Microcytic Hypochromic Anemia PDF

Mcr = P(V x10 RBC HYPOCHROMIC MICROCYTIC ANEMIA NUR NAJMI MOHAMAD ANUAR  CLASSIFICATION OF ANAEMIA Anaemia Aetiological Morphological Morphological...

Mcr = P(V x10 RBC HYPOCHROMIC MICROCYTIC ANEMIA NUR NAJMI MOHAMAD ANUAR  CLASSIFICATION OF ANAEMIA Anaemia Aetiological Morphological Morphological Impaired production Normocytic/ normochromic Increased destruction or Microcytic / hypochromic blood loss Macrocytic  Low Hb > ↓ O2 supply - Classification of Anaemia Microcytic & Normocytic & Hypochromic Macrocytic Normochromic MCV within RR MCV < RR MCH within RR MCV > RR MCH < RR Acute blood loss Defects in Defects in Haemolysis haem globin ACD Non Megaloblastic synthesis synthesis Marrow infiltration megaloblastic Iron deficiency ACD Thalassaemias Haemoglobinopathies Liver disease Sideroblastic B12/Folate Drug –induced (congenital) deficiency MDS IRON DEFICIENCY ANEMIA (IDA) Causes of IDA  Clinical Features Glossitis 25koilonychia1118 Koilonychia angularcheilitis(9-480) Angular stomatitis  HAEMOGLOBIN SYNTHESIS Porphyrin Haem Porphyrin is a complex compound Haem: iron inserted in a with a tetrapyrrole ring structure tetrapyrrole ring  iron porphyrin structure, synthesized in the reticuloendothelial cells (bone marrow). synthesis RBC Erythropoietin produced in kidney → formation, maturation and release of erythrocytes by bone marrow. Early stage of erythrocyte contain porphyrin, then is converted to heme by addition of iron and then to hemoglobin by addition of protein, globin.  Ferritin iron storage protein Each ferritin complex can store about 4500 iron (Fe3+) ions. Ferritin that is not combined with iron is called apoferritin. Apoferritin binds to free ferrous iron and stores it in the ferric state Reflects the amount of BODY IRON STORES men: 20-275 μg/litre women: 5-200 μg/litre 15 μg/litre and less: insufficient iron stores  Transferrin Transports iron from duodenum and macrophages to all tissue Synthesize in liver Contains only 2 atoms of ferric (3+)  Transferrin saturation serum iron divided by the total iron-binding capacity. how much serum iron is bound Normal about 30-50 % Transferrin saturation under 15 %= Iron deficiency  Transferrin receptor Transferrin Transferrin receptor Cells which need iron express high number of transferrin receptors on their surface  FE2+ Ferrous (2+): (more soluble) Ferric (3+): insoluble at physiological pH (less soluble) FE3+ Since free iron is toxic, it must be bound to proteins 2 FORMS OF IRON IRON METABOLISM ~ channelto releaselation To be soluble, Ferric (Fe3+) needs to be reduced to Ferrous (Fe2+) The enzyme that does this is called Duodenal cytochrome b (Dcytb) This enzyme is Vitamin C dependent. From the gut lumen, iron needs to be transferred into the enterocyte before getting to the bloodstream. Therefore, it needs a channel: Non heme iron uses DMT1 Heme iron uses HCP1 Once in the enterocyte, iron need to be moved to the bloodstream. Fe2+ is transported out via ferroportin1(FPN) Once it leaves the enterocyte, the Fe2+ oxidized back to Fe3+ by Hephaestin/Ceruloplasmin (ferroxidase activity) Fe3+ combines with apoferritin to form ferritin, which the temporary storage form of iron. ↳ various of size LanisOCY tosis) BLOOD MORPHOLOGY Small cell (microcytic) Pale cell (hypochromic) Pencil-shaped cell Target cell Low reticulocyte Bone marrow iron- nil  Iron studies Tota Lion Binding Serum f capacity Ferritin Transferrin Tr saturation% TIBC TfR iron Transferrin Receptor Results in IDA       Adapted from Lazarela Vucinic 2008  Treatment for IDA ▪ Treat underlying cause – iron is given to correct the anemia and replenish iron stores a. Oral iron ▪ ferrous sulphate (anhydrous) tablet ▪ ferrous gluconate tablet ▪ ferrous succinate, lactate and fumarate – expensive b. Prophylactic iron therapy given throughout pregnancy (single daily tablet – ferrous sulphate + folic acid) c. Parenteral iron – replenished iron storage quicker ▪ iron-dextran (Imferon) ▪ iron-sorbitol citrate (Jectofer)  reticulocytes immatur at ↑ SIDEROBLASTIC ANEMIA  blog disruptio that of RBC production SIDEROBLASTIC ANEMIA immature ▪ Refractory anaemia with ringed sideroblasts (RARS) Bone marrow ▪ BM produces ringed sideroblasts rather than healthy RBC ▪ abnormal iron accumulation in the mitochondria of erythroid precursors ▪ Abnormal erythroblast containing iron granule in a ring or collar around the nucleus ▪ iron available but cannot incorporate into hemoglobin ▪ Iron overload, ineffective erythropoiesis  Classification of Sideroblastic Anemia Hereditary Acquired ▪ Defects in haem Primary synthesis a) Myelodysplasia (MDS) ▪ More in males Secondary ▪ X-linked a) Malignant disease of the ▪ Erythroid-specific delta- marrow aminolevulinic acid b) Drugs (Anti-TB, isoniazid, synthase 2 gene (ALAS2) cycloserine), Alcohol, Lead)  Heme Synthesis 10 ALA synthage ↑↑↑ not · important just to show distruption Fe2+ Laboratory Finding of Sideroblastic Anemia ▪ MCV, MCH ↓ ▪ Serum iron ↑ ▪ TIBC – N (normal or low ▪ Serum ferritin –N (normal or high) ▪ Bone marrow iron stores-present (essential diagnosis) ▪ Erythroblast iron-ring ▪ Hb electrophoresis-normal I conducted to differentiate between thalassemia  Treatment of Sideroblastic Anemia ▪ Hereditary type – Pyridoxine therapy (Vitamin B6) (cofactor for the ALAS2) ▪ Blood transfusion → iron overload ANEMIA OF CHRONIC DISORDERS ANEMIA OF CHRONIC DISORDER (ACD) ▪ most common cause of anemia in hospitalized patients. ▪ Usually normochromic & normocytic ▪ microcytosis & hypochromia (52%) develop as the disease progresses ▪ Iron stores abundant ▪ but iron is NOT available for erythropoiesis 34 Causes of ACD Occurs in patients with: ▪ Infectious ▪ Non-infectious ▪ Malignant disease that persist for more than 1 or 2 months SECONDARY DISEASE!! 35 PATHOGENESIS OF ACD ?? ▪ Lactoferrin ▪ released from neutrophils during inflammation ▪ competes with transferrin for iron ▪ RBC don’t have lactoferrin receptors ▪ iron molecules cannot be used for Hb synthesis ▪ Cytokines from inflammatory cells (TNF-, IL-1, IFN-) affects erythropoiesis → inhibiting the growth of erythroid progenitors ▪ HEPCIDIN  Control of Iron Export from Cells: -regulate iron Discovery of HEPCIDIN (2000) - Hepatic Bactericidal Protein Hepcidin: "iron regulatory hormone" produced in the liver, is transported in the blood stream, target FERROPORTIN BLOCKS IRON EXPORT FROM THE CELL because iron is trapped Hepcidin demonstrates the strong connection between iron metabolism and defence against pathogens Bacteria need iron for their ribonucleotide reductase (DNA synthesis) Host needs iron for antibacterial enzymes (iron oxide) Bacteria and host compete for free iron FERROPORTIN like a -gatekeeper▪ Major exPORTer of iron. ▪ Transferring absorbed iron from enterocytes into the circulation.  ACD- ROLE OF HEPCIDIN ▪ hepcidin: ▪ increased up to 100 times in ACD ▪ release from liver after stimulation by IL-6 ▪ Acute-phase reactant ▪ Binds to ferroportin ▪ Decreases iron absorption and export from cells  4) IRON IS 1) LOCKED UP IN INFLAMMATION ENTEROCYTES, INCREASES AND DOES NOT HEPCIDIN ENTER THE SYNTHESIS BODY PATHOGENESIS OF ACD - HEPCIDIN 2) HEPCIDIN DECREASES 3) IRON IS IRON EXPORT LOCKED UP FROM INSIDE THE MACROPHAGES MACROPHAGES → TARGET FERROPORTIN ROLE OF HEPCIDIN  Iron overload increases hepcidin expression - increased ferritin (storage of iron), inflammation REGULATION Iron deficiency decreases OF HEPCIDIN hepcidin expression - EXPRESSION anemia, hypoxia Increased erythropoiesis decreases hepcidin expression  Here’s how it works… When iron is low, Hepcidin expression is reduced. Leads to increased FERROPORTIN expression. Therefore, more transport of Fe from cells to blood bound by Tf. Transferrin - When iron level increase, Hepdicin binds to ferroportin. Induces internalisation and lysosomal degradation. Therefore, reduces amount of iron released into circulation from duodenal cells and macrophages.  Symptoms of ACD Symptoms of the underlying Symptoms of the anemia disease ( malignancy or chronic inflammatory disease) 46  Mildly hypochromic, microcytic or normochromic normocytic anemia MCV & MCH normal or mild reduction Serum iron - ↓ Laboratory TIBC - ↓ Finding of ACD because no problem Serum ferritin - N/↑in iron (iron is there but blocked) Hb electrophoresis N not to diagnose , to ↑ CRP/IL-6 show anemia is due to inflammation Treatment of ACD 1. Treatment of the underlying disorder 2. Iron supplementation (IS) 3. Blood transfusion demand (about 30%) patients who have low Hb and are symptomatic 4. Recombinant erythropoietin Iron chelation with deferoxamine - in some patients therapy was associated with a rise in hemoglobin level 5. In future anti-TNF-antibodies - & Tumor Neross Factor 48  DIFFERENTIAL DIAGNOSIS OF HYPOCHROMIC MICROCYTIC ANEMIA * most important part Iron studies in other micro/hypo anaemias %Tr Ferritin Serum iron Transferrin TIBC TfR saturation IDA       Thal N/  N/ N N/ N  minor ACD N /  N/   N/ Congenital sideroblastic    N/ N/ N/ anaemia Adapted from Rodak’s Hematology, 2nd ed. And Bain’s Blood cells 4th ed.  Red cell indices : MCV, MCH and MCHC Variation of RBC in size/ volume: RDW Anemia : blood is lack of oxygen capacity CONCLUSION Anemia → classified by aetiology / morphology Dx: understanding of the disease mechanisms that lead to it Dx: patient’s history, LAB findings, peripheral blood film THANK YOU