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org/diuretics/
Sultan Chaudhry
Diuretics and renal hormones
Physiologic hormones af f ecting the kidney
Hormone Trigger and pathway Site of action
in the
nephron (see
figure)
Net effect
Angiotensin
II (Ang II)
Synthesized in response to
hypotension. (See AKI and
CKD chapters for details of
Ang II production pathway)
Af f erent and
ef f erent
arteriole
1. Af f erent and ef f erent (higher
degree) arteriolar constriction
leading to a rise in GFR.
2. Compensatory sodium absorption
occurs in the proximal as well as
the distal nephron to maintain f luid
balance (via water osmosis
f ollowing sodium).
Atrial
natriuretic
peptide
(ANP)
Released in response to
increased atrial pressure.
Af f erent and
ef f erent
arteriole, distal
convoluted
tubule (DCT).
1. Af f erent arteriolar dilation and
ef f erent arteriolar constriction
leading to an overall increase in
GFR and increase in sodium
f iltration.
2. At the DCT, it inhibits sodium
uptake to ensure volume loss.
Vitamin D3
(calcitriol)
Hypocalcemia DCT Increased calcium uptake.
Parathyroid
hormone
(PTH)
Hypocalcemia and
hyperphosphatemia,and/or
low vitamin D levels.
Ascending limb
of loop of
Henle (LoH)
and DCT
Increased calcium uptake.
Aldosterone Hypovolemia and
hypotension (via Ang II),
and/or hyperkalemia
Collecting duct
(CD)
Increased sodium uptake and
potassium excretion into the urine.
Causes net f luid retention.
Antidiuretic
hormone
(ADH)
Hypovolemia and
hypotension (via Ang II),
increased plasma osmolality
CD Increases f ree water uptake f rom the
collecting duct.
The nephron showi ng reabsorpti on, hormone acti on, and di ureti c acti on.
Diuretics
Diuretic type
(example)
Site of
action
Mechanism (see figure)
Carbonic anhydrase
inhibitor
(acetazolamide)
Proximal
convoluted
tubule
(PCT)
Acetazolamide is a carbonic anhydrase (CA) inhibitor. CA is an
enzyme involved in the breakdown of carbonic acid in the
f ollowing reaction:
H
2
O + CO
2
CA H
2
CO
3
HCO
3

+ H
+
Under physiologic conditions, f iltered bicarbonate combines with
the hydrogen ions to generate carbonic acid, which is acted on by
CA to make CO
2
and H
2
O. As the CO
2
dif f uses into the tubular
cells, more bicarbonate is absorbed f rom the serum. In the
presence of acetazolamide, CA is inhibited, allowing f or the
H
2
CO
3
to build up in the tubules and hence urinary bicarbonate
wasting (H
+
alternatively is reabsorbed via a dif f erent pathway).
This leads to a decreased ability to reabsorb Na
+
in exchange f or
H
+
, leading to mild diuresis.
Osmotic (mannitol) PCT Mannitol is f iltered through the glomerulus but cannot be
reabsorbed. This increases the osmolality of the f iltrate and water
is retained in the tubules to ensure urine osmolality.
Loop (f urosemide) Loop of Blocks the sodium potassium chloride pump (NKCC) in the thick
Henle ascending limb of loop of Henle. This allows f or more sodium and
subsequently f luid loss f rom the nephrons.
Thiazide
(hydrochlorothiazide)
DCT Thiazide diuretics block the activity of sodium chloride channels
(Na-Cl) in the DCT allowing more sodium and water loss.
Potassium Sparing
1. Aldosterone
Antagonists
(spironolactone)
2. Epithelial
sodium channel
(ENaC) blocker
(amiloride and
triamterene)
CD Aldosterone acts on the cells of the collecting ducts and induces
expression of Na/K exchangers and ENaC. This allows f or the
exchange of sodium f or potassium (Na enters the tubular cells
and K is lost in the urine). Aldosterone antagonists competitively
inhibit the action of aldosterone on the principal cells and
theref ore decrease the expression of the exchanger. With the lack
of sodium uptake f rom the nephrons and loss in the urine,
diuresis also takes place.
Aldosterone also controls expression of ENaC channels in the
distal tubules to absorb sodium. Inhibition of the ENaC decreases
Na uptake and K loss f rom the tubular cells. Loss of Na in the
urine leads to mild diuresis.