Page 272 - Basic _ Clinical Pharmacology ( PDFDrive )

258 SECTION III Cardiovascular-Renal Drugs

Lumen- Collecting Interstitium- Lumen- Collecting Interstitium-
urine tubule blood urine tubule blood
Cl –
Principal cell AQP2
ENaC + R Aldosterone V

Na + H 2 O 2 R
+
Na +
K + ATP

2
K + H O
V 2
cAMP R ADH
Intercalated cell
+
–
HCO 3 H O
2
ATP
Cl –
+
H
AQP2 AQP3,4
O
H 2 H O
FIGURE 15–5 Ion transport pathways across the luminal and 2
basolateral membranes of collecting tubule and collecting duct cells.
+
Inward diffusion of Na via the epithelial sodium channel (ENaC) FIGURE 15–6 Water transport across the luminal and basolateral
−
leaves a lumen-negative potential, which drives reabsorption of Cl membranes of collecting duct cells. Above, low water permeability
+
and efflux of K . R, aldosterone receptor. exists in the absence of antidiuretic hormone (ADH). Below, in the
presence of ADH, aquaporins are inserted into the apical membrane,
greatly increasing water permeability. AQP2, apical aquaporin water
channels; AQP3,4, basolateral aquaporin water channels; V 2 , vasopres-
+
Lastly, this is the most important site of K secretion by the kidney sin V 2 receptor.
+
and the site at which virtually all diuretic-induced changes in K
balance occur.
+
The mechanism of NaCl reabsorption in the collecting tubule potential is increased, and K secretion is enhanced. This mecha-
system is distinct from the mechanisms found in other tubule nism, combined with enhanced aldosterone secretion due to
+
+
+
segments. The principal cells are the major sites of Na , K , and volume depletion, is the basis for most diuretic-induced K wast-
+
water transport (Figures 15–5 and 15–6), and the intercalated ing. Reabsorption of Na via the epithelial Na channel (ENaC)
+
+
cells (α, β) are the primary sites of H (α cells) or bicarbonate and its coupled secretion of K are regulated by aldosterone.
(β cells) secretion. The α and β intercalated cells are very similar, This steroid hormone, through its actions on gene transcription,
−
+
except that the membrane locations of the H -ATPase and Cl / increases the activity of both the apical membrane channels and
+
+
−
HCO exchanger are reversed. Principal cells do not contain the basolateral Na /K -ATPase. This leads to an increase in the
3
+
apical cotransport systems for Na and other ions, unlike cells in transepithelial electrical potential and a dramatic increase in both
+
+
other nephron segments. Principal cell membranes exhibit sepa- Na reabsorption and K secretion.
+
+
rate ion channels for Na and K . Since these channels exclude The collecting tubule system is also the site at which the
+
+
anions, transport of Na or K leads to a net movement of charge final urine concentration is determined. In addition to their role
+
+
+
across the membrane. Because Na entry into the principal cell in control of Na absorption and K secretion (Figure 15–5),
+
predominates over K secretion into the lumen, a 10–50 mV principal cells also contain a regulated system of water channels
lumen-negative electrical potential develops. Sodium that enters (Figure 15–6). Antidiuretic hormone (ADH, also called arginine
the principal cell from the tubular fluid is then transported back vasopressin, AVP) controls the permeability of these cells to
+
+
to the blood via the basolateral Na /K -ATPase (Figure 15–5). The water by regulating the insertion of pre-formed water channels
10–50 mV lumen-negative electrical potential drives the transport (aquaporin-2, AQP2) into the apical membrane. Vasopressin
+
−
of Cl back to the blood via the paracellular pathway and draws K receptors in the vasculature and central nervous system (CNS)
+
out of cells through the apical membrane K channel. Thus, there are V receptors, and those in the kidney are V receptors. V
2
2
1
+
is an important relationship between Na delivery to the collecting receptors act via a G protein-coupled, cAMP-mediated process.
s
+
tubule system and the resulting secretion of K . Upstream diuret- In the absence of ADH, the collecting tubule (and duct) is imper-
+
+
ics increase Na delivery to this site and enhance K secretion. If meable to water, and dilute urine is produced. ADH markedly
+
Na is delivered to the collecting system with an anion that cannot increases water permeability, and this leads to the formation of a
−
−
be reabsorbed as readily as Cl (eg, HCO ), the lumen-negative more concentrated urine. ADH also stimulates the insertion of
3