Hormone Trigger and pathway Site of action in the Net effect

nephron (see
figure)

Angiotensin II Synthesized in response to Afferent and efferent 1. Afferent and efferent

(Ang II) hypotension. arteriole (higher
(See AKI and CKDchapters for degree) arteriolar
details of Ang II production constriction leading to
pathway) a rise in GFR.
2. Compensatory sodium
absorption occurs in the
proximal as well as the
distal nephron to
maintain fluid balance
(via water osmosis
following sodium).

Atrial natriuretic Released in response to increased Afferent and efferent 1. Afferent arteriolar
peptide (ANP) atrial pressure. arteriole, distal dilation and efferent
convoluted tubule arteriolar constriction
(DCT). leading to an
overall increase in
GFR and increase in
sodium filtration.
2. At the DCT, it inhibits
sodium uptake to
ensure volume loss.

Vitamin D3 Hypocalcemia DCT Increased calcium uptake.

(calcitriol)

Parathyroid Hypocalcemia and Ascending limb of Increased calcium uptake.

hormone (PTH) hyperphosphatemia,and/or low loop of Henle (LoH)
vitamin D levels. and DCT

Aldosterone Hypovolemia and hypotension (via Collecting duct Increased sodium

Ang II), and/or hyperkalemia (CD) and Thick uptake andpotassium excretion into
Ascending Limb the urine. Causes net fluid retention.

Antidiuretic Hypovolemia and hypotension (via CD Increases free water uptake from the
hormone (ADH) Ang II), increased plasma collecting duct.
osmolality
Diuretic type (example) Site of action Mechanism (see figure)

Carbonic anhydrase inhibitor Proximal Acetazolamide is a carbonic anhydrase (CA) inhibitor. CA is an

(acetazolamide) convoluted enzyme involved in the breakdown of carbonic acid in the following
tubule (PCT) reaction:
H2O + CO2 ←CA→ H2CO3 ↔ HCO3— + H+
Under physiologic conditions, filtered bicarbonate combines with the
hydrogen ions to generate carbonic acid, which is acted on by CA to
make CO2 and H2O. As the CO2 diffuses into the tubular cells, more
bicarbonate is absorbed from the serum. In the presence of
acetazolamide, CA is inhibited, allowing for the H2CO3 to build up in
the tubules and hence urinary bicarbonate wasting (H+ alternatively is
reabsorbed via a different pathway). This leads to a decreased ability
to reabsorb Na+ in exchange for H+, leading to mild diuresis.

Osmotic (mannitol) PCT Mannitol is filtered through the glomerulus but cannot be reabsorbed.
This increases the osmolality of the filtrate and water is retained in
the tubules to ensure urine osmolality.

Loop (furosemide) Loop of Henle Blocks the sodium potassium chloride pump (NKCC) in the thick
ascending limb of loop of Henle. This allows for more sodium and
subsequently fluid loss from the nephrons.

Thiazide DCT Thiazide diuretics block the activity of sodium chloride channels
(hydrochlorothiazide) (Na-Cl) in the DCT allowing more sodium and water loss.

Potassium Sparing CD Aldosterone acts on the cells of the collecting ducts and induces
1. Aldosterone Antagonists expression of Na/K exchangers and ENaC. This allows for the
(spironolactone) exchange of sodium for potassium (Na enters the tubular cells and K
2. Epithelial sodium is lost in the urine). Aldosterone antagonists competitively inhibit the
channel (ENaC) blocker action of aldosterone on the principal cells and therefore decrease the
(amiloride and expression of the exchanger. With the lack of sodium uptake from the
triamterene) 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 from the tubular cells. Loss of Na in the urine
leads to mild diuresis.