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).

Disturbances in Mineral Metabolism

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.

Requirements and Absorption

Excretion

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.

Function

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

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.

Body Distribution

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.

Requirements

Excretion

Almost 60% of the excreted magnesium is fecal, the rest being urinary; 0.75 mEq and 3–7 mEq of magnesium is lost daily in sweat and urine, respectively.

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.

Functions

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.

Deficiency

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.

Raised values of magnesium or hypermagnesemia have been reported in uncontrolled diabetes mellitus, adrenocortical insufficiency, hypothyroidism, advanced renal failure, and acute renal failure.

Pathologic Calcification

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:

• Dystrophic calcification

• Metastatic calcification

• Calcinosis.

It is not always possible to make a clear distinction between these various forms.

Dystrophic Calcification

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.