Ganong's Review of Medical Physiology, 23rd Edition

658 SECTION VIII Renal Physiology
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)
period of 10 to 30 min occurs before their effects on Na + reabsorption
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-mediated
effects, but these are not apparent in terms of Na + excretion
in the whole animal. The mineralocorticoids act
primarily in the collecting ducts to increase the number of active
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
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
Reduction of dietary intake of salt increases aldosterone secretion
(see Figure 22-26), producing marked but slowly developing
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 increasing
intracellular Ca 2+ , which in turn inhibits Na + transport via
ENaCs. Endothelin and IL-1 cause natriuresis, probably by increasing
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 appears
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 angiotensin
I reaching them to angiotensin II. In addition, angiotensin
I is generated in the kidneys.
Prolonged exposure to high levels of circulating mineralocorticoids
does not cause edema in otherwise normal individuals
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
Interstitial
fluid
Aldosterone
Na +
K +
Cl
H 2 N
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.
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 produced
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 absorbed,
but most of the inhibition is produced by the decrease
in plasma osmolality after the water is absorbed.
WATER INTOXICATION
cGMP
Ouabain ANP
N
N
O
Nucleus
sgk and other proteins
More active ENaCs
NH 2
NH
NH2 Amiloride
NH 2 +
Tubular
lumen
Tight
junction
Na +
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 uptake
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