Faculty of Medicine Dr. Tariq Aladily · Atrophic glossitis Hair loss Depression Insomnia Pica . Faculty of Medicine Dr. Tariq Aladily Megaloblastic Anemia •Anemia associated with

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


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


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


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


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


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


Clinical symptoms of IDA

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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


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


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)


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


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



• 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


Anemia of Chronic Disease

• Common in hospitalized patients

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


Pathogenesis

• High level of IL-6

• Activates Hepcidin

• Increased iron storage

• Blocks iron transfer from stores to erythroid cells

• Use of iron by macrophages


Morphology

• RBC are normochromic normocytic, or hypochromic microcytic

• Iron stores in BM are markedly increased

• Serum ferritin is increased

• Treatment: treat the underlying cause


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


Causes

• Majority are idiopathic

• Less commonly, associated with rheumatologic diseases

• Idiosyncritic reaction to drugs (chloramphenicol, gold)

• Some viral hepaitis


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


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


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


Hypothyroidism

• Thyroxin is essential for cell metabolism

• morphology: macrocytic anemia


Chronic liver disease

• Bleeding is common

• Lipid synthesis is impaired, cell membrane defects

• RBCs show long projections (acanthocytes)


• Acanthocyte: long membrane projections


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


Morphology

BM:

• Erythroid cells show megaloblastoid changes

• Aggregates of iron around erythroid nuclei, called ring sideroblasts

Peripheral blood:

• Macrocytic anemia


• Left: PB shows macrocytes

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


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Faculty of Medicine Dr. Tariq Aladily · Atrophic glossitis Hair loss Depression Insomnia Pica . Faculty of Medicine Dr. Tariq Aladily Megaloblastic Anemia •Anemia associated with