MLAB 1415- Hematology Keri Brophy-Martinez

1. MLAB 1415- HematologyKeri 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/