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Faculty of Medicine Dr. Tariq Aladily

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

Clinical symptoms of IDA

Weakness. Pallor. Thinning ,flatting ‘’spooning’’ of finger nail . Inflammatory lesions at the mouth Atrophic glossitis Hair loss Depression Insomnia Pica

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

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)

Faculty of Medicine Dr. Tariq Aladily

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 develop secondary to spinal cord demyelination

Faculty of Medicine Dr. Tariq Aladily

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 high, but with time decreases

Faculty of Medicine Dr. Tariq Aladily • PB: large ovalocyte is specific for megaloblastic

anemia

Faculty of Medicine Dr. Tariq Aladily

Faculty of Medicine Dr. Tariq Aladily

• 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

Faculty of Medicine Dr. Tariq Aladily

Anemia of Chronic Disease

• Common in hospitalized patients

• Associated with chronic diseases with persistent inflammation (chronic infection, rheumatologic diseases, malignancies)

Faculty of Medicine Dr. Tariq Aladily

Pathogenesis

• High level of IL-6

• Activates Hepcidin

• Increased iron storage

• Blocks iron transfer from stores to erythroid cells

• Use of iron by macrophages

Faculty of Medicine Dr. Tariq Aladily

Morphology

• RBC are normochromic normocytic, or hypochromic microcytic

• Iron stores in BM are markedly increased

• Serum ferritin is increased

• Treatment: treat the underlying cause

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

Causes

• Majority are idiopathic

• Less commonly, associated with rheumatologic diseases

• Idiosyncritic reaction to drugs (chloramphenicol, gold)

• Some viral hepaitis

Faculty of Medicine Dr. Tariq Aladily

morphology

• BM is hypocellular, most cells are fat

• Pancytopenia

• Low retic count

• No splenomegaly

Faculty of Medicine Dr. Tariq Aladily • Aplastic anemia: bone marrow is composed of adipose

tissue with very scarce hematopoietic cells

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

Chronic Renal Failure

• Low erythropoietin level

• Decreased erythropoiesis

• Uremia impairs platelets function, bleeding

• Morphology: normochromic normocytic anemia, echinocytes

Faculty of Medicine Dr. Tariq Aladily • Echinocytes: circumferential small cytoplasmic

projections, seen in uremia

Faculty of Medicine Dr. Tariq Aladily

Hypothyroidism

• Thyroxin is essential for cell metabolism

• morphology: macrocytic anemia

Faculty of Medicine Dr. Tariq Aladily

Chronic liver disease

• Bleeding is common

• Lipid synthesis is impaired, cell membrane defects

• RBCs show long projections (acanthocytes)

Faculty of Medicine Dr. Tariq Aladily

• Acanthocyte: long membrane projections

Faculty of Medicine Dr. Tariq Aladily

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

Faculty of Medicine Dr. Tariq Aladily

Morphology

BM:

• Erythroid cells show megaloblastoid changes

• Aggregates of iron around erythroid nuclei, called ring sideroblasts

Peripheral blood:

• Macrocytic anemia

Faculty of Medicine Dr. Tariq Aladily

• Left: PB shows macrocytes

• Right: ring sideroblasts in BM smear (iron stain)

Faculty of Medicine Dr. Tariq Aladily

THE END