ANEMIA OF CHRONIC DISEASE (ACD)

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Lucinda Sharp
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1 ANEMIA OF CHRONIC DISEASE (ACD) seminar Martin Vokurka 2007 Unofficial study material 1

2 VERY COMMON!!! In hospitalized patients is the second most common after iron deficiency OFTEN NEGLECTED!! Unofficial study material 2

3 chronical infections chronical non infectious inflammations autoimmune diseases malignancies trauma, postoperative situations Unofficial study material 3

4 mild to moderate anemia usually normocytic, normochromic, later can become hypochromic and microcytic -accompanies infectious, inflammatory and tumorous diseases (also anemia of inflammation, AI) - can develop rapidly in acute diseases Unofficial study material 4

5 Sequelae: -general sequelae of anemia -in severe diseases it further deteriorates clinical course, quality of life and sometimes even the survival rate Unofficial study material 5

6 General ethiopathogenesis of anemias Anemias are caused by insufficient production or by increased losses of RBC Both can be caused by many factors and often combine Pathogenesis of ACD cannot be explained by only one category but are combined Unofficial study material 6

7 BONE MARROW stem cells, precursors, growth factors erythropoietin cell division: vitamin B 12, folic acid hemoglobin synthesis: globin, porphyrin, iron other factors PRODUCTION RBC destruction PERIPHERY BLOOD bleeding LOSSES PARAMETERS OF RBC hemoglobin, RBC count, hematocrit MCV, MCH, MCHC shape etc. Unofficial study material 7

8 BONE MARROW stem cells, precursors, growth factors erythropoietin cell division: vitamin B 12, folic acid hemoglobin synthesis: globin, porphyrin, iron other factors PRODUCTION RBC destruction PERIPHERY BLOOD bleeding LOSSES PARAMETERS OF RBC hemoglobin, RBC count, hematocrit MCV, MCH, MCHC shape etc. Unofficial study material 8

9 Pathogenesis immune driven (inflammatory cytokines (IL-1β, TNFα, IFNγ) - mildy decrease of RBC survival probably due to activation of macrophage system - impaired erythropoiesis - blunted erythropoietin response - specific iron deficiency for erythropoiesis: iron restricted erythropoiesis Unofficial study material 9

10 - supporting influence of the disease (bleeding incl. blood tests, lack of nutrition, vitamins ) Unofficial study material 10

11 Dysregulation of iron homeostasis -relative iron deficiency for erythropoiesis (low iron concentration) -retention of iron in reticuloendothelial system -later real iron deficiency can develop due to decreased iron absorption Unofficial study material 11

12 IRON Iron is the 4 th most abundant element of the Earth crust Used by all living organisms Unofficial study material 12

13 The man has about 4 gr of iron to gr of body mass Unofficial study material 13

14 Iron Part of heme/non-heme proteins Important functions: Energy formation * oxygen transport (hemoglobin) * electrone transport (cytochroms) Transformation and detoxicication (cyt. P450) Cell and tissue proliferation Immunity Unofficial study material 14

15 The same properties of iron utility make iron potentially toxic element Fenton reaction: Fe 2+ + H 2 O 2 Fe 3+ + OH * + OH - Unofficial study material 15

16 absorption 1-2 mg/den distribution mg/den - utilization recyclation -stores losses 1-2 mg/den Andrews, N. C. N Engl J Med 1999;341: Total amount of iron in the organism is mg Unofficial study material 16

17 absorption distribution REGULATION - utilization recyclation -stores loss Andrews, N. C. N Engl J Med 1999;341: Unofficial study material 17

18 FOOD RBC PHAGOCYTOSIS ENTER ENTEROCYTE MACROPHAGE EXIT FERROPORTIN IRON EXPORTER RESORPTION OF NEW IRON 1-2 mg daily IRON RECYCLATION mg daily Unofficial study material 18

19 What controls iron metabolism? HEPCIDIN Unofficial study material 19

20 Hepcidin (HAMP = hepatic antimicrobial peptide) * 25-amino-acid peptide with 4 cystine bridges * produced in the liver (hepatocytes) * antimicrobial action Unofficial study material 20

21 Regulation of iron metabolism: - decreases iron absorption by enterocytes - causes iron sequestration in macrophages Unofficial study material 21

22 ENTER ENTEROCYTE MACROPHAGE EXIT FERROPORTIN IRON IS NOT RESORBED RESORPTION OF NEW IRON 1-2 mg daily HEPCIDIN IRON IS ACCUMULATED IRON RECYCLATION mg daily Unofficial study material 22

23 Hepcidin effects (Fast) decrease of iron serum concentration Iron is accumulated in macrophages Iron resorption decreases Long-term regulation of iron amount in the body Unofficial study material 23

24 Hepcidin disturbances TOO LITTLE excessive iron resorption TOO MUCH insufficient iron resorption and its accumulation in macrophages Unofficial study material 24

25 Hepcidin regulation IRON Feedback mechanism: much iron decreases further absorption INFLAMMATION (cytokines IL-6) Inflammation increases hepcidin production and interferes with iron metabolism Unofficial study material 25

26 HEPCIDIN IS PROBABLY REGULATORY HORMONE OF IRON METABOLISM IN THE ORGANISM AND IT IS AS WELL ACUTE PHASE REACTANT Unofficial study material 26

27 Inflammation and erythropoiesis INFLAMMATION cytokines hepcidin IRON macrophages ERYTHROPOIESIS DECREASED RBC SURVIVAL Unofficial study material 27

28 IRON AND INFECTIONS 1. Necessary for bacterias 2. Necessary for immunity * killing bacterias (oxygen radicals) * mucosa and skin integrity * proliferation of immunity cells Unofficial study material 28

29 siderocalin/ngal siderophores Fe lactoferrin hepcidin change of iron distribution (decrease of resorption, MΦ sequestration) Unofficial study material 29

30 Hepcidin It is supposed to play a role in ACD pathogenesis, mainly in changes in iron kinetics in this anemia relat. iron deficiency for RBC sweeps iron from bacterias Fe Fe Unofficial study material 30

31 Diagnosis of ACD Anemia (mainly normo-, event. microcytic) Inflammatory disease, cancer Low serum iron concentration This could be true also for iron deficiency anemia FERRITIN increased TRANSFERRIN decreases IRON STORES sufficient Unofficial study material 31

32 HEPCIDIN (not available in clinical practice) Unofficial study material 32

33 Conclusions Iron is vital element which could be toxic Thus it must be regulated on local and systemic level Systemic regulator is peptide HEPCIDIN Iron plays important role in inflammatory processes and infections It is crucial for pathogen elimination but it is as well important for their growth and metabolism Microorganisms and human organism have mechanisms how to acquire iron Defence-oriented iron sequestration may contribute to the pathogenesis of anemia of chronic disease This anemia is frequent and accompanies many inflammatory, infectious and tumorous diseases It must be differentiated from real iron deficiency anemia Unofficial study material 33

34 THE END Unofficial study material 34

Iron Deficiency Anemia

Diagnosis of Iron Deficiency Anemia Using the Abaxis VetScan HM2 Hematology System Contributing Authors: Mary Anna Thrall, BA, DVM, MS, DACVP; Barton Gillespie, BS, DVM Ross University School of Veterinary