2. Iron 22-24 mg is needed per day Mostly is covered by reutilisated iron (haemoglobine from destroyed erythrocytes) Normal daily loss (about 1 mg in men) with hair, skin, urine, faeces and menstrual blood loss in women (about 1,5-2 mg)

3. The average Western diet contains 10–15 mg of iron daily, of which 5–10% (about 1 mg) is normally absorbed Fe 2+ Fe 3+ Animal products Is easily absorbed through the upper small intestine Vegetables Vitamin C enhances absorption Iron inflow

4. Iron absorption Intensify absorptionInhibit absorption Ascorbic acid Fructose Succinic, citric, malic, acetic acids Orange juice Animal proteins (fish, meat) Tea tannins Antacids Enterosobents Carbonates Milk Bran Fats Calcium salt

5. Iron spreading in the organism Componentmg% Haemoglobin230060-65 Ferritin5009-10 Hemosiderin5009-10 Mioglobin1307,5-8,5 Cytochromes, catalases105-7 Transport iron30,1-0,2 total3500100 Долгов В.В., Луговская С.А. 2001.

6. Iron metabolism in the cell ферритин ЖРБ Fe-содержащие ферменты мРНК Долгов В.В., Луговская С.А. 2001.

7. Transferrin – Fe3+ carrier from the absorption location/depot to the tissues (2 iron molecules) Ferritin –Fe3+ depot, up to 2000 iron molecules Hemosiderin – unsoluble, locating in the lysosomes ferritin Iron-containig proteins Долгов В.В., Луговская С.А. 2001.

8. Iron metabolism laboratory indices Serum iron9-30 mkmol/l Unsaturated iron binding capacity46-90 mkmol/l Latent iron binding capacity = Unsaturated iron binding capacity – serum iron 15 – 80 mkmol/l transferrin23-45 mkmol/l Transferrin saturation with iron (TSI)15-45% Serum ferritin30-150 (200 у мужчин) mkg/l serum iron transferrin TSI = Х к х 100

9. On the Earth there about 15-20% of population with latent iron deficiency or clinically manifistated anaemia. 80-90% of all the anaemias.

10. Iron deficiency development stages Prelatent iron deficiency: 59Fe³+ absorption test is increased to 50%, norm is 10- 15%. Latent iron deficiency: Serum iron, ferritin, TSI are decreased, transferrin, CD 71 are increased. Нв, МСН, МСV, RDW – norm. Iron deficiency anaemia: 1. Regeneration stage – reticulocytosis 2. Hyporegeneratory stage – reticulocytopenia, red cell hypoplasia

11. Aetiology 1. Chronic bleeding 2. Increased demands 3. Poor diet 4. Malabsorption 5. Transport problems

12. Chronic blood loss sources Uterine Gastrointestinal Bleeding into a closed cavity Renal diseases Haemorrage Lung diseases

13. Increased demands Pregnancy, lactation Prematurity Intensive sports

14. Nutritive IDA Veggies Anorexy

15. Malabsorbtion Chronic enterites Small intestine resection Gaster resection, Bilrot II type (an end to a side) – a part of duodenum “turns off” Often combines with folates, vit. В 12 deficency

16. Transport problems Inherited hypo-, atransferrinemia Antibodies to transferrin, it’s receptors

17. Classification I. Aetiology II. Stages III. Severity: Mild: Hb 90-120 g/l Moderate: Hb 70-90 g/l Severe: Hb < 70 g/l

18. Clinical features General features of anaemia Sideropenia Weakness High fatiguability Sonitus Decrease of mental operability Miocardiodystrophya Paleness Pica chlorotica Abnormal smell Muscular weakness, muscular atrophy Skin dystrophia Angular cheilosis Subfebrilitet Stress enuresis Predisposition to infections Glossitis Sideropenic dysphagia

19. Differential diagnosis 1. Anaemias of chronic diseases (ACD) 2. Heterozygous thalasemias 3. Sideroblastic anaemias (porphyrns syntesis violation) 4. Thyroprivic anaemia

20. IDA/ACD ParametersIDAACD НbНb ↓↓↓ CausesBleeding, malabsorbtion инфекция, воспаление, опухоль МСН, МСV, color index < 27 pg, < 80 fl, < 0,8≤ 32 pg, ≤ 100 fl, ≤ 1,0 Serum iron< 12 mkmol/l- Serum ferritin< 30 mkg/l> 100 mkg/l TSI< 20%> 20% Hepcidine ↓↑ EPOО/П log ЭПО > 0,9О/П log ЭПО < 0,9

21. IDA/ACD EPO investigation Hb concentration (g/l) and serum EPO level (U/l) dependence (logarithmic scale) in patients with gastrointestinal hemorrage IDA and anaemias of gynecological diseases

22. Hb concentration (g/l) and serum EPO level (U/l) dependence (logarithmic scale) in patients with anaemia of gynecological malignancies Anaemia of malignancy EPO investigation

23. IDA/ACD Parameters Reference values anaemias of gynecological diseases anaemia of gynecological malignancies р SF, mkg/l15 – 100*14,25 ± 6,8422,33 ± 14,92 > 0,05 СRP, mg/l< 8**не было ↑ (0%)у 4 больных ↑ (44%) < 0,01 TNF-1α, ng/l< 8,1**153,85 ± 273,11235,23 ± 317,54 > 0,05 HIF-1α, ng/l 1,5 – 6,0*7,18 ± 8,623,05 ± 2,47> 0,05 Hepcidine, ng/l60 – 85*108,75 ± 40,08233,33 ± 158,45 < 0,05 ДМТ-1, ng/l4,5 ± 1,2*3,73 ± 0,223,88 ± 1,51 > 0,05 ФРП, ng/l3,1 ± 0,2*0,43 ± 0,210,94 ± 0,97 > 0,05

24. IDA/thalassemia Similarity: Hypochromia, reticuloytosis+/- Difference: Ferritin, TSI increase Moderate spleen enlargement Target cells Course with crises or chronic course Incresed indirect bilirubin Absence of blood loss Haemoglobin electrophoresis shows abnormal haemoglobins

25. Sideroblastic anaemia is a hypochromic microcytic hyporegeneratory anaemia as a result of abnormal intracellular iron utilisation for Hb synthesis. The marrow shows increased iron present as granules arranged in a ring around the nucleus in developing erythroblasts (‘ringed sideroblasts’) IDA/sideroblastic anaemia

26. Haem Долгов В.В., Луговская С.А. 2001.

27. Plumbism: Hypochromia, reticulocytopenia Iron overload Metal border on gums Anamnesis (plumbum, alcohol, izoniasid, cicloserinum, chloramphenicol) Sideroblasts in the BM IDA/sideroblastic anaemias

28. Vitamin В6 deficiency – pyridoxine metabolism anomaly — synthetase insufficiency- aminolevulinic acid. Massive doses of pyridoxine partially correct the anaemia (150-250 mg daily per os up to 8 weeks), folic acid 3 mg daily. Congenital form is resistant to the treatment with pyridoxine. Free erythrocytic coproporfirine concentration is increased, and a free erythrocitic protopoffirine is decreased. IDA/sideroblastic anaemias

29. IDA treatment Causes identifying and elimination Neither diet can correct the anaemia Iron drugs – sufficient doses and protractedly (3-6 months) Start with oral medicines Parenerally – in a day: 1. Acute gastrointestinal diseases (ulcer, erosions) during less than 1 month; 2. Resection or diseases of small intestine until all the red cell indices (Нb, МСН, MCV, color index, Ht) and iron metabolism (serum ferritin) are normalized.

30. Drugs Therapeutic dose is 150-200 mg of elementary iron daily Course dose: Serum iron initial, mkmol/lQuantity of elementary iron per course, mg 10-121355 8-103200 <86500-7000

31. Drugs Oral (Fe2+, Fe3+)Parentheral, Fe 3+ Sorbifer durules (100 mg of elementary iron Fe2+ + ascorbic acid). Maltofer (100 mg of elementary iron Fe3+). Ferrofolgamma (100 mg of elementary iron Fe3+ + folic acid+ ascorbic acid + cyanocobalamin). Liquid forms: Tothema (50 mg Fe3+), Ferlatum(40 mgFe3+ ) Ferrum-lec (100 mg of elementary iron in 2 ml), Ectofer (100 mg in 2 ml) for i/m injections; Ferrum-lec (100 mg in 5 ml), Hemofer (100 mg in 5 ml), Venofer (100 mg in 5 ml) for i/v injections