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.
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. 

3. Introduction Trace elements, Ultratrace 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
copper deficiency are seen in Menkes' disease

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 carefully controlled.
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.

10. 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

11. 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.
Innocuous: غير مؤذية. The absorbed arsenic undergoes hepatic biomethylation to form monomethylarsonic acid and dimethylarsinic acid that are less toxic but not completely innocuous.

12. 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.

13. 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)
Weathering: The decay and break up of rocks on the Earth’s surface by natural chemical and mechanical processes.
Arsenic was also used in various agricultural insecticides 

14. ARSENIC Health Effects Absorption
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.

15. 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

16. 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.

17. ARSENIC Laboratory Evaluation of Arsenic Status
For acute exposure, urine is generally the preferred sample due to the short half-life of arsenic in blood.
For very recent exposure (<24 h), serum arsenic testing may be 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
Arsenic circulating in the blood will bind to protein by formation of a covalent complex with sulfhydryl groups of the amino acid cysteine

18. CADMIUM
Cadmium (Cd) is a soft, bluish-white metal, which is easily 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 soil contamination, primarily as a result of human activity, are becoming of concern

19. 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.
Adducts: the product of an addition reaction between two compounds. Cross the placenta

20. 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.

21. 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

22. 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.
body burden: the total amount of a particular chemical present in a human's or animal's body,

23. 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.
Ammunition: الذخيرة
The higher the octane number, the more compression the fuel can withstand before detonating (igniting).
octane rating: standard measure of the performance of an engine 

24. 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.

25. 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.
intelligence quotient

26. 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
Aminolevulinic acid is the first compound in the porphyrin synthesis pathway

27. Pathway of porphyrin synthesis: formation of heme.