RCP 110 Chapter - 19 Diuretics and Renal Function

Diuretics

• Agents that increase urine output.
• The main purpose is to eliminate excess fluid from the body.
• Diuretic therapy reduces extracellular fluid volume.
• Reducing extracellular fluid volume lowers blood pressure.
• Reducing extracellular fluid volume rids the body of excess interstitial fluid.

Renal Structure and Function

• Kidneys are paired retroperitoneal organs.
• They are located on either side of the spinal cord at the level of the umbilicus.
• Each kidney weighs 160–175 g and is 10–12 cm long.
• Kidneys are perfused by renal artery.
• Kidneys have the most blood flow per gram of weight in the body.
• 22% of cardiac output (CO), or 1.1 L/min, goes to the kidneys.
• The kidney is an active organ, not a passive filter.
• The nephron is a functional unit that maintains homeostasis of internal volume and electrolytes.
• Parts of the nephron: glomerulus, proximal tubule, loop of Henle, distal tubule, and collecting duct.
• 20% of total blood flow goes through the nephron at about 130 mL/min.
• 99% of glomerular filtrate is reabsorbed in the tubules.
• 1% of filtrate is excreted as urine.
• Adult urine output is 0.5–1 mL/min or 30–60 mL/hr.
• Urine output less than 30–60 mL/hr is oliguria, and more than 60 mL/hr is polyuria.
• Diuretics interfere with reabsorption in the tubules to increase urine output.
• 70% of Na+ is reabsorbed in the proximal tubules, 20% in loops of Henle, 10% in distal tubules.
• Inhibition of sodium absorption causes less H2O retention.
• K+ is reabsorbed mostly in the proximal tubules.
• Cl- and HCO3- are passively reabsorbed in the tubules.
• Aldosterone increases Na and H₂O reabsorption in the distal tubule.
• Acid-base balance may be caused by H₂O loss.
• Sodium reabsorption preserves neutrality with Cl- and exchanges Na+ for H+ or K+.
• Low Cl- or K+ results in metabolic alkalosis.
• Loss of HCO3- buffer results in metabolic acidosis.

Diuretic Groups

• The primary therapeutic goal of diuretic use is to reduce ECFV.
• Diuretics are relevant to respiratory and critical care clinicians to treat hypertension and congestive heart failure (CHF).
• Major groups of diuretics include osmotic, carbonic anhydrase inhibitors, thiazides, loop, and potassium-sparing.

Osmotic Diuretics

• Osmotic diuretics impair the proximal tubule and ascending limb of loop of Henle from reabsorbing NaCl.
• They produce a net K+ loss in urine.
• Examples: Glycerin, isosorbide, mannitol, and urea
• Mannitol is often selected due to low toxicity.
• They are often used for cerebral edema.

Carbonic Anhydrase Inhibitors

• They work within the proximal tubule.
• They decrease HCO3- and NaCl reabsorption.
• The result is a moderate NaCl increase plus water excretion.
• Weak action plus potential for metabolic acidosis limits use.
• Hypokalemia is a common adverse effect.
• Other uses for Carbonic Anhydrase Inhibitors include treatment of glaucoma, metabolic alkalosis, and altitude sickness.

Loop Diuretics

• Examples of Loop Diuretics: Furosemide, bumetanide, torsemide
• They inhibit NaCl reabsorption at the ascending limb of loop of Henle.
• They are "high-ceiling" diuretics.
• Up to 20% of NaCl and H2O is lost.
• They may cause acute vasodilation within 5 min when administered IV.
• They can decrease pulmonary capillary wedge pressure (PCWP), blood pressure, and SVR.
• Larger doses are required with renal dysfunction.

Thiazide Diuretics

• They block NaCl reabsorption at the distal tubule.
• They are a first-line treatment for mild hypertension (HTN).
• They have a narrow therapeutic margin.
• They may also decrease peripheral vascular resistance.

Potassium-Sparing Diuretics

• They block exchange of Na+ for K+ and H+.
• Potassium-Sparing Diuretics have a weak action.
• They may cause hyperkalemia.
• Spironolactone is a competitive aldosterone antagonist.
• Spironolactone is common in cirrhosis and ascites.
• Triamterene blocks Na+ channels in the collecting ducts.
• Triamterene is short-acting and is metabolized by the liver.
• Amiloride blocks Na+ channels in the collecting ducts.
• Amiloride has a moderately long half-life.

Diuretic Combinations

• Diuretic combinations may produce additive or synergistic effects.
• The most common combination is a loop diuretic plus thiazide.

Adverse Effects

• Hypovolemia and acid-base disorders are most common.
• Hypovolemia symptoms: dizziness, extreme thirst, excessive dryness, decreased urine output, dark-colored urine, and constipation.
• Acid-base disorders: hypokalemia, hypochloremia.
• Other adverse effects include hypokalemia, glucose changes, and ototoxicity.

Special Situations

• Diuretics are not recommended during pregnancy or for breastfeeding women because they can dehydrate the baby.
• Side effects in children are similar to adults, but may require smaller doses.
• Furosemide is effective and least toxic in pediatric practice.
• Loop diuretics may cause nephrocalcinosis.
• For Acute Respiratory Distress Syndrome (ARDS), diuretics are used for noncardiogenic pulmonary edema.
• Diuretics reduce PCWP associated with increased survival.
• For Chronic Lung Disease (CLD) in preterm infants, CLD is lung disease complicated by pulmonary edema.
• A single dose of aerosolized furosemide may transiently improve pulmonary mechanics, but routine or sustained use is not recommended.