TRACE METALS Flashcards
TRACE ELEMENTS
Associated with
enzymes or proteins
Essential: deficiency impairs a biochemical or functional process
TRACE ELEMENTS
The essential trace elements are usually associated with enzymes and serves as (?) in enzymatic reactions.
cofactor
An element is to be considered (?) if the deficiency impairs a biochemical or functional process and replacement of the impairment corrects this impairment.
essential
Laboratory determination
Anti-coagulated blood
Ideal:
anticoagulated blood samples
Low concentration in the plasma and ubiquitous nature
TRACE ELEMENTS
Prevent contamination
TRACE ELEMENTS
Method of choice:
Atomic absorption spectrophotometry
Most abundant trace element in the body wherein about 40 to 50 mg of iron is present per kilogram body weight
Iron
Iron containing proteins are important in the metabolism such as
collagen, tyrosine and catecholamines
of iron is imp for Hb synthesis
Anemia
30%
is the second most abundant trace metal in the body and is known to be a cofactor for almost 300 enzymes
Zinc
Zinc Essential in the:
- Structure
- Regulation
- Catalytic activity of 300 enzymes
important in the synthesis and metabolism of RNA and DNA
Zinc
Zn plays a role in the synthesis, (?) as well as in (?), the decrease in Zn will affect the ability of the islet cell to produce and secrete insulin, that may contribute to the development of Type 2 diabetes
storage and secretion of insulin
conformational integrity of insulin
• Hormone produced by the pancreas to regulate blood sugar
INSULIN
• Associated with Type 2 diabetes
INSULIN
is the third most abundant trace metal in the body
Copper
Cu Sources :
shellfish, liver, nuts and legumes
Cu Dietary requirement:
1.5-3.0 mg/day
Participates in:
- Cellular respiration
- DNA & RNA reproduction
- Maintains cell membrane integrity
- Sequestration of free radicals
: unstable atoms that can damage cell causing cell to age
free radicals
Iron majorly found in the following:
Hemoglobin synthesis in RBC
Ferritin and hemosiderin
myoglobin and non heme enzymes
– most imp use of iron in the body
Hemoglobin synthesis in RBC
as iron stores
Ferritin and hemosiderin
Moderate amount is found in body tissue such as
myoglobin and non heme enzymes
Iron bound to (?) which is the first to become diminished in iron deficiency conditions
transferrin
blood plasma glycoprotein playing a central role iron metabolism; delivers/transfers iron
transferrin
Iron Dietary iron:
ferrous form (Fe2+) for absorption
Primary regulation:
absorption thru the intestines
present in the food
Ferric form (Fe3)
Cannot be absorbed in the intestines
Ferric form (Fe3)
Iron absorption facilitated by
Ascorbic acid & other reducing agents
acid pH in the stomach
- glycoprotein that transports Iron
Transferrin
measure of plasma transferrin level (NV: 56 mol/L)
Total Iron Binding Capacity
best to measure blood’s ability to attach itself to iron and transport iron around the body
Low iron level = anemia
Total Iron Binding Capacity
- found virtually in all cells
Ferritin
Iron store: synthesis of iron-containing compounds
Increased serum ferritin:
Fever
Acute infections
Rheumatoid arthritis
Viral hepatitis
is mainly absorbed from the duodenum.
Zinc
Zinc is mainly absorbed from the.
duodenum
In blood, bound to (?)
albumin and α-2 macroglobulin
(?) contain most of the body’s Zn stores.
bones and the muscle
slow turnover (half-life of ?)
300 days
In the liver, zinc is bound to (?).
metallothionein
: zinc transporter protein
METALLOTHIONEIN
METALLOTHIONEIN half-life is
~2 weeks
Zn Dietary Sources:
o Oyster
o Lamb meat
o Beef
o Seafoods (crab, lobsters)
o Cashew
o Cheese and dairy products
o Beans and legumes
- highest copper concentration
Liver
-containing proteins
Copper
- synthesized in the liver Cu
Ceruloplasmin
-bound Cu
Albumin
- transporter protein Cu
Transcuperin
- sequesters and stores copper Cu
Metallothionein
- Iron depletion
Iron Deficiency
- Iron Deficiency Anemia
Iron Deficiency
Blood loss due to GI bleeding
Iron Deficiency
Chronic drug ingestion
Iron Deficiency
Parasitic infection
Iron Deficiency
Impaired absorption of iron
Iron Deficiency
Renal failure
Iron Deficiency
Iron Overload Common causes:
Hereditary hemochromatosis
Hereditary hemochromatosis
Iron Overload
Sideroblastic anemia
Iron Overload
Chronic ingestion of medicinal iron
Iron Overload
Chronic hepatitis
Iron Overload
Diabetes mellitus
Zinc deficiency
Alcohol abuse
Zinc deficiency
Malabsorption syndrome
Zinc deficiency
Liver and kidney disease
Zinc deficiency
Acrodermatitis enteropathica
Zinc deficiency
Common among premature infants and undernourished children
Copper deficiency
related to malnutrition, malabsorption, and chronic diarrhea and prolonged feeding with low-copper, total-milk diets
Copper deficiency
Cu main cause:
low-copper diet (milk)
Cu Contributing factor in adults:
- osteoporosis/ bone&joint abnormality
- Cardiovascular disease /Coronary Heart Disorders(CVD)
Menke’s disease or “kinky hair syndrome
Copper deficiency
Menke’s disease or “kinky hair syndrome Clinical features:
• Diminished copper conc. in hair
• Decrease in ceruloplasmin
• peculiar hair/stilly hair
Increased tissue and serum levels
Copper toxicity
Mostly caused by Acute copper poisoning coming from fungicides
Copper toxicity
WILSON’S DISEASE
Copper toxicity
WILSON’S DISEASE Triad of Manifestations:
Neurologic disorders
Liver dysfunction
Kayser-Fleischer rings
composed of diff mental signs and symptoms; caused by accumulation of cu+ in the brain (symptoms: Alzheimer’s, dementia, hallucination, schizophrenia)
Neurologic disorders
: sequestration of drugs For bilirubin metabolism and sequestration of drugs
Liver dysfunction
Liver
Liver dysfunction
green-brown discoloration in the cornea
Kayser-Fleischer rings
Decreased release of ferritin
Iron Deficiency
Most serious cause of GI bleeding:
Hookworm anemia
Hookworm:
Bites in the walls of SI
Necator americanus
Kidney disease
EPO - synthesized in the kidney; imp for rbc devt
Iron Deficiency
The following shows symptoms of hemochromatosis
- Hereditary hemochromatosis
is a disorder that causes the body to absorb too much iron from the diet. Sideroblastic anemia, Chronic ingestion of medicinal iron, Chronic hepatitis
Hereditary hemochromatosis
Sideroblastic anemia
Chronic ingestion of medicinal iron
Chronic hepatitis
most common cause of iron overload
- Hereditary hemochromatosis
- Hereditary hemochromatosis
caused by accumulation of iron in the
liver and skin
causes hyperpigmentation of the skin
- Hereditary hemochromatosis
BM produces ringed sideroblasts
Sideroblastic anemia
Hepa C infection
Chronic hepatitis
causes reduction in the effects of antiretroviral drugs
Chronic hepatitis
– low zinc and insulin levels
Diabetes mellitus
– Cofactor of Alcohol Dehydrogenase (function by the liver)
Alcohol abuse
develops among infants; facial rash with diaper rash
Acrodermatitis enteropathica
prominent observable feature
Menke’s disease or “kinky hair syndrome
form of extreme def in cu+ observed among newborns and babies
Menke’s disease or “kinky hair syndrome
problem in the absorption of cu
Menke’s disease or “kinky hair syndrome
affects both mental and physical retardation
Menke’s disease or “kinky hair syndrome
severe cases: weak muscle tone (hypotonia); sagging features
Menke’s disease or “kinky hair syndrome
- agricultural workers/infestations control; inhalation of mist containing cu+ sulfate
fungicides
– most important genetically determined copper accumulation disease
WILSON’S DISEASE
Copper deposits in tissues liver, brain & corned)
WILSON’S DISEASE
quantitative, specific, & sensitive
Direct measurements
involve invasive procedures
is digested and analyzed for iron
Liver biopsy
is used as a substitute for biopsy in monitoring iron overload
quantitative phlebotomy
Examples of Fe Direct measurements
- Quantitative phlebotomy
- Bone marrow biopsy
- Liver biopsy
- performed if liver biopsy is not available; to document iron overload
- Quantitative phlebotomy
- Fe Quantitative phlebotomy
(?) phlebotomies
(?) mL (1 blood bag)
16 to 20
450
digested and analyzed for iron; first option
Liver biopsy
Fe Indirect methods Serum iron is measure by:
- Colorimetric method
- AAS
- Zinc is highest in the morning.
Diurnal variation
- Zinc is highest when fasting;
Postprandial variation
Serum values 10% greater than plasma values
Postprandial variation
The RBC has (?) more zinc than the plasma hence hemolysis should be avoided.
10x
The reference method for zinc measurement is.
AAS
Other methods (Not usually used for medical purposes; tedious):
- Flame Atomic Absorption Spectrometry (FAAS)
- Inductively coupled plasma - mass spectrometry (ICP-MS)
- method of choice for Zn in body fluids
- Flame Atomic Absorption Spectrometry (FAAS)
- reference Testing method in serum or plasma
- Inductively coupled plasma - mass spectrometry (ICP-MS)
Serum or urine copper can measure using (?) which is the method of choice or
AAS
colorimetric method.
Ceruloplasmin is measured by
photometric method and immunochemical methods.
Total Fe++:
60 – 150 µg/dL
TIBC:
250 – 400 µg/dL
Iron Sat’n:
20 – 55%
Ferritin:
Male: 15 – 200 µg/L
Female: 12 – 200 µg/L
Zn PLASMA REFERENCE VALUE:
70 - 120 g/dL (10.7 - 18.4 pmol/L)
Serum Copper
Male: 70 – 140 µg/dL (11 – 22µmol/L)
Female: 80 – 155 µg/dL (13 – 24µmol/L)
Ceruloplasmin:
23 – 50 mg/dL
Constituent of vitamin B12
Cobalt
Folate metabolism
Cobalt
Erythropoiesis
Cobalt
Toxic at high doses
Cobalt
Cobalt Laboratory determination :
AA’S
Naturally occurring; industrial waste
Chromium
Chromium: rich sources
Meat and grains
Chromium
Once absorbed, transported to the tissue by
transferrin
Chromium In glucose metabolism:
Insulin cofactor
Chromium Deficiency :
insulin resistance
Chromium supplementation:
improved glucose tolerance, reduced insulin concentrations, decreased total cholesterol
Prevention of dental caries
Fluoride
Fluoride Excess:
mottling of teeth and calcification in soft tissues
Minimize bone loss or stimulate bone formation
Fluoride
Readily absorbed by the gut and distributed almost totally to the bone and teeth
Fluoride
Fluoride Laboratory determination:
ISE
Manganese
Activator of several enzyme systems Ex:
Arginase, pyruvate carboxylase, superoxide dismutase
Manganese
Transported in plasma by
albumin, a2-macroglobulin and transferrin
Manganese Deficiency :
seizures and epilepsy (rare)
Manganese Excess:
Locura manganica
Manganese madness
Locura manganica
First discovered among children in some parts of south America
Locura manganica
Inhalation of Mg from aerosol gases in mines
Locura manganica
Molybdenum
Essential cofactor for several
oxidase enzymes
: Converts hypoxanthine to uric acid
Xanthine DH/xanthine oxidase
: Catalyzes conversion of acetyl-CoA to acetate
Aldehyde oxidase
: Converts sulfite to sulfate
Sulfite oxidase
Molybdenum is mostly absorbed in
stomach and small intestines
inhibit Molybdenum absorption
Copper and iron
Molybdenum Excess :
inhibition of copper dependent enzymes (ceruloplasmin-or cytochrome oxidase)
Molybdenum Excess:(Facilitates conversion of hypoxanthine to uric acid)
hyperuricemia and gout
Selenium
Cofactor in
glutathione peroxidase and iodothyronine deiodinase
: essential amino acid coded by DNA (Maintains metabolic rate of selenium)
Selenocysteine
: can substitute for methionine as essential amino acid
Selenomethionine
Antioxidant properties
Selenium
Involved in metabolism of thyroid hormone
Selenium
Selenium Deficiency
Cardiomyopathy and skeletal muscle weakness
Osteoarthritis and increased incidence of cancer
Selenium Supplementation
Decreased risk of cancer (stomach, lung and prostate)
Selenium Laboratory determination :
AAS
