irondeficiencyanemia-pathogenesisandlabdiagnosis-150501132717-conversion-gate02.pptx

irondeficiencyanemia-pathogenesisandlabdiagnosis-150501132717-conversion-gate02.pptx

1. I ron D eficiency A nemia Dept . Of General Medicine

2. Iron deficiency is the most common anaemia. 83- 90% of all anemia constitute IDA Every day about 30 mg iron is used to make new hemoglobin. Daily iron loss is around 1 mg. In women menstruation and childbirth increase iron losses to about 1.5 mg/day.

3. The total content of iron in the body - about 4.2g. From them: 75- 80% belongs to the hemoglobin 20 - 25% reserve 5- 10% part of the myoglobin -1% is part of the enzyme for the tissue respiration

4. DIETARY IRON There are 2 types of iron in the diet; heme iron and non- heme iron. Heme iron is present in Hb containing animal food like meat, liver & spleen. Non- heme iron is obtained from cereals, vegetables & beans.

5. Most body iron is present in hemoglobin in circulating red cells The macrophages of the reticuloendotelial system store iron released from hemoglobin as ferritin and hemosiderin. In the plasma, total iron averages 110 µg/dL Majority bound to the transferrin (capacity to bind 330 µg of iron per deciliter) So only one third of transferrin is saturated.

6. Iron Metabolism Iron concentration (Fe) N: 50- 150  g/dl Total Iron Binding Capacity N: 250- 450  g/dl Transferrin saturation Transferrin receptor concentration Ferritin concentration N: 50- 300  g/l

7. IRON ABSORPTION Site- Proximal small intestine i.e. duodenum (first part- maximum absorption) and jejunum. 10% of dietary iron is absorbed it is determined by intraluminal factor i.e. pH and redox potential. Therapeutic ferrous iron is well absorbed on empty stomach. Haem iron is not affected by ingestion of other food items. Heme iron → Acid and gastric juices release it from apoprotein → Oxidised → hemin → directly absorb through mucosal cell intact.

8. Inhibitors Of Iron Absorption Food with polyphenol compounds Cereals like sorghum & oats Vegetables such as spinach and spices Beverages like tea, coffee, cocoa and wine. A single cup of tea taken with meal reduces iron absorption by up to 11%. Food containing phytic acid i.e. Bran Cow’s milk due to its high calcium & casein contents .

9. Promoters of Iron Absorption Foods containing ascorbic acid like citrus fruits, broccoli & other dark green vegetables Foods containing muscle protein Food fermentation aids iron absorption by reducing the phytate content of diet

10. Overview of Iron Homeostasis erythr oblast

11. Iron Absorption a t Molecular Level Iron is converted from Fe 3+ to Fe 2+ by ferrireductase (DCYTB). • Fe 2+ transported across mucosal surface of enterocyte by DMT1 , stored as ferritin. Ferritin releases Fe 2+ which is transported across basolateral surface of enterocyte with help of ferroportin . Fe 2+ converted back to Fe 3+ by Hephaestin . Fe 3+ binds to transferrin in plasma.

12. Regulation of Iron Absorption Regulated at two stages Mucosal uptake At stage of transfer to blood Iron transfer to the plasma depends on the requirements of the erythron for iron and the level of iron stores. This regulation is mediated directly by hepcidin.

13. Iron storage Iron stored in two forms Soluble ferritin Insoluble hemosiderin Hemosiderin deposits are seen on Prussian- blue positivity after staining of tissue sections with potassium ferrocyanide in acid.

14. Iron Transport Transferrin is the major protein responsible for transporting iron in the body Transferrin receptors, located in almost all cells of the body, can bind two molecules of transferrin. One molecule of transferrin binds two molecules of iron. Both transferrin saturation & transferrin receptors are important in assessing iron status

15. Causes of iron deficiency Chronic blood loss Increased demand Malabsorbtion of iron Inadequate iron intake Hemolytic anemia

16. Increased demands Pregnancy Lactation Growing infants and children Menstruating women Hemolytic anemia

17. Decreased intake Decreased iron in the diet Vegetarian diet Low socioeconomic status Lack of balanced diet or poor intake Alcoholism Decreased absorbtion Gastric surgery Achlorhydria Duodenal pathology Chronic renal failure patients Coeliac Sprue Pica

18. Increased iron loss Menorrhagia Gastrointestinal hemorrhage P.Ulcer Oesophagitis Varices Hiatal hernia Malignancy Angiodysplasia Diverticulosis Meckel diverticula Colitis or imperforated bowel disease Hemorrhoids NSAID use Parasites

19. Increased iron loss Bleeding disorder Pulmonary lesions with bleeding Hemoglobinuria – hemosiderinuria (chronic intravascular hemolysis) Hemodialysis Hematuria (chronic) Frequent donation – 250 mg iron /unit- blood

20. Clinical features Fatigue and Other Nonspecific Symptoms irritability, palpitations, dizziness, breathlessness, headache Neuromuscular System B behavioral disturbances , Difficulty in concentration Neurologic development in infants and scholastic performance in older children may be impaired. Sometimes neuralgia pains, vasomotor disturbances, or numbness and tingling.

21. Epithelial T issues Site findings Nails Flattening Koilonychia Tongue Soreness Mild papillary atrophy Absence of filiform papillae Mouth Angular stomatitis Hypopharynx Dysphagia Esophageal webs Stomach Achlorhydria Gastritis

22. Plummer- Vinson syndrome The most common anatomic lesion is a “web” of mucosa at the juncture between the hypopharynx and the esophagus

23. Immunity and Infection Defective lymphocyte-mediated immunity and impaired bacterial killing by phagocytes. Pica “craving to eat earth” Pagophagia is, defined as the purposeful eating of at least one tray of ice daily for 2 months, Food pica- compulsively eating one food, often something that is brittle and makes a crunching sound when chewed. Genitourinary System - Disturbances in menstruation, Skeletal System diploic spaces may be widened, and the outer tables thinned

24. Developmental Stages of Iron Deficiency Anemia (WHO) Pre- latent – reduction in iron stores without reduced serum iron levels Hb, MCV, Transferrin saturation- Normal, Iron absorption - increase, Serum ferritin and marrow iron reduced no clinical manifestation Latent- iron stores are exhausted, but the blood hemoglobin level remains normal clinical picture is caused by the sideropenic syndrome Iron Deficiency Anemia blood hemoglobin concentration falls below the lower limit of normal the clinical manifestations in the form of sideropenic syndrome and general anemic symptoms

25. Stages in the Development of Iron Deficiency Stage 1 (Prelatent) Stage 2 (Latent) Stage 3 (Anemia) Bone marrow iron Reduced Absent Absent Serum ferritin Transferrin saturation Reduced Normal <12 μg/L <16% <12 μg/L <16% Free erythrocyte protoporphyrin, zinc protoporphyrin Serum transferrin receptor Normal increased increased Normal increased increased Reticulocyte hemoglobin content Normal reduced reduced Hemoglobin Normal Normal Reduced Mean corpuscular volume Normal Normal Reduced Symptoms Fatigue, malaise Pallor, pica, in some patients

26. Laboratory diagnosis Complete blood count Bone marrow Serum parameter ferrokinetic Studies

27. Blood And Bone Marrow Findings BLOOD : peripheral smear findings – microcytosis, hypochromia, anisocytosis , poikilocytosis ( eliptocytes and pencil cells

28. Iron Deficiency Anemia Reduced ( N : 80-100 fl) Reduced ( N : 27- 32 pg) Normal to reduced (N: 30- 34 mg/dl) Reduced (N: 4 gm ) Increased (N: 47- 70 µmol/l) Reduced (N :16- 50%) Reduced (N:15–300 µg/l) High ( N : 11.5- 14 %) Normal/Low (N: 0.5- 2.5%) Normal Normal MCV - MCH - MCHC– Iron- TIBC- Transferin Saturation- Ferritin- RDW: Reticulocytes: Platelates: WBC: Smear: Hypochromia,anisocytosis , microcytosis, poikilocytosis

29. Bone Marrow Findings BONE MARROW Early stage - Normoblastic hyperplasia Normoblasts - smaller than normal deficient in hemoglobin Irregular shaped with frayed margins absence of stainable iron WBCs- Giant neutrophil bands or metamyelocytes Storage iron is absent

30. Marrow film- Iron deficiency anemia

31. Marrow film- prussian blue stain

32. Other Investigations Done G.I. endoscopy Duodenal biopsy Stool for hook worms

33. Stages in the Development of Iron Deficiency NORMAL Fe deficiency Fe deficiency Fe deficiency Without anemia With mild anemia With severe anemia (prelatent) (latent) (IDA) Serum Iron 60- 150 60- 150 <60 <40 Iron Binding Capacity 300- 360 300- 390 350- 400 >410 Saturation 25- 55 30 <15 <10 Hemoglobin Normal Normal 9- 12 6- 7 Serum Ferritin 40- 200 <20 <10 0- 10

34. Differential diagnosis of Microcytic anaemia Iron deficiency anemia Anemia of chronic disease Thalassaemia Sideroblastic anemia MCV Reduced Low normal or normal Low Low in inherited but normal in acquired Serum iron Reduced Reduced Normal Raised Serum TIBC Raised Reduced Normal Normal Serum Ferritin Reduced Normal or raised Normal Raised Iron in BM Absent Present Present Present

35. Requirement Of Iron Body wt (kg) x 2.3 x Hb deficient(15-ptHb) + 500/1000mg (for body stores) Oral Iron Therapy – Dose 200-300 mg elemental iron T. Ferrous sulphate(325mg) (65)– BD T. Ferrous fumarate (325mg)(107) – BD T. Ferrous gluconate (325mg) (39)– BD Duration 6 -12 months after correction of anaemia Treatment…

36. Parenteral Iron Therapy – Indications - Unable to tolerate oral iron Acute bleeding Persistent bleeding. Treatment…

37. Inj. Iron dextran 100 mg O.D deep I.M after sensitivity test by giving small dose Newer Parenteral Preparation Inj. Sodium ferric gluconate Inj. Iron sucrose I.V Inj. Ferric Carboxymaltose Treatment…

38. Red Cell Transfusion – Indication – Heart failure Cardiovascular instability Excessive blood loss Cerebral hypoxia Angina pectoris Treatment

39. Thank You