Passive Diffusion is a fundamental biophysical process describing the spontaneous movement of a substance, such as a hormone or drug molecule, across a semi-permeable biological membrane without the expenditure of cellular energy. This transport mechanism is driven entirely by the concentration gradient, meaning molecules move naturally from an area of higher concentration to an area of lower concentration. In endocrinology, this is the primary mechanism by which lipid-soluble, unconjugated steroid hormones, such as cortisol and testosterone, enter the salivary glands from the bloodstream to be measured in saliva.
Origin
The concept is rooted in the physical laws of thermodynamics and Fick’s Law of Diffusion, a mathematical model describing the rate of molecular transport. In pharmacology and physiology, it represents the simplest and most common route for the absorption and distribution of many therapeutic agents and endogenous molecules across cellular barriers. This mechanism’s efficiency is highly dependent on the physicochemical properties of the molecule.
Mechanism
The mechanism relies on the molecule’s ability to dissolve within the lipid bilayer of the cell membrane, which favors compounds that are small, non-ionized, and highly lipophilic, or fat-soluble. The concentration difference between the plasma and the intracellular space provides the necessary driving force. As the free, unbound hormone concentration in the plasma is higher than that in the saliva, the hormone molecules passively diffuse through the salivary acinar cells until equilibrium is approached, thus ensuring that salivary concentration accurately reflects the bioavailable fraction in the blood.
Exogenous hormones influence salivary tests by altering the bioavailable hormone levels that diffuse into saliva, a process highly dependent on the administration route.
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