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<html>
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<head><title>Water: swelling, tension, pain, fatigue, aging</title></head>
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<body>
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<h1>
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Water: swelling, tension, pain, fatigue, aging
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</h1>
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<p>
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I have spoken to many people who believe they should drink "8 glasses of water every day," in addition to
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their normal foods, even if they don't feel thirsty. Many doctors still recite this dangerous slogan, but
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the addition of the qualifying phrase, "or other liquids," has become common.
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</p>
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<p>
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The amount of water a person needs is extremely variable, depending on things such as metabolic rate,
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activity, and the temperature and humidity of the air. Working hard in hot, dry weather, it's possible to
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drink more than two quarts per hour for more than eight hours, without forming any urine, because all of the
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water is lost by evaporation. But in very hot, humid weather, a person with a low metabolic rate can be
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endangered by the smallest amount of water (e.g., "Meteorological relations of eclampsia in Lagos, Nigeria,"
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Agobe, et al., 1981).
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</p>
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<p>
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Most foods contain a considerable amount of water, usually more than 70% of their weight, and some water is
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produced in cells by metabolism. The function of water in the organism has been mystified and neglected
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because of some deeply rooted cultural images of the nature of organisms and their cellular make-up.
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</p>
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<p>
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One silly image that has been perpetuated by schools and textbooks is that biochemistry consists of chemical
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reactions that occur in substances dissolved in water, and that the water is retained by cells because they
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are enclosed by an oily membrane, and because of the osmotic forces produced by the dissolved substances.
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Most grade school kids have seen an osmometer made from an egg, in which the egg causes a column of water to
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rise, and have heard the explanation that this has something to do with the way cells work. Membrane pumps
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are invoked to explain the differences in solute concentrations and "osmotic pressure" inside and outside
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cells. The story is that invisible things on the surface of a cell (in its "membrane") force dissolved
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molecules to move in ways that they wouldn't move spontaneously by diffusion, and that water passively
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follows the "actively transported" solutes. But the evidence shows that both water and its solutes are
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regulated by the bulk phase of the cell, not its surface.
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</p>
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<p>
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In some cultural settings, animism has a kind of charm (water sprites, and such), but in the culture of
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medicine and biology, the animistic conceptualization of cells and their mechanisms has been very
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destructive, because it gets in the way of coherent understanding of physiology. Practically every disease
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would be approached differently if the physiology of water and ions were allowed to advance beyond the
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animistic doctrines of mainstream medicine, such as the "membrane pumps." If all the substances that are
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said to be "actively transported" by pumps into, or out of, cells are considered, the amount of energy
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required to operate the pumps is at least 15 times larger than the total energy available to cells.
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"Specific" pumps are commonly invoked even for novel synthetic chemicals, to explain their unequal
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distribution, inside and outside cells. In many biological situations water is ignored, but when it becomes
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an issue, its distribution is usually mechanistically subordinated to the solutes that are actively
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"pumped."
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</p>
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<p>
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Cells aren't osmometers, in the sense the textbooks say. They do control their water content, but no
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"membrane pumps" are needed. It's more accurate to think of the water of cells as being "dissolved in
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cells," somewhat the way water is contained in jello or boiled eggs. The cell controls its hydration by the
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processes that control its structure, its metabolism, and movements, because water is part of its deepest
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structures and essential functions. The cell's adjustments to changes of hydration and volume appear to be
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regulated by contractile proteins and energy metabolism (Minkoff and Damadian, 1976).
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</p>
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<p>
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Any stress or energy deficit that disturbs cellular structure or function disturbs the interactions among
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water, proteins, and other components of the cell. Excitation causes a cell to take up extra water, not by
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osmosis resulting from an increase in the concentration of solutes in the cell, or because the membrane has
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become porous, but because the structural proteins of the cell have momentarily increased their affinity for
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water.
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</p>
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<p>
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This increased affinity is similar to the process that causes a gel to swell in the presence of alkalinity,
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and it is related to the process called electroosmosis, in which water moves toward a higher negative
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charge. Intense excitation or stress increases the cell's electrically negative charges, and causes it to
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become more alkaline and to swell. Swelling and alkalinity cause the cell to begin the synthesis of DNA, in
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preparation for cell division. Mitogens and carcinogens, including estrogen, cause cells to become alkaline
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and to swell, and substances that block the cell's alkalinization (such as the diuretics acetazolamide and
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amiloride) inhibit cell division. Prolonged alkaline stress alone can cause malignant transformation of
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kidney cells (Oberleithner, et al., 1991).
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</p>
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<p>
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The general idea of "stress" is useful, because it includes processes such as fatigue, osmotic pressure
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changes, disturbed pH, and the enzyme changes that follow, producing substances such as lactic acid, nitric
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oxide, polyamines, estrogen, serotonin, and many more specific mediators. But paying attention to the
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physical factors involved in a stress reaction is important, if we are to see the organism integrally,
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rather than as a collection of "specific biological mechanisms," involving things like the pixie-powered
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"membrane pumps."
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</p>
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<p>
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When a cell shrinks under hyperosmolar conditions, its metabolism becomes catabolic, breaking down proteins
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and glycogen, and sometimes producing lactic acid, which results in an alkaline shift, increasing the cell's
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affinity for water, and causing it to return to normal size. A slight degree of hyperosmolarity increases
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the cell's metabolic rate.
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</p>
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<p>
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Swelling in hypo-osmolar conditions, i.e,, with an excess of water, is anabolic, leading to cellular
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proliferation, and inhibiting the breakdown of protein and glycogen.
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</p>
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<p>
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Respiring cells are always producing some water, by transferring hydrogen from fuel molecules to oxygen.
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Respiration also produces carbon dioxide, which in itself is a Lewis acid (meaning that it binds electrons,
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rather than releasing protons), that associates with cellular proteins, acidifying them in the process. A
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large amount of carbon dioxide can exist inside cells in the bound form. Acidified cytoplasm (like any other
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mostly acidic polymer-gel) releases water and sodium. (This process is physically analogous to the process
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of flushing a water softener with salt, or a demineralizer with acid, to reactivate it.)
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</p>
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<p>
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Besides binding with the cytoplasm, the carbon dioxide can be changed into carbonic acid, by chemically
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combining with water. Carbonic acid is hydrophilic, and so it quickly leaves the cell, taking with it some
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of the oppositely charged ions, such as calcium and sodium. The formation of carbonic acid, which is
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constantly streaming out of the respiring cell, causes some water and some positively ionized metals to
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leave the cell, in an "active" process, that doesn't require any mysterious pumps.
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</p>
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<p>
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As the blood passes through the lungs, carbon dioxide leaves the system, and as carbonic acid is converted
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to carbon dioxide, water is left behind in the blood, along with the counterions (of alkaline metals or
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earths), accounting for slight differences in pH and osmolarity between the bloodstream and the tissue
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cells. Some experiments suggest that the normal osmolarity of various tissues is 2 or 3 times higher than
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that of the blood, which is called "isosmolar" or isotonic.
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</p>
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<p>
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The kidneys adjust the osmolarity of the blood by allowing water and solutes to leave the bloodstream, in
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proportions that usually keep the body fluids in balance with cells. The kidneys are able to compensate for
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many of the imbalances produced by stress and inappropriate diets, for example by forming ammonia and carbon
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dioxide, to compensate for imbalances in the alkalis and acids that are being delivered to the blood by
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other organs. Because of the kidneys' great ability to regulate the flow of solutes between the blood and
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the forming urine, the "membrane pumps" have great importance for medical nephrologists. But the more
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extreme the "active transport" is, the more obvious it becomes that processes other than "membrane pumps"
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are responsible.
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</p>
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<p>
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Some lizards and sea birds have glands near their noses that are called salt glands, because of their
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ability to secrete salt. The salt gland is probably the most extreme case of active transport, but its
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physiology is very similar to the physiology of any other secretory gland or membrane, such as tear glands
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and sweat glands. The mechanism of salt excretion in these glands should really settle the issue of how
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active transport works, but most nephrologists, oculists, and medical researchers in general aren't
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interested in salt glands.
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</p>
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<p>
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Carbon dioxide is the driving force in the salt gland. The constant formation of CO2, and its loss into the
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air, allows a high concentration of salt to be excreted. Blocking the interchange of CO2 and carbonic acid,
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with acetazolamide, or inhibiting the formation of CO2, prevents the excretion of salt.
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</p>
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<p>
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Since respiratory metabolism, governed by the thyroid hormone, is our main source of carbon dioxide, it's
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obvious that thyroid deficiency should impair our ability to regulate water and solutes, such as salt. An
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organism that illustrates this function of thyroid is the young salmon, when it leaves a freshwater river to
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begin its life in the ocean. As it converts its physiology to tolerate the salty environment, its thyroid
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hormone surges. When it's mature, and returns to the fresh water to spawn, its prolactin rises sharply. In
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experiments with rodents, it has been found that drinking a large amount of water increases their prolactin,
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but the same amount of water, with added salt, doesn't.
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</p>
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<p>
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Hypothyroidism is typically associated with increased prolactin secretion. Hypothyroid people typically
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retain water, while losing salt, so the hypothyroid state is analogous to the salmon that has returned to
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the river, and to the mice that drink too much salt-free water.
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</p>
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<p>
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The typical hypothyroid person loses salt rapidly in the urine (and probably in the sweat, too, though that
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is usually diagnosed as cystic fibrosis), and retains water, diluting the urine less than normal. The
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reduced production of carbon dioxide, with increased susceptibility to producing lactate and ammonium,
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causes the cells to be more alkaline than normal, increasing their affinity for water. The rise of estrogen
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that usually accompanies hypothyroidism also increases intracellular pH, loss of sodium, and over-hydration
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of the blood.
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</p>
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<p>
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Hypothyroid muscles typically retain excess water, and fatigue easily, taking up more water than normal
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during exertion. In childhood, mild hypothyroidism often causes the leg muscles to swell and ache in the
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evenings, with what have been called "growing pains." When the problem is more extreme, all the skeletal
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muscles can become very large (Hoffman syndrome), because of the anabolic effect of over-hydration.
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Enlargement of any muscle can result from the excessive hydration produced by thyroid deficiency, but when
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it happens to the muscles behind the eyes (Itabashi, et al., 1988), it often leads to a diagnosis of
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hyperthyroidism, rather than hypothyroidism.
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</p>
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<p>
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The little kids with the Hoffman syndrome don't have the bloated myxedematous appearance that's often
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associated with hypothyroidism. They look athletic to a ridiculous degree, like miniature body-builders. But
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after a few weeks of treatment with thyroid, they regain the slender appearance that's normal for their age.
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The swollen state actually supports enlargement of the muscle, and the cellular processes are probably
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closely related to the muscle swelling and growth produced by exercise. The growth of the muscle cell during
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swelling seems to be the result of normal repair processes, in a context of reduced turnover of cellular
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proteins.
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</p>
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<p>
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The people who believe in membrane pumps that maintain normal solute distributions by active transport know
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that the pumps would require energy (far more than the cell can produce, but they don't confront that
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issue), and so their view requires that they assign a great part of the cell's resources just to maintaining
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ionic homeostasis, and the result of that is that they tend to neglect the actual energy economy of the
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cell, which is primarily devoted to the adaptive renewal of the cell structure and enzyme systems, not to
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driving the systems that don't exist.
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</p>
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<p>
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The "anabolic" balance of the swollen cell is the result of decreased turnover of the cell's components. The
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higher rate of metabolism produced by adequate thyroid function maintains a high rate of renewal of the
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cell's systems, keeping the cell constantly adjusted to slight changes in the organism's needs. The evidence
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of a high rate of bone turnover is sometimes taken as evidence that thyroid can cause osteoporosis.
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</p>
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<p>
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Later, in a more mature person, chronically fatigued and painful muscles that at one time would have been
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diagnosed as rheumatism, may be diagnosed as fibromyalgia. Most doctors are reluctant to prescribe thyroid
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supplements for the problem, but the association of elevated prolactin with the muscle disorder is now
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generally recognized.
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</p>
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<p>
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The hypo-osmolar blood of hypothyroidism, increasing the excitability of vascular endothelium and smooth
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muscle, is probably a mechanism contributing to the high blood pressure of hypothyroidism. The swelling
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produced in vascular endothelium by hypo-osmotic plasma causes these cells to take up fats, contributing to
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the development of atherosclerosis. The generalized leakiness affects all cells (see "Leakiness"
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newsletter), and can contribute to reduced blood volume, and problems such as orthostatic hypotension. The
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swollen endothelium is stickier, and this is suspected to support the metastasis of cancer cells.
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Inflammation-related proteins, including CRP, are increased by the hypothyroid hyperhydration. The heart
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muscle itself can swell, leading to congestive heart failure.
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</p>
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<p>
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Some of the nerve problems associated with hypothyroidism (e.g., carpal tunnel syndrome and "foot drop") are
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blamed on compression of the nerves, from swelling of surrounding tissues, but the evidence is clear that
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hypothyroidism causes swelling in the nerve cells themselves. For example, in hypothyroidism, nerves are
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slow to respond to stimulation, and their conduction of the impulse is slow. These changes are the same as
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those produced by hyper-hydration caused by other means. Hypothyroid nerves are easily fatigued, and
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fatigued nerves take up a large amount of water. Swelling of the spinal cord is probably responsible for the
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"spinal stenosis" commonly seen in domestic animals and people; the mobility of intracellular water
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molecules is distinctly increased in patients with compression of the spinal cord (Tsuchiya, et al., 2003;
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Ries, et al., 2001).
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</p>
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<p>
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The hyperhydration of hypothyroidism has been known to cause swelling and softening of cartilage, with
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deformation of joints, but somehow it has never dawned on surgeons that this process would lead to
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deformation of intervertebral disks.
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</p>
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<p>
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It has been known for a long time that hyperhydration can produce seizures<strong>;</strong>
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at one time, neurologists would test for epilepsy by having the patient drink a pint of water. Although
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there are many reasons to think that the hyperhydration produced by hypothyroidism is a factor in epilepsy,
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physicians have been very reluctant to consider the possibility, because they generally think of thyroid
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hormone as a stimulant, and believe that "stimulants" are necessarily inappropriate for people with
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epilepsy.
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</p>
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<p>
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While it's true that the thyroid hormone increases sensitivity to adrenaline, its most noticeable effect is
|
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in improving the ability to relax, including the ability to sleep soundly and restfully. And it happens that
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increasing norepinephrine (the brain's locally produced form of adrenaline) helps to prevent seizures
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(Giorgi, et al., 2004).
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</p>
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<p>
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Cell swelling increases the sensitivity of nerves, and hyperosmotic shrinkage lowers their sensitivity.
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Increasing carbon dioxide helps to reduce the hydration of tissue (for example, the hydration and thickness
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of the cornea are decreased when carbon dioxide is increased), and increasing carbon dioxide is known to
|
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inhibit epileptic seizures. Another diagnostic trick of neurologists was to have the patient hyperventilate;
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it would often bring on a seizure. The diuretic acetazolamide, which increases the body's carbon dioxide and
|
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reduces water retention, is very effective for preventing seizures.
|
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</p>
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<p>
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The sleep-inducing effect of salty food is probably related to the anti-excitatory effects of
|
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hyperosmolarity, of adequate thyroid function, and of carbon dioxide.
|
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</p>
|
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<p>
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Degenerative diseases, especially cancer, heart disease, and brain diseases, are less prevalent in
|
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populations that live at a high altitude. When oxygen pressure is low, the lungs lose carbon dioxide more
|
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slowly, and so the amount of carbon dioxide retained in the body is greater. If the basic problem in
|
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hypothyroidism is the deficient production of carbon dioxide causing excessive loss of salt and retention of
|
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water, resulting in hypo-osmotic body fluids, then we would expect people at high altitude to have better
|
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retention of salt, more loss of water, and more hypertonic body fluids. That has been observed in many
|
||||
studies. The increased rate of metabolism at altitude would be consistent with the relatively active
|
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"catabolism" of the slightly hyperosmotic condition.
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</p>
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<p>
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After the drug companies began, in the late 1950s, marketing some newly discovered (thiazide) diuretics,
|
||||
which cause sodium to be lost in the urine, their advertising campaigns created a cultish belief that salt
|
||||
caused hypertension. They convinced a whole generation of physicians that pregnant women should limit salt
|
||||
in their diet, take a diuretic preventively, and restrict calories to prevent "excessive" weight gain.
|
||||
Millions of women and their babies were harmed by that cult.
|
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</p>
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<p>
|
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Pre-eclampsia and pregnancy toxemia have been corrected (Shanklin and Hodin, 1979) by both increased dietary
|
||||
protein and increased salt, which improve circulation, lower blood pressure, and prevent seizures, while
|
||||
reducing vascular leakiness. The effectiveness of increased salt in pre-eclampsia led me to suggest it for
|
||||
women with premenstrual edema, because both conditions typically involve high estrogen, hyponatremia, and a
|
||||
tendency toward hypo-osmolarity. Estrogen itself causes sodium loss, reduced osmolarity, and increased
|
||||
capillary leakiness. Combined with a high protein diet, eating a little extra salt usually helps to correct
|
||||
a variety of problems involving edema, poor circulation, and high blood pressure.
|
||||
</p>
|
||||
<p>
|
||||
The danger of salt restriction in pregnancy has hardly been recognized by most physicians, and its danger in
|
||||
analogous physiological situations is much farther from their consideration.
|
||||
</p>
|
||||
<p>
|
||||
One of the things that happen when there isn't enough sodium in the diet is that more aldosterone is
|
||||
synthesized. Aldosterone causes less sodium to be lost in the urine and sweat, but it achieves that at the
|
||||
expense of the increased loss of potassium, magnesium, and probably calcium. The loss of potassium leads to
|
||||
vasoconstriction, which contributes to heart and kidney failure and high blood pressure. The loss of
|
||||
magnesium contributes to vasoconstriction, inflammation, and bone loss. Magnesium deficiency is extremely
|
||||
common, but a little extra salt in the diet makes it easier to retain the magnesium in our foods.
|
||||
</p>
|
||||
<p>
|
||||
Darkness and hypothyroidism both reduce the activity of cytochrome oxidase, making cells more susceptible to
|
||||
stress. A promoter of excitotoxicity, ouabain, or a lack of salt, can function as the equivalent of
|
||||
darkness, in resetting the biological rhythms (Zatz, 1989, 1991).
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Bone loss occurs almost entirely during the night, and the nocturnal rise in cortisol and prolactin has
|
||||
strongly catabolic effects, but many other pro-inflammatory substances also rise during the night, and are
|
||||
probably the basic cause of the increased catabolism. Increased salt in the diet appears to improve some
|
||||
aspects of calcium metabolism, such as reducing parathyroid hormone and increasing ionized calcium, when the
|
||||
diet is deficient in calcium (Tordoff, 1997).
|
||||
</p>
|
||||
<p>
|
||||
The kidneys can produce large amounts of carbon dioxide and ammonia, in the process of preventing the loss
|
||||
of electrolytes, while allowing acid to be lost in the urine. The ammonia is produced by the breakdown of
|
||||
protein. During stress or fasting, the loss of tissue protein can be minimized by supplementing the
|
||||
minerals, potassium, sodium, magnesium, and calcium. Salt restriction can cause aldosterone to increase, and
|
||||
excess aldosterone causes potassium loss, and increases the use of protein to form ammonia (Norby, et al.,
|
||||
1976; Snart and Taylor, 1978; Welbourne and Francoeur, 1977).
|
||||
</p>
|
||||
<p>
|
||||
Aldosterone secretion increases during the night, and its rise is greater in depressed and stressed people.
|
||||
It inhibits energy metabolism, increases insulin resistance, and increases the formation of proinflammatory
|
||||
substances in fat cells (Kraus, et al., 2005). During aging, salt restriction can produce an exaggerated
|
||||
nocturnal rise in aldosterone.
|
||||
</p>
|
||||
<p>
|
||||
During the night, there are many changes that suggest that the thyroid functions are being blocked, for
|
||||
example a surge in the thyroid stimulating hormone, with T4 and T3 being lowest between 11 PM and 3 AM
|
||||
(Lucke, et al., 1977), while temperature and energy production are at their lowest. This suggests that the
|
||||
problems of hypothyroidism will be most noticeable during the night.
|
||||
</p>
|
||||
<p>
|
||||
Rheumatoid arthritis and asthma are two inflammatory conditions that are notoriously worse during the night.
|
||||
Melatonin has been reported to be higher in patients with severe asthma and rheumatoid arthritis, and to
|
||||
promote the secretion of a variety of other pro-inflammatory substances. The peak of melatonin secretion is
|
||||
followed by the peak of aldosterone, and a little later by the peak of cortisol.
|
||||
</p>
|
||||
<p>
|
||||
The use of bright light (which suppresses melatonin) to treat depression probably helps to inhibit the
|
||||
production of aldosterone, which is strongly associated with depression.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Both aldosterone and melatonin can contribute to the contraction of smooth muscle in blood vessels.
|
||||
Constriction of blood vessels in the kidneys helps to conserve water, which is adaptive if blood volume has
|
||||
been reduced because of a sodium deficiency. When blood vessels are inappropriately constricted, the blood
|
||||
pressure rises, while organs don't receive as much blood circulation as they need. This impaired circulation
|
||||
seems to be what causes the kidney damage associated with high blood pressure, which can eventually lead to
|
||||
heart failure and multiple organ failure.
|
||||
</p>
|
||||
<p>
|
||||
Progesterone, which helps to maintain blood volume (partly by preventing vascular leakiness, preventing
|
||||
excessive sodium loss and by supporting albumin synthesis) antagonizes aldosterone. Aldosterone antagonists
|
||||
are now being recognized as effective treatments for hypertension, water retention, congestive heart
|
||||
failure, arrhythmia, diabetes, kidney disease, and a great variety of inflammatory problems. (Synthetic
|
||||
drugs to antagonize aldosterone are most effective when they are most like natural progesterone.) Since
|
||||
aldosterone contributes to fibrosis of the heart and kidneys (nephrosclerosis), progesterone, the
|
||||
"antifibromatogenic steroid," should be helpful for those problems that have been considered irreversible.
|
||||
Aldosterone appears to contribute to the hyperglycemia of diabetes itself, and not just to its
|
||||
complications, by interfering with the interactions of insulin and cortisol (Yamashita, et al., 2004).
|
||||
</p>
|
||||
<p>
|
||||
One of progesterone's fundamental actions is to cause estrogen "receptors" to disintegrate; hypertonicity
|
||||
has this effect in some situations. Estrogen's effects are largely produced by increased tissue hydration.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Aldosterone causes cells to take up sodium, while increasing their pH, i.e., raising their alkalinity
|
||||
(Mihailidou and Funder, 2005). Intracellular sodium has long been known to be a factor, along with swelling
|
||||
and alkalinity, in stimulating cell division (Cone and Tongier, 1971). A lack of salt stimulates the
|
||||
formation of serotonin, which in turn stimulates aldosterone synthesis--that is, a sodium restricted diet
|
||||
activates processes that cause cells to take up sodium inappropriately, in a situation reminiscent of the
|
||||
calcium deficient diet causing inappropriate calcification.
|
||||
</p>
|
||||
<p>
|
||||
Aldosterone, like stress or hypo-osmolarity, activates the enzyme (ODC) which produces the polyamines, that
|
||||
promote cell division, and that can probably account for some of the harmful effects of excessive
|
||||
aldosterone.
|
||||
</p>
|
||||
<p>
|
||||
Eating salty food around bedtime usually has a sleep-inducing effect, and it helps to maintain blood volume
|
||||
(which tends to decrease during the night), and to restrain the nocturnal rise of aldosterone, and other
|
||||
indicators of stress or inflammation. Eating gelatin, which lacks tryptophan, will reduce the formation of
|
||||
serotonin, and is likely to limit the formation of aldosterone.
|
||||
</p>
|
||||
<p>
|
||||
Pregnenolone can sometimes very quickly allow swollen tissues to release their water. This function is
|
||||
probably closely related to its antifibromatogenic function, since swelling and leaking set the stage for
|
||||
fibrosis.
|
||||
</p>
|
||||
<p>
|
||||
Hyperosmotic sodium chloride solutions (e.g., 7.5%) are being used more often for treating trauma and shock,
|
||||
because the concentrated solution increases blood volume by removing water from the extravascular spaces,
|
||||
unlike the "isotonic" saline (0.9% sodium chloride), which usually adds to the edema by leaking out of the
|
||||
blood vessels.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
A 5% sodium chloride solution is effective for promoting healing of damaged corneas, and solutions of 5% to
|
||||
10% sodium chloride are effective for accelerating the healing of wounds and ulcers. Other hypertonic
|
||||
solutions, for example glucose or urea, have been used therapeutically, but sodium chloride seems to be the
|
||||
most effective in a variety of situations.
|
||||
</p>
|
||||
<p>
|
||||
Thyroid hormone, by maintaining oxidative metabolism with the production of carbon dioxide, is highly
|
||||
protective against excessive water retention and loss of sodium and magnesium.
|
||||
</p>
|
||||
<p>
|
||||
Sometimes doctors recommend that constipated people should drink extra water, "to soften the stool." The
|
||||
colon is where water is removed from the intestinal contents, and when it is inflamed, it removes too much
|
||||
water. Several decades ago, it was recognized (Orr, et al., 1931) that hypertonic saline, given
|
||||
intravenously, would stimulate intestinal peristalsis, and could be used to treat paralytic ileus and
|
||||
intestinal obstruction.
|
||||
</p>
|
||||
<p>
|
||||
When water is taken orally, it is absorbed high in the intestine, long before it reaches the colon, so the
|
||||
recommendation to drink water for constipation can produce a situation that's the opposite of intravenous
|
||||
hypertonic saline, by diluting the blood. Using a hypertonic salt solution as an enema can have the same
|
||||
beneficial effect on the intestine as the intravenous treatment.
|
||||
</p>
|
||||
<p>
|
||||
Constipation physiology is probably analogous to the physiology of congestive heart failure, in which
|
||||
muscles are weakened and fatigued by swelling.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
In recent decades, the prevalence of congestive heart failure has increased tremendously, so that it is now
|
||||
often called an epidemic. Hyponatremia (too little salt, or too much water) is a recognized "risk factor"
|
||||
for congestive heart failure. In the failing heart, the muscle cells are swollen, causing the heart wall to
|
||||
stiffen, weakening its ability to pump. Osmotically shrinking the cells can restore their function.
|
||||
</p>
|
||||
<p>
|
||||
The swollen heart, like any muscle, loses the ability to quickly and completely relax, and so it doesn't
|
||||
fill adequately between contractions. Elastic tissues, such as arteries and lungs, stiffen when they are
|
||||
over-hydrated, losing their normal functions. In small blood vessels, swelling narrows the channel,
|
||||
increasing resistance to the flow of blood.
|
||||
</p>
|
||||
<p>
|
||||
When people force themselves to drink a certain amount of water every day, even when they don't feel
|
||||
thirsty, they are activating complex adaptive processes unnecessarily. Thirst is the best guide to the
|
||||
amount of fluid needed.
|
||||
</p>
|
||||
<p>
|
||||
When extra water consumption is combined with a low salt diet--as physicians have so often recommended--a
|
||||
healthy person can adapt easily, but for a hypothyroid person it can have disastrous effects.
|
||||
</p>
|
||||
<p><h3>REFERENCES</h3></p>
|
||||
<p>
|
||||
Br J Obstet Gynaecol. 1981 Jul;88(7):706-10. <strong>Meteorological relations of eclampsia in Lagos,
|
||||
Nigeria.</strong> Agobe JT, Good W, Hancock KW. A retrospective study of the meteorological relations of
|
||||
eclampsia in Lagos, Nigeria supports other observations that the incidence of this disease varies
|
||||
significantly with the weather<strong>. Protective action by arid conditions is consistent with the known
|
||||
effect of dehydration on convulsions of differing aetiologies and is attributable to increased pulmonary
|
||||
transpirational water loss. Exacerbation of eclampsia by cool, humid conditions</strong> may therefore
|
||||
reflect excessive water retention, due partly to suppressed pulmonary transpiration and partly to kidney
|
||||
malfunction in those women.
|
||||
</p>
|
||||
<p>
|
||||
Neuroendocrinology. 2001 Mar;73(3):185-93. <strong>Hypothalamo-pituitary-adrenal axis sensitization after
|
||||
chronic salt loading.</strong> Amaya F, Tanaka M, Hayashi S, Tanaka Y, Ibata Y.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Neuroscience. 1994 Sep;62(2):371-83. <strong>Imaging cell volume changes and neuronal excitation in the
|
||||
hippocampal slice.</strong> Andrew RD, MacVicar BA. <strong>"Brain cell swelling is a consequence of
|
||||
seizure, ischemia or excitotoxicity."</strong>
|
||||
</p>
|
||||
<p>
|
||||
Probl Endokrinol (Mosk). 1981 Sep-Oct;27(5):42-5.<strong>
|
||||
[Sex and age differences in the peripheral blood aldosterone levels]
|
||||
</strong>
|
||||
Bekker VI, Svechnikova NV. <strong>"An increase in the blood aldosterone content in menopause appears to be
|
||||
due to the hyperestrogenic phase (the first menopausal phase in women) and estrogen-stimulated
|
||||
aldosterone synthesis.</strong> Sexual differences in aldosterone secretion disappear with age.
|
||||
Aldosterone content is significantly lower in males and females, age over 80 years, than that in younger
|
||||
subjects, and sexual differences are absent."
|
||||
</p>
|
||||
|
||||
<p>
|
||||
J Appl Physiol. 2002 May;92(5):1911-22.<strong>
|
||||
Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response to osmostimulation in
|
||||
men.</strong>
|
||||
Bestle MH, Olsen NV, Poulsen TD, Roach R, Fogh-Andersen N, Bie P. "In conclusion, chronic hypobaric
|
||||
hypoxemia <strong>1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship,
|
||||
possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2)
|
||||
blunts the natriuretic response to hypertonic volume expansion . . . ."</strong>
|
||||
</p>
|
||||
<p>
|
||||
Metabolism. 1999 Apr;48(4):472-6. <strong>Effects of hypoosmolality on whole-body lipolysis in man.</strong>
|
||||
Bilz S, Ninnis R, Keller U.
|
||||
</p>
|
||||
<p>
|
||||
JAMA. 1984 Jul 27;252(4):524-6. <strong>Impaired osmoregulation at high altitude. Studies on Mt
|
||||
Everest.</strong> Blume FD, Boyer SJ, Braverman LE, Cohen A, Dirkse J, Mordes JP.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Gerontology. 1996;42(4):229-34.<strong>
|
||||
Effect of aging and sodium deprivation on plasma concentration of aldosterone and on plasma renin
|
||||
activity in the rat.</strong>
|
||||
Brudieux R, Rakotondrazafy J.
|
||||
</p>
|
||||
<p>
|
||||
Endocr Res. 1996 Nov;22(4):577-8. <strong>The role of L-aromatic amino acid decarboxylase in
|
||||
serotonin-stimulated aldosterone secretion in response to salt intake.</strong>
|
||||
Burns N, Brett L, Olverman HJ, Nagatsu T, Lee MR, Williams BC.
|
||||
</p>
|
||||
<p>
|
||||
Curr Drug Targets Immune Endocr Metabol Disord. 2004 Mar;4(1):1-10. <strong>Melatonin role in experimental
|
||||
arthritis.
|
||||
</strong>
|
||||
|
||||
Cardinali DP, Garcia AP, Cano P, Esquifino AI.
|
||||
</p>
|
||||
<p>
|
||||
J Lipid Res. 2003 Apr;44(4):727-32. Epub 2003 Jan 16. <strong>Dietary sodium chloride restriction enhances
|
||||
aortic wall lipid storage and raises plasma lipid concentration in LDL receptor knockout mice.</strong>
|
||||
Catanozi S, Rocha JC, Passarelli M, Guzzo ML, Alves C, Furukawa LN, Nunes VS, Nakandakare ER, Heimann JC,
|
||||
Quintao EC. <strong><hr /></strong>
|
||||
</p>
|
||||
<p>
|
||||
Am J Physiol. 1978 Mar;234(3):F235-7. <strong>Acetazolamide and renal ammoniagenesis.</strong>
|
||||
Chapman SK, Hoover MS.
|
||||
</p>
|
||||
<p>
|
||||
Early Hum Dev. 1989 Jun;19(3):191-8. <strong>Muscle cell potassium, RNA and hydration in pregnancy and
|
||||
pre-eclampsia.</strong> Cheek DB, Petrucco OM, Gillespie A, Green RC, Ness D, Dalton M. "Thirty four
|
||||
pregnant women from 26 to 38 weeks gestation and 24 pregnant women with pre-eclampsia gave samples of muscle
|
||||
(rectus abdominis) at caesarean section." "<strong>From 26 to 38 weeks gestation the concentration of K+ per
|
||||
litre of cell water ([Ki]) slowly declined."</strong> "Since other cations per litre of muscle cell
|
||||
water did not change, questions are raised. is the cation gap filled by amino acids or does vascular spasm
|
||||
cause a leakage of K+ from muscle cells? <strong>Does hypotonicity eventually develop leading to water
|
||||
intoxication? The low oncotic pressure in pre-eclampsia (shown here), the negative free water clearance
|
||||
could all favour increased cell hydration (some evidence for this is presented here towards
|
||||
term).</strong>
|
||||
|
||||
Assessment of available information concerning creatinine excretion . . . <strong>leads us to believe that a
|
||||
significant increase in muscle mass occurs...."</strong>
|
||||
</p>
|
||||
<p>
|
||||
Autoimmun Rev. 2005 Nov;4(8):497-502. <strong>Altered circadian rhythms in rheumatoid arthritis patients
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||||
play a role in the disease's symptoms.
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||||
</strong>
|
||||
Cutolo M, Villaggio B, Otsa K, Aakre O, Sulli A, Seriolo B.
|
||||
</p>
|
||||
<p>
|
||||
Eur J Pharmacol. 1979 Oct 15;58(4):425-31. <strong>Antiulcer activity of hypertonic solutions in the rat:
|
||||
possible role of prostaglandins.</strong> Danon A, Assouline G.
|
||||
</p>
|
||||
<p>
|
||||
Peptides. 1990 Jan-Feb;11(1):59-63. <strong>Long-term salt loading impairs pituitary responsiveness to ACTH
|
||||
secretagogues and stress in rats.</strong> Dohanics J, Kovacs KJ, Folly G, Makara GB.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Can J Physiol Pharmacol. 1982 Mar;60(3):331-4. <strong>Role of acidosis in the protein wasting of fasting in
|
||||
the rat and the rabbit.</strong> Hannaford MC, Goldstein MB, Josse RG, Halperin ML. "Therefore, it
|
||||
appears that if more nitrogen is excreted as ammonium, net protein breakdown increases to furnish the
|
||||
substrate for ammoniagenesis...."
|
||||
</p>
|
||||
<p>
|
||||
Neurosci Biobehav Rev. 2004 Sep;28(5):507-24. <strong>The role of norepinephrine in epilepsy: from the bench
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||||
to the bedside.</strong> Giorgi FS, Pizzanelli C, Biagioni F, Murri L, Fornai F.
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||||
</p>
|
||||
<p>
|
||||
Can J Physiol Pharmacol. 1998 Dec;76(12):1120-31. <strong>Bulbospinal serotonergic activity during changes
|
||||
in thyroid status.
|
||||
</strong>
|
||||
|
||||
Henley WN, Bellush LL, Tressler M.
|
||||
</p>
|
||||
<p>
|
||||
Brain Res Mol Brain Res. 1991 Jun;10(3):251-8. <strong>Benzamide derivatives provide evidence for the
|
||||
involvement of a 5-HT4 receptor type in the mechanism of action of serotonin in frog adrenocortical
|
||||
cells.</strong> Idres S, Delarue C, Lefebvre H, Vaudry H. "We have previously shown that <strong
|
||||
>serotonin (5-HT) is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical
|
||||
cells and we have demonstrated that the action of 5-HT is not mediated by the classical 5-HT receptor
|
||||
subtypes i.e. 5-HT1, 5-HT2 and 5-HT3."</strong>
|
||||
</p>
|
||||
<p>
|
||||
Nippon Rinsho. 1992 Sep;50(9):2124-8.<strong>
|
||||
[Effects of pH on the endocrine system and metabolism]</strong> [Article in Japanese] Inoue Y, Kaneko T.
|
||||
"6-phosphofructo-1-kinase, a rate limiting enzyme in glycolysis, seems to be activated directly by a rise in
|
||||
pH. Alkalosis stimulates the production of pyruvic acid and lactic acid."
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Am J Physiol. 1997 Jul;273(1 Pt 2):H104-12. <strong>Endothelial ATP-sensitive potassium channels mediate
|
||||
coronary microvascular dilation to hyperosmolarity.
|
||||
</strong>
|
||||
Ishizaka H, Kuo L.
|
||||
</p>
|
||||
<p>
|
||||
Am J Physiol Cell Physiol. 2001 Oct;281(4):C1403-7. <strong>Hypotonicity induces L-selectin shedding in
|
||||
human neutrophils.</strong> Kaba NK, Knauf PA.<strong> </strong>
|
||||
</p>
|
||||
<p>
|
||||
Ross Fiziol Zh Im I M Sechenova. 2003 Feb;89(2):146-53. [<strong>Effect of melatonin on neurogenic
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||||
vasoreactivity: formation and modulation of the vessel response]
|
||||
</strong>Karachentseva OV, Iartsev VN, Dvoretskii DP, Zhdanova IV.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
J Investig Med. 2002 Mar;50(2):101-9. <strong>Stimulatory effects of hyperprolactinemia on aldosterone
|
||||
secretion in ovariectomized rats.
|
||||
</strong>
|
||||
Kau MM, Chang LL, Kan SF, Ho LT, Wang PS.
|
||||
</p>
|
||||
<p>
|
||||
Biochim Biophys Acta. 1999 Jan 4;1426(1):17-31. <strong>Effect of electric field on physical states of
|
||||
cell-associated water in germinating morning glory seeds observed by 1H-NMR.</strong> Isobe S, Ishida N,
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||||
Koizumi M, Kano H, Hazlewood CF.
|
||||
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|
||||
<p>
|
||||
Eur J Clin Nutr. 2003 Dec;57 Suppl 2:S69-74. <strong>Effects of changes in hydration on protein, glucose and
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||||
lipid metabolism in man: impact on health.
|
||||
</strong>
|
||||
Keller U, Szinnai G, Bilz S, Berneis K. Alterations of cell volume induced by changes of extracellular
|
||||
osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling
|
||||
counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes
|
||||
protein breakdown, glycolysis and glycogenolysis.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Ann Ophthalmol. 1977 Nov;9(11):1383-7. <strong>The effect of hypertonic ointments on corneal alkali
|
||||
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|
||||
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|
||||
<p>
|
||||
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||||
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||||
Fasshauer M, Klein J.
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||||
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||||
<p>
|
||||
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|
||||
its role in the action of tumor promoters.</strong>
|
||||
Lee CH, Cragoe EJ Jr, Edwards AM.
|
||||
</p>
|
||||
|
||||
<p><strong><a href="http://www.gilbertling.org" target="_blank">www.gilbertling.org</a></strong></p>
|
||||
<p>
|
||||
Acta Endocrinol (Copenh). 1977 Sep;86(1):81-8. <strong>Studies on circadian variations of plasma TSH,
|
||||
thyroxine and triiodothyronine in man.
|
||||
</strong>
|
||||
Lucke C, Hehrmann R, von Mayersbach K, von zur Muhlen A.
|
||||
</p>
|
||||
<p>
|
||||
Adv Neurol. 1986;44:619-39.<strong>
|
||||
Ionic changes and alterations in the size of the extracellular space during epileptic activity.</strong>
|
||||
Lux HD, Heinemann U, Dietzel I.
|
||||
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|
||||
<p>
|
||||
J Pediatr. 2002 Oct;141(4):587-92.<strong>
|
||||
The most essential nutrient: defining the adequate intake of water.</strong> Manz F, Wentz A,
|
||||
Sichert-Hellert W.
|
||||
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|
||||
|
||||
<p>
|
||||
Semin Arthritis Rheum. 1995 Feb;24(4):282-90. <strong>Bone and joint manifestations of
|
||||
hypothyroidism.</strong> McLean RM, Podell DN.
|
||||
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|
||||
<p>
|
||||
Clin Invest Med. 1997 Feb;20(1):16-24.<strong>
|
||||
Effective water clearance and tonicity balance: the excretion of water revisited.
|
||||
</strong>
|
||||
Mallie JP, Bichet DG, Halperin ML. "OBJECTIVE: To demonstrate (1)<strong>
|
||||
that hyponatremia is usually due to an inappropriately low rate of excretion of electrolyte-free water
|
||||
and (2) that the measure "effective water clearance" (EWC</strong>) provides better information about
|
||||
renal defence of the body tonicity than does the classic measure free-water clearance, and to provide the
|
||||
rationale for calculating a "tonicity balance," which involves using water and sodium plus potassium intakes
|
||||
and their renal excretion to reveal the basis for changes in body tonicity." "The water load was excreted
|
||||
rapidly by normals, more slowly by patients with CHF, and not at all by patients with SIADH."
|
||||
</p>
|
||||
<p>
|
||||
FEBS Lett. 2000 Jan 7;465(1):64-8. <strong>Hypoosmolarity influences the activity of transcription factor
|
||||
NF-kappaB in rat H4IIE hepatoma cells.</strong> Michalke M, Cariers A, Schliess F, Haussinger D.
|
||||
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||||
<p>
|
||||
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||||
Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system.</strong>
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||||
Mihailidou AS, Funder JW. "Alzamora et al. showed 11beta-hydroxysteroid denydrogenase 1 and 2 (11betaHSD1,
|
||||
11betaHSD2) expression in human vascular<strong>
|
||||
smooth muscle cells, and that aldosterone rapidly raises intracellular pH via sodium-hydrogen exchange;
|
||||
cortisol is without effect and spironolactone does not block the aldosterone response."
|
||||
</strong>
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Epilepsy Res. 1988 Mar-Apr;2(2):102-10. <strong>Evidence of hypothyroidism in the genetically epilepsy-prone
|
||||
rat.</strong> Mills SA, Savage DD.
|
||||
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|
||||
<p>
|
||||
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||||
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|
||||
Yoshida S.
|
||||
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|
||||
<p>
|
||||
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||||
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|
||||
H, Koch K, Steiger A.
|
||||
</p>
|
||||
|
||||
<p>
|
||||
Physiol Behav. 1996 Jan;59(1):133-9. <strong>Nonsteroidal anti-inflammatory drugs alter body temperature and
|
||||
suppress melatonin in humans.</strong> Murphy PJ, Myers BL, Badia P.
|
||||
</p>
|
||||
<p>
|
||||
Probl Endokrinol (Mosk). 1987 Jan-Feb;33(1):18-21. <strong>[Characteristics of the hydration status of
|
||||
patients with hypothyroidism</strong>] Nazarov AN, Lobachik VI, Zhidkov VV, Borisov GI, Abrosimov SV.
|
||||
</p>
|
||||
<p>
|
||||
Pflugers Arch. 1991 Oct;419(3-4):418-20. <strong>Alkaline stress transforms Madin-Darby canine kidney cells.
|
||||
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|
||||
exchange in renal target cells leading to cytoplasmic alkalinization. An alkaline intracellular pH reduces
|
||||
the H+ bonds between repressor proteins and DNA leading to the destabilization of the nuclear chromatin.
|
||||
<strong>We observed that sustained alkaline stress "per se" can lead to malignant transformation of
|
||||
Madin-Darby canine kidney (MDCK) cells."</strong>
|
||||
</p>
|
||||
|
||||
<p>
|
||||
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|
||||
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|
||||
inhibition of aldosterone synthesis the subject was able to maintain potassium balance at a normal serum
|
||||
potassium concentration on a potassium intake of 130 mEq/day which suggests that aldosterone is the major
|
||||
cause of the potassium wasting...."
|
||||
</p>
|
||||
<p>
|
||||
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||||
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||||
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|
||||
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|
||||
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||||
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||||
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|
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||||
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|
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||||
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||||
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||||
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|
||||
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||||
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|
||||
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|
||||
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||||
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|
||||
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|
||||
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||||
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|
||||
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|
||||
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|
||||
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|
||||
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||||
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|
||||
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|
||||
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|
||||
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||||
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||||
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||||
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||||
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||||
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||||
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|
||||
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|
||||
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|
||||
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|
||||
</strong>
|
||||
|
||||
Mg2+ excretion at these sites is likewise enhanced by aldosterone, whereas adrenal aldosterone secretion is
|
||||
regulated by extracellular Mg2+." <strong>
|
||||
"De novo generation of aldosterone within the cardiovasculature is recognized</strong> and findings
|
||||
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|
||||
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|
||||
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|
||||
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||||
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||||
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||||
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||||
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||||
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|
||||
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|
||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
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||||
</p>
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||||
|
||||
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|
||||
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|
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|
||||
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