Microvasculature comprises the microvessels – venules and capillaries of the microcirculation, with a maximum average diameter of 0.3 millimeters. As the vessels decrease in size, they increase their surface-area-to-volume ratio. This allows surface properties to play a significant role in the function of the vessel. Diffusion occurs through the walls of the vessels due to a concentration gradient, allowing the necessary exchange of ions, molecules, or blood cells. The permeability of a capillary wall is determined by the type of capillary and the surface of the endothelial cells. A continuous, tightly spaced endothelial cell lining only permits the diffusion of small molecules. Larger molecules and blood cells require adequate space between cells or holes in the lining. The high resistivity of a cellular membrane prevents the diffusion of ions without a membrane transport protein. The hydrophobicity of an endothelial cell surface determines whether water or lipophilic molecules will diffuse through the capillary lining. The blood brain barrier restricts diffusion to small hydrophobic molecules, making drug diffusion difficult to achieve. Blood flow is directly influenced by the thermodynamics of the body. Changes in temperature affect the viscosity and surface tension of the blood, altering the minimum blood flow rate. At high temperatures the minimum flow rate will decrease and the capillary will expand. This allows heat transfer through the increased surface area of the inner capillary lining and through increased blood flow. At low temperatures the minimum flow rate will increase and the capillary will constrict. This restricts blood flow and decreases the surface area of the capillary, reducing heat transfer. Fluid mechanics are primarily affected by pressure, temperature, heat transfer, and electrokinetics. An increase in pressure increases the flow rate given by the Starling equation. An increase in temperature increases the wettability of the surface, promoting fluid flow. Heat also decreases the viscosity of the lumen. Heat transfer is monitored by thermoreceptors which regulate the amount of capillary beds open for heat dissipation. The surface chemistry of the endothelial cell lining also dictates fluid flow. A charged surface will acquire a layer of stagnant diffuse ions that hinder the flow of ions in the lumen. This decreases the lumen velocity and promotes the exchange of molecules through the capillary lining.
Diffusion Diffusion is the movement of molecules due to a concentration gradient. The molecules move in a random walk pattern in order to achieve a uniform solution.
Surface diffusion of endothelial cells Capillary walls contain a monolayer of endothelial cells. There are two ways for molecules to diffuse through the endothelial monolayer: through gaps between the cells or directly through the cells. Molecules diffuse through the capillary walls due to concentration gradients. Diffusion between the cells changes depending upon the type of capillary. There are three different types of capillaries: continuous, fenestrated, and sinusoidal also called discontinuous. In continuous capillaries the endothelial cells are tightly spaced, allowing only small molecules like ions or water to diffuse through the intercellular clefts (the gaps between the endothelial cells). In fenestrated and sinusoidal capillaries there is more space between the cells, allowing the diffusion of macro-molecules and some proteins. Sinusoidal capillaries have large holes that permit the passage of red and white blood cells. The diffusion of gases and lipid-soluble molecules can occur directly through the endothelial cells, described by Fick's first law:
J = − D ∂ C ∂ x {\displaystyle J=-D{\frac {\partial C}{\partial x}}}
where
J is the flux D is the diffusivity C is the concentration x is the thickness of the barrier
The surface charge of endothelial cells at points of diffusivity can determine which type of molecule can diffuse through the capillary walls. If the surface is hydrophilic, it will allow water and charged molecules to pass through. If it is hydrophobic, non-charged and lipophilic molecules will be able to diffuse through. These intermolecular screening forces are also known as van der Waals forces, which is determined by the Keesom, Debye and London dispersion forces. The lipid bilayer of an endothelial cell membrane is a hydrophobic surface. The non-polar lipids lead to a very high electrical resistivity, given by
R e = R mem A {\displaystyle R_{\text{e}}={\frac {R_{\text{mem}}}{A}}}
where
Re is the resistivity of the membrane Rmem is the specific membrane resistance A is the area This high resistivity prevents ions from crossing the bilayer without an integral membrane protein using facilitated diffusion.
Drug delivery diffusion
Drugs diffuse through capillary walls in the same manner as endogenous molecules. One of the most important examples of this is drug diffusion across the blood brain barrier. The blood brain barrier consists of a bed of continuous capillaries. Typically only small hydrophobic molecules are able to diffuse across the blood brain barrier. This makes it very difficult to get drugs into the brain without invasively administering them directly into the brain. One possible solution is the utilization of nanoparticles. Nanoparticles are synthesized to encapsulate a target drug. The surface of the nanoparticle, if not already hydrophobic, may have polymers attached to the surface to adjust the current polarity. Ligands can also be attached to the surface of a nanoparticle to target certain receptors located within the brain. Once the nanoparticle is through the blood brain barrier it releases the drug into the brain. A specific example of this solution is the delivery of anti-HIV drugs to the central nervous system by TAT-conjugated nanoparticles.
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