Oral Aspects of Metabolic Diseases
Loeb described individual man as a ‘mosaic of many tissues and organs’, each one functioning and metabolizing in its own peculiar way. Each tissue or organ has properties not restricted to it, but common to all parts of the organisms, and it is these common properties which bind the tissues and organs well together into a unit.
Health is largely determined by man’s reaction to his environment, both social and physical, but different individuals behave differently in the same environment and under apparently identical conditions. On this basis we recognize the variations of the substratum upon which environmental factors act. Individual variations in response to the internal and external environment are dependent upon constitution. Each response represents a complex interplay between the genetic and environmental factors acting on the individual.
Certain characteristics of an organism are fixed in the germ cells and give rise to definite metabolic, structural, and functional conditions in the individual. These inherited features represent the core of his constitution, the unchangeable part of it. In actual life; however, it is often difficult to separate this core from effects produced by the environment.
It might be well to visualize man—the organism—as a universe: a universe of cells living together within a restricted framework. Some of the individuals (the cells) of this universe form rather tightly knit communities (the organs) which perform highly specialized tasks. Each individual within the community responds to his inner as well as his outer environment, and each is influenced by his neighbor. The outer environment in this instance is fluid—mostly water. Each individual cell influences the tissue fluid in some manner by removing and/or adding metabolic products. Each cell or organ system reacts to its changing environment within the limits of its inherent capabilities. If an analogy is drawn between the cells as an individual within the organisms and the organisms as an individual within the cosmos, the complexity of the interrelations becomes apparent, even though the nature of the interrelations is nebulous.
Duncan defined metabolism as “the sum total of tissue activity as considered in terms of physicochemical changes associated with and regulated by the availability, utilization, and disposal of protein, fat, carbohydrate, vitamins, minerals, water, and the influences which the endocrines exert on these processes”. Alterations from these normal metabolic processes constitute the disturbances of metabolism. One recognizes immediately that this definition embodies a concept of cellular change as influenced not only by intrinsic factors, but also by such extrinsic factors as food supply, temperature, altitude, society; in other words, by environment.
The volume of literature pertaining to metabolism is rapidly surpassing the ability of investigators to keep pace with it. Obviously it is impossible to provide an in-depth look at any particular area. Excellent references, many recent and some classic, are available. These include Wolbach and Bessey (1942), Schour and Massler (1943 and 1945), Follis (1948 and 1958), Bodansky and Bodansky (1952), Bourne and Kidder (1953), Duncan (1959), Comar and Bronner (1960), Gÿorgy and Pearson (1967), Sebrell and Harris (1967), Greenberg (1967, 1968, 1969, 1970), Vogel (1971), Hokin (1972), Prasad (1976), Underwood (1977), Stanbury, Wyngaarden, and Fredrickson (1978), Alfin-Slater and Kritchevsky (1979), Goodhart and Shills (1980) and Bondy and Rosenberg (1980).
Although hormones are the primary regulators of metabolism, they are ineffective without minerals and vitamins. Minerals are inorganic elements that are essential for life and provide both the structural and regulatory functions of the body. It is observed that there are at least 29 different elements in our body constituting about 4% of the body weight, concentrated mostly in the skeleton. The elements considered essential for normal growth and development of mammals are calcium, phosphorus, magnesium, potassium, sodium, chlorine, iodine, copper, iron, zinc, manganese, cobalt, chromium, selenium, and fluoride.
Minerals that are present in relatively high amounts in the body are referred to as macrominerals and those that are less than 0.005% of the body weight are called the microminerals. Macrominerals or principal elements are nutritionally important minerals whose daily requirement is more than 100 mg. These include sodium, potassium, chloride, calcium, phosphorus, magnesium and sulfur. The microminerals or trace elements are those found in tissues in minute amounts but are found to be essential to life. Their requirement is less than 100 mg/day and these include chromium, copper, cobalt, iron, iodine, manganese, selenium, fluorine, and zinc. The other trace elements that are possibly essential include cadmium, nickel, silicon, tin, and vanadium.
Inorganic and organic combinations of these elements are active in many physiologic processes. They constitute the basic structure of bone and teeth; help maintain the osmotic relations of the body fluids; regulate the acid-base equilibrium of the tissues; form part of hormones; are an integral part of some enzymes; serve as activators of certain enzymatic reactions; and they are an essential part of the oxygen-carrying pigments. Mertz’s definition of ‘essential’ has been widely accepted. He stated that an element is considered essential when a deficient intake consistently results in suboptimal physiologic function that can be prevented or reversed by supplementation with physiologic levels of the element.
It is interesting that in many physiologic processes one mineral element may be substituted for another. For example, strontium or lead may replace calcium in the inorganic structure of bone. Rubidium may replace potassium in a potassium-deficient diet with the result that, even though the animals maintained on the diet die, the characteristic myocardial necrosis found in potassium deficiency will not occur. A thorough understanding of the normal processes of mineral metabolism and the effects of abnormal mineral metabolism is essential in pointing the way to the solution of many of the problems related to calcification of the teeth and jaws that constantly arise during the practice of dentistry.
Although the literature concerned with calcium, phosphorus, and magnesium is voluminous, we still do not have a clear picture of the role of these elements in nutrition. The exact relation of magnesium to calcium and phosphorus metabolism is not known. For convenience, we shall discuss each element separately, trying to combine or integrate our knowledge whenever possible.
Calcium is the fifth most abundant element in the body, and in crystalline form, with phosphorus, in a proteinaceous matrix, forms the major structural support of the body (bones). The total calcium in the body is 100–170 gm, about 99% of which is found in bones existing as carbonate or phosphate of calcium while about 0.5% is present in soft tissue and 0.1% in extracellular fluid. The normal serum calcium level is about 9–11 mg/dl. The calcium in plasma is of three types: ionized calcium, protein bound calcium, and complexed calcium. About 40% of the total calcium is in ionized form, which is also physiologically active form of calcium. The level of the blood calcium is largely controlled by the action of the parathyroid glands, which are stimulated by low serum calcium levels and inhibited by high serum calcium levels.
The Food and Nutrition Board of the National Academy of Sciences, National Research Council, recommends a daily dietary calcium intake of 360 mg for newborn infants and 800 mg for children and adults. Adolescents and pregnant and lactating women are advised to increase their daily dietary calcium intake by 50% to 1,200 mg. Calcium is taken in diet principally as calcium phosphate, carbonate, and tartrate. Unlike sodium and potassium that are readily absorbed, the absorption of calcium in man is an inefficient process. Only about one-third of the daily dietary intake of calcium is absorbed under normal conditions. About 40% of average daily dietary intake of calcium is absorbed from the gut, mainly from the duodenum and first half of jejunum against an electrical and concentration gradient.
In well-balanced diets, the ratio of calcium to phosphorus is of little significance, but in less balanced diets, this ratio assumes considerable importance. Phytic acid, which is found in cereals, forms an insoluble calcium phytate with ingested calcium and renders it nonavailable. Since this substance constitutes over 50% of the phosphate of cereals and is hydrolyzed only to the extent of 30–60% in the alimentary tract, the phosphate-calcium ratio is thus upset, interfering with the normal absorption of calcium. Vitamin D increases absorption of calcium from the intestine. Under normal metabolic conditions for fat splitting and fat absorption, the ingestion of fat has been found to aid calcium absorption, but in conditions in which there is excessive fat excretion, such as in sprue or idiopathic steatorrhea, calcium is lost in the feces as calcium soaps.
Citrates, that may lower the pH of the intestinal tract, form calcium citrate which is relatively soluble. The addition of citrates to a rachitogenic diet seems to render the diet nonrachitogenic and also aid calcification. It has therefore been suggested that the lowering of the intestinal pH aids absorption of calcium and that the calcium citrate ion, though relatively soluble, aids the deposition of calcium in bones by raising the pH of the calcifying tissue or of the fluids surrounding the calcifying tissue. High protein diets have also been shown to increase calcium absorption, probably through the formation of soluble calcium compounds with the amino acids produced by the digestion of the protein.
Oxalic acid interferes with calcium absorption by forming an insoluble calcium oxalate. For example, spinach contains sufficient oxalic acid to render all its calcium nonavailable, with some oxalic acid to spare for other calcium which might be present in the diet. The presence of hypochlorhydria or achlorhydria also exerts an adverse influence upon calcium and phosphate absorption, since normal secretion of hydrochloric acid by the stomach is necessary for optimal absorption of calcium and phosphate.
Many factors affect the utilization of absorbed calcium and phosphorus. Obviously, conditions which produce profound disturbance of any vital metabolism may have an indirect influence upon the metabolism of these minerals. Those factors; however, which appear to have a well-defined effect on calcium and phosphorus metabolism, are the parathyroid hormone, vitamin D, thyroid, calcitonin, and the steroid hormones.
Calcium is excreted in both the feces and the urine, with 80% of the total amount being excreted in the feces. Fecal calcium consists not only of unabsorbed calcium, but also of calcium which has been absorbed and re-excreted. Although the small intestine is the predominant site in which the calcium is re-excreted, all segments of the intestinal tract probably excrete some calcium. Unless there is excessive perspiration, the dermal losses do not exceed 50 mg/dl. The normal daily urinary calcium excretion in adults is less than 250 mg for women and 300 mg for men. The calcium in the urine is excreted mainly as calcium chloride and calcium phosphate. The renal threshold for calcium is approximately 7 mg/dl of serum calcium. The urinary excretion of calcium is increased by increased plasma calcium, deprivation of phosphate, excessive vitamin D, increased urinary excretion of sodium, immobilization, corticosteroid administration, increased dietary calcium, metabolic acidosis, hyperthyroidism, and idiopathic; whereas urinary excretion of calcium is decreased by decreased ultrafiltrable plasma calcium, decreased glomerular filtration rate, parathyroid hormone, decreased dietary calcium, increased dietary phosphate, increased calcium utilization as in growth, pregnancy, and lactation.
Calcium plays a large role in the formation of bones and teeth, in the maintenance of skeletal structure, tooth structure, normal membrane permeability, normal heart rhythm and other neuromuscular excitability, in the coagulation of blood, muscle contraction, and as a secondary or tertiary messenger in hormone action. Variations of serum calcium ion concentration from the limited optimal range of 9–11 mg/dl have profound effects. A low concentration of calcium ions (about 8 mg/dl) produces hyperirritability and tetany with characteristic carpopedal spasm and at times laryngospasm and convulsions, while high concentration produces depressed nerve conductivity and muscle rigor.
Hypocalcemia is said to exist when serum calcium is less than 8.5 mg/dl. The commonest cause of hypocalcemia is hypoalbuminemia, closely followed by renal failure. The other common cause of hypocalcemia is surgically induced hypoparathyroidism. Hypercalcemia occurs when serum calcium levels exceed 11.0 mg/dl and the most common cause is primary hyperparathyroidism, malignancy, and endocrine causes such as acute adrenal insufficiency and renal failure.
Experimental calcium deficiency in rats leads to a derangement of blood coagulation and of the integrity of the capillaries. Internal hemorrhages and generalized paralysis of the young born of calcium-deficient females are common. In addition, stomach ulcers have been described in rats, and lens opacities (cataracts) have been described in rabbits deficient in calcium. Hyperplasia and hypertrophy of the parathyroid glands of rats maintained on calcium-deficient diets have also been observed. In adult animals maintained on low calcium diets, sterility and reduction in lactation are frequently found. There are no descriptions of the teeth of animals maintained on a low calcium diet.
The etiology of osteoporosis was once thought to be a lack of adequate bone matrix. But evidences indicate that it may be due to a longterm negative calcium balance. Skeletal mass in old age is proportional to skeletal mass at maturity, indicating that infant and childhood calcium intake may play a major role in the occurrence and severity of the disease in later years. Based on these findings, the treatment of osteoporosis has changed over the years. Androgen and estrogen therapies have been replaced by increased calcium intake and strontium and sodium fluoride ingestion. The role of strontium and fluoride in bone metabolism is not fully known, but they do act to sustain bone mass in elderly osteoporotic patients. Long-term metabolic balance studies indicate that in a majority of osteoporotic patients, calcium balance can be achieved with a high calcium intake. The importance of calcium, strontium, and sodium fluoride in the prevention and treatment of senile osteoporosis have been found encouraging.
Total body phosphorus is approximately 500–800 gm, of which 85–90% is in the skeleton, leaving approximately 100 gm in soft tissues. There are multiple pools of phosphorus having different turnover rates; bones and teeth have the lowest rates. A major portion of phosphorus is incorporated into organic phosphorus compounds (phospholipids of cell membranes, nucleic acids, etc). The normal inorganic phosphate level of blood in adults ranges from 2–4 mg/dl, while in children its range is from 3–5 mg/dl. These blood levels are maintained by a balance of various factors, such as parathyroid hormone, phosphatase activity, and vitamin D. Phosphorus is; however, not as finely regulated as plasma calcium but is under some hormonal control via PTH and renal production of 1,25 (OH)2D3.
The suggested daily dietary intake of phosphorus ranges from 240 mg for infants to 800 mg for adults. As with calcium, adolescents, pregnant and lactating women are advised to increase their daily dietary phosphorus intake by 50% to 1,200 mg. 90% of daily dietary phosphate is absorbed. Absorption of phosphorus takes place in the small intestine in the form of soluble inorganic phosphate. Approximately 70% of food phosphorus is absorbed in the form of orthophosphate after intestinal phosphatase releases the food-bound phosphorus during the digestive process. An excess of calcium, iron, or aluminum may interfere with the absorption of phosphorus because of a tendency to form insoluble phosphates in the intestinal tract.
Regulation of calcium and phosphorus is under the similar control mechanisms by kidney with respect to parathormone and vitamin D. Excretion of phosphorus occurs primarily in the urine. Phosphate uptake is sodium dependent, about 85% of filtered PO4 is reabsorbed by the proximal tubules. Phosphate reabsorption is increased when dietary intake is reduced by a parathormone-dependent mechanism. Almost two-thirds of the total phosphorus excreted is found in the urine as phosphates of various cations. Fecal phosphorus, which is usually composed of unabsorbed as well as re-excreted phosphate, is usually excreted as calcium phosphate.
Although most of the body phosphorus is intimately associated with calcium in the metabolism of bones and teeth, a much higher proportion of phosphorus than of calcium is concerned in other vital processes. Phosphates form an intermediate stage in the metabolism of fats and carbohydrates by their function in phosphorylation. They are used in building the more permanent organic phosphates, including some catalysts, essential to the structure and function of cells. Phosphates are utilized in the formation of phosphoproteins, such as milk casein, and in the formation of the nerve phosphatides and the nucleoproteins of cells. They provide the energy-rich bonds in such compounds as adenosine triphosphate, which is important in muscle contraction, and they form part of such coenzymes as pyridoxal phosphate, which is necessary in decarboxylation and transamination of certain amino acids, such as tyrosine, tryptophan and arginine.
When young rats are placed on a low phosphorus diet, there is some retardation in growth. The only specific gross or microscopic alterations are found in the skeletal system, where severe rickets is present (Fig. 15-1). This finding appears after the rats have been on the experimental phosphorus-deficient diet for only one week.
Figure 15-1 Phosphorus deficient diet.
(A) Sagittal section of mandibular joint of a normal rat 70 days of age. (B) Sagittal section of mandibular joint of rat 70 days old, which received a phosphorus-deficient diet since weaning at 21 days of age. Courtesy of Dr Herman Becks
Phosphate depletion in man is nonexistent under most dietary regimens. Long-term antacid use; however, will render phosphate unabsorbable. Lotz and coworkers have described such a condition, which is characterized by weakness, malaise, anorexia, and bone pain. Increased calciuria results in a negative calcium balance with bone demineralization. Rickets and osteomalacia are important dietary deficiency disorders of calcium, phosphorus, or vitamin D. The other causes of hypophosphatemia may be due to decreased intake (starvation, malabsorption, or vomiting) or increased cell uptake as in high dietary carbohydrate, liver disease, or increased excretion due to diuretics, hypomagnesemia, and increased parathormone. Hyperphosphatemia, on the other hand, is due to factitious hemolysis, increased intake of vitamin D, increased release from bone as in malignancy or decreased excretion.
Magnesium is the fourth most abundant and important cation in humans. It is extremely essential for life and is present as intracellular ion in all living cells and tissues. Magnesium appears to participate in practically every phosphorylating mechanism. In addition, this ion is necessary for the activity of certain enzymes, such as phosphatase and cocarboxylase.
Although the concentration of magnesium in the intracellular fluids is not as great as the concentration of potassium, magnesium is widely distributed in the tissues of the animal body. The body of a 70 kg man contains approximately 25 mg of magnesium. Over half of this amount is found in the bones, and one quarter in the muscles. The remainder is distributed between liver, pancreas, erythrocytes, serum, and cerebrospinal fluid.
The recommended daily dietary allowance for magnesium ranges from 50 mg for infants to 400 mg for teenage males. A daily increase of 150 mg is suggested during pregnancy and lactation. Like calcium, magnesium is ingested in inorganic and organic forms. It is also absorbed and excreted in the same manner as calcium. Absorption takes place primarily in the small bowel. Besides other factors, the size of magnesium load is important as absorption is doubled when normal dietary Mg requirement is doubled and vice versa. Since there is a common transport mechanism from intestinal tract for both Ca and Mg, decreased absorption occurs in the presence of excess Ca. The absorption is also affected in hurried bowel and damaged mucosal states. Vitamin D, parathormone, growth hormone, high protein intake, and neomycin therapy increase absorption. High calcium diets raise the requirement for magnesium.
Hypermagnesemia is rare because of the renal capacity to excrete excess ion. The administration of magnesiumcontaining antacids to patients with renal insufficiency has resulted in central nervous system depression. Somjen and coworkers have also reported severe voluntary muscle paralysis with hypermagnesemia. Controlled human hypomagnesemia was studied by Shils, who noted a concurrent hypocalcemia and hypokalemia despite normal dietary calcium and phosphorus intake. Clinically the patients exhibited personality change, anorexia, nausea and vomiting, and carpopedal spasms.
High magnesium intake will produce rickets in growing animals, especially if the phosphorus and calcium intake is relatively low. The normal serum magnesium level is 1–3 mg/dl. When the level reaches 5 mg/dl, mild sedative or hypnotic effects may occur. Profound coma and even death may result when the serum level reaches 18–21 mg. A distinct but not fully understood relationship exists between magnesium, calcium, parathyroid hormone, and bone metabolism. Buckle and coworkers have shown that hypomagnesemia and hypocalcemia have identical effects on the parathyroid glands, i.e. increased parathyroid hormone production. An apparent contradiction exists in that despite elevated hormone levels, many affected individuals exhibit hypocalcemia. Studies have indicated that the parathyroid hormone produced is defective, although some investigators have described hypomagnesemic patients who were refractory to exogenous parathyroid extract, suggestive of a bone defect rather than a glandular abnormality.
Magnesium is involved as a cofactor and as an activator to a wide spectrum of enzymatic actions. It is essential for peptidases, ribonucleases, glycolytic enzymes and cocarboxlylation reactions. Magnesium exerts an effect on neuromuscular irritability similar to that of calcium ions. High levels depress nerve conduction and low levels may produce tetany (hypomagnesemic tetany). As constituent of bones and teeth, about 70% of body magnesium is present as apatites in bones, enamel, and dentin.
In humans, ‘overt’ magnesium deficiency occurs rarely. In experimental animals, magnesium deficiency leads to disturbances in the neuromuscular and vascular systems as well as to changes in the teeth, liver, and kidneys. The effects of magnesium-deficient diets on the teeth and their supporting structures have been thoroughly described by Becks and Furuta and by Klein and his associates. Diets containing only 13 ppm of magnesium caused the ameloblasts from the labial side near the apex of the growing incisor tooth in rats to show various stages of localized degeneration with subsequent formation of enamel hypoplasia. The hypoplastic areas increased in size and number with the duration of the experiment, although the changes were noted in all animals after 41 days.
The syndrome of human magnesium-deficiency tetany was first described by Vallee and his associates in 1960. The condition is virtually identical with that of hypocalcemic tetany from which it can be differentiated only by chemical means. Clinically, patients with this deficiency exhibit a semicoma; severe neuromuscular hyperirritability, including carpopedal spasm and a positive Chvostek’s sign; athetoid movements; marked susceptibility to auditory, visual, and mechanical stimuli; a decreased serum magnesium; and a normal serum calcium concentration. Precipitating factors are severe dietary inadequacy of magnesium or excessive losses of this ion due to vomiting, intestinal malabsorption, and the administration of large amounts of magnesium free parenteral fluids which induce a large urine volume. The tetany appears when the serum magnesium level is depressed below 1.30 mEq per liter. Treatment by the intramuscular injection of magnesium sulfate is followed by a prompt rise in serum magnesium and a concomitant disappearance of the tetany and convulsions. Discontinuance of the therapy in the presence of precipitating factors results in a rapid reappearance of tetany.
Pathologic calcification implies the abnormal deposition of calcium salts together with smaller amounts of iron, magnesium, and other mineral salts. Pathologic calcification is commonly classified as:
In the dystrophic form of calcification, calcium salts are deposited in dead or degenerating tissues. This is the most frequent type of pathologic calcification and is found in a wide variety of tissues. Areas of tuberculous necrosis, blood vessels in arteriosclerosis, scars and areas of fatty degeneration are commonly recognized as sites of dystrophic calcification by the general pathologist. This type of calcification is not dependent upon an increase in the amount of circulating blood calcium, but appears to be related to a change in the local condition of the tissues. A local alkalinity in comparison with adjacent undamaged tissues appears to be an important factor in initiating the precipitation of calcium in degenerating or nonvital tissues.
In the mouth, areas of dystrophic calcification may frequently be found in the gingiva, tongue or cheek. Such areas are also found in the benign fibromas of the mouth and adjacent structures (Fig. 15-2). One of the most common intraoral dystrophic calcifications is found in the pulp of teeth, and this has been discussed in Chapter 13 on Regressive Alterations of the Teeth. Boyle described the pulp calcifications as calcific degeneration of the pulp tissue. They are usually found in the teeth of older persons, although they also may be seen in young people. They may occur in the wall of blood vessels or in the perineural connective tissue of the pulp, or they may be rather diffusely scattered both in the pulp chamber and in the root canal. They appear as fine fibrillar calcifications which may coalesce to form large masses of calcific material.
Hill classified calcific degenerations of the pulp into two types. The first, a nodular type, is a result of calcification of hyalinized connective tissue. Such calcification is usually perivascular or perineural and is often associated with increased fibrosis. The calcium deposits are most frequently found in the coronal portion of the pulp chamber and increase in size by accretion and deposition of calcium along the collagenous fibrils. The second type of calcification of the pulp is that found in and around necrotic cells and corpora amylacea. It occurs in a multicentric manner and is most frequently found in the radicular portion of the pulp canal. This type of calcification always shows a nidus in the center and increases in size by concrescence which is obvious on histologic examination.
Many of the deposits of calcareous material are found in degenerative processes of the pulp as well as in pulps which are the seat of inflammatory processes. In these cases the calcifications probably have the same relation to body health as calcifications within arterial walls in arteriosclerosis. This type of calcification probably does not cause pulpal inflammation, and there is no justification for considering it a source of dental infection. The other types of pulp stones or pulp nodules (denticles) are discussed in Chapter 13 on Regressive Alterations of the Teeth.
In metastatic calcification, calcium salts are precipitated in previously undamaged tissues. This precipitation is due to an excess of blood calcium and occurs particularly in such diseases as hyperparathyroidism, which depletes the bone calcium and causes a high level of blood calcium. Metastatic calcifications also occur in hypervitaminosis D. In this type of calcification, the deposits of calcium occur mainly in the kidneys, lungs, gastric mucosa, and media of blood vessels. Since any degenerating or necrotic tissue will also be calcified when there is an increase in blood calcium levels, the differentiation between metastatic calcification and dystrophic calcification becomes extremely difficult.
Calcinosis is the presence of calcifications in or under the skin. There are two forms of calcinosis: calcinosis circumscripta, which, as the name suggests, is a circumscribed form, and calcinosis universalis, which is a generalized form. Calcinosis universalis is often associated with scleroderma and sometimes dermatomyositis. These different forms of calcinosis have been discussed by Johnson (Fig. 15-3).
The sodium found in the body is mainly associated with chloride and as NaCl and NaHCO3. The sodium ion content of the normal (70 kg) adult male ranges from 83–97 gm. Over one-third of this amount is in the skeleton, of which 65–75% is unexchangeable. Most of the remaining sodium is extracellular and accounts for 90% of the basic ions of both extracellular fluid and plasma. Enamel ash contains about 0.3%. The question of whether the sodium of the dental tissues is associated with the inorganic or organic fractions or with small quantities of tissue fluid present in the teeth remains unanswered.
The minimal requirement of salt is thought to be about 0.5 gm. The lower limit of salt intake is not really known. The estimate of 0.5 gm was reached based on the salt intake of breastfed infants. Breast milk contains 0.4 gm NaCl per liter. Interestingly, cow’s milk contains 1.7 gm NaCl per liter. The maximal intake without accumulating edema fluid is 35–40 gm per day. In the United States, the average dietary intake of sodium is 10–15 gm per day. The normal blood level is 160 mg/dl of whole blood, or 340 mg/dl of plasma (147.8 mEq/liter of plasma).
Under conditions of profuse sweating, 1 gm of salt should be ingested for each liter of water in excess of 4 liters. Sweat may contain 2–3 gm of salt per liter in hot environments if the person has not been acclimatized; after acclimatization, 0.5 gm of salt per liter is found.
The kidney is the principal organ for the excretion of water and salt. Abnormal losses of either sodium or chloride must be balanced by the kidney. When the diet is low in salt, or when there is profuse sweating, practically no sodium or chloride is found in the urine. The regulatory mechanism controlling the reabsorption of sodium and chloride by the renal tubules is controlled in part by the adrenal glands. An inadequate intake or excessive loss of sodium stimulates the adrenal cortex to secrete aldosterone, a steroid hormone which acts directly on the renal tubules to increase reabsorption and to conserve sodium. The adrenal glands also control, to a smaller degree, the salt content of s/>