Essential Trace Elements in Humans

Arsenic

Cadmium

Chromium

Manganese

Molybdenum

Nickel

Selenium

Silicon

Vanadium Zinc

Cobalt Copper Fluorine Iron

Lead Lithium impairs the crucial roles each of these processes play in wound healing. Zinc levels less than 100 mg/100 ml have been associated with impairments in wound healing.

In zinc deficiency, fibroblast proliferation and collagen synthesis are decreased, leading to decreased wound strength and delayed epithelialization. These defects are readily reversed with repletion of zinc to normal levels. Cellular and humoral immunity are impaired with zinc deficiency, resulting in an increased susceptibility to wound infection and resultant increased possibility of delayed healing. Zinc levels can be severely depleted in settings of major stress,58 and in patients receiving long-term steroids. In these settings, it is recommended that patients receive vitamin A and zinc supplements to improve wound healing.

The current recommended daily allowance for elemental zinc is 15 mg, remembering that approximately 25% of zinc sulfate is elemental and only 20% is absorbed. No studies have shown improvement in wound healing after the administration of zinc to patients who are not zinc deficient.

Zinc should be avoided during the acute phase response, because it has been associated with an increase in the febrile response.59

Iron is required for the hydroxylation of proline and lysine, and as a result, severe iron deficiency can result in impaired collagen production. As a part of the oxygen transport system, iron can affect wound healing, but this occurs only in settings of severe iron-deficiency anemia. In the clinical setting, iron deficiency is common and can result from blood loss, infectious causes, malnutrition, or an underlying hematopoietic disorder.

Determination of the presence or absence of a deficiency of one or more of the micronutrient minerals can be a complex problem, frequently requiring the integration of clinical, nutritional, and biochemical data. Using a combination of techniques, it is usually possible to determine with confidence whether an individual subject or small groups of subjects have a deficiency of specific trace elements, but simple reliable tests that can be used in population studies are still lacking an emphasis on the importance of sign and symptom recognition.60

In addition, disease states add to the complexity of trace element status assessment. For example, micronutrient deficiencies may occur in patients with malignancy due to a variety of possible causes, including unbalanced or insufficient dietary intake and adverse effects of treatment. Further, many cancer patients show signs of a chronic inflammatory response that can affect circulating concentrations of certain vitamins and trace elements. Blood concentrations of zinc and selenium are frequently lower than their respective reference ranges, although copper and manganese concentrations rise above their respective reference ranges. However, interestingly, none of these micronutrients show significant correlation with C-reactive protein.61

More recently, the ratio of neutrophils to lymphocytes has received considerable attention and is said to be of more value in terms of understanding the relationship of inflammation to mortality and heart disease.62

The surface of learning has barely been scratched with regard to the physiologic roles of trace elements. Table 10.4 summarizes the most common roles for the most important trace elements.

The assessment of trace element status is fraught with problems. Unreliable histories, contamination concentrations in medications and nutrients, analytical techniques, bioavailability, and excretion are all problematic. Because pragmatic serum levels leave much to be desired, assumption of a period without adequate nutrition should be presumed, and supplementation from day 1 of any so-called artificial feeding may be in the best interests of the patient.

Concentrations of trace elements in human tissues characteristically vary widely. Examination of some of the factors that contribute to the marked variability and skewness of the concentrations revealed that distributions of concentrations are satisfactorily normal (Gaussian) after logarithmic transformation, ash weight is the best frame of reference in which to report results, the distributions of metal concentrations are not further normalized by adjustments that assume that tissue lipid or collagen contains a fixed fraction of the metal found in the parenchyma, and the choice of sample site (i.e., hepatic) is often of minimal significance.64

To illustrate the frustration of trace element assessment, aluminum, copper, zinc, and selenium levels were determined in serum, urine, and tissue samples of burned patients. Relationships between wound healing and trace elements were evaluated. Trace element levels were determined using atomic absorption spectro-photometry. During 20 d of treatment, a significant rise in aluminum levels was determined in serum, urine, and tissue samples of patients. After day 5 of treatment, copper levels increased significantly only in urine samples. Zinc levels decreased in serum and tissue samples. However, high values of zinc in urine were measured within the first week, and then the levels returned to the initial value. There was a significant decrease in zinc in serum and tissue samples taken from patients with burns during treatment. Urine selenium levels showed a significant rise within the first 15 d.65

A variety of sources (Table 10.5) were proposed to assess functional, regulatory, sequestrated, and transport/storage sites.

Finally, the kinetics of trace elements (Table 10.6) must be appreciated. Meticulous review of biological systems must take place. Needs, toxicities, nutritional state, and disease all play a role in determining dosing.

Oral or enteral feeding requirements, respectively, can only be presumed sufficient, with corroborating calorie counts by a competent registered dietitian, and with the tolerability evidence of at least 1 to 2 L of most commercially available enteral

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