Trace elements

Trace Elements and their deficiencies

1. TRACE ELEMENTS AND THEIR DEFICIENCY Monika U 18BCHA12

2. OVERVIEW Introduction Classification Trace Elements and their deficiencies Summary

3. INTRODUCTION Naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100 mcg/day Constituents of living organisms, and are necessary for their growth, development, and health. 3

4. CLASSIFICATION ‹#› Essential trace elements Iron, Zinc, Copper, Co, Cr, fluoride, Iodine, Manganese, Molybdenum and Selenium Probably essential trace elements Nickel, Tin, Vanadium, Si, Bo Non essential trace elements Aluminium, Gold, Barium, Br, lead, silver, mercury, rubidium, strontium, titanium, zirconium,

5. ESSENTIAL TRACE ELEMENTS ‹#› Trace elements Iron, zinc and copper Ultra trace elements Manganese, selenium, cobalt, chromium, fluoride, iodine, and molybdenum

6. IRON ‹#› Most essential trace element Iron is essential for the delivery of oxygen to cells. Body content – 4 - 6g Hb – 68% Ferritin – 13 % Myoglobin – 3% Iron enzymes – 0.2%

7. 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 menstrual cycle) ‹#›

8. DIETARY SOURCES : 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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10. Oral preparations of iron: Ferrous sulphate Ferrous fumarate Ferrous gluconate Ferrous succinate Iron Calcium complex Ferric Ammonium citrate Adverse effects : E pigastric pain, nausea, vomiting, gastritis, metallic taste, constipation or diarrhoea and Staining of teeth ‹#›

11. Parenteral preparations: Iron dextran Iron sorbitol citric acid complex Adverse effects: Pain at injection site, pigmentation Fever, headache, palpitations, anaphylaxis ‹#›

12. IRON DEFICIENCY When iron is deficient, Hb cannot be produced. Insufficient Hb leads to microcytic and hypochromic red blood cells. Unable to deliver sufficient oxygen to the tissues. This is known as Iron Deficiency Anemia. Estimation : 80% of world population may be Iron deficient and 30% may suffer from Iron deficiency anemia Iron deficiency affects about 15% of the worldwide population.

13. Those with 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 d eficiency. 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. ‹#›

14. SYMPTOMS : Asymptomatic Weakness, headache, irritability, and varying degrees of fatigue and exercise intolerance. TREATMENT : 3 - 6 mg of elemental iron / kg /day

15. IRON TOXICITY AND OVERLOAD Iron is essential for cellular metabolism, but too much can be toxic. Iron Poisoning can be life-threatening. Can damage the intestinal lining and cause abnormalities in body pH, shock and liver failure. Most common form of Iron overload is known as hemochromatosis. Can happen over time and accumulates in tissues like heart and the liver.

16. Primary Fe overload is most frequently associated with hereditary hemochromatosis (HH). HH is a single-gene homozygous recessive disorder leading to abnormally high Fe absorption, culminating in Fe overload. Secondary Fe overload may result from excessive dietary, medicinal, or transfusional Fe intake or be due to metabolic dysfunction. HH causes tissue accumulation of iron, affects liver function, and often leads to hyperpigmentation of the skin.

17. Some conditions associated with severe hemochromatosis include diabetes mellitus, arthritis, cardiac arrhythmia or failure, cirrhosis, hypothyroidism, impotence, and liver cancer. TREATMENT Treatment may include therapeutic phlebotomy or administration of chelators, such as deferoxamine. Transferrin can be administered in the case of atransferrinemia.

18. Laboratory Evaluation of Iron 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. Total Iron Content (Serum Iron) Measurement of serum iron concentration refers specifically to the Fe3 bound to transferrin and not to the iron circulating as free hemoglobin in serum. The specimen may be collected as serum without anticoagulant or as plasma with heparin.

19. Total Iron-Binding Capacity Total iron-binding capacity (TIBC) refers to the amount of iron that could be bound by saturating transferrin and other minor iron-binding proteins present in the serum or plasma sample. Typically, about one-third of the iron binding sites on transferrin are saturated. TIBC ranges from around 250 to 425 g/dL. Percent Saturation The percent saturation, also called the transferrin saturation, is the ratio of serum iron to TIBC. The normal range for this is approximately 20% to 50%, but it varies with age and sex.

20. Transferrin ‹#› Transport protein Binds to two iron molecules Transports iron to various organs and tissues Determination of transferrin gives TIBC (Total Iron Binding Capacity) Transferrin is increased in iron deficiency and decreased in iron overload and hemochromatosis, chronic infections and malignancies Transferrin can be measured by RIA, ELISA & chemiluminescence

21. Ferritin A universal intracellular protein that stores iron & releases it in a controlled fashion. Produced by almost all living organisms, including algae, bacteria, higher plants, animals. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is decreased in iron-deficiency anemia and increased in iron overload and hemochromatosis, chronic infections, malignancy, and viral hepatitis. I RMA (Immunoradiometric Assay), ELISA, Chemiluminescence ‹#›

22. ZINC Second most abundant trace element. Zinc (Zn) is a bluish white, lustrous metal. Zinc and its compounds are used in a production of alloys, especially brass (with copper), in galvanizing steel, in die casting, in paints, in skin lotions, in treatment of Wilson’s disease, and in many medications. Essential for growth and development. Involved in functioning of over 300 different enzymes, including superoxide dismutase. Cofactor – DNA polymerase, Alkaline phosphatase, Carboxypeptidase ‹#›

23. REGULATION : Growth and Reproduction Immune system, Collagen synthesis, Wound healing, Bone metabolism, Taste, smell & vision Reduce the time period of diarrhea High dose of zinc prevents dysmenorrhea Zinc required in producing testosterone For common cold ‹#›

24. Body content - 2.5g 60% in muscle, 30% in bone, 10% in body tissues and organs Daily requirement : 3 - 14 mg Diet rich in zinc : red meat, fish, sea food, pumpkin, cashews, beans, dark chocolate ‹#›

25. ZINC DEFICIENCY : Causes growth retardation, slows skeletal maturation, causes testicular atrophy, and reduces taste perception. Old age, pregnancy, lactation, and alcoholism are also associated with poor zinc nutrition. Leukemia, cirrhosis, hepatitis, sickle cell anemia, Malnutrition 19

26. Zinc deficiency is also associated with Acrodermatitis enteropathica Anorexia Esophageal squamous cell carcinoma Cognitive and motor impairment Diarrhea and pneumonia In severe cases, lymphopenia may occur; death follows an overwhelming infection. ‹#›

27. SYMPTOMS : In children- growth retardation & skeletal abnormalities In adults- ↓smell & taste, ↓appetite, skin lesions, and hair loss TREATMENT : Zinc supplements 45 – 100 mg/day

28. TOXICITY : Zinc is relatively nontoxic. Nevertheless, high doses (1 g) or repetitive doses of 100 mg/day for several months may lead to disorders, especially gastrointestinal tract symptoms, decrease in heme synthesis due to an induced copper deficiency, and hyperglycemia. Exposure to ZnO fumes and dust may cause “zinc fume fever.” The symptoms include chemically induced pneumonia, severe pulmonary inflammation, fever, hyperpnea, coughing, pains in legs and chest, and vomiting.

29. REFERENCE INTERVALS FOR ZINC : Zinc in serum: 70–120 g/dL Zinc in urine of normal subjects: 140–800 g/24 hours Zinc in urine of compliant patients on oral zinc therapy for Wilson’s disease: 2,000 g/24 hours

30. COPPER ‹#› Copper (Cu) is a relatively soft yet tough metal with excellent electrical and heat conducting properties. Copper is widely distributed in nature. 3rd most important trace element Important in helping to prevent certain types of anemia Richest dietary source : Organ meat Diet rich in copper: Red meat, shellfish , nuts, chocolate, seafood, whole-grain foods. RDA – 1.3 - 1.5 mg/day

31. 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. About half of dietary copper is excreted in feces. The exact mechanisms by which copper is absorbed and transported by the intestine are unknown Toxic – 5mg/kg Adequate – 34 mcg/kg Deficient - <8.5 mcg/kg ‹#›

32. 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 ‹#›

33. DEFICIENCY : Copper deficiency is observed in premature infants. Copper deficiency is related to malnutrition, malabsorption, chronic diarrhea, hyperalimentation, and prolonged feeding with low-copper, total-milk diets. Subclinical copper depletion contributes to an increased risk of coronary heart disease. An extreme form of copper deficiency is seen in Menkes disease

34. DEFICIENCY SYMPTOMS Fragile hair Depigmented skin Myeloneuropathy Edema Hepatosplenomegaly Osteoporosis Anemia, neutropenia ‹#›

35. Menkes disease Congenital X-linked genetic disorder Mutation in genes coding for the copper-transport protein ATP7A gene Causes Cu deficiency. Growth failure, kinky hair etc ‹#›

36. Clinical forms : Include progressive mental deterioration Coarse feces Disturbance of muscle tone Seizures Severe hypothermia. Symptoms of Menkes disease usually appear at the age of 3 months and death usually occurs in 5-year-olds.

37. TOXICITY : Wilson's disease Hepatolenticular degeneration and progressive lenticular degeneration, Autosomal recessive disorder Mutation in ATP7b gene Causes excessive accumulation of Cu. Wilson’s disease usually presents between the ages of 6 and 40 years. Its manifestations include neurologic disorders, liver dysfunction, and Kayser-Fleischer rings (green-brown discoloration) in the cornea caused by copper deposition. ‹#›

38. 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. ( Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body )

39. CLINICAL FEATURES : Diarrhea, vomiting Cardiac & renal failure Hepatic necrosis Encephalopathy TREATMENT : Life long treatment Avoidance of high Copper diet In early stages Zn may be effective as it competes with Cu for absorption Penicillamine ‹#›

40. REFERENCE INTERVALS OF COPPER : Copper in serum : 700–1500 g/L Mean levels for copper serum in women and children are slightly 8–12% higher. Copper in serum (pregnancy at term) : 118–320 g/L Copper in urine : 15–60 g/24 hours or 3–35 g/24 hours or 2–80 g/L Copper in RBCs : 90–150 g/L

41. IODINE Soil near the ocean or sea is higher in iodine than soil inland. More than half of the iodine is found in thyroid gland Essential component for thyroid hormones , including thyroxine. Most of the iodine in the diet comes from iodized salt. Natural sea salt has very low iodine. 32

42. Iodine induced hyperthyroidism : - Multinodular goiter, excess iodine exposure cause hyperproduction of thyroid hormones and clinically significant thyrotoxicosis .

43. I odine induced hypothyroidism: Large goiter can cause a cough and make it difficult for you to swallow or breathe. Within a goiter, nodules can develop. ( HYPOTHYROIDISM)

44. RDA : Adult male and female - 150 mcg/day Higher during lactation and pregnancy Consuming diets high in goitrogens such as cabbage, cassava and millet, limits the bioavailability of Iodine. Deficiency result in cretinism. Upper Limit for adults is 1100 mcg per day.

45. 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 ‹#›

46. CHROMIUM ‹#› Regulates plasma lipoprotein concentration and reduces cholesterol and triglycerides. Cooking in stainless steel can increase chromium’s content. Chromium exists in two main valency states: trivalent and hexavalent. Chromium(VI) is better absorbed and more toxic than chromium(III) and has also been listed as a carcinogen implicated in lung cancer. Found in – grains, cereals, fruits, processed meat.

47. RDA : 20 – 35 mcg/ day DEFICIENCY : U ncommon; total parenteral nutrition, diabetes, or malnutrition. Chromium deficiency is characterized by glucose intolerance, glycosuria, hypercholesterolemia, decreased longevity, decreased sperm counts, and impaired fertility TOXICITY : Lung Carcinoma, Bronchogenic Carcinoma in stainless steel workers, Dermatitis, skin ulcers ‹#›

48. Reference Intervals for Chromium : Chromium in whole blood: 0.7–28.0 g/L Chromium in serum: 0.05–0.5 g/L Chromium in urine: 0.1–2.0 g/24 hr Chromium in RBCs: 20–36 g/L

49. MANGANESE ‹#› Shown to be essential for normal growth and development Role in human health is unclear Dietary sources: meat, fish, poultry, dry fruits and nuts

50. BIOLOGICAL ROLE M anganese superoxide dismutase, Arginase, Glutamate synthase & Pyruvate carboxylase DEFICIENCY Experimental animals - ↓growth, ↓fertility, ataxia, skeletal deformities, abnormal fat and CHO metabolism ‹#›

51. TOXICITY : Neurotoxic- extrapyramidal parts affected Headache Hepatic dysfunction RDA – 2-11 mg/day ‹#›

52. MOLYBDENUM ‹#› Molybdenum (Mo) is a silvery white metal that is very hard. Molybdenum in human tooth enamel may have a role in lowering the risk of tooth decay. Act as a catalyst for enzymes and helps facilitate breakdown of certain amino acids, corrosion inhibitors, flame retardants, smoke repressants, lubricants, and molybdenum blue pigments. RDA : 45mg/day Pregnancy and Lactation - 50mg/day

53. DEFICIENCY : Molybdenum cofactor deficiency is a recessively inherited error of metabolism. SYMPTOMS : include seizures, anterior lens dislocation, decreased brain weight, and usually death prior to age 1 year. TOXICITY : High dietary and occupational exposures to molybdenum have been linked to elevated uric acid in blood and an increased incidence of gout.

54. REFERENCE INTERVALS FOR MOLYBDENUM Molybdenum in whole blood: 60 g/L Molybdenum in serum: 0.1–3.0 g/L Molybdenum in red cells: 18 g/L Molybdenum in urine: 8–34 g/L

55. 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.

56. DEFICIENCY : Selenium deficiency has been associated with cardiomyopathy, skeletal muscle weakness, and osteoarthritis. A significant negative correlation was observed between selenium intakes and cancer of the large intestine, rectum, prostate, breast, ovary, and lungs and leukemia. Keshan disease : An endemic cardiomyopathy that affects mostly children and women in childbearing age in certain areas in China, has been associated with selenium deficiency

57. Functions in human body: ‹#› P rotects 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

58. Selenium deficiency occurs due to : Hemolytic anemia Clansman's thrombasthenia (platelet disorder) Gastrointestinal cancer Malnutrition ‹#›

59. 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

60. Health benefits: Prevents arthritis Used for bodybuilding 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 ‹#›

61. XENON ‹#› A trace element in earth’s atmosphere Xenon is a medical gas capable of establishing neuroprotection, inducing anesthesia and nuclear medicine as a contrast agent Acts through N-methyl-d-Aspartate receptor.