DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Interstitial
space
CA inhibitors
Tight junction Lumen Transport of
diuretics into
Lumen
proximal tubule
Na + –Cl – symport inhibitors
697
Na + Na + Na+ Proximal
Blood in
K + K
Symporter
Antiporter
+
H + tubule
K +
H Na +
Na
HCO – HCO – +
+ 3 HCO – 3 ATPase
3
Symporter
Na
H +
2 CO 3
H 2 CO 3
Distal
CA
Cl – Cl
convoluted
–
Cl
H
Cl –
2 O CA
–
CO
Glomerulus
tubule
2
CO 2
Blood
out Collecting
CA
Thiazide
duct
inhibitors
diuretics
Thick system
ascending
limb
K + -sparing diuretic
Na + –K + –2Cl – symport inhibitors
Loop
MR-MRA
(inactive) MRA
K +
diuretics
MRA
K + K +
Nucleus
MR-Aldo MR
ATPase Na + Aldo Aldo
Na
Na +
+
mRNA
Cl – 2Cl – Symporter 2Cl –
(+)
Cl Aldo-induced proteins
–
K + K +
(+)
K +
Na +
K + Na + Na +
Na +
ATPase
Ca 2+
Renal papilla
K +
K +
K + K +
Mg 2+
(by ADH release). Opposite changes occur during a net
negative Na + balance.
Changes in water intake and output adjust ECFV
toward normal, thereby expanding or contracting total
ECFV. Total ECFV is distributed among many body
compartments; however, since ECF volume on the arterial
side of the circulation pressurizes the arterial tree, it
is this fraction of ECFV that determines MABP, and it is
this fraction of ECFV that is “sensed” by the cardiovascular
system and kidneys. Since MABP is a major determinant
of Na + output, a closed loop is established (Figure
25–14). This loop cycles until net Na + accumulation is
zero; i.e., in the long run, Na + intake must equal Na + loss.
The preceding discussion implies that three fundamental
types of perturbations contribute to venous
congestion and/or edema formation:
1. A shift to the right in the renal pressure-natriuresis
relationship (e.g., chronic renal failure) causes
Na + channel
inhibitors
Figure 25–13. Summary of the site and mechanism of action of diuretics. Three important features of this summary figure are worth special
note. 1. Transport of solute across epithelial cells in all nephron segments involves highly specialized proteins, which for the most
part are apical and basolateral membrane integral proteins. 2. Diuretics target and block the action of epithelial proteins involved in solute
transport. 3. The site and mechanism of action of a given class of diuretics are determined by the specific protein inhibited by the
diuretic. CA, carbonic anhydrase; MR, mineralocorticoid receptor; MRA, mineralocorticoid receptor antagonist; Aldo, aldosterone.
reduced Na + excretion for any level of MABP. If
all other factors remain constant, this would
increase total-body Na + , ECFV, and MABP. The
additional ECFV would be distributed throughout
various body compartments according to the state
of cardiac function and prevailing Starling forces
and would predispose toward venous congestion
and/or edema. Even so, in the absence of any other
predisposing factors for venous congestion and/
or edema, a rightward shift in the renal pressurenatriuresis
curve generally causes hypertension
with only a slight (usually immeasurable) increase
in ECFV. As elucidated by Guyton (1991), ECFV
expansion triggers a series of events: expanded
ECFV → augmented cardiac output → enhanced
vascular tone (i.e., total-body autoregulation) →
increased total peripheral resistance → elevated
MABP → pressure natriuresis → reduction of ECFV
and cardiac output toward normal. Most likely, a
CHAPTER 25
REGULATION OF RENAL FUNCTION AND VASCULAR VOLUME