1. MLAB 1415- Hematology Keri Brophy-Martinez Chapter 9: Iron Metabolism and Hypochromic Anemias

2. Iron Metabolism Primary function Oxygen transport and storage Distribution Types of iron-containing compounds Functional, assisting in enzymatic and metabolic functions Transportation or storage Location RBCs- majority here Macrophages of spleen& liver- where destruction of RBC occurs, liberating iron Hepatocytes and enterocytes- storage of iron

3. Iron Metabolism Iron absorption and storage is influenced by : The amount and type of available iron in the diet Is it a nutritional deficiency Incomplete absorption due to GI tract problems Current iron stores Increased demand (pregnancy, the growth years) Excessive loss due to acute or chronic hemorrhage menstrual period for women of childbearing years, GI bleeding for men

4. Forms of Iron Nonheme Ionic or ferric Found in vegetables and whole grains Heme Found in red meats Easily absorbed

5. Iron Metabolism Transport Transferrin Transports iron to bone marrow to be used in hgb synthesis Synthesized in the liver Storage Primarily in the liver Ferritin Soluble iron, quick release for heme synthesis Hemosiderin Partially degraded iron, slow release

6. Iron Balance Loss of iron Secretions of urine, bile, sweat and exfoliation of intestinal epithelial cells of GI tract Approx. 1 mg/ day Regulation of iron Delicate balance between loss and absorption

7. Laboratory Assessment of Iron Serum iron Total iron binding capacity (TIBC) Percent saturation Serum ferritin

8. Clinical Syndromes of Iron Metabolism Iron Deficiency Anemia (IDA) AKA Sideropenic anemia This is the most common form of anemia. IDA occurs when the iron stores in the body are inadequate to preserve homeostasis.

9. Causes of IDA Dietary Blood Loss Hemodialysis Malabsorption

10. 3 Stages of IDA Stage 1 Decrease in storage iron (ferritin decrease) No anemia RBC morphology normal RDW can be elevated Stage 2 Decrease in iron for erythropoiesis No anemia or hypochromia RBC slightly microcytic Stage 3 Decrease in Blood Hgb Decrease in peripheral tissue oxygen delivery All lab tests abnormal Microcytic, hypochromic anemia

11. Clinical Features of IDA SOB Lethargy Pallor Gastritis Pica Koilonychia

12. IDA: Lab features Decreased RBC, Hgb, Hct, MCV, MCH, MCHC Normal to decreased Retic Peripheral blood smear microcytic- hypochromic Targets, elliptocytes, teardrops If IDA is caused by bleeding, leukocytosis and thrombocytosis are possible.

13. IDA: Lab Findings Bone marrow Decrease in stainable iron Decrease in erythroid hyperplasia M:E ratio decreased Chemistry Decrease in serum iron and ferritin Increased TIBC

14. Anemia of Chronic Disease (ACD) Anemia that occurs in patients with chronic infections, chronic inflammatory disorders, trauma, organ failure or neoplasms Occurs due to biochemical changes during inflammation Hallmark is normal iron stores but low serum iron

15. Anemia of Chronic Disease Mechanisms Block in release of iron from macrophages due to increased cytokines Cytokine inhibition of EPO production Cytokine inhibition of erythropoiesis Shortened erythrocyte survival

16. ACD: Lab Features Typical lab findings Decreased RBC, Hgb, Hct, MCV, MCH, serum iron Increased ferritin Normal MCHC Normal to decreased Retic, TIBC Peripheral blood smear normocytic-normochromic Targets, elliptocytes, teardrops Bone marrow M:E ratio increased

17. Anemia’s Associated with Abnormal Heme Synthesis Sideroblastic Anemia Lead Poisoning Porphyrias

18. Sideroblastic Anemia (SA) First step in heme synthesis is affected Characterized by: Increase in total body iron Presence of ringed sideroblasts in bone marrow Hypochromic anemia

19. Sideroblastic anemia Classification Hereditary Acquired 2 Forms Idiopathic Secondary type Certain therapeutic drugs Chronic transfusions (for aplastic anemia, leukemia, thalassemia) Alcoholism and food fads Use of iron utensils or increased iron in water.

20. Sideroblastic anemia Mechanism Adequate iron but it can not be incorporated into hgb synthesis. Iron enters mitochrondria of metarubricyte, but accumulates leading to formation of ringed sideroblasts Eventually, mitochrondria rupture

21. Lead poisoning Lead interferes with iron storage in the mitochondria Lead damages the activity of enzymes used for heme synthesis Basophilic stippling pronounced

22. Lead Poisoning

23. Lab features of SA Peripheral blood Pappenheimer bodies Hypochromic, normochromic RBCs Normal to increased platelets Chemistry Increased serum iron, ferritin

24. Hemochromatosis Condition caused by increased iron absorption which deposits in vital organs such as the liver, spleen and pancreas which then becomes fibrotic Hyperpigmentation of skin Therapy consists of iron removal by therapeutic phlebotomy or chelation

25. Porphyrias Excessive production of porphyrins in the bone marrow (or liver) Rare disease caused by accumulation of porphyrins in developing RBC’s Defect in one or more of the enzymes in heme synthesis pathway Characterized by dermal photosensitivity and rash caused by the sun. The original werewolf was probably a person with erythropoietic porphyria.

26. References Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: F.A Davis. McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology. Upper Saddle River: Pearson Education, Inc. http://healthmap.wordpress.com/2008/11/