Iron metabolism and disorders. Georg Stüssi DIM Fortbildung
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1 Iron metabolism and disorders Georg Stüssi DIM Fortbildung
2 Iron metabolism Iron deficiency anemia Anemia of chronic disorders Iron overload
3 Distribution of iron in adults Adult men 35 45mg iron/kg BW Each RBC contains 10 9 atoms of iron 2x10 20 iron atoms are incorporated into RBC/day 1 g/l Ferritin corresponds to storage of 8 10mg iron. N. Andrews, NEJM, 1999
4
5 Enteral resorption Proximal jejunum/duodenum Resorption: 10% of nutritional iron supply Increased resorption: 40% DMT1 (Divalent metal ion transporter 1) Ferric reductase Fe 3+ => Fe 2+ Ferroportin: Basolateral transporters
6 Heme and non heme iron
7 Iron uptake
8 HFE Chromosome 6 (6p21.3) Atypical HLA molecule Aggregates with 2 microglobulin No peptide binding Membrane protein Inhibits the cellular iron uptake by interacting with the transferrin receptor 1.
9 Hepcidin Key player in iron homeostasis R. Fleming, NEJM, 2005
10 Hepcidin First description Nemeth et al., Science 2001 Synthesis in the liver Deficiency: Iron overload Overexpression: Hypochromic microcytic anemia Increased synthesis upon stimulation with IL 6 (inflammation)
11 Summary Enteral resorption DMT1 HCP1 Ferric reductase Basolateral membrane Ferroportin Hephaestin Serum transport Transferrin Cellular uptake TFR1/2 Regulation HFE (direct) Hepcidin (indirect)
12 Overview iron metabolism
13 Iron metabolism Iron deficiency anemia Anemia of chronic disorders Iron overload
14 Anemia diagnostics
15 Iron deficiency anemia
16
17 Laboratory evaluation Serum iron Ferritin Transferrin Total iron binding capacity (TIBC) Transferrin saturation Soluble transferrin receptor (stfr)
18 Serum iron Serum Eisen Non bound iron in the serum Large diurnal variability Concentration evening = ½ morning No test for iron deficiency
19 Ferritin
20 Ferritin and iron deficiency Low ferritin = Iron deficiency
21 Produced in the liver Transferrin/TIBC Transferrin One molecule binds to iron Total iron binding capacity (TIBC) Iron 18 mol/l TIBC 56 mol/l Saturation: 32% Iron deficiency < 16%
22 Soluble transferrin receptor (stfr) Shedded form of TfR > 80% of the TfR is expressed in the erythroid bone marrow stfr Erythroid activity in the bone marrow Increased stfr Increased erythropoiesis Hemolysis, Bleeding MDS (ineffective Erythropoiesis) TfR increased/erythroblast Iron deficiency
23 Iron deficiency vs chronic inflammation Iron TIBC stfr Ferritin Normal Iron deficiency Inflammation
24 Time course of IDA Normal Iron Iron deficiency Anemia Microcytic anemia Ferritin normal Hb normal normal MCV normal normal normal
25 DD Iron deficiency
26 Iron supplementation
27 Venofer Calculation of iron supplementation BW (kg) x [Target Hb actual Hb (g/l)] x mg Simple: 200mg iron / 1g/dl Hemoglobin No more than 500mg/week No more than 300 (200) mg/infusion Test dosage
28 Iron carboxymaltose (Ferinject ) 15mg/kg BW Maximum 1000mg/week
29 1000mg SFR 1000mg SFR bei Verwendung von Ampullen à500mg SFR bei Verwendung von Ampullen à100mg
30 Response after iron supplementation Reticulocyte Hb (CHr) Reticulocytes Nails/hair Hemoglobin RBC indices Ferritin steady state 4 days 5 10 days 1 2 weeks 1 2 months 3 months 3 months
31 Iron metabolism Iron deficiency anemia Anemia of chronic disorders Iron overload
32 Anemia of chronic disorder G Weiss, NEJM, 2005
33
34 Iron deficiency vs ACD vs both
35 Treatment of ACD
36 Iron metabolism Iron deficiency anemia Anemia of chronic disorders Iron overload
37
38 Iron overload
39 Hemochromatosis
40 Hemochromatosis
41 Anemia and iron overload With iron overload => anemias with ineffective erythropoiesis Thalassemia syndromes Congenital dyserythropoitic anemias Sideroblastic anemias Without iron overload => anemias with peripheral destruction Autoimmune hemolytic anemias Sickle cell anemia Paroxysmal nocturnal hemoglobinuria
42 mg Iron
43 Deferoxamin (Desferal ) Kontinuierliche s.c. Applikation erforderlich. Medikamenten Preis bei 2g pro Tag: 50Fr/Tag, 1 500Fr/Monat
44 Deferiprone (Ferriprox ) Bei kurzer Halbwertszeit Verteilung über den ganzen Tag (bis 10 Tabletten). Medikamenten Preis bei 10x500mg pro Tag: 45Fr/Tag, 1 350Fr/Monat
45 Deferasirox (Exjade ) Einmal tägliche Einnahme. Auf nüchternen Magen, 30 min. vor einer Mahlzeit. Die Tabletten werden in Wasser oder Orangensaft aufgelöst. Medikamenten Preis bei 3x500mg pro Tag: 125Fr/Tag, 3 750Fr/Monat
46 Vielen Dank für Ihre Aufmerksamkeit!
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Additional Blood Tests CBC W/Auto Diff The CBC is used as a broad screening test to check for such disorders as anemia, infection, and many other diseases. It is actually panel of tests that examines different