain Na+ and become edematous when exposed to high

levels of mineralocorticoids.

REGULATION OF

WATER EXCRETION

WATER DIURESIS

The feedback mechanism controlling vasopressin secretion

and the way vasopressin secretion is stimulated by a rise and

inhibited by a drop in the effective osmotic pressure of the

plasma are discussed in Chapter 18. The water diuresis pro-

duced by drinking large amounts of hypotonic fluid begins

about 15 min after ingestion of a water load and reaches its

maximum in about 40 min. The act of drinking produces a

small decrease in vasopressin secretion before the water is ab-

sorbed, but most of the inhibition is produced by the decrease

in plasma osmolality after the water is absorbed.

WATER INTOXICATION

During excretion of an average osmotic load, the maximal

urine flow that can be produced during a water diuresis is

about 16 mL/min. If water is ingested at a higher rate than this

for any length of time, swelling of the cells because of the up-

take of water from the hypotonic ECF becomes severe and,

rarely, the symptoms of water intoxication may develop.

Swelling of the cells in the brain causes convulsions and coma

and leads eventually to death. Water intoxication can also

TABLE 38–9 Changes in Na+ excretion that would
occur as a result of changes in GFR if there were no
concomitant changes in Na+ reabsorption.

GFR

(mL/min)

Plasma

Na+

(μEq/mL)

Amount

Filtered

(μEq/min)

Amount

Reabsorbed

(μEq/min)

Amount

Excreted

(μEq/min)

125 145 18,125 18,000 125

127 145 18,415 18,000 415

124.1 145 18,000 18,000 0

FIGURE 38–19 Renal Principal cell. Na+ enters via the ENaCs

in the apical membrane and is pumped into the interstitial fluid by

Na, K ATPases in the basolateral membrane. Aldosterone activates the

genome to produce serum- and glucocorticoid-regulated kinase (sgk)

and other proteins, and the number of active ENaCs is increased.

Tubular

lumen

Na+

Interstitial

fluid

K+ cGMP

Ouabain ANP

Amiloride

Cl

H 2 N

Na+

O

N

N NH

NH 2

NH 2 +

NH 2

Tight

junction

Nucleus

sgk and other proteins

More active ENaCs

Aldosterone