Trace Elements

Dr Manjuprasad

Moderater:Dr Ravichandra V

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Overview

• Introduction

• Classification

• Individual trace elements

• conclusion

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Introduction

• Naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100 mg/day

• Minerals for 5% of our diet

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Classification

• Essential trace elements

Iron, zinc, copper

Co, Cr, fluoride, iodide, Mn, Mo, & Se

• Probably essential trace elements

Ni, tin, vanadium, Si, Bo

• Non essential trace elements

Al, Au, Ba, Br, lead, silver, mercury, rubidium, strontium, titanium, ziroconium,

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Essential trace elements

• Trace elements

Iron, zinc and copper

• Ultra trace elements

Manganese, selenium, cobalt, chromium, fluoride, iodine, and molybdenum

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Iron

• Most essential trace element

• Body content – 4-6g

Hb – 68%

ferritin – 13 %

haemosiderin – 12%

myoglobin – 3%

iron enzymes – 0.2%

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• Iron dependent enzymes:

Cytochrome oxidase, xanthine oxidase and peroxidase

• Body requirement

Daily requirement – 0.5 - 2 mg/day

3 - 5mg/day (pregnancy)

Daily excretion – 0.9mg/day

1.3mg/day (during menses)

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• Dietary source:

Leafy greens, whole grains, beans , pulses, liver, spleen, mollusks

• Iron is absorbed in ferrous

form, which is measurable

in blood as free iron

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Transferrin • Transport protein

• Binds to two iron molecules

• Transports iron to various organs and tissues

• S.Iron + total iron bound transferrin – total iron in circulation

• Determination of transferrin gives TIBC

• Transferrin can be measured by RIA, ELISA & chemiluminescence

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Ferritin • Protein having 24 subunits binds to 4000 iron

molecules

• Measurements used to assess iron stores in the body

• ↑ferritin levels may be seen in hepatitis, cirrhosis, hepatic carcinoma also in leukemia, NHL

• RIA, ELISA

chemiluminescence

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• Deficiency state:

asymptomatic

weakness, headache, irritability, and varying degrees of fatigue and exercise intolerance.

Treatment:

3-6mg of elemental iron/kg/day

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• Oral preparations of iron:

Ferrous sulphate

Ferrous fumerate

Ferrous gluconate

Ferrous succinate

Iron calcium complex

Ferric ammonium citrate

Adverse effects: epigastric pain, nausea, vomiting, gastritis, metallic taste, constipation or diarrhea

Liquid prep- staining of teeth13

• Parenteral preparations:

Iron dextran

Iron sorbitol citric acid complex

• Adverse effects:

Pain at injection site, pigmentation

Fever, headache, palpitations, anaphylaxis

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Acute iron poisoning

• 60mg/kg elemental iron

• Vomiting, abdominal pain, bloody diarrhea, shock, dehydration, cyanosis, acidosis, coma

• Treatment:

• Gastric lavage with sodium bicarbonate solution

• Desferrioxamine 15 mg/kg per hour IV, ↑ to max 35 mg/kg per hour

• Correction of acidosis and shock

(if fails dialysis)15

Zinc • Second most abundant trace element

• Cofactor – DNA polymerase, alkaline phosphatase, carboxypeptidase

Regulate- growth, immune system, collagen synthesis, wound healing, bone metabolism, reproduction, taste, smell & vision

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• Reduce the time period of diarrhea

• High dose of zinc prevents dysmenorrhea

• Zinc required in producing testosterone

• For common cold

• In treatment of warts

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• Body content 2.5g

60% in muscle, 30% in bone, 10% in body tissues and organs

• Daily requirement: 3-14mg

• Diet rich in zinc: red meat, fish, sea food, pumpkin, cashews, beans, dark chocolate

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• Zinc deficiency:

Leukemia, cirrhosis, hepatitis, sickle cell anemia,

Malnutrition

Symptoms:

In children- growth retardation & skeletal abnormalities

In adults- ↓smell & taste, ↓appetite, skin lesions, and hair loss

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Zinc deficiency is also associated with

• Acrodermatitis enteropathica

• Anorexia

• Esophageal squamous cell carcinoma

• Cognitive and motor impairement

• Diarrhea and pneumonia

Treatment:

• Zinc supplements 45 – 100mg/day

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Copper

• 3rd most important trace element

• Diet rich in copper: red meat, shell fish, water pumped through copper pipes

• Body content of copper is 80-120mg

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• 40-60% absorbed in duodenum

• Transported through metallozymes eg ascorbic acid

• 90% bound to ceruplasmin, 9% to albumin and 1% is free

• Body content of Cu is 80-120mg

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Body functions:

• Erythropoiesis

• Nerve conduction and immune function

• Fertility and to maintain pregnancy

• Act as a catalyst for copper containing enzymes

Eg: tyrosinase, ascorbic acid

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• Toxic – 5mg/kg

• Adequate – 34mcg/kg

• Deficient - <8.5mcg/kg

• RDA – 09 - 1.3mg/day

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Deficiency symptoms:

• Fragile hair

• Depigmented skin

• Myeloneuropathy

• Edema

• Hepatosplenomegaly

• Osteoporosis

• Anemia, neutropenia

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Menkes disease

• Congenital X-linked genetic disorder

• Mutation in ATP7A gene

• Inactivating mutation in this gene causes Cu deficiency

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Wilsons disease

• Autosomal recessive disorder

• Mutation in ATP7b gene

• Causes excessive accumulation of Cu

Clinical features:

• Diarrhea, vomiting

• Cardiac & renal failure

• Hepatic necrosis

• encephalopathy27

Treatment:

• life long treatment

• Avoidance of high Cu diet

• In early stages Zn may be effective as it competes with Cu for absorption

• Penicillamine

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Chromium

• In 1957, extracted from pork kidney and they named it as “glucose tolerance factor” as it corrected hyperglycaemia.

• Regulates plasma lipoprotein concentration and reduces cholesterol and triglycerides.

• Found in – grains, cereals, fruits, processed meat

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RDA : 20 – 35 mcg/ day

• In improving lean body mass

Deficiency:

• Limited to hospitalized patients on TPN

Toxicity :

• Lung Ca, Bronchogenic Ca in stainless steel workers

• Dermatitis, skin ulcers30

Fluoride

• Very important in preventing dental caries

• Promotes remineralization of decalcified enamel

• Available as tooth paste, solutions and gels

Excess cause flurosis

• Rx- tooth bleeching,

microabrasion,

replacement

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Iodine

• Thyroid hormone synthesis and also have broad spectrum germicidal action

• Iodine induced hyperthyroidism:

-In individuals of nodular goiter in endemic area

-thyrotoxicosis due to underlying areas of autonomy (Jod Basedow phenomenon)

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Iodine induced hypothyroidism:

• people at risk are- autoimmune thyroiditis, Graves hyperthyroidism previously treated with radioactive iodine

• Unusually sensitive to inhibitory effect due to sustained activity on Na/I symporter

( Wolff Chaikoff effect ).

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Iodine deficiency prophylaxis:

• Iodised salt

• Iodised oil

• Iodised water

• Iodine tablets or drops

• Biofortification of vegetables with iodine

• Also available as ointment, solution, mouth gargles

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Manganese

• Shown to be essential for normal growth and development

• Role in human health unclear

• Dietary sources: meat, fish, poultry, dry fruits and nuts

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• Biological role: manganese superoxide dismutase

arginase, glutamate synthase & pyruvate carboxylase

• Deficiency :

Experimental animals - ↓growth, ↓fertility, ataxia, skeletal deformities, abnormal fat and CHO metabolism

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• Toxicity:

Neurotoxic- extrapyramidal parts affected

Headache

Hepatic dysfunction

• RDA – 2-11mg/day

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Molybdenum

• Act as a catalyst for enzymes and helps facilitate breakdown of certain amino acids

• Molybdenum in human tooth enamel may have a role in lowering the risk of tooth decay.

• Deficiency – esophageal carcinoma

• RDA: 45mcg/day

pregnancy and lactation 50mcg/day38

Selenium • Least abundant trace element

• Recommended intake for adults 50-200 μg/day

Functions in human body:

Selenium in Glutathione peroxidase (GTH-Px)-important role immune system function, also plays a crucial role in the control of oxygen metabolism.

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Functions in human body:

• protects body from oxidative damage.

• Low GTH-Px in platelets leads to bleeding disorders

& edema due to damage to capillary membranes

• Protects phagocytes from destruction

• GTH-Px protects eye lens tissues and neurons from damage

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• Low Selenium leads to Keshan’s disease, which is a type of cardiac myopathy discovered in china where soil Selenium was absent.

Selenium deficiency occurs due to:

•Hemolytic anemia

•Clansman's thrombasthenia (platelet disorder)

•Gastrointestinal cancer

•Malnutrition 41

• Vanadium• Control of sodium pump, inhibition of ATPase

• Tin• Interaction with riboflavin metabolism

• Silicon• Structural role in connective tissue, in metabolism

of osteogenic cells

• Nickel• Component of enzyme urease

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Boron

• Boron is a vital trace mineral that is required for the normal growth and health of the body.

• apples, oranges, red grapes, kiwis, dates, as well as certain vegetables, avocado, soybeans and nuts are rich sources of boron

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Health benefits:

• Prevents arthritis

• Used for body building

• Estrogen Production: Boron can improve the production of estrogen in menopausal women

• Embryonic development: Boron appears to be essential for reproduction and the development of the fetus

• Proper cell membrane functions

• Lowers plasma lipid levels

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Lithium

• Discovered in 1817 as mood stabilizing agent

MOA:

• Inositol depletion theory

• Inhibition of NMDA receptor mediated signalling

• Inhibition of GSK3

• BDNF upregulation

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Adverse effects:

• Nephrogenic diabetes insipidus

• Thyroid function abnormalities

• mental confusion

• hyperreflexia

• gross tremor

• dysarthria

• Seizures

• cardiac arrhythmias,

• hypotension, and

• albuminuria.46

Uses

• BPD

• Mania

• Depression

• Cancer induced leukopenia & agranulocytosis

Preparation:

• Lithium carbonate 150/300/600mg

• Lithium citrate syrup 8mEq/5ml

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Xenon

• A trace element in earths atmosphere

• Xenon is a medical gas capable of establishing neuroprotection, inducing anesthesia and nuclear medicine as a contrast agent

• Acts through NMDA receptor

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Bibliography • Pharmacological aspects of therapeutics – Goodman and Gilman –

12th edition

• Textbook of medical pharmacology – Dr.PadmajaUdaykumar – third edition

• Katzung BG, Masters SB, Trevor AJ. Basic and Clinical Pharmacology.12th ed:

• Food and Nutrition Board of the Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press, Washington DC, 2000. www.nap.org (Accessed on May 03, 2012).

• Turnlund JR. Copper. In: Modern nutrition in health and disease, 10th, Shils ME, Shike M, Ross AC, et al (Eds), Lippincott Williams and Wilkins, Baltimore 2006. p.286.

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• Trace elements in human nutrition. Report of a WHO expert committee. Report No. 532, World Health Organization, Geneva, 1973.

• Danks D. Hereditary disorders of copper metabolism in Wilson's disease and Menkes' disease. In: The metabolic basis of inherited disease, 5th, Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (Eds), MacGraw-Hill, New York 1983.

• Stamp TC. Fluoride. In: Encyclopedia of food science, food technology, and nutrition, Macrae R, Robinson RK, Sadler MJ (Eds), Academic Press, London 1993. p.1932.

• Nielsen FH. Ultratrace minerals. In: Modern nutrition in health and disease, 9th, Shils ME, Olson JA, Shike M, Ross AC (Eds), Williams and Wilkins, Baltimore 1999. p.283.

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