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Body Water Compartments, Osmolality, Tonicity & Regulation of Body Fluid

Notes for MD Anaesthesiology Examination

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I. TOTAL BODY WATER (TBW) IN A 70 KG MAN

TBW correlates inversely with body fat. Women (~50–55% body weight is water) and obese individuals have proportionally less TBW; neonates and lean athletes have more (up to 75%).

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II. FUNCTIONALLY DISTINCT COMPARTMENTS OF BODY WATER

Summary Table (70 kg man)

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A. Intracellular Fluid (ICF) — 28 L

• Two-thirds of TBW; contained within cells
• Bounded by the cell (plasma) membrane
• Dominant cation: K⁺ (140 mEq/L) — maintained by the Na⁺/K⁺-ATPase (3 Na⁺ out : 2 K⁺ in)
• High intracellular protein concentration (16 g/dL) acts as non-diffusible anion
• The 3:2 unequal exchange ratio of the pump is critical — without it, trapped intracellular proteins would create hyperosmolality and osmotic cell swelling
• Mg²⁺ (50 mEq/L) and phosphate (75 mEq/L) are the other major intracellular solutes
• Ischaemia or hypoxia → inhibition of Na⁺/K⁺-ATPase → progressive cell swelling

B. Extracellular Fluid (ECF) — 14 L

• One-third of TBW; outside cells
• Dominant cation: Na⁺ (145 mEq/L) — the primary determinant of ECF osmotic pressure and volume
• Changes in total body Na⁺ content = changes in ECF volume

1. Interstitial Fluid (ISF) — 10.5 L

• Fluid bathing the cells; forms from plasma by filtration across the capillary wall
• Capillary wall is virtually impermeable to plasma proteins → ISF protein content is very low (~2 g/dL)
• Most interstitial water is in gel form, bound to extracellular proteoglycans; free fluid is minimal
• Interstitial fluid pressure is normally slightly negative (≈ −5 mm Hg)
• When ISF volume progressively increases and pressure becomes positive → free fluid accumulates → clinical oedema
• The interstitial compartment acts as an overflow reservoir for the intravascular compartment

2. Intravascular Fluid (Plasma) — 3.5 L

• Confined to the vascular endothelium
• Small ions (Na⁺, K⁺, Cl⁻) freely cross the endothelium → plasma and ISF electrolyte composition are nearly identical
• Plasma proteins (albumin, 7 g/dL) do not cross capillary clefts → generate colloid oncotic pressure (~25 mm Hg), the main force retaining fluid within vessels
• Plasma proteins are the only osmotically active solutes not freely exchanged between plasma and ISF

3. Transcellular Fluid (minor compartment, ~1–2 L)

• Includes CSF, synovial, pleural, pericardial, peritoneal, intraocular, and GI secretions
• Functionally distinct because it is actively secreted and has a different composition
• Clinically relevant in conditions like bowel obstruction or ascites where large volumes accumulate as "third space"

Electrolyte Composition of Body Fluid Compartments

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III. OSMOLALITY AND TONICITY

A. Definitions and Distinctions

In clinical practice, osmolarity ≈ osmolality (1 L water ≈ 1 kg water), so the terms are often used interchangeably. Normal value: 280–295 mOsm/kg H₂O.

• 1 mOsm/L difference between two solutions generates an osmotic pressure of 19.3 mm Hg
• Substances that ionize contribute n osmoles per mole, where n = number of ionic species (NaCl → 2 Osm theoretically, but due to ionic interaction NaCl behaves as though only ~75% ionized)

B. Calculation of Plasma Osmolality

• Na⁺ multiplied by 2 to account for accompanying anions (Cl⁻ and HCO₃⁻)
• Normal: 280–295 mOsm/kg
• Osmolar gap = Measured − Calculated > 10 mOsm/kg → presence of unmeasured osmoles (methanol, ethanol, mannitol, ethylene glycol)

C. Tonicity vs. Osmolality — The Critical Distinction

BUN is NOT included in tonicity — urea freely crosses cell membranes (via UT family transporters), equilibrates across the membrane, and therefore does not cause sustained changes in cell volume. It is an "ineffective osmole."

• Adding mannitol (impermeant) to ECF → sustained cell shrinkage ✓
• Adding urea to ECF → transient cell shrinkage, then re-swelling as urea equilibrates ✗ (no sustained tonicity effect)

D. Isotonic / Hypotonic / Hypertonic Solutions

E. Fluid Exchange Between Compartments — Key Principles

1. Volume of a compartment depends on its total solute content; ECF volume is governed by total body Na⁺
2. In steady state, ICF osmolality = ECF osmolality — water shifts freely across membranes to maintain equality
3. Solutes confined to ECF (NaCl, NaHCO₃, mannitol) — when added, expand only the ECF
4. Permeant solutes (urea) distribute throughout TBW and do not change cell volume

• Capillary hydrostatic pressure (P_c) → filtration out
• Plasma oncotic pressure (π_c) → reabsorption in
• Net: fluid filtered at arterial end, reabsorbed at venous end; ~10% excess enters lymphatics (~2 mL/min)

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IV. PRIMARY METHODS OF REGULATION OF BODY FLUID WATER

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A. Osmoreceptor–ADH (Vasopressin)–Renal Axis

Sensing

• Osmoreceptor cells in the anterior hypothalamus (anterior to the 3rd ventricle, separate from but closely associated with supraoptic and paraventricular nuclei)
• Exquisitely sensitive — stimulated by increases in plasma osmolality of as little as 1–2% (~1–2 mOsm/kg above the set-point of ~285 mOsm/kg)
• Respond primarily to Na⁺ concentration in arterial blood
• Cell shrinkage = stimulation; cell swelling = inhibition

ADH (Vasopressin) Synthesis and Release

• Synthesized in supraoptic and paraventricular nuclei of the hypothalamus as prepro-hormone
• Transported down axons via the supraopticohypophysial tract → stored and released from the posterior pituitary
• Basal plasma ADH: 0.5–2 pg/mL → urine osmolality maintained above plasma (1–3 L/day urine)
• When ADH < 0.5 pg/mL → free water diuresis, urine osmolality < 100 mOsm/kg, up to 18–24 L/day
• At plasma osmolality ~295 mOsm/kg → urine maximally concentrated to 1000–1200 mOsm/kg
• Urine osmolality range: 50–1200 mOsm/L depending on ADH

Mechanism of Action — Aquaporin-2 (AQP2)

• ADH acts on V2 receptors in collecting duct principal cells
• V2 receptor → Gs protein → adenylate cyclase → ↑cAMP → PKA activation
• PKA phosphorylates aquaporin-2 (AQP2) vesicles → insertion into apical membrane of collecting duct
• ↑ Water permeability of late distal tubule and collecting duct → ↑ water reabsorption
• Water exits basolaterally through constitutively expressed AQP3 and AQP4 into medullary capillaries

Corticopapillary Osmotic Gradient (enables concentration)

• Medullary interstitium osmolality rises from cortex (~300 mOsm/L) to papilla (~1200 mOsm/L)
• Maintained by countercurrent multiplication (loop of Henle deposits NaCl in medullary interstitium) and urea recycling (inner medullary collecting duct deposits urea)
• ADH-driven water reabsorption relies on this pre-existing gradient

Negative Feedback Loop

↑ Plasma osmolality
       ↓
Osmoreceptor shrinkage → ↑ ADH + ↑ Thirst
       ↓
↑ Water reabsorption (kidney) + Drinking
       ↓
↓ Plasma osmolality (restored to normal)

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B. Thirst Mechanism

• Threshold for thirst activation (~5–10 mOsm/kg above the ADH threshold) — slightly higher than for ADH
• Thirst centre is distributed across multiple brain areas; stimulated by osmoreceptors in the hypothalamus
• Under normal conditions, water balance is regulated more by ADH secretion than by thirst; in severe dehydration, thirst becomes essential
• Thirst is also stimulated by angiotensin II and by non-osmotic stimuli (volume depletion, dry mouth)

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C. Non-Osmotic Regulation of ADH

Anaesthetic relevance: Major surgery, laryngoscopy, and post-operative nausea are potent non-osmotic stimuli for ADH release, contributing to post-operative hyponatraemia, especially when hypotonic IV fluids are given.

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D. Renin–Angiotensin–Aldosterone System (RAAS) — Volume Regulation

• ↓ Renal perfusion → ↑ Renin → ↑ Angiotensin I → ACE → Angiotensin II
• Angiotensin II: vasoconstriction + ↑ aldosterone + stimulates thirst and ADH release in hypothalamus
• Aldosterone → ↑ Na⁺/K⁺-ATPase in collecting duct → ↑ Na⁺ reabsorption → passive water follows
• Net effect: ↑ ECF volume

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E. Atrial Natriuretic Peptide (ANP) / Brain Natriuretic Peptide (BNP)

• Released from atrial myocytes in response to ↑ atrial stretch (ECF volume expansion)
• Actions: ↑ GFR, ↓ aldosterone, ↓ ADH release, ↓ renin → natriuresis and diuresis
• Negative feedback on RAAS and ADH axis — buffers volume expansion

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F. Renal Mechanisms — The Final Effector

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V. SUMMARY DIAGRAM — INTEGRATED WATER BALANCE

WATER INTAKE                           WATER LOSS
  Oral fluids    ←──────────────────→  Urine (primary regulated output)
  Food water                           Insensible (skin + lungs ~800 mL/day)
  Metabolic water (~300 mL/day)        Sweat (variable)
                                       Faeces (~100 mL/day)

Sensors: Osmoreceptors (hypothalamus) → ↑ Osmolality ≥ 1–2%
         Baroreceptors → ↓ Volume ≥ 10–15%

Effectors:
  1. ADH (vasopressin) → AQP2 → ↑ water reabsorption by collecting duct
  2. Thirst → ↑ water intake
  3. RAAS → ↑ Na⁺ reabsorption → passive water retention
  4. ANP/BNP → ↑ natriuresis + ↓ ADH (volume overload correction)

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VI. CLINICALLY RELEVANT ANAESTHETIC CORRELATIONS

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KEY EXAMINATION POINTS

1. TBW = 60% body weight = 42 L in 70 kg man; ICF = 28 L (2/3), ECF = 14 L (1/3)
2. Na⁺ governs ECF volume; K⁺ governs ICF osmolality — maintained by Na⁺/K⁺-ATPase
3. Osmolality ≠ Tonicity: BUN contributes to osmolality but NOT to tonicity (freely permeable); glucose and Na⁺ are effective osmoles
4. ADH set-point ~285 mOsm/kg; threshold ~280 mOsm/kg; maximal response ~295 mOsm/kg
5. Thirst threshold is 5–10 mOsm/kg higher than ADH threshold
6. AQP2 insertion in the apical membrane of collecting duct principal cells is the molecular mechanism of ADH action
7. The corticopapillary gradient (300–1200 mOsm/L) is the permissive gradient; ADH action is the regulated switch
8. Non-osmotic ADH release is a critical perioperative concern — nausea, pain, and surgical stress are potent stimuli
9. Starling forces govern ICF↔ECF distribution; capillary oncotic pressure (albumin) retains fluid intravascularly

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