(P) Lec 3: Trace Elements (Part 1) Flashcards
Trace elements are found in the body in very ____ concentrations
Little
Trace elements are known to constitute less than ____% of the total body weight
0.01%
Indicate their percentages when in the body:
- Water
- Electrolytes
- Trace Elements
- Water: 96%
- Electrolytes: 3.98%
- Trace Elements: The remaining
Classification of Trace Elements
What type of trace element?
- If the replacement of the deficient element corrects an impairment
- It cannot be synthesized by the body in large amounts hence it should be present in the diet
Essential
Classification of Trace Elements
A deficiency of these elements may be due to the ff. EXCEPT:
A. Decreased intake
B. Increased secretion and excretion
C. Excessive cellular stress
D. Impaired absorption
E. Genetic abnormalities
C. Excessive cellular stress
Classification of Trace Elements
Excess concentrations are associated with at least some degree of toxicity leading to what?
Intoxication
Classification of Trace Elements
Essential trace elements are often associated with 1.) what enzymes and 2.) what proteins as cofactors?
- Metalloenzymes
- Metalloproteins
Classification of Trace Elements
Includes: Copper (Cu), Chromium (Cr), Cobalt (Co), Iron (Fe), Manganese (Mn), Molybdenum (Mo), Zinc (Zn), Selenium (Se), Iodine (I), and Fluorine (F)
Essential
Classification of Trace Elements
What type of trace element?
- Any element that is not considered as the other type
- These are of medical interest primarily because many of them are toxic in the body
Non-Essential
Biological Functions of Trace Elements
Fill in the blanks
1. ____ transport
2. Respiration
3. ____ activities
4. ____ activator or cofactor
5. Protection from ____
6. Tissue repair
7. Immune system
8. Growth and reproductive process
- Electron
- Hormonal
- Enzyme
- Free radicals
Biological Functions of Trace Elements
Which among coenzymes and cofactors are organic and inorganic?
- Organic = Coenzymes
- Inorganic = Cofactors
Biological Functions of Trace Elements
This is an enzyme composed of zinc and copper which has an antioxidant effect and are known to be scavengers of free radicals
Superoxide Dismutase (SOD)
Note: Superoxide by itself is a free radical
Biological Functions of Trace Elements
Whenever a free radical is present in the body, such as a superoxide (2(O2)), the Superoxide Dismutase will produce what 2 products?
Oxygen (O2) and Hydrogen Peroxide (H2O2)
Biological Functions of Trace Elements
Upon the production of water and peroxide using the Superoxide Dismutase (SOD), it will be acted upon by what 2 possible enzymes to convert them into water (H2O) and oxygen (O2)?
- Catalase
- Peroxidase
Biological Functions of Trace Elements
(2(O2)) [superoxide] + SOD [superoxide dismutase] = ?
- Oxygen (O2)
- Hydrogen Peroxide (H2O2)
Biological Functions of Trace Elements
H2O2 [hydrogen peroxide] + catalase/peroxidase = ?
Water (H2O) and Oxygen (O2)
Biological Functions of Trace Elements
This is a known component of glutathione that regenerates Vitamin B & C important for free-radical protection
Selenium
Biological Functions of Trace Elements
This is an active agent of wound healers and its component facilitates wound healing
- Active agent: Zinc sulfate
- Facilitator of wound healing: Zinc
- The most abundant trace element in the body
- A known constituent of Hgb and myoglobin as it is able to carry oxygen
- An agent in redox reactions and electron transport
- Only excreted during menstruation through the sloughing off of the epithelium
Iron
Functions of Iron
- Iron serves as a ____ with cytochrome oxidase, xanthine oxidase, peroxidase, and catalase
- It is transported by the 2 transport proteins known as ____ and ____
- It comes in 2 forms: ____ (Fe3+) and ____ (Fe2+)
- Cofactor
- Transferrin and albumin
- Ferric (3) and Ferrous (2)
Accumulation of free iron in plasma is toxic, so therefore an excess of it should be stored in the form of ____ or ____
Ferritin or Hemosiderin
- In what parts (2) of the intestine is iron absorbed?
- Between the ferric and ferrous form, what form exists in our diet and what form does it convert into for it to be absorbed?
- Duodenum and Jejunum
- Ferric (diet) to Ferrous (inside our body)
In order for Ferric iron to be converted into Ferrous iron, what (4) components must it interact with?
- HCl (from the stomach)
- Organic acids
- Vitamin C
- Ferric reductases (responsible for conversion)
Once the iron is in ferrous form, it will be absorbed in the duodenum and jejunum where it will later on complex with what (2) transport proteins?
Transferrin and Albumin
Transferrin and albumin are able to deliver iron to different parts of the body such as the BM, liver, and spleen where it will be stored in the form of what? (2)
Ferritin and Hemosiderin
- This is composed of 4,500 atoms of iron
- Is formed when iron combines with apoferritin produced by the organs that store iron (BM, spleen, and liver)
Ferritin
If apoferritin is not present due to inflammation or infection, iron cannot bind with it to be stored as ferritin, therefore it will be stored as?
Hemosiderin
- This is stained using a Prussian Blue/Pearl stain
- It is seen as small oxide granules producing blue to black granules
- Aka the EXTRACELLULAR form of iron however it is NOT THE PRIMARY storage form
Hemosiderin
Note: This is only the storage form if apoferritin is not present
In cases of overstimulation of macrophages wherein there is an increased amount of apoferritin, an increased amount of iron will combine with apoferritin which does what to the circulating iron in the blood?
Decreases
Refers to:
- Excess iron in plasma
- Toxicity as it can result to low oxidation of cells that can lead to DNA destruction
Iron Overload
Causes of Iron Overload
- Refers to when RBCs lyse which releases the Hgb that contains iron
- When there is increased ceruloplasmin in blood (protein that transports copper)
- A reduction or failure of iron to be incorporated to form heme or a protoporphyrin ring (e.g. lead poisoning, thalassemia, and Vit. B16 deficiency)
- When iron cannot be absorbed by the small intestine (e.g. pernicious anemia)
- During cases of hemosiderosis and repeated transfusions resulting to an increased RBC load
- Hemolytic anemia (increased RBC destruction)
- Increased mobilization of iron
- Decreased blood cell formation
- Defective iron storage
- Increased rate of absorption
Causes of Iron Overload
- This is a protein responsible for the transport of copper which is known to facilitate iron mobilization from ferritin to transferrin
- An increase of this protein means increased iron mobilization and is present in cases of hepatic cirrhosis
Ceruloplasmin
Iron overload is collectively referred to as ____ ____ which can result to the malfunctioning of the organs where iron accumulates (endocrine glands, liver, and heart)
Hereditary Hemochromatosis
Causes of Iron Deficiency
- An example of this is iron-deficiency anemia (IDA)
- Happens in cases of hemorrhage
- During an impairment with the mobilization of iron due to decreased ceruloplasmin
- Generalized iron deficiency
- Chronic loss
- Impaired release of iron from the RES
Laboratory Evaluation of Iron
- Non-hemolyzed serum is needed (a hemolyzed sample could result to a false positive)
- An early morning sample (12hr fasting) is also needed due to the diurnal variation of iron
- This measures the free iron (bound with transferrin and albumin but not with apoferritin) in the blood
Serum Iron
Laboratory Evaluation of Iron
Iron is theoretically expected to be increased in the ____ and decreased in the ____
- Increased: Morning
- Decreased: Afternoon
Laboratory Evaluation of Iron
A form of iron that refers to those that are bound with transferrin and albumin but not bound to apoferritin
Free Iron
Laboratory Evaluation of Iron
Give the normal values of serum iron for males and females
- Males = 65-117 ug/dL or 11.6-31.7 umol/L
- Females = 50-170 ug/dL or 9.0-30.4 umol/L
Measuring Serum Iron Levels
- When measuring iron, it should be separated from binding proteins, through the use of a ____
- When separating, you cannot use ____
- Once separated, ferric iron will now be reduced to ferrous iron through the use of reducing agents such as ____
- Once reduced, the ferrous iron is now complexed with ____ such as ferrene, terosite, 2, 4, 6-tripyridyl-S-triazine (TPTZ), and sulfonated bathophenanthroline (SBP)
- The end product/color is measured via ____
- Strong acid
- Trichloroacetic acid (TCA)
- Ascorbic acid (or any acid substance)
- Chromogens
- Spectrophotometry
Laboratory Evaluation of Iron
- A test considered as an indirect measure of serum transferrin or free transferrin
- The amount of iron that could be found by saturating the binding proteins (transferrin) present in the sample
- Can differentiate iron-deficiency anemia (IDA) from anemia of chronic disease (ACD)
- Normal values range from 240-250 ug/dL or 43-80.6 umol/L
Total Iron Binding Capacity (TIBC)
Total Iron Binding Capacity (TIBC)
Increased or Decreased TIBC?
1. Iron Deficiency Anemia (IDA)
2. Anemia of Chronic Disease (ACD)
- IDA - increased
- ACD - decreased
Total Iron Binding Capacity (TIBC)
This condition leads to low iron circulation due to the overstimulation of macrophages. This stimulation results in the production of apoferritin, to which iron binds, consequently increasing ferritin.
Anemia of Chronic Disease (ACD)
Laboratory Evaluation of Iron
- Aka transferrin saturation
- Measures the percent (%) transferrin bound with iron
- Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD)
- Normal values range from 20-55%
Percent Saturation
Percent Saturation
Increased or Decreased Percent Saturation?
1. Anemia of Chronic Disease (ACD) with decreased TIBC
2. Iron-Deficiency Anemia (IDA) with increased TIBC
- ACD - increased
- IDA - decreased
Serum Transferrin
Increased or Decreased Serum Transferrin?
1. Iron-Deficiency Anemia (IDA)
2. Anemia of Chronic Disease (ACD)
- IDA - increased
- ACD - decreased
Laboratory Evaluation of Iron
- A direct measurement of free transferrin
- Is measured in the lab using a nephelometry assay
- An index of iron nutritional status
- Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD)
- Normal values range from 200-400 mg/dL
Serum Transferrin
Laboratory Evaluation of Iron
- Is measured using ELISA or Chemiluminescence
- An index of iron stores
- Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD)
Serum Ferritin
Serum Ferritin
Increased or Decreased Serum Ferritin?
1. Anemia of Chronic Disease (ACD)
2. Iron-Deficiency Anemia (IDA)
- ACD - increased
- IDA - decreased
- The second most abundant element in the body
- A component of more than 300 enzymes
- It promotes a healthy immune system, it promotes wound healing, ovulation, sperm development, DNA synthesis, and growth development
- It synthesizes the metabolism of proteins, glucose, and cholesterol
Zinc
- The absorption of zinc is through ____, which is similar to how copper is absorbed
- These (2) serve as transport proteins of zinc
- Zinc is ____ proportional to copper
- Metallothionine
- Albumin and A2-Macroglobulin
- Inversely
- An intoxication of this is rare as the more one has of this element, the better
- Exposure to its oxide fumes and dust may cause “Fume Fever” with chemically-induced symptoms such as pneumonia, severe pulmonary inflammation, fever, hyperpnea, coughing, pains in legs and chest, and vomiting
Zinc Excess
- This causes dwarfism, delayed sexual maturation, hypovoletism, and testicular atrophy
- There is prolonged wound healing causing Acrodermatitis enterophatica
Zinc Deficiency
- This is an inherited condition wherein there is a zinc malabsorption that results in a decreased zinc level in the body.
- It is characterized by dermatitis, hyperpigmented lesions, alopecia, growth retardation, infection, facial rash, and diaper rash
- Is common in infants and presents with prolonged wound healing
Acrodermatitis enterophatica (zinc deficiency)
- A trace element with excellent electrical and heat conducting properties
- Assumes 4 different states: (0, +1, +2, +3)
- An important cofactor for several metalloenzymes and is critical for the reduction of iron during heme synthesis
Copper
Among the 4 different states of copper:
1. Which is the most stable?
2. Which is present in the diet?
3. Which can be absorbed by the intestine?
- Cu(+2)
- Cu (+1)
- Cu (2+)
Note: Cu+1 is oxidized into Cu+2
- This is formed when your copper molecule is combined with apoceruloplasmin
- This is the form that can be distributed all throughout the body as 90% of it in the body is in this form
Ceruloplasmin
Its metalloenzymes include: ceruloplasmin, cytochrome C oxidase, SOD, tyrosinase, lysyl oxidase, dopamine hydroxylase, clotting factor V, metallothionine, and an unknown enzyme cross-linking keratin in hair
Copper
- This is a constituent of erythrocuprein found inside the RBCs with antioxidant activity together with superoxide dismutase
- Is absorbed in both the intestines and stomach
- Its transport proteins include: transcuprein, albumin, ceruloplasmin, and low molecular weight components in the portal system
Copper
Fates of Copper
- Upon entering the liver, copper complexes with apoceruloplasmin producing ____
- It will then go through the bile canaliculus and mix together with the bile, making it the biliary ____ of copper
- Copper chaperones can bind with thionine producing ____, a non-toxic storage form of copper
- Ceruloplasmin
- Excretion
- Metallothionein
Metallothionein could be excreted in the ____ or stored as Metallothionein before entering the circulation as ____
- Bile
- Ceruloplasmin
Copper’s Biological Functions
- A cofactor of the superoxide dismustase metalloenzyme
- A cofactor for lysyl oxidase (an enzyme that cross-links proteins into fiber)
- A cofactor for tyrosinase
- A cofactor for norepinephrine and B-dopamine monooxygenase
- A cofactor for metallothionein
- Antioxidant defense
- Collagen formation
- Melanin production
- Production of neurotransmitters
- Metallothionein
Match the enzyme with the function (Copper)
- Antioxidant Defense
- Collagen Formation
- Melanin Production
- Production of Neurotransmitters
- Metallothionein
A. Tyrosinase
B. Norepinephrine and B-dopamine monooxygenase
C. Copper chaperones bound to thionine
D. Superoxide dismutase
E. Lysyl oxidase
- D
- E
- A
- B
- C
Copper can be excreted through what 4 body fluids?
- Bile (98% excretion)
- Urine
- Sweat
- Menstruation (small amount)
What disease falls under copper overload disorders?
Wilson’s Disease
What 2 diseases fall under copper deficiency disorders?
- Menke’s Kinky Hair Syndrome
- Increased Zinc Absorption
- Aka hepatolenticular degeneration; a decrease in ceruloplasmin which increases the copper in blood
- It also presents with an increase in urinary excretion of copper in response to an increased amount
- Increased metallothionein is also a manifestation
- Can be treated with D-penicillamine, Dimercaprol, and Ammonium tetramolybdate
- Affects the CNS, liver, kidneys, heart, bones, and eyes
Wilson’s Disease (Copper Excess)
This refers to the presence of a brown pigment deposit in the cornea of the eye due to increased copper
Identify the diagnostic symptom and which disease does it correspond to
Kayser-Fleischer Ring (Wilson’s Disease)
Zinc Excess
D-penicillamine, Dimercaprol, and Ammonium tetramolybdate as treatments:
1. Promotes the ____ excretion of copper
2. Ammonium tetramolybdate ____ copper absorption in the stomach and small intestine
- Urinary
- Inhibits
- A sex-linked connective tissue defect involving copper transport (extreme form of deficiency)
- Manifested by steely and peculiar hair and mental retardation
Menke’s Kinky Hair Syndrome (copper deficiency)
- Increased zinc supplement results in decreased absorption of this element
- Zinc can be used to treat Wilson’s disease
- May result in connective tissue defects, hypotonia or decreased muscle tone, Menke’s kinky hair, and kidney, liver, and CNS defects
- Symptoms include hypothermia, mental deterioration, and seizures due to a decreased copper level
Increased Zinc Absorption (copper deficiency)
- This potentiates insulin action making it a good supplement for diabetic patients
- Comes from the Greek word for “color”
- A glucose tolerance factor and very important for carbohydrate metabolism
- Higher amount found in hair than in serum
- Known sources include Brewer’s yeast (Saccharomyces cerevisae)
Chromium
Note: The Greek word is “chroma”
- Is incorporated into bone crystals
- Able to correct calcium deficiency
- Enhances bone formation preventing osteoporosis (has the same action as calcium)
- Excess levels showcase the discoloration/mottling of elements in teeth
Fluorine
Note: Not advised to use toothpastes with too much fluoride
- A component of Vitamin B12 which has the same structure with heme
- Absorbed by the same mechanisms as iron (jejunum and duodenum)
Cobalt
- Used for steel production
- A high dosage is not toxic except when inhaled
- Also deposited in the brain of MRI patients (the dye contains trace elements)
- A known constituent of several metalloenzymes including pyruvate carboxylase, mitochondrial superoxide dismutase, arginase, and glucokinase
Manganese
Acute manganese aerosol intoxication commonly known as what (2)?
Locura Manganica/Manganese Madness
Note: Is common in younger people
Manganese is a known constituent of several metalloenzymes including pyruvate carboxylase, mitochondrial superoxide dismutase, arginase, and glucokinase
What 3 elements can also be used as a replacement for the aforementioned enzymes in cases of manganese deficiency?
Magnesium, Iron, and Copper
- Low levels of this may result in chronic toxicity which resembles Parkinson’s disease, epilepsy, hip abnormalities, joint disease, congenital malformation, heart and bone problems, and stunted growth in children
- In cases of liver disease, a decrease in excretion of this element is evident causing an increase of it in the blood
Manganese
This condition in manganese deficiency presents with akinesia, rigidity, tremors, and mask-like faces
Parkinson’s Disease (the deficiency only mimics the disease)
- This serves as a basis for the treatment of Wilson’s Disease
- It inhibits copper and iron absorption
- Is rapidly eliminated in both urine (predominant) and bile
- A very important cofactor of xanthine oxidase, xanthine dehydrogenase, sulfite oxidase, and aldehyde oxidase
Molybdenum
Molybdenum is a necessary cofactor for the function of xanthine oxidase, xanthine dehydrogenase, sulfite oxidase, and aldehyde oxidase which forms what complex?
Molybdopterin complex
What kind of Molydenum deficiency?
- Is rare, with a single case reported as a result of total parenteral nutrition in a man with Crohn’s disease
- A recessively inherited error of metabolism due to a lack of functional molybdopterin
- Dietary Molybdenum Deficiency
- Molybdenum Cofactor Deficiency
What kind of Molydenum deficiency?
Symptoms include seizures, anterior lens dislocation, decreased brain weight, and usually death prior to 1 year of age
Molybdenum Cofactor Deficiency
- This is rarely reported as there are few known cases of human exposure to excess molybdenum
- High exposures have been linked to elevated uric acid in blood (increased gout incidence)
Molydenum Toxicity
- This is naturally present in soil (root crops and vegetables)
- A very important component of glutathione peroxidase in the form of selenocysteine
- Known to regenerate Vitamin E and C
- Involved in the metabolism of thyroid hormones (e.g. deiodinase enzymes and thioredoxin reductase)
Selenium
This is an enzyme that plays a part in cellular antioxidant defense mechanisms against free radicals to which selenium is a component of
Glutathione Peroxidase
Evolution of Selenium
- In the 1930’s, it was a ____
- In the 1940’s, it was a ____
- In the 1950’s, it was declared as an ____
- In the 1960’s to 1970’s, it was viewed as an ____
- Toxic element
- Carcinogen
- Essential element
- Anticarcinogen
- Acute oral exposure may produce gastrointestinal and cardiovascular symptoms
- Chronic oral exposure can cause dermal effects and neurological problems
Selenium Excess
Acute or Chronic Exposure (Selenium)?
Gastrointestinal symptoms (nausea, vomiting, and diarrhea) and cardiovascular symptoms (tachycardia)
Acute
Acute or Chronic Exposure (Selenium)?
Dermal effects (diseased nails and skin and hair loss) and neurologic problems (unsteady gait or paralysis)
Chronic
- An endemic cardiomyopathy that affects mostly children and women of childbearing age in certain areas in China
- Has also been associated with the resultant increased virulence of the coxsackievirus (destruction of cardiac cells)
Keshan Disease (Selenium Deficiency)
- An endemic osteoarthritis that occurs during adolescent and preadolescent years especially in North China, North Korea, and Eastern Siberia
- Presents with chondronecrosis (necrosis of cartilage)
Kashin-Beck Disease (Selenium Deficiency)
What are the 2 diseases under Selenium Deficiency?
- Keshan Disease
- Kashin-Beck Disease
Identify the Trace Element(s)
Absorbed in the duodenum and jejunum
Iron and Cobalt
Identify the Trace Element(s)
Absorbed in the stomach and intestines
Copper
Identify the Trace Element(s)
Intoxication is rare or very little evidence points to toxicity when high amounts are present in the system
- Zinc
- Manganese (EXCEPT when inhaled)
Identify the Trace Element(s)
Exposure to fumes and dust can be toxic (has an aerosol exposure route)
- Zinc
- Manganese
Identify the Trace Element(s)
Has ionic states
- Iron (+2 and +3)
- Copper (0 to +3)
Identify the Trace Element(s)
Has something to do with the heme molecule
- Iron
- Cobalt
Identify the Trace Element(s)
Can be stored in the liver
- Iron
- Copper
Identify the Trace Element(s)
Wilson’s Disease
Copper (excess)
Identify the Trace Element(s)
Menke’s Kinky Hair Syndrome
Copper (deficiency)
Identify the Trace Element(s)
Locura Manganica
Manganese
Identify the Trace Element(s)
Increased Zinc Absorption
Copper (deficiency)
Identify the Trace Element(s)
The basis for the treatment of Wilson’s disease
Molybdenum
Identify the Trace Element(s)
Excreted through the bile
- Copper
- Molybdenum
Identify the Trace Element(s)
Glutathione Peroxidase
Selenium
Identify the Trace Element(s)
Was initially considered a carcinogen
Selenium
Identify the Trace Element(s)
Has an oral exposure route
Selenium (excess)
Identify the Trace Element(s)
Keshan Disease
Selenium (deficiency)
Identify the Trace Element(s)
Kashin-Beck Disease
Selenium (deficiency)
Identify the Trace Element(s)
Has an inversely proportional relationship with each other
Zinc and Copper
Identify the Trace Element(s)
Involves diseases/disorders that are inherited
- Copper (Menke’s Kinky Hair)
- Molybdenum (Molybdenum Cofactor Deficiency)
- Zinc (Acrodermatitis enterophatica)
Identify the Trace Element(s)
Acrodermatitis enterophatica
Zinc
Identify the Trace Element(s)
Brewer’s yeast or Saccharomyces cerevisiae
Chromium
Identify the Trace Element(s)
Mimicry of Parkinson’s Disease
Manganese