Biomedical Engineering Reference
In-Depth Information
molecules that are transported within the microvascular networks such as proteins.
Examples of these types of molecules are oxygen and carbon dioxide.
Most molecules, however, are not lipid soluble and cannot diffuse readily through the
cell membrane. These molecules are typically soluble in water and can only pass through
the microvascular wall at the intercellular clefts or via active transport mechanisms within
the endothelial cell membrane. As discussed in the previous chapter, the intercellular cleft
accounts for less than 1/1000 of the total capillary surface area. This very small area how-
ever accounts for the vast majority of the movement of non-lipid soluble molecules, such
as ions, glucose, and water. The diffusion of molecules through the intercellular cleft is so
fast that it allows for the rapid approach to equilibrium across the capillary wall. In fact,
equilibrium is reached within half of the capillary length. The remaining portion of the
capillary is left as a safety reservoir. The diffusion of molecules through the intercellular
cleft occurs at a rate that is approximately 80 times greater than the blood flow through
the capillary.
The process of diffusion through the intercellular cleft is principally regulated by the
permeability of the pore to the specific molecule. As noted in Chapter 6, the pore diameter
is on the order of 7 nm. Water molecules, ions, glucose, and some other metabolically
important molecules all have a molecular radius that is smaller than the 7 nm pore size
and therefore can permeate through the pore easily. Plasma proteins typically have a
molecular size that is greater than 7 nm and therefore cannot diffuse through the pore. In
the early 1950s, studies were conducted to determine the average permeability of the inter-
cellular cleft to physiologically important molecules. From these studies, it was found that
most physiologically important molecules have a permeability that is in the range of
water. For instance, sodium chloride in solution has a permeability that is equal to 96% of
water's permeability through the intercellular cleft. Glucose, a molecule that is 10 times
the weight of water, has a permeability in the range of 60% of water's permeability
through the intercellular cleft. Albumin, which has a molecular weight that is approxi-
mately 4000 times larger than water, has a permeability of 0.1% of water's permeability
through the intercellular cleft. In most engineering applications, diffusion is principally
regulated by the concentration gradient across the membrane. While that is partially true
within capillaries, the permeability is much more easily controlled and is therefore the
principal regulator of diffusion within the microcirculation (e.g., not the concentration gra-
dient as with most standard engineering applications). For most physiologically important
molecules (i.e., glucose, salts, water) the permeability is so large that very small differences
in the concentration gradient cause very large changes in the rate of movement across the
capillary wall. Also, the energy that would be required to maintain a large concentration
gradient for each biologically important molecule would exceed the body's capacity.
An important application of vascular permeability is drug delivery mechanisms. In gen-
eral, there are two methods to deliver drugs to body: local delivery and systemic delivery.
Local delivery is of less interest to biofluid mechanics analysis because the drug is typi-
cally directly injected into the site of interest. However, for systemic delivery, the drug can
either be given orally, injected into a muscle, injected into the interstitial space, or injected
into a vein. For all of these routes, except for intravenous injection, the drug will enter
the vascular system via diffusion through microcirculation beds. For all injection methods,
the drug will typically bind to plasma proteins and be delivered to all of the organs in the
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