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PATHOPHYSIOLOGY OF EDEMA
12 : 1
601
Thiazide
Potassium
sparing
Pharmacodynamic effects
Increases
excretion of Na,
K, Ca, Mg
Increases
excretion of Na,
K, Mg, decrease
excretion of Ca
Increases
excretion of
Na, decrease
excretion of Ca,
K, Mg
Site of action
Transporters
affected
Na+ K+ 2Cl- co
transporter
Collecting tubule
% of filtrate
20-30%
reabsorbed at site
of action
6-11%
< 5%
Bioavailability
40-90%
30-90%
50-100%
Pathophysiology of edema
Cardiac: Fluid retention is a consistent finding in almost all
acute and most chronic heart failure patients. It manifests as
pulmonary and peripheral edema. The pathophysiology of
edema in heart failure involves the activation and interplay of
multiple neurohumoral and cellular systems. Pathobiologically
important alterations occur in the sympathetic nervous
system, the renin-angiotensin-aldosterone system (RAAS),
the vasopressin axis, and vasodilatory/ natriuretic pathways.
These disturbances are translated at the renal circulatory and
tubular level in such a way that avid retention of sodium and
water occurs3. The state of the arterial circulation, as governed
by cardiac output and peripheral vascular resistance, is the chief
determinant of sodium and water retention in heart failure4.
In particular, either a primary decrease in cardiac output or
arterial vasodilatation brings about arterial underfilling, which
activates neurohumoral reflexes that in turn incite sodium
and water retention. Sympathetic nervous system activity
contributes to peripheral and renal vasoconstriction and to
sodium and water retention. Activation of renal sympathetic
nerves leads to angiotensin II release, stimulating the reninangiotensin-aldosterone system. Sympathetic stimulation
also prompts release of arginine vasopressin, excess levels of
which lead to water retention and hyponatremia. Angiotensin
II acts as a potent vasoconstrictor, stimulates aldosterone
release from the adrenal gland, and promotes renal tubule
sodium reabsorption. Aldosterone increases reabsorption of
sodium in the collecting duct.
Tubulointerstitium
Infiltration T cells, M
All, NO
602
Na reabsorption
Primary
Na retention
Glomeruli
HYPOALBUMINEMIA
Kf
SNGFR
Filtered Na
UNa V
Secondary
Na retention
Intravascular
volume
PC
Overwhelmed mechanisms
of edema removal
PCOP
EDEMA
603
604
605
606
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