Explain body fluid compartments with their regulation
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Body Fluid Compartments and Their Regulation
1. Overview and Total Body Water
Total body water (TBW) makes up 60% of body weight in an average adult male (~42 L in a 70-kg man) and ~50% in females (who carry more adipose tissue). In premature neonates and newborns it reaches 70–75%. TBW is inversely correlated with body fat — muscle is ~75% water, fat is only ~10% water.
2. The Two Primary Compartments
TBW is divided into two major compartments:
| Compartment | % Body Weight | % of TBW | Volume (70-kg man) |
|---|---|---|---|
| Total Body Water | 60% | 100% | 42 L |
| Intracellular Fluid (ICF) | 40% | 67% | 28 L |
| Extracellular Fluid (ECF) | 20% | 33% | 14 L |
| — Interstitial fluid | 15% | 25% | 11 L |
| — Plasma | 5% | 8% | 3 L |
| — Transcellular | ~2% | ~4% | 1–2 L |
3. Compartments in Detail
A. Intracellular Fluid (ICF)
- Constitutes 2/3 of TBW (~28 L in 70 kg man)
- Composed of trillions of individual cells, but treated collectively as one compartment because its ionic composition is remarkably similar across cell types
- Dominant cation: K⁺ (~42 mEq/kg body weight, mostly freely exchangeable)
- Also rich in Mg²⁺, phosphate, and organic anions (proteins, nucleotides)
- ICF volume is determined indirectly: TBW − ECF volume (no unique marker exists for direct measurement)
B. Extracellular Fluid (ECF)
ECF (~14 L) is divided into two main sub-compartments by the capillary wall:
Interstitial Fluid (~11 L, ~75% of ECF)
- Fluid bathing cells; essentially an ultrafiltrate of plasma
- The capillary wall is virtually impermeable to large proteins → interstitial fluid has very low protein content
- Gibbs-Donnan equilibrium slightly elevates diffusible cation and anion concentrations in interstitial fluid compared to plasma
Plasma (~3 L, ~25% of ECF)
- The non-cellular component of blood; continuously exchanges with interstitial fluid via capillary pores
- Key difference from interstitial fluid: high protein concentration (~7 g/dL, contributing ~0.8 mOsm/L oncotic pressure)
- Plasma + red blood cells = blood (~5 L, ~7% of body weight); hematocrit ~0.42 (men), ~0.38 (women)
Transcellular Fluid (~1–2 L)
- Specialized ECF in synovial, peritoneal, pericardial, intraocular spaces, and cerebrospinal fluid
- Composition may differ markedly from plasma
Dominant ECF cation: Na⁺ — sodium and its accompanying anions (Cl⁻, HCO₃⁻) are the major determinants of ECF volume.
4. Ionic Composition
| Ion | ECF (plasma) | ICF |
|---|---|---|
| Na⁺ | 142 mEq/L | 10 mEq/L |
| K⁺ | 4 mEq/L | 140 mEq/L |
| Ca²⁺ (free) | 2.4 mEq/L | ~0.0001 mEq/L |
| Mg²⁺ | 1.2 mEq/L | 58 mEq/L |
| Cl⁻ | 103 mEq/L | 4 mEq/L |
| HCO₃⁻ | 24 mEq/L | 10 mEq/L |
| Phosphate | 4 mEq/L | 75 mEq/L |
| Protein | 16 mEq/L | 74 mEq/L |
| Osmolarity | ~300 mOsm/L | ~300 mOsm/L |
Key rule: intracellular osmolarity always equals extracellular osmolarity at steady state. Water shifts freely across cell membranes to maintain this equilibrium.
5. Barriers Separating Compartments
Cell Membrane (ICF ↔ ECF)
- Highly selective; maintains the Na⁺/K⁺ gradient via Na⁺/K⁺-ATPase
- Water crosses freely via aquaporins in response to osmotic gradients
- Large molecules, charged ions cross only via specific transporters or channels
Capillary Wall (Plasma ↔ Interstitial Fluid)
- Highly permeable to small solutes and water, but impermeable to proteins
- Fluid movement governed by Starling forces:
- Capillary hydrostatic pressure → drives fluid out
- Plasma oncotic pressure (colloid osmotic pressure, ~28 mmHg) → draws fluid in
- Interstitial hydrostatic pressure and oncotic pressure oppose or assist respectively
- Net filtration at arteriolar end → reabsorption at venous end
- Residual filtered fluid is returned via lymphatics
6. Osmolarity and Tonicity
Plasma osmolarity (normally ~290–300 mOsm/L) is estimated by:
Plasma Osm = 2 × [Na⁺] + Glucose/18 + BUN/2.8
- Multiplying Na⁺ × 2 accounts for its balancing anions (Cl⁻, HCO₃⁻)
- Na⁺ is the dominant determinant; glucose and urea contribute smaller amounts
Tonicity (effective osmolality) refers to solutes that cannot cross cell membranes freely:
- Isotonic (~282 mOsm/L): no cell volume change (e.g., 0.9% NaCl, D5W initially)
- Hypotonic (<282 mOsm/L): water enters cells → cell swelling
- Hypertonic (>282 mOsm/L): water exits cells → cell shrinkage
Urea freely crosses cell membranes → it is an ineffective osmole (contributes to osmolarity but not tonicity).
7. Regulation of Body Fluid Compartments
A. Osmoregulation (Water Balance)
Plasma osmolality is maintained within a remarkably narrow window (~285–295 mOsm/kg) by a high-sensitivity feedback loop:
Osmoreceptors in the paraventricular and supraoptic nuclei of the hypothalamus are equipped with mechanical stretch receptors that depolarize when cells shrink (hyperosmolality).
↑ Osmolality triggers:
- Thirst → increased water intake
- ADH (Vasopressin) release from posterior pituitary → binds V2 receptors on principal cells of collecting ducts → cyclic AMP cascade → translocation of aquaporin-2 (AQP2) to luminal membrane → increased water reabsorption → concentrated urine (up to 1,200 mOsm/kg)
↓ Osmolality triggers:
- Thirst suppression
- ADH suppression → collecting ducts become impermeable to water → dilute urine (as low as 50 mOsm/kg)
Non-osmotic stimuli for ADH release include: volume depletion, hypotension, sympathetic activation, pain, nausea, and hypoxia. Large decreases in blood pressure override the osmotic set point, causing massive ADH release regardless of osmolality to preserve volume.
"A 1-mOsm change in plasma osmolality results in a 95-fold change in urine osmolality" — Mulholland & Greenfield's Surgery
The countercurrent mechanism (loop of Henle + vasa recta) creates the hypertonic medullary interstitium necessary for ADH to concentrate urine:
- TAL actively pumps NaCl (without water) into interstitium
- Descending limb is water-permeable → fluid concentrates
- Urea recycling in medulla further enhances hypertonicity
B. Volume Regulation (ECF/Sodium Balance)
ECF volume is primarily determined by total body sodium content (Na⁺ + accompanying anions). Volume regulation is achieved through the kidney via several hormonal systems:
Renin-Angiotensin-Aldosterone System (RAAS)
Renin is released by juxtaglomerular cells of the afferent arteriole in response to:
- Decreased afferent arteriolar pressure (baroreceptor)
- Decreased NaCl delivery to macula densa (via NKCC2)
- Increased sympathetic outflow
Renin cleaves angiotensinogen → Angiotensin I → (ACE, in lungs/kidneys) → Angiotensin II, which:
- Directly increases Na⁺ reabsorption in the proximal tubule
- Stimulates aldosterone release from adrenal cortex
- Causes systemic vasoconstriction (V1 receptor)
Aldosterone → increases ENaC activity on luminal membrane of cortical collecting duct → Na⁺ reabsorption, K⁺ excretion. WNK kinases modulate aldosterone's differential effects during hypovolemia (conserve both Na⁺ and K⁺) vs. hyperkalemia (excrete K⁺ while reabsorbing Na⁺).
Atrial Natriuretic Peptide (ANP)
Released from atria when stretched by increased ECF volume:
- Dilates afferent arteriole, constricts efferent arteriole → ↑ GFR
- Inhibits ENaC in collecting ducts → natriuresis
- Net effect: ECF volume reduction back toward normal
Vasopressin (V1 Receptor) and Sympathetic System
- Vasopressin also enhances Na⁺ reabsorption in TAL and collecting duct
- Sympathetic activation → renal vasoconstriction → ↓ GFR → ↑ renin → volume retention
8. Fluid Shifts Between Compartments
Key principles governing fluid shifts (Costanzo):
- ECF volume is determined by its total solute content — primarily Na⁺ salts
- ICF osmolarity = ECF osmolarity at steady state (maintained by free water movement)
- Effective osmoles (NaCl, mannitol) stay confined to ECF and drive water movement
- Ineffective osmoles (urea) distribute throughout TBW without osmotic shift
| Disturbance | ECF Volume | Osmolarity | ICF Volume |
|---|---|---|---|
| Isotonic volume loss (diarrhea) | ↓ | Normal | Normal |
| Pure water loss (diabetes insipidus) | ↓ (slight) | ↑ | ↓ |
| Hypertonic NaCl gain | ↑ | ↑ | ↓ |
| Isotonic NaCl gain (IV saline) | ↑ | Normal | Normal |
| SIADH (water retention) | ↑ (slight) | ↓ | ↑ |
| Adrenal insufficiency (Na⁺ loss) | ↓ | ↓ | ↑ |
9. Measuring Compartment Volumes
The dilution principle (indicator dilution method) is used:
| Compartment | Markers |
|---|---|
| TBW | ³H₂O, ²H₂O (deuterium), antipyrine |
| ECF | ²²Na, sulfate, mannitol, inulin |
| Plasma | Radioiodinated albumin (RISA), Evans blue dye |
| ICF | Calculated: TBW − ECF |
| Interstitial fluid | Calculated: ECF − Plasma volume |
Summary
The body's ~42 L of water is partitioned into ICF (28 L, K⁺-rich) and ECF (14 L, Na⁺-rich), separated by the cell membrane (osmotically driven) and capillary wall (Starling forces). Regulation operates through two parallel systems: osmoregulation (hypothalamic osmoreceptors → ADH → aquaporin-2 insertion → urine concentration) maintains constant osmolality, while volume regulation (RAAS → aldosterone + ANP + sympathetics) controls total body Na⁺ and thus ECF volume. These two systems interact — notably, severe hypovolemia overrides osmolality setpoints, causing ADH release even in hypotonic states, prioritizing volume preservation over tonicity.
Sources: Guyton and Hall Textbook of Medical Physiology; Costanzo Physiology 7e; Mulholland & Greenfield's Surgery 7e; National Kidney Foundation Primer on Kidney Diseases 8e
Short and long term regulation of body fluid balance
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