* * * * * * * * * * * * * Hereditary Iron Overload “Hemochromatosis” Heterogeneous group of inherited disorders representing mutations of genes which control iron absorption and storage Iron accumulates in liver, heart, pancreas, joints, gonads; clinical manifestations seen earlier in men Treated with phlebotomy to remove iron-rich RBCs Mutations: HFE (most common), TfR2, hemojuvelin, hepcidin and ferroportin genes Hemoglobin switch Taken from C.Shanmuganathan and D. Kamat. Pediatric Annals 2013;42:12:502-508 Hgb A = α 2 β 2 Hgb F = α 2 γ 2 Hgb A2= α 2 δ 2 Hemoglobin Structure-Function relationships/1 Modified from Dean & Schechter: NEJM, 299:752-763, 1978 by Babior & Stossel: Hematology: A Pathophysiologic Approach, Churchill Livingstone, 1994, pg. 28. Erslev & Gabuzda,eds.Pathophysiology of Blood, Philadelphia: W.B. Saunders, 1975, pg. 17. Hemoglobin Structure-Function Relationships/2 26.6 RBC Membrane Lipid Composition (/Pages/500/520/520, html. Downloaded 07/22/2013, Oakland Children’s Hospital Medical Center.) RBC Membrane Schematic Structure Modified from Molecular Medicine?. Copyright, Daniele Focosi 2001-2013. Updated weekly. Available at . Accessed 7/17/13. 4.1 Modified from Hillman & Finch: Red Cell Manual, 5th ed. F.A.DavisCo., 1985, pg. 14. Elimination of peroxides; Protection against oxidants ADP ATP ADP ATP RBC Metabolism Requirements ATP for energy to maintain membrane integrity, water content, and deformability NADH to maintain reduced heme Fe 2,3 DPG for enhanced 02 release under conditions of low tissue 02 tension NADPH to facilitate removal of toxic oxidants and prevent denaturation of globin The Aging RBC Young RBC Senescent RBCs Day 120 Day 7 Recycling of RBC Components Protoporphyrin ring broken, releasing CO, tetrapyrrole and Fe Unconjugated bilirubin bound to albumin transported to liver for conjugation In the gut, conjugated bilirubin is converted to urobilinogen which is excreted in stool or reabsorbed and excreted by the
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