Integrated Clinical Science – Diuretics & Renal Tubule Physiology (PHAR 341)

Question-and-Answer flashcards covering nephron physiology, classes of diuretics, specific drug prototypes, mechanisms of action, clinical uses, and adverse effects, as presented in the PHAR 341 Integrated Clinical Science (Cardiology I) lecture on Diuretics.

What are the three basic processes of urine formation in the nephron?

Filtration in the glomerulus, reabsorption of valuable solutes/water, and secretion of additional unwanted substances.

Which nephron segment is responsible for 100 % glucose, amino-acid, and protein reabsorption?

The proximal convoluted tubule (PCT).

Roughly what percentage of filtered Na⁺, Cl⁻ and H₂O is reabsorbed in the PCT?

About 65 %.

Which nephron segment concentrates urine by reabsorbing water but not salt?

The thin descending limb (TDL) of the Loop of Henle.

What transporter is blocked by Carbonic Anhydrase Inhibitors in the PCT?

The Na⁺/H⁺ exchanger (NHE3) that depends on carbonic anhydrase activity.

Name the prototype Carbonic Anhydrase Inhibitor and its primary clinical use.

Acetazolamide; useful in acute glaucoma, high-altitude sickness prevention, metabolic alkalosis, and diuretic resistance.

Why can acetazolamide cause metabolic acidosis?

Inhibition of bicarbonate reabsorption leads to HCO₃⁻ loss and systemic acidification.

Which osmotic diuretic is commonly used to maintain high urine flow and reduce cerebral edema?

Mannitol.

Why does mannitol therapy risk hypernatremia?

It removes water preferentially, leaving Na⁺ concentration in plasma higher.

Which transporter in the thick ascending limb is inhibited by loop diuretics?

The Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2).

Give the prototype loop diuretic and whether it is a potassium-sparing or potassium-wasting diuretic.

Furosemide; potassium-wasting diuretic

List two major electrolyte side-effects of loop diuretics.

Hypokalemia (potassium wasting) and hypocalcemia.

What serious auditory adverse effect is associated with high-dose loop diuretics?

Ototoxicity (hearing damage).

Which transporter in the distal convoluted tubule is inhibited by thiazide diuretics?

The Na⁺/Cl⁻ cotransporter (NCC).

Name the prototype thiazide diuretic and its most common therapeutic use.

Hydrochlorothiazide; first-line treatment of essential hypertension.

How do thiazides affect serum calcium levels?

Decreased intracellular Na⁺ enhances basolateral Na⁺/Ca²⁺ exchange, promoting Ca²⁺ reabsorption.

What metabolic adverse effects can long-term thiazide use produce?

Hyperglycemia and hyperlipidemia (reduced insulin sensitivity and increased hepatic glucose production).

Which two drug classes make up the potassium-sparing diuretics?

Aldosterone receptor antagonists (e.g., spironolactone) and epithelial Na⁺ channel (ENaC) blockers (e.g., amiloride).

What is the main therapeutic rationale for adding a potassium-sparing diuretic to a loop or thiazide regimen?

To counteract potassium wasting and prevent hypokalemia.

Which potassium-sparing diuretic is also used to treat primary aldosteronism?

Spironolactone.

Name a serious electrolyte risk when combining ACE inhibitors with spironolactone.

Hyperkalemia.

Which hormone increases water reabsorption in the collecting duct, and what receptor does it act on?

Antidiuretic hormone (ADH, vasopressin) acting on V₂ receptors.

What drug acts as an ADH (V₂) receptor antagonist and is used for hyponatremic heart failure?

Conivaptan.

What neurologic complication can rapid correction of hyponatremia with ADH antagonists cause?

Osmotic demyelination syndrome (central pontine myelinolysis).

List three common indications for prescribing diuretics in general.

Hypertension, edema associated with congestive heart failure/cirrhosis/renal disease, and prevention of calcium kidney stones.

Which over-the-counter substances can exert mild diuretic effects by inhibiting ADH release or action?

Caffeine, theophylline, and ethanol.

What is meant by 'sequential nephron blockade'?

Using diuretics acting on different nephron segments simultaneously to produce additive or synergistic diuresis.

Explain why loop diuretics are considered the most efficacious diuretics.

They inhibit NKCC2 in the thick ascending limb, a segment reabsorbing ∼25 % of filtered NaCl and generating the medullary concentration gradient, leading to profound natriuresis and water loss.

Why can loop diuretics precipitate arrhythmias?

Rapid volume depletion and hypokalemia disturb cardiac electrical conduction.

How do osmotic diuretics differ from conventional diuretics in their mechanism?

They increase tubular osmotic pressure, pulling water into the lumen without directly blocking specific ion transporters.

Which nephron segment is under chief regulation by aldosterone for Na⁺ reabsorption and K⁺ secretion?

The cortical collecting duct/tubule (CCT).

What is the key transporter responsible for K⁺ secretion in the collecting duct and how is it affected by loop or thiazide diuretics?

The ROMK (renal outer medullary K⁺) channel; upstream Na⁺ loss increases Na⁺ delivery to CCT, enhancing Na⁺ reuptake via ENaC and driving K⁺ secretion through ROMK, causing hypokalemia.

Which diuretic class can be used prophylactically for altitude sickness and why?

Carbonic anhydrase inhibitors; they cause metabolic acidosis that stimulates ventilation and improves oxygenation at high altitude.

Why should potassium-sparing diuretics not be combined with potassium supplements or salt substitutes containing KCl?

Both raise serum K⁺ levels, risking life-threatening hyperkalemia.

What percentage of filtered Na⁺ is normally reabsorbed in the thick ascending limb of the Loop of Henle?

Approximately 25 %.