L 1 Body Fluid Compartments and Osmolarity — Study Notes

Homeostasis and Overview

  • Homeostasis as the central unifying concept of physiology and medicine.
    • Dynamic self-regulation: parameters fluctuate within a narrow, predictable range; feedback mechanisms restore normal ranges when changes occur.
    • Health results from maintained homeostasis; loss leads to pathology; medical interventions aim to correct imbalances and restore homeostatic mechanisms.
  • Focus of this lecture: location of body water, movement between compartments, and the mechanisms driving water movement.

Diffusion, Membrane Permeability, and Flux

  • Diffusion: movement of molecules from an area of high concentration to an area of low concentration.
    • Example: glucose diffusion across a semi-permeable membrane from Compartment 1 to Compartment 2.
    • Over time, concentrations equilibrate as the gradient diminishes (e.g., 20 mmol/L → 10 mmol/L in each compartment).
  • Flux equation (conceptual):
    Flux=Permeability×Surface Area×(Concentration<em>1−Concentration</em>2)\text{Flux} = \text{Permeability} \times \text{Surface Area} \times (\text{Concentration}<em>1 - \text{Concentration}</em>2)
  • Medical relevance: tissue permeability, surface area, and concentration gradients determine diffusion rates (e.g., oxygen diffusion in lungs affected by edema, fibrosis, or emphysema).
  • Lipid bilayer diffusion: hydrophilic heads face water; hydrophobic tails form a non-polar interior, limiting diffusion of charged/polar molecules; diffusion is facilitated by channels if needed.
  • Implications: non-polar molecules (O2, CO2, fatty acids, steroid hormones) diffuse readily; ion channels increase diffusion rates for ions; pharmacologic inhibition of channels can be effective.
  • Membrane transport overview: primary active transport (Na+/K+-ATPase) and secondary active transport establish intracellular and extracellular compositions; the lipid bilayer then limits diffusion of polar substances.
  • Aquaporins: membrane water channels determine cell permeability to water; number and type of aquaporins control water movement across membranes.

Molarity, Osmolarity, and Osmolality

  • Molarity (M): moles of solute per liter of solution.
  • Osmolarity (Osm/L): total number of osmotically active particles per liter of solution.
    • Example: dissolving 1 mole of NaCl in 1 L water yields 2 particles (Na⁺ and Cl⁻), so [Osm] = 2 Osm/L, whereas molarity is 1 M.
  • Osmolality (Osm/kg): osmotically active particles per kilogram of solvent; at body temperature, 1 L water ≈ 1 kg, so osmolarity ≈ osmolality.
  • Important relationship: osmolarity and osmolality are effectively interchangeable in physiological contexts.

Osmosis

  • Osmosis: movement of water from high water concentration (low solute) to low water concentration (high solute) through a semi-permeable membrane.
  • Practical rule: water moves toward the compartment with higher osmolarity (more solute particles).
  • Illustrative thought: when solute number changes between compartments, water shifts to restore osmotic balance; if the membrane is permeable to the solute, equilibration occurs and osmotic gradients dissipate.

Effective vs. Ineffective Osmoles

  • Steady-state gradients are maintained by pumps/transporters (e.g., Na⁺/K⁺-ATPase) and secondary transport.
  • Permeant solutes (e.g., glucose, urea) can diffuse across membranes; they are “ineffective” osmoles because they do not sustain a long-term osmotic gradient once equilibrated.
  • Non-permeant (impermeant) solutes effectively contribute to osmolarity and tonicity because they remain in their original compartment.
  • Example: introduce 100 mOsm/L of urea into the extracellular fluid while the extracellular space is large relative to the cell.
    • Initially, osmolality rises to 400 mOsm/L (ECF), water leaves the cell → cell volume decreases, cell osmolarity rises.
    • Over time, urea diffuses into the cell, equilibrating the osmolarities and returning cell volume toward original size.
    • Net effect: total osmolarity of both compartments rises temporarily, but compartments equilibrate; cell volume normalizes as urea diffuses.
  • Reversing the process (remove urea from extracellular fluid) causes water to move back into the cell as the cell osmolarity remains higher until equilibrium.

Osmotic Pressure and Osmosis Dynamics

  • Osmotic pressure builds as solute concentration increases; water movement across a semi-permeable membrane continues until hydrostatic pressure counterbalances osmotic pressure.
  • Water flow direction depends on relative osmotic pressures; when membrane is permeable to water but not the solute, the compartment with higher osmotic pressure draws water and expands until equilibrium.
  • Consider shapes of compartments to illustrate osmotic gradients and potential changes in volume and osmolarity during osmosis.

Tonicity and Extracellular Osmolarity

  • Isotonic: a solution with impermeant solutes having the same osmolarity as the cell; no net water movement; cell volume remains constant.
  • Hypertonic: impermeant solutes higher outside; water leaves the cell; cell shrinks until intracellular osmolarity matches exterior.
  • Hypotonic: impermeant solutes lower outside; water enters the cell; cell swells until osmolarities equalize.
  • Permeant vs. impermeant solutes and tonicity:
    • Permeant solutes (glucose, urea) may initially change cell size but do not contribute to long-term tonicity once equilibrated.
    • Impermeant solutes determine tonicity.
  • Iso-osmotic, hyper-osmotic, and hypo-osmotic terms refer to osmolarity relative to extracellular fluid, independent of solute permeability.
  • Special note on isotonic saline: 154 mM NaCl has an effective osmolarity less than 308 mOsm/L due to osmotic coefficient effects (~0.93 for NaCl), yielding ~286 mOsm/L.

Body Fluid Compartments: Composition and Volumes

  • Total Body Water (TBW): roughly 60% of body weight; influenced by body fat and age.
    • Infants ~70% TBW; children ~65%; elderly ~55%.
    • Higher TBW in infants partly due to higher surface-area-to-mass and metabolic rate, making dehydration more rapid.
  • Intracellular Fluid (ICF): contains ~2/3 of TBW.
  • Extracellular Fluid (ECF): contains ~1/3 of TBW; subdivided into Interstitial Fluid and Plasma.
    • Interstitial Fluid: ~3/4 of ECF.
    • Plasma: ~1/4 of ECF.
    • Transcellular Fluids: cerebrospinal, lymph, synovial, peritoneal, pericardial, pleural, and ocular fluids.
  • Example: 70 kg adult
    • TBW ≈ 42 L (60% of body weight)
    • ICF ≈ 28 L (2/3 of TBW)
    • ECF ≈ 14 L (1/3 of TBW)
    • Interstitial Fluid ≈ 10.5 L (3/4 of ECF)
    • Plasma ≈ 3.5 L (1/4 of ECF)
    • Plasma volume accounts for about 8% of TBW
  • Infant example (3.5 kg):
    • TBW ≈ 2.45 L
    • ICF ≈ 1.63 L
    • ECF ≈ 0.82 L
    • Interstitial ≈ 0.615 L
    • Plasma ≈ 0.205 L

Fluid Dynamics Across Compartments

  • Plasma ↔ Interstitial Fluid: capillary exchange drives nutrient/waste/gas exchange; composition of plasma and interstitial fluid are nearly identical except for plasma proteins.
    • Fluid movement out of capillaries is driven by capillary hydrostatic pressure; proteins left behind generate colloid osmotic pressure that promotes reabsorption.
  • Interstitial ↔ Intracellular Fluid: water movement follows osmotic gradients; primary active transport (Na⁺/K⁺-ATPase) and secondary transport establish ionic concentrations; osmolarity between ICF and ECF tends to equilibrate under steady state.
  • Net principle: water moves to equalize osmotic pressures and osmolarities; disruptions alter compartments and volumes accordingly.

Application of Fluid Dynamics: Predicting Changes from Perturbations

  • General assumption: gains or losses affect the ECF first; then shifts occur between ECF and ICF to restore osmolar balance.
  • Scenario 1: Gain of “pure” water (1 L enters ECF)
    • ECF volume increases (e.g., 15 L → 16 L depending on baseline).
    • Osmolarity of ECF decreases (dilution).
    • Water shifts into the ICF to restore osmolar balance; ECF osmolarity rises as water leaves ECF.
    • TBW increases; plasma protein concentration decreases due to dilution of plasma water; hematocrit effect is nuanced: plasma dilution lowers hematocrit, cell volume increases could raise hematocrit; net effect often small in hematocrit.
  • Scenario 2: Loss of water (isotonic-like water loss; e.g., sweat or diabetes insipidus)
    • Water loss reduces both ECF and ICF volumes; osmolarity increases in both compartments similarly; no large change in osmolar balance if solute remains in compartments.
  • Scenario 3: Gain isotonic saline (1 L of saline into circulation)
    • Adds 300 mOsm of impermeant solute and 1 L of water to ECF.
    • Since osmolarity of ECF remains the same, no water movement between compartments due to osmotic gradients.
    • Plasma protein concentration and hematocrit decrease due to plasma dilution.
  • Scenario 4: Gain of NaCl (high salt intake with 1 L water)
    • ECF osmolarity increases (e.g., 344 mOsm/L), generating an osmotic gradient from ICF to ECF.
    • Solutes remain largely in their compartments (impermeant solutes); water shifts to equilibrate, increasing ECF volume and decreasing ICF volume.
    • After equilibration, total osmolarity may settle to a new level (e.g., 315 mOsm/L in this example).
    • Thirst centers are activated; additional water intake might be required (e.g., ~2.3 L of pure water) to return to 300 mOsm/L.
    • Plasma protein concentration and hematocrit decrease due to dilution and shifts in compartments.
  • Scenario 5: Adding pure water intravenously via D5W (isotonic glucose, dextrose 5% in water)
    • Initially expands the ECF; after glucose is metabolized, net effect is addition of pure water causing expansion of both ECF and ICF compartments.
    • Osmolarity decreases slightly due to added water; the process provides carbohydrates and energy.
    • Overall, both ECF and ICF volumes expand; a small reduction in osmolarity occurs due to added water.

Quick Reference: Key Formulas and Concepts

  • Osmolarity and osmoles
    • 1 mole of particles = 1 osmole.
    • 1 osmolal solution = 1 Osm/kg H2O.
  • Effective (non-permeant) vs. ineffective (permeant) osmoles
    • Effective osmoles contribute to osmotic gradient and tonicity because they do not diffuse away.
    • Ineffective osmoles diffuse across membranes and do not sustain a long-term osmotic force.
  • Estimating plasma osmolarity (quick rule of thumb)
    • A rough estimate: Osmolarityplasma≈2[Na+]+Glucose (mg/dL)18+BUN (mg/dL)2.8\text{Osmolarity}_{\text{plasma}} \approx 2[\mathrm{Na^+}] + \frac{\text{Glucose (mg/dL)}}{18} + \frac{\text{BUN (mg/dL)}}{2.8}
    • Note: exam questions may not require exact calculation of total plasma osmolarity, but this is a commonly used quick estimate.
  • Practical notes about NaCl and osmolarity
    • Na⁺ and Cl⁻ do not act independently; their effective osmolality is less than the sum of individual molarities due to interactions; for NaCl, the osmotic coefficient is about 0.93.
    • Example: 154 mM NaCl has an effective osmolarity of approximately 0.93×2×154≈286 mOsm/L.0.93 \times 2 \times 154 \approx 286\ \text{mOsm/L}.
  • Important points about tonicity
    • The tonicity of a solution is determined by impermeant solutes; permeant solutes may initially affect cell size but do not contribute to long-term tonicity once equilibrated.
    • Isotonicity is relative to the cell’s own osmolarity; a solution can be iso-osmotic yet not isotonic if it contains permeant solutes that equilibrate.
  • Typical body fluid proportions (summary)
    • TBW ≈ 60% of body weight (approximate; varies with age and fat content).
    • ICF ≈ 2/3 of TBW; ECF ≈ 1/3 of TBW.
    • ECF subdivisions: Interstitial Fluid ≈ 3/4 of ECF; Plasma ≈ 1/4 of ECF; Transcellular Fluids include CSF, lymph, synovial, etc.
  • Sample numerical breakdowns
    • 70 kg adult: TBW ≈ 42 L; ICF ≈ 28 L; ECF ≈ 14 L; Interstitial ≈ 10.5 L; Plasma ≈ 3.5 L.
    • 3.5 kg infant: TBW ≈ 2.45 L; ICF ≈ 1.63 L; ECF ≈ 0.82 L; Interstitial ≈ 0.615 L; Plasma ≈ 0.205 L.

Practical Takeaways

  • Water moves to equilibrate osmolarity across compartments; which direction water moves depends on relative osmolarities and membrane permeability to solutes.
  • The extracellular compartment (ECF) is the first to change in most perturbations; subsequent shifts between ECF and ICF restore osmotic balance.
  • Isotonic saline expands ECF but does not change osmolarity; pure water or hypotonic solutions tend to shift water into cells; hypertonic solutions draw water out of cells.
  • D5W is used clinically to expand both compartments after glucose metabolism; initial expansion is in ECF, followed by ICF expansion as water distributes and osmolarity shifts.
  • Keep in mind the relationship between TBW, compartments, osmolarity, and volume changes when predicting fluid balance in health and disease.