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Trace Elements. Part 2. MERCURY. Mercury is one of two (the other is bromine) elements that are liquid at room temperature and pressure Extremely toxic mercury compound, dimethyl mercury, looks like water but is three times as dense.
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Trace Elements Part 2
MERCURY • Mercury is one of two (the other is bromine) elements that are liquid at room temperature and pressure • Extremely toxic mercury compound, dimethyl mercury,looks like water but is three times as dense. • There are three naturally occurring oxidation states of mercury: Hg(0), Hg(I), and Hg(II). • Mercury is released to atmosphere as: • a product of the natural outgassing of rock (30,000 tons per year) • and as a fungicide (6,000 tons per year) • and it is incorporated into dental amalgams (90 tons per year) • Mercury is also used in electrical switches
MERCURY • Health Effects • Mercury has no known function in normal human physiology. • Mercury and its compounds have been used in medicine, although they are much less common due to the known toxic effects • Mercury(I) chloride has traditionally been used as a diuretic, topical disinfectant, and laxative. • However, mercury compounds are found in some over-the-counter drugs, including: • topical antiseptics, stimulant laxatives, diaper-rash ointment, eye drops • Mercury is widely used in the production of mascara.
MERCURY • Absorption, Transport, and Excretion • Routes of exposure include • Inhalation, primarily as elemental mercury vapor but occasionally as dimethyl mercury; • Ingestion, as HgCl2, and also consumption of high-mercury foods such as certain fish species; • Liquid metallic mercury passes the gastrointestinal tract almost unabsorbed • Methyl mercury is efficiently absorbed • Cutaneous, methyl mercury HgCl2is rapidly absorbed through skin, even through latex gloves; and
MERCURY • Injection, liquid mercury and mercury-containing tattoo pigments are relatively inert due to low water solubility. • Dental amalgams likely cause a slight increase in blood and urine mercury levels with uncertain but probably have insignificant health consequences • Mercury enters the food chain primarily by volcanic activity • and manmade sources such as coal combustion and smelting. • Most of the dietary intake comes from consumption of meat and fish products. • The kidney is the major storage organ after inorganic mercury exposure.
MERCURY • Fecal and urinary excretions are the main elimination routes for inorganic and organic mercury. • A special form of elimination is the transfer of mercury from a mother through the placenta to the fetus • Toxicity • The toxicity of mercury is primarily through reaction with sulfhydryl groups (MSH), primarily by inactivating proteins by binding to cysteine groups in proteins. • Liquid elemental mercury is essentially nontoxic, but elemental mercury vapor is toxic. • Inorganic, ionized forms of mercury are toxic. Further bioconversion to an alkyl mercury, such as methyl mercury, yields a very toxic species of mercury that is highly selective for lipid-rich mediums such as the neuron.
MERCURY • Organic mercury and elemental mercury vapor are toxic to both the central and peripheral nervous systems. • Mercury attacks the CNS well before a victim shows symptoms. • There seem to be two primary general modes of mercury toxicity, both of which result from binding of mercury to proteins: • Direct toxicity and • Immunogenic reaction to altered proteins resulting in sensitization.
MERCURY • Mercury intoxication can manifest in many signs and symptoms that affect several organ systems, including headache, tremor, impaired coordination, abdominal cramps, etc.. • Because many of these are relatively nonspecific signs and symptoms, laboratory testing provides a key role in assessing mercury intoxication. • Laboratory Evaluation of Mercury Status • Mercury is usually determined as total mercury levels in blood and urine without regard to chemical form.
Chromium • Chromium is used in the manufacturing of stainless steel • 10.5% chromium content by mass • Occupational exposure to Chromium occurs in wood treatment, stainless steel welding and the leather tanning industry • Chromium exists in two main valence states: • trivalent and hexavalent • Chromium (VI) is better absorbed and much more toxic than Chromium (III) • listed as a carcinogen implicated in lung cancer
Chromium • Health Effects • Chromium (III) is an essential dietary element & plays a role in maintaining normal metabolism of glucose, fat and cholesterol. • increases the effect of insulin, the count of insulin receptors on the cell surface and the sensitivity of cells to insulin • Chromium is important for normal sperm count and fertility. • Chromium passes through cell membranes due to its similarity to essential phosphate & sulfate oxyanions.
Absorption, Transport, and Excretion Once absorbed, chromium in the blood is bound to transferrin. Both transferrin and albumin are involved in chromium absorption and transport. Transferrin binds the newly absorbed chromium, while albumin acts as an acceptor and transporter of chromium, if the transferrin sites are saturated. Other plasma proteins, including γ and β globulins and lipoproteins, bind chromium.
Toxicity Chromium (VI), powerful oxidizing agents, is reduced intracellularly to reactive intermediates, producing free radicals and oxidizing DNA, both potentially inducing cell death. Severe dermatitis and skin ulcers can result from contact with Chromium (VI) salts. Eczema has been reported in printers, cement workers, metal workers, painters and leather tanners. When inhaled, Cr (VI) is a respiratory tract irritant, resulting in airway irritation, airway obstruction, and possibly lung cancer. Low-dose, chronic chromium exposure typically results only in transient renal effects. Elevated urinary 2-microglobulin levels (an indicator of renal tubular damage)
Deficiency Dietary chromium deficiency is relatively uncommon Most cases occur in persons with special problems such as total parenteral nutrition, diabetes, or malnutrition. Chromium deficiency is characterized by glucose intolerance, glycosuria, hypercholesterolemia, decreased longevity, decreased sperm counts, and impaired fertility.
Laboratory Evaluation Inductively coupled plasma mass spectrometry (ICP-MS) Cr is determined by AAS or ICP-MS Samples include serum, urine.
Copper Copper has excellent electrical and heat conducting properties. Copper is widely distributed in nature both in its elemental form and in compounds. Copper forms alloys with zinc (brass), tin (bronze) and nickel (cupronickel, widely used in coins)
Health Effects • Copper is distributed through the body with the highest concentrations found in liver, brain, heart, and kidneys. • Copper is an important cofactor for several metalloenzymes including: • ceruloplasmin, cytochrome C oxidase, clotting factor V,and others • It is critical for the reduction of iron in heme synthesis.
Absorption, Transport and Excretion An average day’s diet may contain 10 mg or more of copper. The amount of copper absorbed from the intestine is 50%–80% of ingested copper. The exact mechanisms by which copper is absorbed and transported by the intestine are unknown. Copper is transported to the liver and bound to albumin, transcuperin. In the liver Copper is incorporated into ceruloplasmin(contains 6 atoms) for distribution throughout the body.
Deficiency • Copper deficiency is observed in premature infants • Copper deficiency is related to malnutrition, malabsorption, chronic diarrhea, prolonged feeding with low Copper total milk diets. • Signs of copper deficiency include: • Neutropenia and hypochromic anemia in the early stages, • Osteoporosis and various bone and joint abnormalities that reflect deficient copper-dependent cross-linking of bone collagen and connective tissue, • Decreased pigmentation of the skin and general pallor, and • In the later stages, possible neurologic abnormalities (apnea, psychomotor retardation). • slowing-down of thought and a reduction of physical movements
Deficiency • An extreme form of Cu deficiency is seen in “Menkes disease” • Deficiency in a transmembrane protein that transport copper across the cell membranes. • Symptoms of Menkes disease usually appear at the age of 3 months and death usually occurs in 5-year-olds. • It is progressive brain disease characterized by retardation of growth. • Protein provides copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system.
Toxicity • Wilson’s disease is a genetically determined copper accumulation disease. • copper isn't eliminated properly and instead accumulates • Its manifestations include neurologic disorders, liver dysfunction, and Kayser-Fleischer rings (green-brown discoloration) in the cornea caused by copper deposition. • Early diagnosis of Wilson’s disease is important because complications can be effectively prevented and in some cases the disease can be halted with use of zinc acetate or chelation therapy. • blocks copper absorption from the intestinal tract.
Laboratory Evaluation of Copper Status • Serum copper and urine copper are used to: • monitor the nutritional adequacy • to screen for Wilson’s disease, • copper toxicity in premature children, • and in children with Indian childhood cirrhosis (ICC), which is not limited to Indian children. • Environmental ingestion of copper appears to be the most plausible explanation for ICC
Iron • Iron is fourth most abundant element in the earth’s crust. • Iron is classified as a trace element in the body. • Iron ions readily form complexes with certain ligands and are able to participate in redox chemistry between the ferrous (Fe(II)) and ferric (Fe(III)) states, allowing iron to: • fill many biochemical roles as a carrier of other biochemically active substances (e.g., oxygen) • and as an agent in redox and electron transfer reactions (e.g., via various cytochromes). • Iron’s high activity is a two-edged sword, and free iron ions in the body also participate in destructive chemistry, primarily in catalyzing the formation of toxic free radicals. • Hence, very little free iron is normally found in the body.
Health Effects • Of the 3 to 5 g of iron in the body, approximately 2 to 2.5 g of iron is in hemoglobin, mostly in RBCs and red cell precursors. • A moderate amount of iron (130 mg) is in myoglobin, the oxygen-carrying protein of muscle. • A small (8 mg), but extremely important, pool is in tissue where iron is bound to several enzymes that require iron for full activity. • These include peroxidases, cytochromes, and many of the Krebs cycle enzymes. • Iron is also stored as ferritin and hemosiderin, primarily in the bone marrow, spleen, and liver. • Only 3 to 5 mg of iron is found in plasma, almost all of it associated with transferrin, albumin, and free hemoglobin.
Absorption, Transport, and Excretion Absorption of iron from the intestine is the primary means of regulating the amount of iron within the body. Typically, only about 10% of the 1 g/day of dietary iron is absorbed. To be absorbed by intestinal cells, iron must be in the Fe(II) (ferrous) oxidation state and bound to protein. Because Fe(III) is the predominant form of iron in foods, it must first be reduced to Fe(II) by agents such as vitamin C before it can be absorbed. In the intestinal mucosal cell, Fe(II) is bound by apoferritin, then oxidized by ceruloplasmin to Fe(III) bound to ferritin.
Absorption, Transport, and Excretion • In plasma, transferrin carries and releases Fe to the bone marrow, where it is incorporated into hemoglobin of RBCs. • Ferroportin controls the release of iron from cells. • ferroportin plays an essential role in the export of iron from cells to blood • The recently discovered peptide hormone hepcidin largely controls iron metabolism by its ability to modulate the release of iron from cells by inhibiting ferroportin. • Iron regulation is primarily through modified absorption from the upper gastrointestinal tract.
Deficiency Iron deficiency affects about 15% of the worldwide population. Those with a higher than average risk of iron deficiency anemia include pregnant women, young children and adolescents, and women of reproductive age. Increased blood loss, decreased dietary iron intake, or decreased release from ferritin may result in iron deficiency. Reduction in iron stores usually precedes both a reduction in circulating iron and anemia, as demonstrated by a decreased red blood cell count, mean corpuscular hemoglobin concentration, and microcytic RBCs.
Toxicity • Iron overload states are collectively referred to as hemochromatosis, whether or not tissue damage is present. • Primary iron overload is frequently associated with hereditary hemochromatosis (HH) which is characterized by a high Fe absorption, culminating in Fe overload. • HH causes tissue accumulation of iron, affects liver function and often leads to hyper pigmentation of the skin. • Secondary Fe overload may result from excessive dietary, medicinal, or transfusional Fe intake or be due to metabolic dysfunction. • Treatment may include therapeutic phlebotomy or administration of chelators, such as deferoxamine. • Transferrin can be administered in the case of atransferrinemia.
Laboratory Evaluation • Disorders of iron metabolism are evaluated primarily by: • packed cell volume, • hemoglobin, • red cell count and indices, • total iron and TIBC, • percent saturation, • transferrin, • and ferritin
Manganese Various Manganesecompounds are widely used as fertilizers, animal feeds, pharmaceutical products, dyes, paint dryers, catalysts, wood preservatives, in production of glass and ceramics. Highest levels of Manganeseare found in fat and bone. Elimination through bile.
Health Effects • Manganese is biochemically essential as a constituent of metalloenzymesand as an enzyme activator. • Manganese containing enzymes include arginase, pyruvate carboxylase, and manganese superoxide dismutase in mitochondria. • Manganese-activated enzymes include hydrolases, kinases, decarboxylases, and transferases. • Many of these activations are nonspecific, so other metal ions (magnesium, iron, or copper) can replace manganese as an activator. • Such activation masks the effects of manganese deficiency.
Absorption, Transport, and Excretion • Dietary manganese is poorly absorbed (from 2%–15%), mainly from the small intestine. • Dietary factors that affect manganese absorption include iron, calcium, phosphates, and fiber. • inhibitors of manganese absorption
Deficiency Blood clotting defects, hypocholesterolemia, dermatitis, and elevated serum calcium, phosphorus, and alkaline phosphatase activity have occurred in some subjects who underwent experimental manganese depletion. Low levels of manganese are associated with epilepsy. Manganese deficiency was suggested as an underlying factor in hip abnormalities, joint disease, and congenital malformation. Manganese deficiency can cause heart and bone problems and, in children, stunted growth.
Toxicity Manganese toxicity causes nausea, vomiting, headache, memory loss, anxiety, and compulsive laughing or crying. In chronic form, manganese toxicity resembles Parkinson’s disease A clinical condition named (manganese madness) has been described in Chilean manganese miners who have experienced acute manganese aerosol intoxication.
Laboratory Evaluation Urine manganese is used in conjunction with serum manganese to evaluate possible toxicity or deficiency. It has been suggested that whole blood manganese may best reflect manganese stored in tissues.
