In-Depth Notes on Diuretics and Kidney Function

Learning Objectives (ILOs)

• Describe how the kidney filters the blood:
  • The kidney filters blood, reabsorbing essential substances and regulating water and sodium excretion.
• Regulation of water and sodium ions:
  • Body regulates excretion through hormones and feedback mechanisms.
• Major classes of diuretic drugs:
  • Loop diuretics, Thiazides, Potassium-sparing diuretics, Carbonic anhydrase inhibitors, Osmotic diuretics.
  • Example: Furosemide (loop), Hydrochlorothiazide (thiazide), Spironolactone (potassium-sparing).
• Mechanism of action for diuretics:
  • They alter nephron cellular function affecting ion pumps and filtrate composition.
• Clinical uses of diuretics:
  • Management of fluid overload conditions (e.g., heart failure, HTN, edema).

Anatomy of the Kidney

• Blood supply:
  • Renal artery → Segmental arteries → Interlobar arteries → Afferent arterioles → Glomerulus.
• Nephrons:
  • 1.3 million per kidney; composed of proximal and distal convoluted tubules and loops of Henle.
  • Cortical nephrons: Short loops limited to the cortex.
  • Juxtamedullary nephrons: Long loops extending into the medulla.

Kidney Filtration and Reabsorption

• Reabsorption Overview:
  • 99% of fluid reabsorbed; glucose, amino acids, salts also actively reabsorbed.
  • Influencing factors: hormones and drugs affect reabsorption.
• Proximal Convoluted Tubule:
  • Reabsorbs approx. 67% of Na+, Cl−, K+.
  • Mechanisms include:
  • Na+-H+ antiporter.
  • Symporter for Na+ and bicarbonate.
  • Na+ ions exit via Na+K+-ATPase.

Renal Tubular Function

• Na+-K+ ATPase: Main active transporter in the nephron.
• Thick ascending loop of Henle:
  • Impermeable to water; reabsorbs 20-30% NaCl.
  • Uses Na+/K+/2Cl- co-transporter leading to dilution of filtrate.

Diuretics Overview and Mechanisms

• Diuretics Action:
  • Increase Na+ and water excretion; decrease net absorption leading to diuresis.
  • Act directly on nephron cells or modify filtrate content.
• Major therapeutic sites:
  • Thick ascending limb of Henle, early distal convoluted tubule, collecting ducts and tubules.

Loop Diuretics

• Example: Furosemide.
• Power and mechanism:
  • Most potent; causes 20-25% Na+ excretion by inhibiting Na+/K+/2Cl- co-transporter.
  • Can also lead to metabolic alkalosis due to plasma volume decrease while maintaining HCO3- levels.
• Clinical applications:
  • Heart failure, renal failure, hypertension.

Thiazide Diuretics

• Examples: Bendroflumethiazide, Hydrochlorothiazide.
• Mechanism of action:
  • Bind to distal nephron Na+/Cl- co-transport system to induce natriuresis.
• Use:
  • Effective for hypertension; less powerful than loop diuretics.

Potassium-Sparing Diuretics

• Aldosterone Antagonists: Spironolactone, Eplerenone.
  • Compete with aldosterone to inhibit Na+ retention and promote K+ retention.
  • Beneficial in conditions of excessive potassium loss.
• Non-Aldosterone Potassium-Sparing Diuretics: Triamterene, Amiloride.
  • Act on collecting ducts to decrease Na+ reabsorption and minimize K+ excretion.

Carbonic Anhydrase Inhibitors

• Example: Acetazolamide.
  • Inhibits carbonic anhydrase, increases bicarbonate, Na+, K+ excretion leading to alkaline urine.
  • Utilized for treating glaucoma.

Osmotic Diuretics

• Example: Mannitol.
  • Increases osmolarity of tubular fluid, inhibiting water reabsorption; used in acute renal failure scenarios.