Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 38Renal Function & Micturition 659

occur when water intake is not reduced after administration of
exogenous vasopressin or when secretion of endogenous vaso-
pressin occurs in response to non-osmotic stimuli such as sur-
gical trauma.

REGULATION OF K

• EXCRETION

Much of the filtered K+ is removed from the tubular fluid by
active reabsorption in the proximal tubules (Table 38–5), and
K+ is then secreted into the fluid by the distal tubular cells. The
rate of K+ secretion is proportional to the rate of flow of the tu-
bular fluid through the distal portions of the nephron, because
with rapid flow there is less opportunity for the tubular K+
concentration to rise to a value that stops further secretion. In
the absence of complicating factors, the amount secreted is ap-
proximately equal to the K+ intake, and K+ balance is main-
tained. In the collecting ducts, Na+ is generally reabsorbed and
K+ is secreted. There is no rigid one-for-one exchange, and
much of the movement of K+ is passive. However, there is
electrical coupling in the sense that intracellular migration of
Na+ from the lumen tends to lower the potential difference
across the tubular cell, and this favors movement of K+ into
the tubular lumen. Because Na+ is also reabsorbed in associa-
tion with H+ secretion, there is competition for the Na+ in the
tubular fluid. K+ excretion is decreased when the amount of
Na+ reaching the distal tubule is small, and it is also decreased
when H+ secretion is increased.

DIURETICS

Although a detailed discussion of diuretic agents is outside the
scope of this book, consideration of their mechanisms of ac-
tion constitutes an informative review of the factors affecting
urine volume and electrolyte excretion. These mechanisms are
summarized in Table 38–10. Water, alcohol, osmotic diuret-
ics, xanthines, and acidifying salts have limited clinical useful-
ness, and the vasopressin antagonists are currently undergoing
clinical trials. However, many of the other agents on the list
are used extensively in medical practice.
The carbonic anhydrase-inhibiting drugs are only moderately
effective as diuretic agents, but because they inhibit acid secre-
tion by decreasing the supply of carbonic acid, they have far-
reaching effects. Not only is Na+ excretion increased because H+
secretion is decreased, but also HCO 3 – reabsorption is
depressed; and because H+ and K+ compete with each other and
with Na+, the decrease in H+ secretion facilitates the secretion
and excretion of K+.
Furosemide and the other loop diuretics inhibit the Na–K–
2Cl cotransporter in the thick ascending limb of Henle’s loop.
They cause a marked natriuresis and kaliuresis. Thiazides act
by inhibiting Na–Cl cotransport in the distal tubule. The
diuresis they cause is less marked, but both loop diuretics and
thiazides cause increased delivery of Na+ (and fluid) to the
collecting ducts, facilitating K+ excretion. Thus, over time, K+

depletion and hypokalemia are common complications in

those who use them if they do not supplement their K+

intake. On the other hand, the so-called K+-sparing diuretics

act in the collecting duct by inhibiting the action of aldoster-

one or blocking ENaCs.

EFFECTS OF DISORDERED

RENAL FUNCTION

A number of abnormalities are common to many different

types of renal disease. The secretion of renin by the kidneys

and the relation of the kidneys to hypertension are discussed

in Chapter 39. A frequent finding in various forms of renal

disease is the presence in the urine of protein, leukocytes, red

cells, and casts, which are proteinaceous material precipitated

in the tubules and washed into the bladder. Other important

consequences of renal disease are loss of the ability to concen-

trate or dilute the urine, uremia, acidosis, and abnormal reten-

tion of Na+(see Clinical Box 38–3).

TABLE 38–10 Mechanism of action

of various diuretics.

Agent Mechanism of Action

Water Inhibits vasopressin secretion.

Ethanol Inhibits vasopressin secretion.

Antagonists of V 2 vasopressin

receptors such as astolvaptan

Inhibit action of vasopressin on

collecting duct.

Large quantities of osmotically

active substances such as

mannitol and glucose

Produce osmotic diuresis.

Xanthines such as caffeine and

theophylline

Decrease tubular reabsorption of

Na+ and increase GFR.

Acidifying salts such as CaCl 2 and

NH 4 Cl

Supply acid load; H+ is buffered,

but an anion is excreted with Na+

when the ability of the kidneys to

replace Na+ with H+ is exceeded.

Carbonic anhydrase inhibitors

such as acetazolamide (Diamox)

Decrease H+ secretion, with resul-

tant increase in Na+ and K+ excre-

tion.

Metolazone (Zaroxolyn), thia-

zides such as chlorothiazide (Di-

uril)

Inhibit the Na–Cl cotransporter in

the early portion of the distal tu-

bule.

Loop diuretics such as furosemi-

de (Lasix), ethacrynic acid (Ede-

crin), and bumetanide

Inhibit the Na–K–2Cl cotransport-

er in the medullary thick ascend-

ing limb of the loop of Henle

K+-retaining natriuretics such as

spironolactone (Aldactone), tri-

amterene (Dyrenium), and

amiloride (Midamor)

Inhibit Na+–K+ “exchange” in the

collecting ducts by inhibiting the

action of aldosterone (spironolac-

tone) or by inhibiting the ENaCs

(amiloride).