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Structural Barriers to Distribution

Organs or tissues differ in the amount of a chemical that they receive or to which they are exposed.  This is primarily due to two factors, the volume of blood flowing through a specific tissue and the presence of special "barriers" to slow down toxicant entrance.  Organs that receive larger blood volumes can potentially accumulate more of a given toxicant.  Body regions that receive a large percentage of the total cardiac output include the liver (28%), kidneys (23%), heart muscle, and brain.  Bone and adipose tissues have relatively low blood flow, even though they serve as primary storage sites for many toxicants.  This is especially true for those that are fat soluble and those that readily associate (or complex) with minerals commonly found in bone.

Tissue affinity determines the degree of concentration of a toxicant.  In fact, some tissues have a higher affinity for specific chemicals and will accumulate a toxicant in great concentrations in spite of a rather low flow of blood.  For example, adipose tissue, which has a meager blood supply, concentrates lipid-soluble toxicants.  Once deposited in these storage tissues, toxicants may remain for long periods of time, due to their solubility in the tissue and the relatively low blood flow.

During distribution, the passage of toxicants from capillaries into various tissues or organs is not uniform.  Structural Barriers to Distribution exist that restrict entrance of toxicants into certain organs or tissues.  The primary barriers are those of the brain, placenta, and testes.

The blood-brain barrier protects the brain from most toxicants.  Specialized cells called astrocytes possess many small branches, which form a barrier between the capillary endothelium and the neurons of the brain.  Lipids in the astrocyte cell walls and very tight junctions between adjacent endothelial cells limit the passage of water-soluble molecules.  The blood-brain barrier is not totally impenetrable, but slows down the rate at which toxicants cross into brain tissue while allowing essential nutrients, including oxygen, to pass through.

The placental barrier protects the developing and sensitive fetus from most toxicants distributed in the maternal circulation.  This barrier consists of several cell layers between the maternal and fetal circulatory vessels in the placenta.  Lipids in the cell membranes limit the diffusion of water-soluble toxicants.  However, nutrients, gases, and wastes of the developing fetus can pass through the placental barrier.  As in the case of the blood-brain barrier, the placental barrier is not totally impenetrable but effectively slows down the diffusion of most toxicants from the mother into the fetus.

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