Human Physiology, 14th edition (2016)

612 Chapter 17

are categorized as loop diuretics, thiazides, carbonic anhydrase
inhibitors, osmotic diuretics, or potassium-sparing diuretics.
The most powerful diuretics, which inhibit salt and water
reabsorption by as much as 25%, are the drugs that inhibit active
salt transport out of the ascending limb of the nephron loop. Exam-
ples of these loop diuretics are furosemide (Lasix) and ethacrynic
acid. The thiazide diuretics (e.g., hydrochlorothiazide ) inhibit salt
and water reabsorption by as much as 8% through inhibition of salt
transport by the first segment of the distal convoluted tubule. The
carbonic anhydrase inhibitors (e.g., acetazolamide ) are much
weaker diuretics; they act primarily in the proximal tubule to pre-
vent the water reabsorption that occurs when bicarbonate is reab-
sorbed. Largely because it also promotes the urinary excretion of
bicarbonate, acetazolamide is used to treat acute mountain sickness
(as previously described).
When extra solutes are present in the filtrate, they increase
the osmotic pressure of the filtrate and in this way decrease the
reabsorption of water by osmosis. The extra solutes thus act as
osmotic diuretics. Mannitol is sometimes used clinically for
this purpose. Osmotic diuresis can occur in diabetes mellitus
because glucose is present in the filtrate and urine; this extra
solute causes the excretion of excessive amounts of water in

the urine and can result in severe dehydration of a person with

uncontrolled diabetes.

All of these diuretics cause increased delivery of Na^1 to the

cortical collecting ducts, which directly and indirectly stimu-

lates increased K^1 secretion as previously described. This may

cause excessive elimination of K^1 in the urine, which can dan-

gerously lower the plasma K^1 concentration (a condition called

hypokalemia ). Hypokalemia may produce neuromuscular dis-

orders and ECG abnormalities. People who take diuretics are

usually on a low-sodium diet and must often supplement their

meals with potassium chloride (KCl) to offset their loss of K^1.

For this reason, potassium-sparing diuretics are some-

times used. Spironolactones (Aldactone) are aldosterone antag-

onists that compete with aldosterone for cytoplasmic receptor

proteins in the cells of the cortical collecting duct. These drugs

thus block the aldosterone stimulation of Na^1 reabsorption and

K^1 secretion. Triamterene (Dyrenium) is a different type of

potassium-sparing diuretic that acts on the tubule more directly

to block Na^1 reabsorption and K 1 secretion. Combinations

of spironolactone or triamterene together with hydrochloro-

thiazide ( Aldactazide and Dyazide, respectively) are sometimes

prescribed for the diuretic treatment of hypertension.

Figure 17.30 Sites of action of clinical diuretics. The different diuretic drugs act on the nephron tubules at various sites to
inhibit the reabsorption of water. As a result of these actions, less water is reabsorbed into the blood and more is excreted in the urine.
This lowers the blood volume and pressure.

Proximal convoluted tubule Distal convoluted tubule

NaCl

NaCl

NaK2Cl

NaCl

Na+

Na+

K+

Amino acids

Glucose

HCO 3 , PO 4

Passive

Passive

Cortex

Medulla

Glomerulus

Increasing

NaCl and urea

concentrations

Urea

Urea

H 2 O

H 2 O

Descending

limb

Ascending

limb

Thick

ascending

limb

Cortical

collecting

duct

Medullary

collecting

duct

H 2 O

H 2 O

no

ADH

H 2 O

H 2 O

no

ADH

Collecting

duct

Thiazide

diuretics

Carbonic

anhydrase

inhibitors

Loop

diuretics

Potassium-sparing

diuretics

(with ADH)

(with ADH)

NaK2Cl

–3–