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Trace Elements

Trace Elements. Introduction. Almost half of the elements listed in the periodic table have been found in the human body. The essential and nonessential have biochemical importance, whether minor or major.

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Trace Elements

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  1. Trace Elements

  2. Introduction • Almost half of the elements listed in the periodic table have been found in the human body. • The essential and nonessential have biochemical importance, whether minor or major. • The essential trace elements are usually associated with an enzyme (metalloenzyme) or another protein (metalloprotein) as an essential component or cofactor. • Deficiencies typically impair one or more biochemical functions and • excess concentrations are associated with at least some degree of toxicity.

  3. Introduction • Trace elements, • Such as iron, copper, and zinc, • Found in mg/L concentrations, • Ultratrace elements, • Such as selenium, chromium, and manganese, • Found in less than µg/L concentrations • Examples of conditions that could result in deficiency of trace elements: • Decreased intake, • Impaired absorption, • Increased excretion, • And genetic abnormalities

  4. The World Health Organization has established the dietary requirement for nutrients as the smallest amount of the nutrient needed to maintain optimal function and health. Any element that is not considered essential is classified as nonessential. Nonessential trace elements are of medical interest primarily because many of them are toxic.

  5. Sample Collection and Processing • Specimens must be collected with precise attention to details such as: • anticoagulant, collection apparatus, and specimen type(serum, plasma, or blood) • By the low concentration in biologic specimens and the ubiquitous presence in the environment, extraordinary measures are required to prevent contamination of the specimen. • This includes using special sampling and collection devices, specially cleaned glassware, and water and reagents of high purity. • Water and other reagents, pipettes, and sample cups must be carefully evaluated for use in trace and ultratrace analyses.

  6. Sample Collection and Processing • In addition, the laboratory environment must be carefullycontrolled. • Recommended measures include placing the trace elements laboratory in a separate room incorporating rigorous contamination control features, such as: • sticky mats at doors, • nonshedding ceiling tiles, • Carefully controlled air flow to minimize particulate contamination, • disposable booties worn over shoes, • particle monitoring equipment, etc. • Many useful measures are borrowed from those employed in semiconductor clean rooms.

  7. Instrumentation and Methods Atomic Emission Spectroscopy (AES) Atomic Absorption Spectroscopy Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

  8. Instrumentation and Methods • Interferences • They are classified: • Spectroscopic • Spectral interferences generally result from a spectral overlap with the spectrum of the target analyte. • For example, in AA certain molecular species may have broad absorption spectra that may overlap the line spectra of the elements of interest, leading to false elevations of the target element concentrations.

  9. Instrumentation and Methods • Nonspectroscopic • Matrix interferences involve the bulk physical properties of the sample to be analyzed. Anything that could interfere with atomization of the sample • in AA, a flame may not be hot enough for efficient atomization

  10. Instrumentation and Methods • Elemental Speciation • The toxicity of elements may depend on its chemical form. • For example, • arsenobetaine is a relatively nontoxic form of arsenic • Methylated forms of arsenic are intermediate in toxicity, and • Inorganic arsenic, such as As(V) and As(III), are highly toxic. • In the medical evaluation of patients, it can be important to know whether an elevated arsenic level is due to relatively innocuous forms, • such as arsenobetaine, perhaps from a seafood meal ingested up to 3 days before the specimen collection, • or by dangerous forms such as inorganic arsenic • In addition, the concentrations of methylated forms may be useful information for monitoring recovery from toxic exposure.

  11. Instrumentation and Methods • Hyphenated Techniques • Hyphenated techniques allow for the speciation determinations. • In a hyphenated analysis, the combination of two or more complementary analytic techniques is used to measure the specific form of an analyte. • A classic example of this approach is liquid chromatography ICP-MS (LC-ICP-MS). • The sample is injected into a liquid chromatograph, which separates the different chemical forms of the analyte, with each form eluting at a different retention time.

  12. ARSENIC • Arsenic is ubiquitous. • Its content in earth’s crust is estimated at 1.5–2.0 mg/kg. • The predominant natural sources are volcanoes and weathering of minerals. • Anthropogenic sources of arsenic release three times more arsenic than do natural sources. • Production of metals, • Burning of coal, • Fossil fuels, • Timber (treatment) and • Its use in agriculture (insecticides)

  13. ARSENIC • Health Effects • Arsenic is currently considered to be nonessential, with no known function in human physiology. • Therefore, arsenic is of medical interest principally due to its toxicity. • In 2000, the U.S. Food and Drug Administration (FDA) approved the use of arsenic trioxide for the treatment of acute promyelocytic leukemia (APL) • Absorption • The main routes of exposure are ingestion of arsenic containing foods, water, and beverages or inhalation of contaminated air.

  14. ARSENIC • Toxicity • Acute exposure: The symptoms may include: • Gastrointestinal (nausea, diarrhea) • Bone marrow (pancytopenia) • Cardiovascular (ECG changes) • Central nervous system (encephalopathy) • Renal (renal failure) • Hepatic (Hepatitis) • Chronic exposure may include: • Dermatologic, hepatic, cardiovascular, CNS, and malignant changes

  15. ARSENIC If exposure occurred within 24 h or for patients who cannot provide a urine specimen (e.g., dialysis patient), arsenic can be detected in blood. However, in most cases it is best detected by urine due to the short half-life of arsenic in blood.

  16. ARSENIC • Laboratory Evaluation of Arsenic Status • For acute exposure, urine is generally the preferredsample due to the short half-life of arsenic in blood. • For very recent exposure (<24 h), serum arsenic testing maybe helpful. • For chronic or past exposures (3 weeks), analysis of hair or nails may be useful. • Keratin, the major structural protein in hair and nails, contains many cysteine residues

  17. CADMIUM Cadmium (Cd) is a soft, bluish-white metal, which iseasily cut with a knife. Principal industrial uses of cadmium include manufacture of pigments and batteries, as well as in the metal-plating and plastics industries. Cadmium-containing waste products and soilcontamination, primarily as a result of human activity,are becoming of concern

  18. CADMIUM • Health Effects • Cadmium has no known role in normal human physiology (Newborn babies are practically free of cadmium). • Cadmium forms protein-Cd adducts. • These are believed to exhibit cadmium toxicity via denaturation of the cadmium-bound proteins, resulting in a loss of function. • Cadmium concentrations in organs increase with age (eg. liver, kidney). • Smoking increases accumulation of cadmium. • The placenta can accumulate cadmium as well. • Smoking during pregnancy enhances cadmium levels as compared with nonsmokers.

  19. CADMIUM • Absorption • Smokers of tobacco products have about twice the cadmium abundance in their bodies as nonsmokers. • For nonsmokers, the primary exposure to cadmium is through ingested food. • In blood, cadmium is bound mostly (70%) to the RBCs. • Cadmium in blood reflects the average uptake during the past few months and can be used for monitoring purposes.

  20. CADMIUM • Toxicity • Chronic cadmium exposure • Renal dysfunction is a common presentation • Breathing of cadmium vapors can result in lung damage similar to emphysema. • Cadmium exposure can also affect the liver, bone, immune, blood, and nervous systems. • Acute effects of inhalation of fumes containing cadmium include: • respiratory distress due to chemical pneumonitis and edema and can cause death

  21. CADMIUM • Laboratory Evaluation of Cadmium Status • Blood cadmium indicates recent exposure • Urine cadmium indicates body burden • the total accumulation of toxins in your body • Contamination of the sample must be guarded against. • In particular, one should avoid the use of containers containing colored plastics; yellow-colored plastic in particular often contains cadmium.

  22. LEAD • Lead is widely distributed in earth’s crust. • Lead is used in production of storage batteries, ammunition, solder, and foils. • Tetraethyl lead was once used extensively as an additive in gasoline (petrol) for its ability to increase the fuel’s octane rating. • Recently, there were massive recalls of toys produced in China, due to their high lead contents. • Health Effects • Lead plays no known role in normal human physiology.

  23. LEAD • Absorption • Exposure to lead is primarily respiratory or gastrointestinal. • Enhanced gastrointestinal absorption may occur in children younger than 6 years of age. • Lead is transported to the blood, where 94% is transferred to the erythrocytes (RBCs) and primarily bound to hemoglobin and about 6% is in the plasma. • The half-life in whole blood is 2 to 3 weeks. Lead is then primarily distributed to soft tissues, such as liver, kidneys, and brain, and the final storage of lead is in soft tissue and bone. • Absorbed lead is excreted primarily in urine (76%)and feces (16%), and the remaining 8% is excreted in hair,sweat, nails, and others.

  24. LEAD • Toxicity • Symptoms of toxicity in children are usually seen at blood levels of 60 µg/dl • IQ declines are seen in children with blood lead levels of 10 µg/dl or higher. • Other CNS symptoms of lead toxicity in children may include headache, behavioral changes, seizures, severe cognitive and behavioral problems. • Other conditions may include acute nephropathy and anemia. • In adults, the following may be observed: • peripheral neuropathies, motor weakness, chronic renal insufficiency and systolic hypertension, and anemia.

  25. LEAD • Laboratory Evaluation of Lead Status • The most common specimen type is whole venous blood. • This is preferred over plasma and serum because circulating lead is predominantly associated with RBCs. • A variety of other sample types are sometimes used, such as hair, nails, and urine. • Urine lead may be useful for detecting recent exposures to lead or to monitor chelation therapy. • Other testing, may be useful for screening in occupational exposures such as: • Plasma aminolevulinic acid, (first compound in the porphyrin synthesis pathway) • Whole blood zinc protoporphyrin (ZPP), or • when the insertion of iron is inhibited, as in lead poisoning, then protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. • Free erythrocyte protoporphyrins

  26. Pathway of porphyrin synthesis: formation of heme.

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