Biology of Malnutrition

1. Biology of Malnutrition Part 3

2. Micronutrient Deficiencies • Focus is on • Vitamin A • Iron • Iodine

3. Iron deficiency a significant concern worldwide • Iron deficiency occurs most often when there is a regular, significant loss of blood, as in the monthly cycle of women. • Iron deficiency anemia due to insufficient hemoglobin is the primary symptom of iron deficiency.

4. Prevalence • Deficiency and anemia estimated to affect 3.5 billion people worldwide • Anemia incidence 3-4 times higher in developing countries than industrialized • 1/3 of adult males are anemic in developing countries – about 5% in industrialized

5. Prevalence of Anemia in Developing Countries • Pregnant women: 56% • Non-pregnant women: 44% • School-age children: 53% • Preschool children: 42% • Older adults: 51% • Adult men: 33%

6. Other Causes of Iron Deficiency • Deficient intake • Malaria • Parasites • Other infections • Other nutrient deficiencies for blood production (A, B vitamins, etc.)

7. Iron – Why do we need it? • Because it is readily oxidized, iron is part of many proteins involved in oxygen transport and oxidation/ reduction reactions: • Hemoglobin – the protein of red blood cells that carries oxygen molecules • Myoglobin – a protein similar to hemoglobin found in the cytoplasm of muscle cells • Enzymes and electron carrier molecules in the energy metabolism pathway • Proteins involved in drug metabolism, the immune system, and protection against free radicals

8. The Hemoglobin Molecule

9. Iron • Body iron content • 2/3 functional - being used • 1/3 stored

10. Stages of Iron Deficiency • Iron depletion • Decrease of stores (ferretin) • Iron deficiency hematopoiesis • Iron stores depleted with insufficient absorption to counteract normal losses • Leads to decreased hemoglobin production • Iron deficiency anemia • Hemoglobin falls below a set standard

11. A Negative Iron Balance Leads to Progressively More Severe Conditions

12. Normal Values

13. Iron is transported by special transport proteins • Iron can be stored by attachment to a protein called Ferritin in the mucosal lining of the intestine. • Iron is transported through the blood attached to another protein, Transferrin.

14. Iron in the Body

15. What foods contain iron? • Heme iron is part of hemoglobin and myoglobin and is obtained from meat of all types. • About 20% absorbed • Non-heme iron is found in leafy green vegetables, legumes, and meat and is absorbed at about half (or less) the rate of heme iron. • Non-heme iron can also leach out of iron cookware into food.

16. Food Sources of Iron

17. Absorbability of Iron • Amount of iron in a food and absorbability can be significantly different in plant foods • Fiber, phytate, tannins and oxalate bind iron and prevent absorption • Concurrent intake of Vitamin C can enhance absorption of nonheme iron up to 6 fold

18. Economic Sequelae of Deficiency • Mean value of productivity losses due to iron deficiency thought to be about US$4 per capita • 0.9% GDP for a range of developing countries

19. Dominant Effects • Cognitive defects in children • Thought to be due to not enough oxygen to brain or a decreased amount of neurotransmitters (Fe dependent) • Maternal deaths due to severe anemia • Lowered effectiveness of money spent on education • Decreased productivity

20. Iodine • A major global problem BUT • “Progress towards the elimination of IDD through universal salt iodization appears to be one of the most significant successes in the field of noncommunicable disease.” • 4th Report of The World Nutrition Situation

21. Iodine • Iodine is needed for the synthesis of thyroid hormones. • Regulates metabolic activites of all cells • Like selenium, its availability depends on soil concentrations; it is also abundant in seawater and hence in seafood and seaweed. • Lack of iodine causes enlargement of the thyroid glands (goiter). • Chronically high intakes of iodine can cause impaired thyroid function.

22. Iodine • Plays a key role in cell replication • Especially relevant for the brain • Neural cells multiply mainly in utero and during the first 2 years of life • Fetal deficiency leads to • Increased rates of spontaneous abortion • Stillbirths • Congenital anomalies • Cretinism • Psychomotor deficits • Neonatal mortality

23. Thyroid Hormones Contain 3-4 Atoms of Iodine

25. Goiter Develops When Iodine Is Lacking

26. Goiter

27. Adult Deficiency • Goiter and its complications • Hypothyroidism • Impaired mental function

28. Vitamin A

29. Vitamin A serves varied functions in the human body • A major role of vitamin A is as part of the visual pigment rhodopsin • Forms of vitamin A are also involved in: • Gene expression • Maintenance of epithelial tissue • Regulation of growth and differentiation of cells, including some cells of the immune system

30. Rhodopsin absorbs light, which signals visual cortex of brain Reconversion and replenishing of rhodopsin must occur before it can respond again to light When amt. of rhodopsin is limited, difficult to see in dim light “night blindness” When A pool is low, dark adaptation is slowed down As part of rhodopsin, retinol binds with the protein opsin

31. In regulation of gene expression, retinoic acid binds to a protein receptor • Retinoic acid is involved in cell differentiation by activation of DNA receptors • leads to gene expressions for a variety of structural proteins such as enzymes and those in epithelial cells (skin keratins)

32. Cell differentiation function of Vitamin A • Often accompanied by cell proliferation – the continuous development of cells in tissue formation • Necessary for the production, structure and normal function of epithelial cells in the lungs, trachea, skin, GI tract, etc. • Also essential for the production of mucous-forming cells in these organs

33. Vitamin A and Immunity • Deficiency is associated with decreased resistance to infection • Functions through the cell-mediated and anti-body-mediated responses • such as macrophage and natural killer cell activity, and growth and maintenance of B-lkymphcytes • The maintenance of the epithelial tissues and mucus production all act as barriers to invading pathogens as well (non-specific immunity)

34. Vitamin A occurs in several forms • Retinoids, including retinol, retinal and retinoic acid, are common in animal tissues; they can serve vitamin A functions directly • Beta-carotene is a precursor of vitamin A found in plant tissues; it is also an antioxidant • Converted/split by intestine into retinol and retinal • retinol then oxidized to retinoic acid and retinal

35. Absorption, transport and storage of vitamin A • Vitamin A is a fat-soluble vitamin and is absorbed and transported with lipids • Vitamin A is stored in the liver; recorded instances of toxicity involve excess consumption of polar bear liver by Arctic explorers

36. Good dietary sources of vitamin A • Best sources include: • beef liver • carrots (as beta-carotene) • mustard greens (as beta-carotene) • eggs • apricots (as beta-carotene) • Note that beta-carotene is much less toxic in higher doses than is the preformed animal forms of vitamin A

37. Food Sources of Vitamin A

38. What are the symptoms of vitamin A deficiency? • Dry, hard skin • Dry cornea and eventual blindness (Xerophthalmia) • Night blindness (insufficient retinal for rhodopsin formation) • Impaired immune function

39. Steps in Vitamin A Deficiency • Body stores are depleted leading to impairment of physiologic functions • 1st integrity of the epithelial barriers and then the immune system is compromised • Finally the visual system is impaired

40. Xeropthalmia – Sequence of Events • Night blindness is a common early symptom of low levels of Vitamin A • Mucus forming cells deteriorate and are no longer able to synthesize the mucus that lubricates the body • The eye especially needs mucus to keep the surface moist and to wash away dirt and other particles that settle on the eye

41. Xeropthalmia – Sequence of Events • Deterioration of the eye results from bacterial invasion • Role of A in resistance to infection • Conjunctival xerosis (abnormal dryness of the lining of the eyelids and the outer surface of the eyeball) and Bitots spots (drying out of the eye and appearance of hardened epithelial cells) appear as Vit. A deficiency worsens

42. Xeropthalmia – Sequence of Events • Finally, corneal ulcerations and keratomalacia (softening of the cornea) results in scarring • Can see effects from barely detectable to blindness

43. Other Problems in Vitamin A Deficiency • Keratinized cells in the outer layer of skin replace the normal epithelial cells in the underlying skin layers • Hair follicles become plugged with keratin • Skin has a bumpy appearance and rough texture and is very dry • Deficiency also causes a decrease in appetite and poor growth

44. Treating Vitamin A Deficiency • 15,000 to 60,000 micrograms of Vitamin A every 6 months can prevent deficiency in children • Improving the vitamin A status of young children reduces mortality rates by about 23% in populations where there is vitamin A deficiency

45. Treating Vitamin A Deficiency • What about food? • Vegetables are the major source of pro-vitamin A in children where animal products are limited • Kids don’t like these foods • Insufficient dietary fat intake limits absorption of what they do get

46. Can you have too much vitamin A? • Toxic levels can be reached by excess consumption of liver and supplements of preformed vitamin A (not beta-carotene) • Symptoms of toxicity include: • Nausea, vomiting • Headache, blurred vision • Lack of muscular coordination