Download Mercury(I)

Part 2
 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:
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a product of the natural out gassing 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
 Health
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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
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Mercury(I) chloride has traditionally been used as a diuretic, topical
disinfectant, and laxative.
However, mercury compounds are found in some over-thecounter drugs, including:
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Effects
topical antiseptics, stimulant laxatives, diaper-rash ointment, eye drops
Mercury is widely used in the production of mascara.
 Absorption,
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Routes of exposure include
1.
2.
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;
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3.
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Transport, and Excretion
Liquid metallic mercury passes the gastrointestinal tract almost
unabsorbed
Methyl mercury is efficiently absorbed
Cutaneous, methyl mercury is rapidly absorbed through skin, even
through latex gloves; and
3.
4.
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.
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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.
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:
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Direct toxicity and
 Immunogenic reaction to altered proteins resulting in
sensitization.
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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
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Evaluation of Mercury Status
Mercury is usually determined as total mercury levels in blood
and urine without regard to chemical form.
 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
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 Health
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Effects
Chromium (III) is an essential dietary element & plays a role
in maintaining normal metabolism of glucose, fat and
cholesterol.
Chromium is important for normal sperm count and fertility.
Chromium passes through cell membranes due to its
similarity to essential phosphate & sulfate oxyanions.
 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.
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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)
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 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.
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Cr
is determined by AAS or ICP-MS
Samples include serum, urine.
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Inductively coupled plasma mass spectrometry (ICP-MS)
 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)
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 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:

 It
ceruloplasmin, cytochrome C oxidase, clotting factor V, and
others
is critical for the reduction of iron in heme
synthesis.
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 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.
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 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).
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 An
extreme form of Cu deficiency is seen in
“Menkes disease”
 Symptoms of Menkes disease usually appear at the
age of 3 months and death usually occurs in 5-yearolds.
 It is progressive brain disease characterized by
retardation of growth.
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 Wilson’s
disease is a genetically
determined copper accumulation
disease.
 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.
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 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.
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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:
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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.
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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.
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Only 3 to 5 mg of iron is found in plasma, almost all of it
associated with transferrin, albumin, and free hemoglobin.
 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.
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 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.
 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.
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 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.
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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.
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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.
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HH causes tissue accumulation of iron, affects liver function and
often leads to hyper pigmentation of the skin.
 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
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 Various
Manganese compounds are widely used as
fertilizers, animal feeds, pharmaceutical products, dyes,
paint dryers, catalysts, wood preservatives, in production
of glass and ceramics.
 Highest levels of Manganese are found in fat and bone.
 Elimination through bile.
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 Manganese
is biochemically essential as a constituent of
metalloenzymes and 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.
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Such activation masks the effects of manganese deficiency.
 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.
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 Blood
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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.
 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.
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 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.
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