Physiological Principles of Liquid Compartments

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Body Water Distribution Kinetics

Water is distributed in two large biological compartments defined by semipermeable barriers:

• Intracellular Fluid (LIC): It constitutes two thirds (2/3) of the ACT. Its composition is dominated by the potassium cation (K⁺) and organic anions such as proteins and phosphates.
• Extracellular Fluid (ECF): It comprises the remaining third (1/3) of the ACT and is subdivided into two subcompartments by the vascular endothelium:
  • Interstitial Space (LIS): Represents 75% of the LEC.
  • Intravascular or Plasma Space (LIV): It constitutes 25% of the remaining ECF. Its main ionic composition is dominated by sodium (Na⁺) and chlorine (Cl^-).

The differential permeability to solutes and the metabolic activity of the Na⁺/K⁺-ATPase pump determine that the effective osmolarity is identical in the transmembrane equilibrium state, with a normal plasma osmolarity calculated according to the equation:

Osm_effective = 2 · [Na⁺] + ([Glucose])/(18)

Gibbs-Donnan Equilibrium and Starling Forces

Gibbs-Donnan equilibrium describes the behavior of charged ions in solution near a semipermeable membrane that is impermeable to a negatively charged macromolecule (plasma proteins such as albumin). As a consequence, intravascular plasma contains a slightly higher concentration of positively charged cations and a lower concentration of negatively charged diffusible anions than interstitial fluid.

The net flow of water through the capillary endothelium is historically governed by Starling's law, which assumes a dynamic balance between hydrostatic and oncotic pressures. However, contemporary physiology has reformulated this model by incorporating the central role of the microstructure of the endothelial glycocalyx.

The Starling Equation Modified by the Glycocalyx

The classical equation has been replaced by the modified Starling model, which recognizes that the interstitial oncotic pressure (π_i) does not exert a direct force of attraction from the deep interstitium, but rather the gradient is generated between the plasma and the subglycocalyx space:

J_v = K_f · [ (P_c - P_i) - σ · (π_c - π_sg) ]

Where:

• J_v is the net filtration flux across the capillary membrane.
• K_f is the capillary filtration coefficient (hydraulic conductivity and surface area).
• P_c and P_i are the capillary and interstitial hydrostatic pressures, respectively.
• σ is the Staverman reflection coefficient (ability of the glycocalyx to restrict the passage of macromolecules; σ = 1 represents absolute impermeability).
• π_c is the oncotic pressure of the plasma and π_sg is the oncotic pressure in the subglycocalyx area, which is almost zero under conditions of normal physiological capillary flow.

This new physiological understanding has transcendental therapeutic implications: massive volume infusion destroys the delicate endothelial glycocalyx through shear and hypervolemia, which reduces the reflection coefficient σ to values close to zero. Under these circumstances, any minor elevation of intravascular hydrostatic pressure results in a massive leak of water and proteins into the interstitial space, perpetuating tissue edema without improving actual perfusion.