Ch. 18 - Trace Elements Flashcards
An element is considered _____ if a deficiency impairs a biochemical or functional process.
Essential
What would be the treatment for the deficiency of an essential element?
Replacement
This type of trace element is of medical interest primarily because many of them are toxic.
Nonessential
The essential trace elements are often associated with an enzyme called _____ or a protein called _____ as a cofactor.
Metalloenzyme
Metalloprotein
This is a crystalline, silver-white ductile metal.
It is the most abundant metal on earth.
Aluminum (Al)
The human body absorbs how much of inhaled aluminum?
1.5% - 2%
The human body absorbs how much of ingested (orally taken) aluminum?
0.01% - 5%
The absorption efficiency of aluminum is dependent on what factors?
Chemical form
Particle size
Dietary exposure to chelators
What are the chelating agents to aluminum?
Citric and Lactic acid
In plasma, Al is bound to carrier proteins such as _____.
Transferrin
Al binds to various _____ in the blood and distributes to every organ.
Ligands
How much of the Al in the body is found in the bone?
50%
How much of the Al in the body is found in lung tissue?
25%
How much of the Al in the body is excreted through urine?
95%
How much of the Al in the body is excreted in the bile?
2%
The amount of Al in this body organ increases with age.
Lungs
This trace element has been shown to interfere with enzymatic processes and will produce encaphalopathy in animals.
Aluminum
What are the signs and symptoms of Al toxicity?
Encephalopathy Osteomalacia/aplastic bone disease (painful spontaneous fractures, hypercalcemia, and tumor calcinosis) Proximal myopathy Increased risk of infection Microcytic anemia Increased left ventricular mass Decreased myocardial function
What are the clinical manifestations of Al toxicity?
Anemia
Bone disease
Progressive dementia with inc. conc. of Al in the brain
Al toxicity can cause what disease in infants?
Impaired neurologic development
This is a ubiquitous element displaying both metallic and non-metallic properties.
Arsenic (As)
This is the largest source of As exposure for most people.
Food
What is the main current use of As?
Wood preservative
Enumerate other current and past uses of As.
Pesticides Pigments Poison gases Ammunition manufacturing Semiconductor proecessing Medicines
The clinical signs and symptoms of As exposure depends on these factors.
Duration and extent of exposure to organic and methylated species of As
Underlying clinical status of patient
What are the symptoms for acute As exposure?
Gastrointestinal (nausea, emesis, abdominal pain, rice water diarrhea)
Bone marrow (Pancytopenia, anemia, basophilic stippling)
Cardiovascular (ECG changes)
CNS (Encephalopathy, polyneuropathy)
Renal (Renal insufficiency, renal failure)
Hepatic (Hepatitis)
What are the symptoms for chronic As exposure?
Dermatologic (Mees’ line, hyperkeratosis, hyperpigmentation, alopecia)
Hepatic (Cirrhosis, hepatomegaly)
Cardiovascular (Hypertension, peripheral vascular disease [PVD])
CNS (“Socks and gloves” neuropathy, tremor)
Malignancies (Squamous cell, hepatocellular, skin, bladder, lung, renal carcinoma)
What are the symptoms for chronic As exposure specifically concerning the CNS?
“Socks and gloves” neuropathy
Tremor
Chronic exposure to As has been shown to cause _____, a severe form of PVD which leads to gangrenous changes.
Blackfoot disease
What are the dermatological symptoms for chronic As exposure?
Mees’ line
Hyperkeratosis
Hyperpigmentation
Alopecia
What are the chelating agents for As poisoning?
Dimercaprol (aka. British anti-Lewisite)
Penicillamine
Succimer
Arsenic trioxide can be used for the treatment of what disease?
Acute Promyelocytic leukemia
What are the main routes for As exposure?
Ingestion
Inhalation
What are the organic forms of As?
Arsenocholine
Arsenobetaine
This form of As is commonly found in fish and seafood , are considered relatively non-toxic, and are cleared rapidly.
Organic form
This form/species of As are highly toxic and occur naturally in rocks, soil, and groundwater.
Inorganic form
This form/species of As are intermediate in toxicity and arise primarily from metabolism of inorganic As, but small amounts may arise from food.
Methylated
Give examples of organic methylated As compounds.
Monomethylarsonic acid (MMA) Dimethylarsenic acid (DMA)
This organic methylated arsenic compound was formed by the hepatic metaolism of As(3+).
Monomethylarsonic acid (MMA)
This organic methylated arsenic compound was formed by the hepatic metaolism of As(5+).
Dimethylarsenic acid (DMA)
(T/F) Inorganic methylated forms are more toxic than its organic counterparts and they are eliminated slowly, usually 1 - 3 weeks.
F (Inorganic less toxic than organic (As3+ and As 5+)
This is a soft bluish-white metal that can be easily cut with a knife.
Cadmium (Cd)
What are the most common uses of Cd?
Manufacture of pigments, batteries, metal plating, plastic
What is the largest source of airborne Cd exposure?
Burning of fossil fuel
Incineration of municipal waste
What is the chelating agent for Cd exposure/
EDTA
What is the reference dose for Cd in drinking water?
0.0005 mg/kg/d
What is the reference dose for dietary exposure to Cd?
0.001 mg/kg/d
Absorption of Cd is (higher/lower) in females than in males due to differences in iron stores.
Higher
How much of inhaled Cd is absorbed in the body?
10-50%
For nonsmokers, what is the primary source of Cd exposure?
Ingested food
A what percent of the ingested Cd is excreted in the feces due to the low absorbance of Cd from the gut?
90%
Inhaled Cd can cause what toxic effects?
Respiratory distress Lung damage (Emphysema-like symptoms)
Acute Cd exposure can cause what toxic effects?
Nausea
Vomiting
Abdominal pain
Chronic Cd exposure can cause what toxic effects?
Slow onset of preteinuria
The toxicity of Cd is believed to be a result of _____ causing denaturation of the associated proteins, resulting in a loss of function.
Protein-Cd adducts
This element comes from the Greek word chroma meaning color.
Chromium (Cr)
This is the 21st most abundant element
Cr
What are the most common uses of Cr?
Manufacturing stainless steel Wood treatment Chrome plating Leather tanning Lead chromate or strontium chromate paints
What are the two main valencies of Cr?
Trivalent Cr(3+) Hexavalent Cr(6+)
(T/F) Cr(6+) is better absorbed and much more toxic that Cr(3+)
T
This element is responsible for the red color of rubies and the green color of emerald.
Chromium (Cr)
This proteins bind the newly absorbed Cr at site B.
Transferrin
This as an acceptor and transporter of Cr when transferrin sites are saturated.
Albumin
Aside from transferrin and albumin, enumerate other plasma proteins that can bind Cr.
Beta-globulins
Gamma-globulins
Lipoproteins
This element is an essential dietary element and plays a role in maintaining normal metabolism of glucose, fat, and cholesterol..
Chromium (Cr(3+))
What is the estimated safe and adequate daily intake of Cr for adults?
50 - 200ug/d
Intracellularly, this valence state of CR is reduced to reactive intermediates, producing free radicals and oxidizing deoxyribonucleic acid (DNA), both potentially inducing cell death.
Cr(6+)
What is the primary means for Cr to enter the body?
Ingestion
Inhalation
What is the mode of excretion of Cr?
Urine
Cr deficiency is characterized by what conditions?
Glucose inteolerance Glycosuria Hypercholesterolemia Decreased longevity Decreased sperm counts Impaired fertility
Contact with Cr(6+) salts can induce what conditions?
Severe dermatitis
Skin ulcers
Cr(3+/6+)-protein complex is responsible for allergic reactions due to Cr toxicity
Cr(3+)
(Low/High)-dose, (chronic/acute) Cr exposure typically results in transient renal effects.
Low
Chronic
This element is known to be a soft yet tough metal with excellent electrical and heat conducting properties.
Copper (Cu)
What are the four oxidation states of Cu?
Cu(0-3+)
Among the oxidation states of Cu, what is the most stable?
Cu(2+)
This element is an importnant cofactor for several metalloenzymes and is critical for reduction of iron in heme synthesis.
Copper (Cu)
How much of ingested copper is absorbed from the intestines?
50% - 80%
What is the average daily intake of Cu?
10 mg or more
At low concentrations, how is copper transported by the intestines?
Active transport
At high concentrations, how is copper transported by the intestines?
Passive transport
In the liver, copper is incorporated into _____ for ditribution throughout the whole body.
Ceruloplasmin
98% of copper is excreted by the _____ and the other 2% is excreted through _____ and _____.
Bile
Urine and sweat
Copper deficiency is observed in premature infants and copper absorption is impaired in what clinical conditions?
Sever diffuse diseases of small bowel
Lymphosarcoma
Scleroderma
An extreme form of copper deficiency can be seen in _____ disease, with symptoms usually appear at the age of 3 months and death occuring at the age of 5.
Menkes
What are the signs of Cu deficiency?
Neutropenia and Hypochromic anemia in the early stages
Osteoporosis and various bone and joint abnormalities
Decreased pigmentation of the skin and general pallor
Neurologic abnormalities in the late stages (Hypotonia, apnea, psychomotor retardation)
What color is exhibited in Cu-induced emesis?
Blue-green
This is a genetically determined Cu-accumulation disease that usually present between the ages of 6 - 40 years old.
Wilson’s disease
What are the clinical findings when a patient is suffering from copper deposition? (Wilson’s disease)
Neurologic disorders
Liverdysfunction
Kayser-Fleischer rings (green-brown discoloration) in the cornea
What treatments can be done to stop Wilson’s disease?
Zinc acetate
Chelation therapy
These are key diagnostic steps in diagnosing Wilson’s disease.
Serum ceruplasmin levels
Direct measurement of free copper
This is the 4th most abundant metal and the most abundant transitional metal
Iron (Fe)
What are the two valence forms of Fe that are able to partcipate in redox chemistry?
Ferrous (Fe(2+))
Ferric (Fe(3+))
Ferrous (Fe(2+)) and Ferric (Fe(3+)) states allows iron to fill numerous biochemical roles such as _____ and _____.
Carrier of other biochemically active substances
Agent in redox and electron transfer reaction (eg. via various cytochromes)
This type of Fe in the body participates in destructive chemistry, primarily in catalyzing the formation of toxic free radicals.
Free iron
This is the primary means of regulating the amount of iron within the body.
Absorption of Fe in the intestines
To be absorbed by intestinal cells, iron must be _____ and _____.
In ferrous (Fe2+) oxidation state Bound to protien
This is the predominant form of Fe in food.
Ferric (Fe3+)
What agents in the intestinal epithelium reduces Fe(3+) to Fe(2+) state?
Vitamin C
Ferric reductases
What peptide hormone regulates iron absorption in the upper gastrointestinal tract by modulating the export of iron from cells by ferroportin.
Hepcidin
Absorption and transport capacity of iron can be increased in conditions such as _____ …
Iron deficiency
Anemia
Hypoxia
Iron is lost primarily by _____ and _____.
Desquamation and red cell loss to urine and feces
How much iron is present in the human body?
3-5g
Of the total Fe in the body, how much is present in hemoglobin, mostly in RBCs and red cell precursors?
2-2.5g
Of the total Fe in the body, how much is present in myoglobin, the oxygen carrying protein of the muscle?
~130mg
This is the oxygen carrying protein of the muscle?
Myoglobin
Of the total Fe in the body, how much is bound to tissue enzymes that require iron for full activity?
8mg
Enumerate some enzymes that require iron for full activity.
Peroxidases
Cytochromes
Many of the Krebs cycle enzymes
Iron is stored as _____ and _____, primarily in the bone marrow, spleen and liver.
Hemosiderin
Ferritin
This is a protein that transports Fe to the different parts of the body.
Apotransferrin
How much of iron is excreted through menstrual cycle?
20-40mg
Enumerate those that have a higher than average risk of acquiring iron deficiency anemia.
Pregnant women
Young children
Adolescents
Women of reproductive age
These conditions may result in iron deficiency anemia.
Increased blood loss
Decreased dietary iron intake
Decreased released from ferritin
A decrease in these lab results would indicate iron deficiency anemia.
RBC count
MCHC
Microcytic RBCs
Iron overload states are collectively referred to as _____.
Hemochromatosis
Primary iron overload is most frequently associated with what disease?
Hereditary Hemochromatosis (HH)
This is a single-gene homozygous recessive disorder leading to abnormally high Fe absorption, culminating in Fe overload.
Hereditary Hemochromatosis (HH)
What effects can Hereditary Hemochromatosis (HH) have?
Tissue accumulation of Fe
Affects liver function
Often leads to hyperpigmentation of the skin caused by slight decrease in transferrin
What condition are associated with severe hemochromatosis?
Diabetes mellitus Arthritis Cardiac arrhythmia or failureCirrhosis Hypothyroidism Impotence Liver cancer
What is the treatment for Fe overload?
Therapeutic phlebotomy or administration of chelators, such as deferoxamine
What chelator is used for the treatment of Fe overload?
Deferoxamine
This iron related disease may result from excessive dietary, medicinal, or transfusional Fe intake or due to metabolic dysfunction.
Secondary Fe overload
This condition has been used to specifically designate a condition of iron overload as demonstrated by an increased serum iron and total iron-binding capacity (TIBC) or transferrin, in the absence of demonstratable tissue damage.
Hemosiderosis
This element is soft, bluish white, highly malleable, and ductile. It is a poor conductor of electricity and heat and us resistant to corrosion.
Lead (Pb)
What are the most common uses of lead (Pb)?
Production of storage batteries, ammunition, solder, and foils, crayons and children’s toys.
What substances can weaken lead absorption?
Iron Calcium Magnesium Alcohol Fat
What factors can enhance lead absorption?
Low dietary zinc, ascorbic acid, and citric acid
About 99% of lead is taken up by _____ where it interferes with heme synthesis.
Erythrocytes
How much of absorbed lead is excreted in the urine?
76%
How much of absorbed lead is excreted in the feces?
16%
How much of absorbed lead is excreted in the hair, sweat, and nails?
8%
Blood lead levels greater than or equal to ___ug/dL in children can lead to a decrease in IQ.
10
Lead toxicity exhibits this characteristic property in the blood film.
Basophilic stippling
This element is a heavy, silvery metal also called quicksilver.
Mercury (Hg)
Along with bromine, it is one of two elements that are liquid in room temperature.
Mercury (Hg)
What are the three naturally occurring oxidation states of mercury?
Hg(0-2+)
What are the most common uses of Hg?
Dental amalgrams Electronic switches Germicides Fungicides Fluorescent light bulbs
Enumerate over-the-counter drugs that contain Hg.
Topical antiseptics Stimulant laxatives Diaper-rash ointment Eye drops Nasal sprays Eye cosmetics, mascara
What are the routes of exposures of mercury?
Inhalation, elemental Hg vapor
Ingestion of HgCl2 and mercury containing foods (fish)
Cutaneous absorption of methyl mercury (MeHg) through the skin and latex gloves
Injection of relatively inert liquid mercury/ mercury-containing tattoo pigments
Dental amalgrams
Lead in the body is eliminated in approximately how many days?
60 days
This type of mercury can accumulate in the brain and may take up to several years to be eliminated.
Organic mercury
What are the main elimination routes for lead?
Feces
Urine
(T/F) Organic and elemental mercury vapor are toxic to only the CNS and not the peripheral NS
F (Toxic to both CNS and peripheral nervous system
The inorganic salts of mercury can affect what parts of the body?
Skin
Eyes
Gastrointestinal tract
Kidneys
The toxicity of mercury is primarily through reaction with _____, resulting in dysfunction and inactivation.
Protein sulfhydryl groups (MSH)
This type of Hg is poorly absorbed and relatively nontoxic.
Liquid elemental Hg
Inorganic, ionized forms of mercury are (toxic/nontoxic).
Toxic
This is an alkyl Hg that yields a very toxic (most toxic) species of Hg that is highly selective for lipid-rich mediums such as the brain.
Methyl Hg (MeHg)
This type of Hg binds with cysteine and can cross the blood-brain barrier causing an accumulation of Hg in the brain
Methyl Hg (MeHg)
This is the 12th most abundant element in the earth’s crust.
Manganese (Mn)
What are the most common uses of Mn?
Fertilizers
Animal feeds
Dyes
Paint dryers
Of the dietary manganese, how much is absorbed in the small intestine?
2-15%
Mn absorption is age dependent, with infants retaining (higher/lower) levels of Mn than adults.
Higher
Highest levels of Mn can be found in what tissues/parts of the body?
Fat
Bone
Mn elimination occurs predominantly through the _____.
Bile
What are the functions of Mn?
Constituent of metalloenzymes
Enzyme activator
Enumerate some Mn containing enzymes
Arginase
Pyruvate carboxylase
Mn superoxidase dismutase in the mitochondria
Enumerate some Mn activated enzymes
Hydrolases
Kinases
Decarboxylases
Transferases
Enumerate conditions that can be observed in people who have Mn depletion.
Blood clotting defects
Hypocholesterolemia
Dermatitis
Elevated serum calcium, phosphorus, and alkaline phosphatase activity
What conditions have been associated with low levels of Mn?
Epilepsy Stunted growth Hip abnormalities Joint disease Congenital malformation Heart and bone problems
Chronic Mn toxicity resembles what disease?
Parkinson’s disease with akinesia, rigidity, tremors and mask-like faces
This condition is a result of acute Mn aerosol intoxication.
Locura manganica (Mn madness)
This element is a hard, silvery white metal most commonly used in corrosion inhibitors, flame retardants, and smoke depressants.
Molybdenum (Mo)
What are the three types of Molybdenum (Mo)?
Molybdenite
Wulfenite
Powelite
Absorption of 25% - 80% of ingested Mo occurs predominantly in the _____ and _____.
Stomach
Small intestine
Majority of absorbed Mo is retained in what organs?
Liver
Skeleton
Kidney
In blood, Mo is bound to _____ and _____.
alpha2-macroglobulin
RBC membranes
(T/F) Mo can cross the placental barrier
T
Enumerate the three enzymes containing Mo
Xanthine oxidase
Aldehyde oxidase
Sulfite oxidase
Mo is eliminated through _____ and _____.
Urine
Bile
High dietary and occupational exposures to Mo have been linked to what conditions?
Elevated uric acid in blood
Increased incidence of gout
This is a naturally occurring metalloid with many chemical and physical properties similar to those of sulfur.
Selium (Se)
WHat are the most common uses of Se?
Nutritional supplements
Rubber production
Anti-dandruff shampoo
What is the biologic function of Se?
Cellular antioxidant
Metabolism of thyroid hormones
Where does absorption of Se occur?
Gastrointestinal tract (~50%)
How is Se excreted from the body?
Via urine, feces, sweat and exhalation of volatile forms
Glutathione peroxidase in the form of _____, is part of the cellular antioxidant defense system against free radicals. Se is also involved in the metabolism of thyroid hormones
Selenocysteine
This is a disease associated with Se deficiency and is an endemic cardiomyopathy that affects mostly children and women in childbearing age in certain areas in China.
Keshan disease
What is the treatment for Keshan disease?
Selenium supplementation
This is a disease associated with Se deficiency and is an endemic osteoarthritis that occurs during adolescent and preadolescent years.
Kashin-Beck disease
Acute oral exposure to extremely high levels of Se may produce what symptoms?
Gastrointestinal symptoms (nausea, vomiting, diarrhea) Cardiovascular symptoms (Tachycardia)
Chronic exposure to very high levels of Se can cause what effects?
Deram effects, including diseased nails and skin, hair loss
Neurologic problems such as unsteady gait or paralysis
What form of Se is carcinogenic?
Selenium sulfide
This is a bluish white lustrous metal that is stable in dry air and becomes covered with a white coating when exposed to moisture.
Zinc (Zn)
What are the most common uses of Zn?
Production of alloys, especially brass (with copper) Galvanizing steel Die casting Paints Skin lotions Treatment for Wilson's disease
Absorption of Zn mainly occurs in what organ?
Small intestine, specifically jejunum
What percent of Zn is absorbed in the muscle?
60%
What percent of Zn is absorbed in the skeletal system?
30%
What percent of Zn is absorbed in the eyes, prostate, hair and other tissues?
10%
In blood, what percent of Zn is located in the RBCs?
80%
In blood, what percent of Zn is located in the plasma?
17%
In blood, what percent of Zn is located in the white blood cells?
3%
Enumerate factors that can increase Zn absorption.
Presence of animal protein and amino acids in a meal
Intake of calcium and unsaturated fatty acids
Enumerate factors that can decrease Zn absorption.
Intake of iron
Taking Zn on an empty stomach
Presence of copper at high levels
Age
The main biochemical role of this element is seen in its influence on the activity of more than 300 enzymes
Zinc (Zn)
Enumerate conditions that are caused by Zn deficiency.
Growth retardation
Slows skeletal maturation
Causes testicular atrophy
Reduces taste perception
Infants with this disease first develop a characteristic facial and diaper rash. If untreated, may progress and include growth retardation, diarrhea, impaired Tcell immunity, insufficient wound healing, infections, delayed testicular development in adolescence, and early death
Acrodermatitis enteropathica (Zn malabsorption)
Zn deficiency in (infants/adolescence) is manifested by slow growth or weight loss, altered taste, delayed puberty, dwarfism, impaired dark adaptation, alopecia, emotional instability and tremors.
Adolescence
High doses (1g) or repetitive doses of 100mg/d of Zn for several months may lead to what conditions?
Gastrointestinal tract symptoms
Decrease in heme synthesis due to an induced copper deficiency
Hyperglycemia
Exposure to ZnO fumes and dust may cause this disease with symptoms including chemically induced pneumonia, severe pukmonary inflammation, fever, hyperpnea, coughing, pains in legs and chest, and vomiting
Zinc fume fever
What are the essential trace elements?
Cr Fe Mn Se Mo Zn
What are the nonessential trace elements?
Al As Cd Pb Hg