HYPOCHROMIC ANEMIA & IRON METABOLISM

1. HYPOCHROMIC ANEMIA & IRON METABOLISM

2. OBJECTIVE • Iron metabolism • Iron distribution & transport • Dietary iron • Iron absorption • Iron requirements • Disorders of iron metabolism • Hypochromic anemia

3. IRON • To accept & donate electron (Fe2+ Fe3+) • component of cytochromes, oxygen-binding • molecules • cell growth,proliferation, differentiation • damage tissues • H2O2 OH Fe2+ Fe3+

4. Iron Metabolism • Iron distribution & transport • transferrin, transferrin receptor • ferritin , hemosiderin (Fe3+) • myoglobin, iron-containing enzymes • Dietary iron • Iron absorption • Iron requirements

5. DAILY IRON CYCLE

7. The distribution of body iron Amount of iron Male Female % in average adult (g) (g) of total Hb 2.4 1.7 65 ferritin & hemosiderin 1.0 0.3 30 Myoglobin 0.15 0.12 3.5 Heme enzyme 0.02 0.15 0.5 Transferrin-bound 0.004 0.003 0.1 iron

8. Iron Metabolism • Iron distribution & transport • Dietary iron • ferric hydroxides • ferric-protein complexs • heme-protein complexes • Iron absorption • Iron requirements

9. GI Absorption of Iron

10. INTRACELLULAR IRON TRANSPORT

11. Iron Metabolism • Iron distribution & transport • Dietary iron • Iron absorption • Iron requirements

12. Estimated daily iron requirements, Units are mg/day Adult men 0.5-1 Postmenopausal female 0.5-1 Menstruating female 1-2 Pregnant female 1.5-3 Children 1.1 Female (age 12-15) 1.6-2.6

13. DISORDERS OF IRON METABOLISM Diseases of iron deficiency 1. Iron-deficiency anemia (IDA) 2. Anemia of chronic disease (ACD) Diseases of iron overload

14. What is iron-deficiency anemia ? It is the lack of iron in the blood, which is necessary to make hemoglobin.

15. Symptoms Fatigue - Sometimes out of proportion to anemia Atrophic glossitis Pica Koilonychia (Nail spooning) Esophageal Web

16. Causes of Iron Deficiency • Chronic blood loss • Uterine • GI tract • Increased demands • Prematurity • Growth • Pregnancy • Malabsorption • gastrectomy • Poor diet

17. Iron Deficiency Anemia (IDA) • Most common cause of anemia • Microcytic hypochromic anemia • MCV, MCH, MCHC are reduced • blood film : small red cells (microcytic) : pale red cells (hypochromic)

18. Laboratory findings 1. Red cell indices & blood film 2. Bone marrow iron 3. Serum iron & iron binding capacity 4. Serum transferrin receptor (sTfR) 5. Serum ferritin 6. Zinc protoporphyrin

19. TIBC Normal Iron def. ACD Iron overload Serum iron & iron binding capacity

20. Anemia of Chronic Diseases (ACD) • Chronic inflammatory diseases • Infections • Non-infectious • Malignant diseases • release of iron from macrophage to plasma • red cell life span • response to EPO • release IL-1 & TNF

21. Iron Overload • Increased iron absorption • Increased iron uptake • Repeated red cell transfusions

22. HYPOCHROMIC ANEMIAS • Iron-deficiency anemia (IDA) • Anemia of chronic disease (ACD) • Sideroblastic anemia • Thalassemia • Lead poisoning

23. The Cause of Hypochromic Anemia Iron Protoporphyrin • Iron deficiency • Chronic inflammation or malignant • Sideroblastic anemia Heme Globin + • Thalassemia Hemoglobin

24. Sideroblastic Anemia • A defect in heme synthesis • Hereditary & Acquired • mitochondrial defects • pyridoxal-6-phosphate • mutation in the d-aminolevulinic acid synthase • (ring sideroblasts in BM) • myelodysplasia syndrome • Hypochromic & microcytic red cells

25. Lead Poisoning • Inhibits both heme & globin synthesis • Interferes with the breakdown of RNA by inhibiting pyrimidine 5’nucleotidase • accumulation of denatured RNA in red cells • (basophilic stippling) • Hypochromic anemia • Ring sideroblasts (BM) • Free erythrocyte protoporphyrin is raised

26. Differential diagnosis of hypochromic anemia IDA ACD Thalassemia Siderblastic anemia Serum iron N TIBC N N serum ferritin N/ N BM iron stores - + + + Erythroblast iron - - + ring forms Hb N N HbA2 N electrophoresis

27. Hemochromatosis A genetically determined form of iron overload that results in progressive hepatic, pancreatic, cardiac, and other organ damage

28. Hemochromatosis • It is one of the most common genetic disorders in the U.S. • Present in heterozygous (one gene) form in 12% of nonblacks and 30% of blacks • Present in homozygous form (2 gene) in 1 in 200 nonblacks and 1 in 100 blacks • Homozygotes will die of iron overload unless they give blood frequently • Homozygotes absorb three times more iron from food than other people • Even heterozygotes may be at risk for iron overload, increasing risk of heart disease

29. Hemochromatosis: Risk Factors • Higher risk in people of northern European descent • Men tend to manifest symptoms earlier because they have no way to dispose of excess iron (menstruation, pregnancy, lactation) • Men may develop symptoms in their 30s but may not be diagnosed until their 50s • Women often develop symptoms after menopause

30. Hemochromatosis: Symptoms • Joint pain • Fatigue • Lack of energy • Abdominal pain • Loss of sex drive • Heart problems • Abnormal pigmentation of the skin, making it look gray or bronze

31. Hemochromatosis: if untreated, may result in • Arthritis • Liver disease: cirrhosis, cancer, liver failure • Damage to the pancreas, leading to diabetes • Heart abnormalities, including arrhythmias and heart failure • Impotence or early menopause • Thyroid or adrenal problems

32. Hemochromatosis: Diagnosis and Treatment • Testing: serum ferritin and transferrin saturation can reveal excess stores of iron; followed by HFE (genetic) test and possible liver biopsy • Treatment: regular phlebotomy to remove excess iron • Avoidance of iron supplements and sources of iron in the diet, especially heme iron • Awareness of iron cooking vessels

33. The End