Water balance and osmoregulation

Body Fluid Compartments - The Body's Pools

• Total Body Water (TBW) is approximately 60% of body weight.
  • Intracellular Fluid (ICF): 2/3 of TBW. High in $K^+$.
  • Extracellular Fluid (ECF): 1/3 of TBW. High in $Na^+$.
    • Interstitial Fluid: 3/4 of ECF.
    • Plasma: 1/4 of ECF.
• 📌 60-40-20 Rule: For a 70kg person, 60% TBW (42L), 40% ICF (28L), 20% ECF (14L).
• Calculated plasma osmolality: $2 \times [Na^+] + [Glucose]/18 + [BUN]/2.8$

⭐ This formula is crucial for identifying osmolar gaps in toxicology cases.

ADH & Osmoregulation - The Thirst Tamer

• Function: Primary hormone regulating plasma osmolality and free water excretion.
• Source: Synthesized in the hypothalamus (supraoptic/paraventricular nuclei); released from the posterior pituitary.
• Triggers for Release:
  • Primary: ↑ Plasma osmolality (hypertonicity).
  • Secondary: ↓ Blood volume/pressure, Angiotensin II.
• Mechanism: Binds to V2 receptors on principal cells of the collecting duct → Gs pathway → ↑cAMP → insertion of Aquaporin-2 (AQP2) channels into the apical membrane.
• Result: ↑ H₂O reabsorption → concentrated urine & diluted plasma.

⭐ Osmoreceptors in the hypothalamus are incredibly sensitive, triggering ADH release with just a 1-2% change in plasma osmolality.

RAAS & Volume Regulation - The Salt Saver System

Primary regulator of ECF volume and blood pressure via Na⁺ balance.

• Trigger: Juxtaglomerular Apparatus (JGA) senses ↓ renal perfusion, ↓ NaCl delivery (macula densa), or ↑ sympathetic tone → releases Renin.

• Cascade:

• Angiotensin II Effects:

  • Vasoconstriction (↑ SVR)
  • Aldosterone release
  • ADH release
  • ↑ Na⁺ reabsorption (PCT)
  • Stimulates thirst

• Aldosterone Action: Acts on principal cells (collecting duct) → ↑ ENaC & Na⁺/K⁺ pumps → ↑Na⁺ reabsorption, ↑K⁺ secretion.

⭐ ACE inhibitors (e.g., lisinopril) also block bradykinin breakdown, which can cause a persistent dry cough.

Water Balance Disorders - Too Much, Too Little

• Diabetes Insipidus (DI): Intense thirst (polydipsia) & polyuria with dilute urine, leading to hypernatremia.
• SIADH: Excessive ADH leads to water retention, concentrated urine, and dilutional hyponatremia.

High-Yield Points - ⚡ Biggest Takeaways

• ADH (Vasopressin) is the key hormone regulating plasma osmolality by controlling free water reabsorption.
• It acts on V2 receptors in the collecting duct, inserting aquaporin-2 channels into the apical membrane.
• Hypothalamic osmoreceptors are the primary drivers of ADH release and the thirst mechanism.
• SIADH leads to euvolemic hyponatremia, while Diabetes Insipidus causes hypernatremia and polyuria.
• Urine osmolality ranges from ~50 to ~1200 mOsm/kg.