Page 185 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Diuresis and Diuretics Loop diuretics (e.g., furosemide and
bumetanide) are highly effective. They inhibit
Increases in urine excretion above 1 mL/min the bumetanide-sensitive co-transporter BSC
+
+
–
(diuresis) can have the following causes: (! p. 162 B6), a Na -2Cl -K symport carrier, in
! Water diuresis: Decreases in plasma the thick ascending limb (TAL) of the loop of
osmolality and/or an increased blood volume Henle. This not only decreases NaCl reabsorp-
lead to the reduction of ADH levels and, thus, tion there, but also stalls the “motor” on the
to the excretion of “free water” (! p. 164). concentration mechanism (! p. 166). Since
! Osmotic diuresis results from the presence the lumen-positive transepithelial potential
Kidneys, Salt, and Water Balance lumen, which is subsequently excreted. non-reabsorbed Na now arrive at the collect-
of non-reabsorbable, osmotically active sub-
(LPTP) in the TAL also falls (! p. 162 B7), para-
2+
+
and Mg
stances (e.g., mannitol) in the renal tubules.
cellular reabsorption of Na , Ca
2+
is
These substances retain H 2O in the tubule
also inhibited. Because increasing amounts of
+
ing duct (! p. 181 B3), K secretion increases
+
Osmotic diuresis can also occur when the con-
centration of an reabsorbable substance (e.g.,
and the simultaneous loss of H leads to hypo-
+
kalemia and hypokalemic alkalosis.
glucose) exceeds its tubular reabsorption
capacity resulting, for example, in hypergly-
Loop diuretics inhibit BSC at the macula densa,
cemia (! p. 158). The glucosuria occurring in
thereby “tricking” the juxtaglomerular apparatus
diabetes mellitus is therefore accompanied by
the tubular lumen. The GFR then rises as a result of
perbicarbonaturia can lead to osmotic diuresis
the
tubuloglomerular
corresponding
feedback
to the same reason (! p. 176).
(! p. 184), which further promotes diuresis.
7 diuresis and a secondary increase in thirst. Hy- (JGA) into believing that no more NaCl is present in
! Pressure diuresis occurs when osmolality in
the renal medulla decreases in the presence of Thiazide diuretics inhibit NaCl resorption in
the distal tubule (TSC, ! p. 162 B8). Like loop
increased renal medullary blood flow due, in diuretics, they increase Na + reabsorption
most cases, to hypertension (! p. 170). downstream, resulting in losses of K and H . +
+
! Diuretics (! A) are drugs that induce diure- Potassium-sparing diuretics. Amiloride
sis. Most of them (except osmotic diuretics like block Na channels in the principal cells of the
+
mannitol) work primarily by inhibiting NaCl connecting tubule and collecting duct, leading
reabsorption (saluretics) and, secondarily, by to a reduction of K excretion. Aldosterone anta-
+
decreasing water reabsorption. The goal of gonists (e.g., spironolactone), which block the
therapeutic diuresis, e.g., in treating edema cytoplasmic aldosterone receptor, also have a
and hypertension, is to reduce the ECF volume.
potassium-sparing effect.
Although diuretics basically inhibit NaCl transport
throughout the entire body, they have a large degree Disturbances of Salt and Water
of renal “specificity” because they act from the
tubular lumen, where they become highly concen- Homeostasis
trated due to tubular secretion (! p. 160) and When osmolality remains normal, distur-
tubular water reabsorption. Therefore, dosages that
do not induce unwanted systemic effects are ther- bances of salt and water homeostasis (! B and
apeutically effective in the tubule lumen. p. 170) only affect the ECF volume (! B1 and
Diuretics of the carbonic anhydrase inhibitor 4). When the osmolality of the ECF increases
type (e.g., acetazolamide, benzolamide) decrease (hyperosmolality) or decreases (hypo-
+
Na /H exchange and HCO 3 reabsorption in the osmolality), water in the extra- and intracellu-
–
+
proximal tubule (! p. 174ff.). The overall extent of di- lar compartments is redistributed (! B2, 3, 5,
uresis achieved is small because more distal seg- 6). The main causes of these disturbances are
ments of the tubule reabsorb the NaCl not reab-
sorbed upstream and because the GFR decreases listed in B (orange background). The effects of
due to tubuloglomerular feedback, TGF (! p. 184). these disturbances are hypovolemia in cases 1,
–
In addition, increased HCO 3 excretion also leads to 2 and 3, intracellular edema (e.g., swelling of
non-respiratory (metabolic) acidosis. Therefore, this the brain) in disturbances 3 and 5, and extra-
172 type of diuretic is used only in patients with concomi- cellular edema (pulmonary edema) in distur-
tant alkalosis. bances 4, 5 and 6.
Despopoulos, Color Atlas of Physiology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.