Distribution And Storage

Once a toxin enters the bloodstream, it is distributed rapidly throughout the body. However, organs do not all receive equal distributions, nor do they store them with equal efficiency. Moreover, the location where most of a toxin is stored is not necessarily the primary site of toxic effect. For example, 90% of the lead in adult humans is stored in the bones, but its effects are on the kidney, nervous system, and blood cell production.

Individual organs and tissues will then take toxins according to the blood flow through the organ (organ perfusion), their affinity for the toxin, and the presence of any transport barriers. Most capillaries have large pores between the cells that form their wall. In some tissues, however, there are few or no pores. The most notable case is the blood-brain barrier. This prevents passage of polar compounds of medium molar mass. Its behavior is similar to that of an intact plasma membrane in that it is permeable to nonpolar compounds. Thus, mercuric chloride, which is mainly in ionic form, does not penetrate, whereas methyl mercury does. Other tissues have barriers as well, including the peripheral nerves, the placenta, the eyes, and the testes.

The major sites of storage for toxins are (1) bound to plasma proteins, (2) the liver and kidneys, and (3) adipose tissue. Plasma proteins form complexes with many toxicants, serving to solubilize and transport them. The effect of protein binding depends on how the proteins compete with processes that detoxify or excrete them. If they give up the toxicants readily, they may help to transport them to the detoxification site. If, on the other hand, protein binding is relatively strong, it may sequester the toxins away from detoxification.

Toxins are often concentrated in the liver or kidneys, possibly due to their role in detoxifying and excreting them. They contain their own binding proteins. An example is metallothionein, which figures in cadmium storage and in the transfer of cadmium from the liver to the kidney. Toxins absorbed in the stomach and intestines must pass through the liver before reaching other parts of the body, thus giving that organ a chance to biotransform them. Toxins that have been inhaled or absorbed dermally may reach other tissues before the liver.

Adipose tissue (also called depot fat) is the tissue where energy is stored in lipid form. The cells in these tissues contain droplets of triglycerides occupying more than 90% of the cytoplasm. Naturally, they tend to concentrate hydrophobic toxins. Even nonhydrophobic compounds can be stored in lipids after being conjugated with fatty acids. Toxins can be stored in adipose tissue without causing harm there. However, lipid storage of toxins has resulted in acute toxicity in humans who had stored subacute doses in their fatty tissues, later liberating an acute dose to the blood by depleting their fats in a weight-loss program.

The bones also store some toxins, notably lead, radium, and fluoride.

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