Sodium and Water Balance

TBW & Fluid Spaces - Aqua Realms

• TBW: ~60% body weight (♂), ~50% (♀); ↓ age/obesity.
• 📌 60-40-20 Rule (% body wt): TBW 60%, ICF 40%, ECF 20%.
• ICF (2/3 TBW): $K^+$, $PO_4^{3-}$ main ions.
• ECF (1/3 TBW): $Na^+$, $Cl^-$ main ions.
  • Plasma: 1/4 ECF.
  • ISF: 3/4 ECF.
• Markers: TBW ($D_2O$); ECF (Inulin); Plasma Vol (Evans Blue, $^{131}I$-Alb).
• Derived: ICF = TBW - ECF; ISF = ECF - Plasma.
• Plasma Osmolality: $2[Na^+] + \frac{[Glucose]}{18} + \frac{[BUN]}{2.8}$.

⭐ Normal: 280-295 mOsm/kg $H_2O$. $Na^+$ salts are main ECF osmoles.

Nephron Na$^+$ Handling - Salty Segments

• Proximal Convoluted Tubule (PCT):
  • Major site: Reabsorbs ~65-70% filtered Na$^+$.
  • Apical: Na$^+$/H$^+$ exchanger (NHE3), SGLT, Na$^+$-Amino Acid, Na$^+$-PO$_4^{3-}$ cotransporters.
  • Basolateral: Na$^+$/K$^+$ ATPase.
  • Isosmotic reabsorption (water follows Na$^+$).
• Thick Ascending Limb (TAL) - Loop of Henle: Key Diluting Segment
  • Reabsorbs ~20-25% filtered Na$^+$.
  • Apical: Na$^+$-K$^+$-2Cl$^-$ cotransporter (NKCC2). 📌 NKCC2: "Na K Cl Comes 2gether".
  • Basolateral: Na$^+$/K$^+$ ATPase.
  • Impermeable to water $ ightarrow$ tubular fluid becomes dilute.
  • Generates corticomedullary osmotic gradient.
  • Target for Loop Diuretics (e.g., Furosemide).

  ⭐ Loop diuretics (e.g., Furosemide) inhibit the NKCC2 cotransporter in the TAL, leading to potent natriuresis.

• Distal Convoluted Tubule (DCT) - Early: Diluting Segment
  • Reabsorbs ~5-8% filtered Na$^+$.
  • Apical: Na$^+$-Cl$^-$ cotransporter (NCC).
  • Basolateral: Na$^+$/K$^+$ ATPase.
  • Largely impermeable to water.
  • Target for Thiazide Diuretics.
• Collecting Duct (Principal Cells):
  • Fine-tunes Na$^+$ reabsorption (~2-3%).
  • Apical: Epithelial Na$^+$ Channel (ENaC).
  • Aldosterone sensitive: $\uparrow$ ENaC & Na$^+$/K$^+$ ATPase activity.

Nephron H₂O Handling & Osmoregulation - Water Works

• Segmental $H_2O$ Reabsorption:
  • PCT: ~65-70%; obligatory, iso-osmotic (AQP1). Follows Na⁺.
  • Descending LOH: ~15%; freely permeable (AQP1); concentrates tubular fluid.
  • Ascending LOH: Impermeable to $H_2O$; diluting segment.
  • Late DCT & CD: ~10-20%; facultative, ADH-regulated (AQP2).
• Antidiuretic Hormone (ADH/AVP):
  • Source: Hypothalamus (SON/PVN) → Posterior Pituitary.
  • Stimuli: ↑ Plasma osmolality (main), ↓ ECF volume.
  • Action: V₂ receptors (principal cells) → ↑cAMP → AQP2 insertion (apical) → ↑$H_2O$ reabsorption. 📌 ADH = Adds Da $H_2O$.
• Osmoregulation:
  • Maintains plasma osmolality (280-295 mOsm/kg).
  • ADH enables urine concentration (max 1200 mOsm/kg) or dilution (min 50 mOsm/kg).
  • Requires medullary hypertonicity (countercurrent mechanism).

⭐ Central Diabetes Insipidus (↓ADH) causes excretion of large volumes of dilute urine (Urine Osm < 100-200 mOsm/kg, Sp. Gr. < 1.005), leading to hypernatremia if water intake is inadequate.

Integrated Regulation & Imbalances - Hormonal Harmony & Havoc

Regulators: RAAS, ADH, ANP, SNS.

• RAAS: From ↓renal perfusion/↓$Na^+$. AngII (vasoconstriction, ↑$Na^+$ reabsorption) & Aldosterone (↑$Na^+$ reabsorb, $K^+$ secrete).
• ADH (Vasopressin): From ↑Posm/↓volume. ↑$H_2O$ reabsorption (collecting ducts via aquaporins).
• ANP/BNP: From ↑atrial/ventricular stretch. Promotes natriuresis (↑$Na^+$ excretion), diuresis, ↓RAAS.
• SNS: ↑Renin, ↑$Na^+$ reabsorption, renal vasoconstriction.

Imbalances:

• SIADH: ↑ADH → hyponatremia (↓$Na^+$), concentrated urine.
• Diabetes Insipidus (DI): ↓ADH action → hypernatremia (↑$Na^+$), dilute urine.
• Edema: Pathological fluid accumulation.

⭐ SIADH: Urine Osm >100 mOsm/kg & Urine Na+ >40 mEq/L with plasma hyponatremia.

High‑Yield Points - ⚡ Biggest Takeaways

• ADH (Vasopressin) primarily regulates water reabsorption in collecting ducts via aquaporin-2 channels.
• Aldosterone controls sodium reabsorption and K+ secretion in the distal nephron (DCT & CD).
• RAAS activation (due to ↓ renal perfusion) leads to increased Na+ and water retention.
• ANP, released with atrial stretch, promotes natriuresis and diuresis, opposing RAAS.
• Hypothalamic osmoreceptors sense plasma osmolality, influencing ADH release and thirst.
• Effective Circulating Volume (ECV) is the key determinant of RAAS activity, not total body water.
• SIADH causes euvolemic hyponatremia due to excessive water retention and ADH activity.