Iron Metabolism and Iron Deficiency Anemia Demir Metabolizması ve Demir Eksikliği Anemisi

Deficiency of iron  Anemia Hereditary deficiencies of enzymes of heme synthetic pathway  Porphyrias

(forhemesynthesis) (for storage) Hemosiderin Fe Enterocyte Fe+2 Fe DCYTB Transferrin Endosome Mitochondria Ferritin ?? Fe Figure:Iron Absorption and Storage ?? DMT1 TR DMT1 H BloodNormoblast Fe+2 Fe FP1 Fe+3 TfR TR: Transferrin receptorH: Hephaestin DMT1: Divalent metal transporter FP1: Ferroportin Other proteins playing –uncertain- role in iron homeostasis: HFE, hemojuvelin, TfR2

Fe Aconitase TR geneFer gene Fe x TFTR IRP-1 Fer gene TR gene IRP-1 REGULATION of INTRACELLULAR IRON METABOLISM Healthy StateIron Deficiency Sensors and Controllers of Intracellular Iron Supply= IRP-1 (Aconitase) & IRP-2 Fer Unstable TR mRNA Stable TR mRNA Fe

Endotel Kupffer Fe IL-6 Hepcidin x x Hepatosit DEMİR HOMEOSTAZINDA ROL OYNAYAN BİR HORMON VAR MIDIR ? H e p a ti k S i n ü z o i d Fe

FP1 Fe FP1 Fe Hepcidin x x

Causes of Iron Overload Primary 1) Hereditary hemochromatosis (HFE- and non-HFE) 2) Hereditary atransferrinemia 3) Aceruloplasminemia Secondary 1) Ineffective erythropoiesis (thalassemia, sideroblastic anemia) 2) Transfusional hemochromatosis (aplastic anemia, MDS, sickle cell anemia, end-stage renal disease) 3) Chronic dietary or medicinal intoxication 4) Alcoholic cirrhosis 5) Porphyria cutanea tarda Iron chelation therapy by DFO-infusion pump in a patient with thalassemia

HEPCIDIN in HEREDITARY HEMOCHROMATOSIS Surprisingly, serum hepcidin is decreased in HFE- and some kinds of non-HFE hereditary hemochromatosis. Probably, HFE plays a role in regulation of hepcidin production. Therefore, HFE disruption leads to decreased hepcidin production. Hepcidin Fe Iron sensing mechanism HFE Ferroportin TfR2 Increased iron

Iron Requirements in Males and Females of Various Ages mg (Iron Deficiency Anemia) Occurs If (Iron Intake < Iron Loss)

SERUM IRON PARAMETERS in IDA PERIPHERAL SMEAR in IDA Iron: 5  g/dL (60-150)  TIBC (transferrin level): 467  g/dL ( )  Transferrin saturation: % 7 (15-45)  Ferritin:2 ng/mL (15-200)  Transferrin receptor level  = microcytosis = hypochromia = anisocytosis

Total Demir Bağlama Kapasitesi = Serum Transferrin Aktivitesi (~Düzeyi) Serum Demiri = Demir Bağlamış Olan Transferrin Serbest Demir Bağlama Kapasitesi = Serbest Transferrin Transferrin Saturasyonu = Serum Demiri / Total Demir Bağlama Kapasitesi Transferrin Saturasyonu = Serum Demiri / (Serum Demiri + Serbest Demir Bağlama Kapasitesi) Transferrin Saturasyonu, Total ve Serbest Demir Bağlama Kapasiteleri Nelerdir ?

Differential Diagnosis of IDA Other common causes of hypochromic microcytic anemia are; Thalassemia trait Anemia of chronic disease (anemia of inflammation) These two disorders may be confused with IDA. Generally history, CBC, serum iron parameters are enough to differentiate between them. Occasionally, Hb electrophoresis & bone marrow iron staining may be necessary.

IronTIBCTS Ferritin Iron Deficiency Anemia  Anemia of Chronic Disease NN NN NNNN Thalassemia trait NN N NN NN Normal TS= % Demir EA TS= % 5 Kronik Hst. Anemisi TS= % 14 Demir Yüklenmesi TS= % 100 İnefektif Eritropoez TS= % 85 Differential Diagnosis of Iron Deficiency Anemia

Treatment & Follow-up in IDA Removal of the Underlying Disease (if present) Iron Supplementation (Iron pills, 200 mg/day on empty stomach in adults) Anemia generally resolves within 2 months, but iron pills should be continued until iron stores get full (~ 6- 9 months) In the case of treatment failure one should consider: incorrect diagnosis, an additional cause of anemia, ongoing blood loss, bad patient compliance & malabsorption Indications for Parenteral Iron: Malabsorption Patient intolerance of pills Bad patient compliance to PO treatment Ongoing heavy blood loss

INVESTIGATION of THE CAUSE of IDA If the patient is at increased risk of IDA (e.g., women with suboptimal nutrition, infants, adolescents, pregnant women, women with multiple previous pregnancies) careful history, PE  GUIAC test for occult GI blood loss & microscopic exam of stool for parasites will be sufficient. If suspicion of an underlying disease condition appears after simple tests or if the patient is a man or a postmenapausal woman the bowel, urinary and respiratory tracts must be carefully investigated for any bleeding lesion (e.g. peptic ulcer, colonic cancer).

Bu nedenle demir eksikliği anemisi için risk altındaki kişilere (gebelik, bazı infantlar) proflaksi uygulanması gereklidir: Demir eksikliği anemisi bir halk sağlığı sorunudur. Dünya Sağlık Örgütü’nün verilerine göre dünya nüfusunun yaklaşık % 30 kadarı anemiktir ve bunların çok büyük çoğunluğu demir eksikliği anemisidir.