Diuretics and Kidney Function

• CHF stands for Congestive Heart Failure, which is when the heart cannot pump blood effectively.
• Diuretics are substances or drugs that increase urine production.
• Edema refers to swelling caused by atypical fluid buildup in the body's cell spaces.
• Glomerular Filtration is the process where blood fluids filter through the glomerulus capillaries, eventually exiting via renal ducts.
• Hypovolemia is when there's a physiological drop in total blood volume.
• Nephrocalcinosis refers to the excessive buildup of calcium within kidney tissues and tubules.
• Nephrons are the kidney's functional units and microscopically regulate water, electrolyte balance, and each kidney holds about 2 million nephrons.
• Ototoxicity is damage to hearing or balance caused by drugs or chemicals.
• Reabsorption is the process where water, sodium, amino acids, and sugar return from filtrate back into the blood, primarily in the proximal tubule of the nephron.

Diuretics

• Diuretics increase urine output.
• The primary purpose of diuretics is to eliminate excess fluid.
• The main goal when using diuretic treatments is to decrease the body's extracellular fluid to lower blood pressure and decrease excess interstitial fluid.
• Diuretics were first used in 1958.

Renal Structure and Function

• Kidneys are retroperitoneal organs on either side of the spinal cord at the level of the umbilicus.
• Kidneys are paired and weigh 160-175g and are 10-12 cm long each.
• Kidneys are supplied with blood via the renal artery.
• Kidneys receive 22% of cardiac output (CO), about 1.1L/min
• Kidneys are not passive organs.

Urine

• The glomerulus starts blood fluid filtration into the proximal tubule.

• Urine flows in the following order: Glomerulus -> Proximal Tubule -> Loop of Henle -> Distal tubule -> Collecting Ducts -> Ureter -> Bladder

• Nearly 250 nephron units work to maintain homeostasis via secretion, reabsorption, and filtration of electrolytes.

• Kidneys cannot regenerate nephrons.

• Nephrons maintain fluid volume and electrolyte balance by filtration, secretion, and reabsorption.

• Glomerular Filtration is filtration from blood into the proximal tubule within the glomerulus, and becomes glomerular filtrate.

• The Urinary Tract consists of collecting ducts that move urine from nephrons to the ureter and bladder for storage and removal.

Glomerular Filtration Details

• 20% of total blood flows through the nephron at about 130 mL/min.
• 99% of glomerular filtrate gets reabsorbed by the tubules.
• 1% of glomerular filtrate is excreted.
• Typical adult urine output is 0.5-1 mL/min or 30-60 mL/hr.
• Oliguria is a urine output less than 30-60 mL/hr
• Polyuria means that urine output is more than 60 mL/hr.
• Diuretics increase urine output by stopping reabsorption in the tubules.

Electrolyte Filtration and Reabsorption

• Sodium (Na+) is heavily reabsorbed in the tubules
• 70% of Sodium is reabsorbed in the proximal tubules
• 20% of Sodium is reabsorbed in the loop of Henle
• 10% of Sodium is reabsorbed in the distal tubules
• Less water retention is caused due to Sodium reabsorption inhibition.
• Potassium (K+) is mainly reabsorbed by the proximal tubules.
• Chloride (Cl-) and Bicarbonate (HCO3) passively reabsorbed in the tubules.
• Aldosterone increases sodium and water reabsorption in the distal tube.

Acid-Base Balance

• Acid-Base balance may be affected by water loss and sodium reabsorption.
• Metabolic Alkalosis may be caused by low chloride or potassium levels.
• Loss of HCO3 leads to Metabolic Acidosis
• The main diuretic goal is to reduce Extracellular Fluid Volume (ECFV).
• Decreasing Extracellular Fluid Volume, is relevant for heart failure and hypertension.

Diuretics Groups

• Osmotic
• Carbonic Anhydrase Inhibitors
• Thiazides
• Loop
• Potassium sparing

Osmotic Diuretics

• Osmotic diuretics work by stopping NaCl reabsorption in the proximal tubule and the ascending limb of the loop of Henle, and cause a net loss of K+ in urine.
• Useful for Cerebral Edema.
• Lower toxicity makes Mannitol common, and it does increase ICP.

Carbonic Anhydrase Inhibitors

• These inhibitors work in the proximal tubule, decreasing HCO3 and NaCl reabsorption
• A moderate NaCl increase and water excretion is the main result.
• The limited use of these inhibitors is due to its weak action and potential for metabolic acidosis.
• Hypokalemia is the most common side effect.
• It is used for Glaucoma, Metabolic Alkalosis, and Altitude sickness.

Loop Diuretics

• Loop Diuretics inhibit NaCl reabsorption in the ascending limb of the loop of Henle.
• These diuretics are called "High ceiling" diuretics (Up to 20% of NaCl and H2O is lost).
• IV administration may cause vasodilation within 5 minutes.
• Larger doses are needed when treating renal dysfunction.
• i.e. Furosemide (Lasix), Bumetanide, and Torsemide

Thiazide Diuretics

• Thiazide Diuretics act by blocking NaCl reabsorption in the distal tube.
• Commonly used to treat mild hypertension (HTN).
• A decreased peripheral vascular resistance is a common side effect, and has a narrow therapeutic margin

Potassium Sparing Diuretics

• Potassium Sparing Diuretics prevent sodium/potassium/H+ exchange, and has a weak action.

• Hyperkalemia is a common side effect.

• i.e. Spironolactone, Triamterene, Amiloride

• Diuretics may have additive or synergistic effects when combined.

• Loop diuretic + Thiazide is the most common combination

Diuretics Combinations

• Hypovolemia and acid-base disorders are common.
• Hypovolemia symptoms include: Dizziness, extreme thirst, excessive dryness, decreased/dark urine output, and constipation.
• Acid-Base disorder symptoms include: Hypokalemia and Hypochloremia
• Other side effects include: Hypokalemia, Glucose changes, and Ototoxicity
• Diuretics are not safe with breastfeeding or pregnancy due to possible dehydration to the baby.
• Children have similar side effects as adults
• Furosemide is effective/least toxic in pediatric practice.
• Loop diuretics may cause nephrocalcinosis.

Acute Respiratory Distress Syndrome (ARDS)

• Noncardiogenic pulmonary edema
• Reduction in PCWP is associated with increased survival

Chronic Lung Disease (CLD)

• Lung disease complicated by pulmonary edema
• Single dose of aerosolized furosemide may improve pulmonary mechanics effectively but sustained use is not recommmended.