A Compartmental Model Predicts that Dietary Potassium Affects Lithium Dynamics in Rats
| Title: | A Compartmental Model Predicts that Dietary Potassium Affects Lithium Dynamics in Rats |
|---|---|
| Authors: | Everts, Helen B.; Jang, Hye-Kyung; Boston, DVM, Raymond C.; Canolty, Nancy L. |
| Publisher: | Journal of Nutrition |
| Date Published: | May 01, 1996 |
| Reference Number: | 26 |
Lithium is the treatment of choice for manic depression, but therapy often results in nephrogenic diabetes insipidus and lithium intoxication. To investigate the effects of dietary potassium on potential side effects of lithium therapy, a mathematical model was built using the modeling program SAAM (Simulation, Analysis, And Modeling). Experimental data modeled were from adult male Sprague-Dawley rats fed diets with or without lithium and one of three levels of potassium for 17 d. A five-compartment model of lithium dynamics was built that was consistent with data from rats fed lithium-containing diet adequate in potassium. This model was then compared with data from rats fed the other two lithium-containing diets. The model predicts that both the fractional transfer coefficient and rate of transport of lithium to the serum compartment from the kidney compartment are lower in rats fed the potassium-adequate diet than in those fed the potassium-deficient diet, and even lower in those fed the potassium-supplemented diet. In addition, fractional transfer coefficients into the serum compartment from the sampled and simulated tissue compartments changed differently with time depending on the amount of dietary potassium. The model also predicts that there would be less accumulation of lithium in the kidney, sampled tissue and simulated tissue compartments with supplemental dietary potassium. The model suggests that potassium supplementation, after a 7-d delay, protects against nephrogenic diabetes insipidus and the potentially toxic accumulation of lithium by decreasing the reabsorption of lithium from the kidneys and increasing lithium efflux from the tissues.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The kidney collecting ducts of rats fed lithium are less able to reabsorb water because lithium inhibits the vasopressin-stimulated adenylate cyclase process. Lithium gets into little tubes in the kidneys called tubules by using the same paths (or channels) that sodium does. In rats, lithium probably accumulates in the cells, leaving little room for K. Other tests have shown that K supplementation reduces chronic, excessive thirst and urination without reducing lithium's effectiveness. Everts, et al., tried to find out why.
They divided 32 adult male rats into three experimental groups and three control groups. One group was fed a K-deficient diet; one a K-adequate diet; one a K-supplemented diet. All rats fed lithium lost weight: the K-supplemented rats lost the least; the K-adequate rats lost the second least; the K-deficient rats lost the most. Rats fed lithium urinated more that control rats. K-adequate rats urinated the most; K-deficient and K-supplemented rats urinated about the same amounts. K-supplemented rats accumulated the least lithium. K-deficient and K-adequate rats accumulated about the same amount of lithium (though K-adequate rats consumed more lithium). K-supplemented rats excreted the most lithium, followed by K-adequate, followed by K-deficient.
Everts, et al., used the mathematical model to study the effects of dietary potassium on lithium turnover -- how it moves through rat tissue, blood serum, gut, kidney and urine. The model results suggested that supplemental dietary potassium resulted in less reabsorption of lithium from the kidneys. Evert, et al., hypothesized that with deficient or only adequate dietary K, lithium enters the cells of the kidneys collecting tubules and inhibits VP-stimulated water reabsorption. It is this inability to reabsorb water that results in excessive urination. Increased dietary K starts a process which degrades the sodium channels in kidney cell membranes, making them more selective for K. This may result in K transport through the sodium channel. That is, the lithium can no longer get through the sodium channels, but the K can. This results in less lithium reabsorption through these channels resulting in increased lithium excretion and increased water absorption because now that lithium is no longer there to inhibit it, the antidiuretic hormone, VP can do its job. In short, high K levels alter sodium channels, making it easier for K to use them. This decreases kidney reabsorption of lithium. All this results in less accumulation of lithium in the body which may explain how increased K decreases excessive urination associated with NDI. The model used by the authors provides a foundation for more research to refine and expand our understanding of K and lithium dynamics.