Faculty of Medicine Dr. Tariq Aladily

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2 Iron deficiency anemia The most common anemia worldwide Only 10% of ingested iron is absorbed Most dietary iron occurs in meat products Absorbed in duodenum

3 Hepcidin By inhibiting ferroportin, hepcidin reduces iron uptake from enterocytes and suppresses iron release from macrophage to RBCs With low body stores of iron, hepcidin synthesis falls and this turn facilitates iron absorption

4 Causes of IDA Decreased dietary intake (vegetarians) Impaired absorption (GI disease; celiac, Crohn) Increased demand (pregnancy, childhood, adolescence) Chronic blood loss (GI bleeding, menorrhagea) People at increased risk of anemia are: infants, elderly, teenagers, low socioeconomic class

5 Stages of IDA Decline in serum ferritin and the absence of stainable iron in the bone marrow Decrease in serum iron and a rise in the serum iron-binding capacity Inability to synthesis hemoglobin, myoglobin, and other iron-containing proteins is diminished Beginning microcytosis Although erythropoietin is high, low iron stores in BM blunt its effectiveness, no much increase in erythroid cells (normal to low retic) Thrombocytosis is common IDA is a chronic disease

6 Iron deficiency anemia: hypochromic mircocytic RBCs (low MCV, MCH), poikelocytosis (high RDW), target cells

7 Iron stain in bone marrow specimen: normal (left) vs low (right)

8 Clinical symptoms of IDA Weakness. Pallor. Thinning,flatting spooning of finger nail. Inflammatory lesions at the mouth Atrophic glossitis Hair loss Depression Insomnia Pica

9 Megaloblastic Anemia Anemia associated with impairment in DNA synthesis in hematopoietic cells with special morphologic features (large immature erythroid precursors) Two types: Vitamin B12 and folate deficiency Vitamin B12 and folate are coenzymes required for synthesis of thymidine

10 Causes of Vit B12 deficiency Low intake (vegans) Impaired GI absorption (intrinsic factor deficiency, malabsorption disease, gastrectomy) Loss of storage takes a long time Vit B12 is important in for neuronal functions

11 Causes of folate deficiency Low intake (inadequate diet, infancy) Impaired absorption (malabsorption, chronic alcoholism, anti-convulsants, oral contraceptives) Increased loss (dialysis) Increased demand: pregnancy Impaired utilization (methotrexate, Vit B12 deficiency)

12 Pernicious Anemia Abnormal autoreactive T-cell response initiates direct gastric mucosal injury, also triggers formation of autoantibodies Type 1 antibody: blocks Vit B12 from binding to intrinsic factor Type 2 antibody: blocks Vit B12-intrinsic factor complex to its ileal receptor Type 3 antibody: blocks Proton pumps on parietal cells (not specific) With time, anemia develops, gastric glands become atrophic Neurologic symptoms Dr. develop Tariq Aladily secondary to spinal cord demyelination

13 Morphology BM: erythroid precursors are large with immature nuclear chromatin (megaloblastoid) RBCs are large, oval, hyperchromatic Granulocytes: hypersegmented neutrophils (>4 lobes), giant metamyelocyte Megakaryocytes: Large, hyperlobated nuclei Increased erythropoietic level as well as impaired DNA synthesis leads to increased apoptosis in nucleated RBCs and hemolysis BM cellularity is initially Dr. Tariq high, Aladily but with time decreases

14 PB: large ovalocyte is specific for megaloblastic anemia

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16 Comparison of normoblasts (left) and megaloblasts (right). The megaloblasts are larger, have relatively immature nuclei with finely reticulated chromatin, and have an abundant basophilic cytoplasm

17 Anemia of Chronic Disease Common in hospitalized patients Associated with chronic diseases with persistent inflammation (chronic infection, rheumatologic diseases, malignancies)

18 Pathogenesis High level of IL-6 Activates Hepcidin Increased iron storage Blocks iron transfer from stores to erythroid cells Use of iron by macrophages

19 Morphology RBC are normochromic normocytic, or hypochromic microcytic Iron stores in BM are markedly increased Serum ferritin is increased Treatment: treat the underlying cause

20 Aplastic Anemia Primary bone marrow failure Defect in stem cell proliferation In the majority of patients autoimmune mechanisms are suspected In some, genetic mutations, overlap with PNH Can be inherited (Fanconi) or acquired

21 Causes Majority are idiopathic Less commonly, associated with rheumatologic diseases Idiosyncritic reaction to drugs (chloramphenicol, gold) Some viral hepaitis

22 morphology BM is hypocellular, most cells are fat Pancytopenia Low retic count No splenomegaly

23 Aplastic anemia: bone marrow is composed of adipose tissue with very scarce hematopoietic cells

24 Myelophthisic anemia Infiltrative disease that destroys bone marrow cells Leads to pancytopenia Most commonly seen in malignancy: acute leukemia, plasma cell myeloma, metastatis), less commonly by granuloma No splenomegaly

25 Chronic Renal Failure Low erythropoietin level Decreased erythropoiesis Uremia impairs platelets function, bleeding Morphology: normochromic normocytic anemia, echinocytes

26 Echinocytes: circumferential small cytoplasmic projections, seen in uremia

27 Hypothyroidism Thyroxin is essential for cell metabolism morphology: macrocytic anemia

28 Chronic liver disease Bleeding is common Lipid synthesis is impaired, cell membrane defects RBCs show long projections (acanthocytes)

29 Acanthocyte: long membrane projections

30 Myelodysplastic syndrome Neoplastic disease Old age Affects erythroid, myeloid or megakaryotic lineages, alone or in combination DNA mutations in progenitor cells Defective cell maturation and function Hematopoietic ells cannot exit BM BM is hypercellular but peripheral blood is hypocellular Anemia is macrocytic, low retic count

31 Morphology BM: Erythroid cells show megaloblastoid changes Aggregates of iron around erythroid nuclei, called ring sideroblasts Peripheral blood: Macrocytic anemia

32 Left: PB shows macrocytes Right: ring sideroblasts in BM smear (iron stain)

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