Introduction
The body is primarily composed of water and distributed into fluid compartments. These fluid compartments contain water and solutes.
Solutes are substances (e.g. sodium chloride (NaCl)) dissolved in a solvent (e.g. water) to form a solution.
Some of the most important solutes within the body’s fluid compartments are electrolytes (e.g. sodium ion (Na+), chloride ion (Cl–), potassium ion (K+), calcium ion (Ca2+), magnesium ion (Mg2+), phosphate ion (PO3–), and bicarbonate ion (HCO3–)). Other important solutes are nonelectroytes (e.g. proteins, glucose, and urea).
Not only are solutes essential for various bodily functions, but they also play an instrumental role in mediating fluid movement between fluid compartments.
Fluid movement within the body is carefully regulated, and fluid volume and composition in each fluid compartment equilibrate via various mechanisms in order to help achieve and maintain homeostasis. Homeostasis represents a state of steady internal, physical, and chemical conditions, including water and electrolyte balance within healthy ranges, that living systems strive to preserve.
Mechanisms used to help achieve and maintain homeostasis as it pertains to water and solute movement within the body include Starling’s law of the capillary, osmosis, passive transport (simple and facilitated diffusion), as well as active transport.
Water movement across the capillary membrane, and thus between the intravascular and interstitial fluid compartments, is governed by Starling’s law of the capillary and by osmosis. Note that the intravascular and interstitial fluid compartments are part of the extracellular fluid (ECF) compartment, which is fluid found outside of cells.
Water movement across the cell membrane, and thus between the interstitial and intracellular fluid (ICF) compartments (i.e. between the ECF and ICF compartments; between the fluid found outside of cells and the fluid found inside of cells) occurs via osmosis.
Solute movement between compartments occur through either passive or active transport mechanisms.
Starling’s Law of the Capillary
Starling’s law of the capillary describes the process of fluid filtration (or reabsorption) across a capillary membrane in order to help achieve and maintain homeostasis between the intravascular and extravascular fluid compartments.
The Starling Principle (from Starling’s hypothesis in 1896) has undergone some changes over time; from the addition of the Staverman’s osmotic reflection coefficient (in 1951), to the substitution of the subglycocalyx oncotic pressure for the interstitial oncotic pressure (in 2010).
The Starling Principle states that fluid movement between the intravascular and interstitial fluid compartments is governed by the hydrostatic and colloid osmotic (oncotic) pressure gradients between these two fluid compartments. Furthermore, the Revised Starling Principle acknowledges the critical role of the endothelial glycocalex (an endothelial surface layer that helps control vascular permeability) in modulating fluid movement.
The Revised Starling Principle includes the balance between these forces:
(i) the hydrostatic pressure gradient against the capillary membrane: this is the “push” pressure, or the force exerted by the fluid against the capillary wall; for example, driving fluid out of the intravascular fluid compartment and into the interstitial fluid compartment,
(ii) the colloid osmotic (oncotic) pressure gradient (osmotic pressure generated by high molecular weight substances such as proteins (e.g. albumin)) across the capillary membrane: this is the “pull” pressure, or the force created by the colloid concentration; for example, drawing fluid from the interstitial fluid compartment and into the intravascular fluid compartment,
(iii) the integrity of the endothelial glycocalyx,
(iv) the integrity of the endothelial membrane, and
(v) the composition and structure of the extracellular matrix.

Classical Starling Principle:
Jv = Kf [(Pc – Pi) – (πc – πi)]
Modified Starling Principle:
Jv = Kf [(Pc – Pi) – σ(πc – πi)]
Revised Starling Principle:
Jv = Kf [(Pc – Pi) – σ(πc – πg)]
Where Jv = transcapillary net fluid filtration (or reabsorption if negative: Jv is positive when flow is from the intravascular fluid compartment into the interstitial fluid compartment, Jv is negative when flow is from the interstitial fluid compartment into the intravascular fluid compartment), Kf = net permeability of capillary membrane or capillary filtration coefficient (some texts use “Kf” while others use “LpS”, where LpS = hydraulic permeability (Lp) x surface area (S)), Pc = capillary hydrostatic pressure, Pi = interstitial hydrostatic pressure, πc = capillary oncotic pressure, πi = interstitial oncotic pressure, πg = subglycocalyx oncotic pressure, σ = Staverman’s osmotic reflection coefficient.
Osmosis
Osmosis is the diffusion of a solvent (e.g. water) through a semipermeable membrane from a solution of lower solute (e.g. NaCl) concentration into a solution of higher solute concentration to equilibrate the solute concentration on both sides of the semipermeable membrane.
Solutes exert an osmotic effect in a solution. This effect is dependent on the number of solutes within a solution, as well as the solute’s ability to pass through a membrane that separates the two fluid compartments.
A semipermeable membrane is a membrane that allows certain substances to pass through it, but not others.
A permeable solute is a solute that freely passes through a semipermeable membrane, and is known to be an ineffective osmole. It does not generate an osmotic pressure gradient, and therefore does not contribute to the effective osmolarity, and does not cause water movement through the semipermeable membrane.
An impermeable solute is a solute that does not freely pass through a semipermeable membrane, and is known to be an effective osmole. It generates an effective osmotic pressure gradient, and therefore contributes to the effective osmolarity, and causes water movement through the semipermeable membrane.
Osmosis is driven by the effective osmotic pressure gradient, which is determined by the difference in impermeable solute concentration (which is almost entirely dependent on Na+) between two solutions on either side of a semipermeable membrane, dictating the direction and extent of solvent diffusion.
The effective osmolarity is also referred to as the tonicity. Therefore, another way to state the above, is that water movement dependents on the difference in tonicity between two solutions on either side of a semipermeable membrane. Water moves from an area of lower tonicity into an area of higher tonicity.
It is very important to note that osmolarity (ineffective + effective osmoles) and tonicity (effective osmoles) of a particular solution may not necessarily be equal.
Since salt is NaCl, the principle that “water follows salt” means that water moves to the area with a higher Na+ concentration.

Passive Transport
Some membranes are permeable to certain solutes.
Passive transport of a solute depends on its ability to pass through a semipermeable membrane, as well as the presence of a concentration gradient, allowing these solutes to diffuse from an area of higher solute concentration to an area of lower solute concentration, moving with their concentration gradient.
Simple diffusion is when small, non-polar molecules (e.g. oxygen and carbon dioxide) can easily pass through a membrane.
Facilitated diffusion is when larger, polar molecules (e.g. ions and glucose) cannot easily pass through a membrane. Instead, they utilize specific transmembrane protein channels within the membrane to move with their concentration gradient.
Since these solutes move with their concentration gradients (from an area of higher solute concentration to an area of lower solute concentration), passive transport does not require energy.
Active Transport
Other membranes tightly control which solutes get in and out. They do this by use of transport mechanisms (e.g. specialized pumps).
A prime example of this is the sodium-potassium pump (Na+-K+-ATPase), which uses active transport to move Na+ out of a cell and K+ into a cell, with both actions occurring against their respective concentration gradients.
Since these solutes move against their concentration gradients (from an area of lower solute concentration to an area of higher solute concentration), active transport requires energy in the form of ATP.
Stay tuned for “A Comprehensive Guide to Understanding IV Fluid Therapy, Part 4”.
References
- DiBartola, S. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice, Fourth Edition. Elsevier Saunders, 2012
- Ettinger S, Feldman E, Cote E. Textbook of Veterinary Internal Medicine, 8th Edition, Elsevier, 2017
- Pardo M, Spencer E, Odunayo A, et al. 2024 AAHA Fluid Therapy Guidelines for Dogs and Cats. J Am Anim Hosp Assoc 2024 Jul 1:60(4):131-163
- Davis H, Jensen T, Johnson A, et al. 2013 AAHA/AAFP Fluid Therapy Guidelines for Dogs and Cats. J Am Anim Hosp Assoc 2013 May-Jun;49(3):149-59
- Silva C, Pedro M. Intravenous fluid therapy: essential components and key considerations. Porto Biomedical Journal 10(4):e296, July/August 2025
- Levick J. Revision of the Starling principle: new views of tissue fluid balance. NIH. Accessed April 25, 2026.
- Michel C, Woodcock T. Advances in the Starling Principle and Microvascular Fluid Exchange; Consequences and Implications for Fluid Therapy. NIH. Accessed April 25, 2026.
- Michel C, Woodcock T, Curry F. Understanding and extending the Starling principle. Accessed April 28, 2026.
- Levick J, Michel C. Microvascular fluid exchange and the revised Starling principle. European Society of Cardiology. Accessed April 28, 2026.
- Dr. Danelia de Kock’s Veterinary School notes
Read Part 1 of our series: A Comprehensive Guide to Understanding IV Fluid Therapy in Dogs and Cats, Part 1: What is IV Fluid Therapy?
Read Part 2 of our series: A Comprehensive Guide to Understanding IV Fluid Therapy in Dogs and Cats, Part 2: What is the Distribution of Water and Solutes within the Body?


