Trace Metals and Iron Studies PDF

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Summary

- Trace Elements, non-organic elements required for health. - Trace, found in the body at ug amounts. Include Fe, Cu and Zn. - Ultratrace, found in the body at ng amounts. Include Se, Mn, Cr. - Iron and copper have the most clinical significance. - A lack of trace elements can be caused by o Less in...

Description

MLSC-3111, Clinical Biochemistry II -

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Trace Elements, non-organic elements required for health. Trace, found in the body at ug amounts. Include Fe, Cu and Zn. Ultratrace, found in the body at ng amounts. Include Se, Mn, Cr. Iron and copper have the most clinical significance. A lack of trace elements can be caused by o Less intake o Impaired absorption o Increase excretion o Genetic abnormalities Excessive levels of trace metals are often toxic to the body. Because of this, we must detect deficient and toxic levels of trace metals. Trace metals are mainly examined through inductively coupled plasma MS (ICP-MS) and GC-MS.

Sample Collection and Processing -

Trace metals are ubiquitous in our environment and found in very small concentrations. Anticoagulant, collection procedure and specimen types are critical for acceptable samples. Diligence is essential during testing and collection. Royal Blue Tube, metal-free potassium EDTA tube used for trace metal samples. Glassware for testing must be acid washed to remove metals. Plastic ware however is suitable. Requires high purity water used in GC for testing. Testing is also done in separate rooms with controlled air flow. PPE (with booties) and particle monitoring equipment is required.

Lead -

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Sources of exposure were frequent pre-1972 when lead based paint and lead water pipes was commonly used. Lead toxicity is multifaceted and has many symptoms Protein Binding, lead binds to proteins to cause death due to vascular collapse or brain involvement. In early childhood, lead accumulation causes developmental problems (decrease IQ and growth). Inhibits Enzymes in Heme Synthesis, 99% of lead absorbed in the body binds to RBCs. This interferes with heme synthesis and causes basophilic stippling in RBCs.

Lead Testing -

Blood Lead Level (BLL), uses whole venous blood and is done on ICP-MS. ALA and FEP, elevated in lead poisoning. However, these assays are not commonly done and are usually referred to a reference lab if needed. The ALA and FEB assays are used of screening tests for lead toxicity (both increased).

MLSC-3111, Clinical Biochemistry II Arsenic -

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White, odourless, tasteless and comes in the form of powder that is water soluble. Because of this, it is the most common poison used in history. Causes acute and chronic toxicity. o Acute, onset of 2 hours from ingestion. Patient usually dies of hemorrhagic gastroenteritis (bloody vomiting). Urine specimens are ideal for analysis because it is cleared rapidly from the blood and into the urine. o Chronic, causes transverse white lines on the nails over time (Mee’s lines). Because of this, hair and nail specimens are helpful in diagnosing chronic exposure since it deposits at those sites. Antidotes for Arsenic include dimercaprol and penicillamine.

Mercury -

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One of only two metals that are liquid at room temperature. Exposure is mainly from occupational, household (batteries, thermometers) and cosmetic (mascara) hazards. Mercury will rapidly vaporize and can cause harmful nervous, digestive, and immune harm if inhaled. Toxic effects will arise due to protein binding. o Acute, involve convulsions, nausea, vomiting, etc. o Chronic, affects the CNS and causes neuropathy. Used to be used in felt hat manufacturing, resulting in workers being chronically exposed to mercury. Resulted in them suffering from neuropathy (Mad as a hatter). Vaccines used to contain thimerosol as a preservative, but that compound metabolized to ethyl mercury and is no longer used. Antidotes include EDTA, penicillamine and dimercaprol. All of these chelate mercury to make it excretable.

Copper -

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Essential trace metal required for heme synthesis, clotting factor V and is a component of metalloenzymes. Present in two forms: o Albumin Bound, also bound to transcuprien where it is transported to the liver. o In the Liver, where 80-95% of it is incorporated into ceruloplasmin and transported to the peripheral tissue. Deficiencies are rare without genetic causes. o Premature Infants, related to malnutrition/malabsorption. o Adults, usually follows an intestinal bypass. Requires parental nutrition.  Parenteral Nutrition, an administration of the nutrients that the patient cannot eat or absorb by either tube feeding formula or by mouth.

MLSC-3111, Clinical Biochemistry II

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Administered using an IV solution to put the deficient nutrients directly into the blood. TPN samples may be received. If a sample is taken above an IV it will look like a vanilla milkshake. If this happens, ultracentrifuge the sample or extract the IV solution with PEG. Diluting the sample may also work, but dilution may result in the analytes being diluted below analytical ranges. Signs of deficiency include neutropenia, micro hypo anemia, skin pallor, and neurological abnormalities. Menkes Syndrome, a sex-linked recessive disease that effects the transport of copper from the intestine too the blood leading to decreased intestinal copper absorption. Children show steely or kinky hair. Toxicity is uncommon but can occur due to the intake of copper sulfate (used in pools for water treatment). Wilson’s Disease, autosomal recessive disease that causes copper accumulation. Affects the livers copper secretion abilities when ceruloplasmin production is inhibited. Free copper will accumulate in the liver, brain, and kidney to cause damage in all sites. o Kayser-Fleischer Rings, rings around the cornea (copper deposition) of patients with high copper accumulation in Wilson’s Disease.

Copper Testing -

Copper Deficiency, ceruloplasmin, serum copper, and urine copper will be low. Copper Toxicity, ceruloplasmin and serum copper will be low and urine copper will be high. Copper accumulates in the tissue and not the blood. A defect in ceruloplasmin production will cause low bound copper and increased free copper. Also causes plasma copper levels to decrease with excess free copper still being excreted in the urine.

Iron -

An essential element that is contained in the porphyrin ring of heme molecules. Free iron however is highly toxic to cells. Iron metabolism is controlled by the intestine and there is little control of iron excretion. Metabolism requires vitamin C to convert Fe3+ to Fe2+. 75% of iron is incorporated into Hb, 20% in the storage form and 5% in myoglobin. Normal iron intake will balance the normal loss of iron. Iron is transported by transferrin where it is taken to RBC mitochondria or to cells for storage. The storage form is ferritin, and it is water soluble. Iron can also be found as hemosiderin which is not water soluble. Iron has marked diurnal variation and is highest in the morning and lowest in the evening.

MLSC-3111, Clinical Biochemistry II

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Decreased iron can be due to o Inadequate Intake o Increased Iron Loss o Increased Demand o Protein Loss o Inflammatory States Iron deficiency Anemia, most common single-nutrient deficiency. Affects 15% of the worldwide population. Iron stores (ferritin) diminish before reduction in circulating iron. Increased iron may be due to o Increased red cell destruction, (hemolytic anemias) o Decreased/inefficient red cell production, (aplastic, pernicious anemias) o Abnormal heme synthesis, (lead poisoning, enzyme deficiencies) o Chronic blood transfusions o Increased release of stored iron, (liver necrosis) o Increased absorption/uptake of iron, (hemochromatosis, iron therapy) o Acute ingestion of iron pills Iron Overload, seen in hereditary hemochromatosis caused by a mutation in the HFE gene. HFE down regulates iron absorption and the mutated version will increase iron absorption by at least 100%. Hereditary hemochromatosis caused iron deposits in the organs and skin and is treated with therapeutic phlebotomy and chelation. Hemosiderosis, caused by an iron overload from RBC lysis. STAT iron can be done on children who have ingested iron supplement pills excessively.

Iron Testing -

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Diagnosis for IDA can be done in hematology using iron indices and morphology. Serum Iron, refers to the iron bond to Ferritin. Morning samples are preferred due to the diurnal variation. Falsely elevated in hemolyzed and icteric samples. Ferritin, consists of iron and apoferritin. Represents the body’s iron stores as ferritin is the storage form of iron. The body release iron from ferritin as needed. Ferritin will decrease before serum iron does. o Iron Deficiency, decreased ferritin. o Iron Overload, increased ferritin. Ferritin is a positive APR and is increased in chronic inflammation/infection. As a result, a normal ferritin level can be seen in iron deficiency if the patient is undergoing a coexisting APR. TIBC, the theoretical amount of iron that could be bound if transferrin was saturated (proteins that are available to bind iron). It is an indirect measure of transferrin as about 1/3 of transferrin is saturated with iron. TIBC on V350 o Add excess reagent Fe to the sample, saturates all transferrin binding sites.

MLSC-3111, Clinical Biochemistry II

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o Remove excess unbound Fe, mixture is put through a column (chromatography). o Measure Total Iron, analyzed in a serum eluate. Measured iron reflects proteinbound iron which is a reflection of the amount of transferrin in the sample. Decreased serum iron will lead to increased transferrin production (body tries to collect more iron in a deficiency). Increases the TIBC. Seen in IDA and iron deficiency in general. Increased serum iron will lead to decreased transferrin production (body does not need as much iron stores). Decreases the TIBC. Seen in hemochromatosis, chronic infection and malignancy. Transferrin, measured immunochemically through nephelometry. It binds Fe in the blood so it can circulate in the body. Transferrin is elevated in IDA and decreased in iron overload. Transferrin and TBIC should correlate (transferrin is proportional to TIBC). TIBC and transferrin have similar clinical relevance, but both are used since transferrin directly reflects nutritional status in patients. Fe (%) Saturation, calculated as the ratio of iron to TIBC (serum iron/TIBC). o High Fe Saturation, iron overload. Sensitive screen for hereditary hemochromatosis (>0.60 in males, >0.50 in females) o Low Fe Saturation, IDA if less than 0.15....