faculty of medicine dr. tariq aladily · atrophic glossitis hair loss depression insomnia pica ....
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Faculty of Medicine Dr. Tariq Aladily
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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
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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
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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
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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
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Faculty of Medicine Dr. Tariq Aladily
• Iron deficiency anemia: hypochromic mircocytic RBCs (low MCV, MCH), poikelocytosis (high RDW), target cells
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Faculty of Medicine Dr. Tariq Aladily
• Iron stain in bone marrow specimen: normal (left) vs low (right)
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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
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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
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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
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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)
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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
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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
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Faculty of Medicine Dr. Tariq Aladily • PB: large ovalocyte is specific for megaloblastic
anemia
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Faculty of Medicine Dr. Tariq Aladily
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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
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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)
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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
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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
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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
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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
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Faculty of Medicine Dr. Tariq Aladily
morphology
• BM is hypocellular, most cells are fat
• Pancytopenia
• Low retic count
• No splenomegaly
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Faculty of Medicine Dr. Tariq Aladily • Aplastic anemia: bone marrow is composed of adipose
tissue with very scarce hematopoietic cells
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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
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Faculty of Medicine Dr. Tariq Aladily
Chronic Renal Failure
• Low erythropoietin level
• Decreased erythropoiesis
• Uremia impairs platelets function, bleeding
• Morphology: normochromic normocytic anemia, echinocytes
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Faculty of Medicine Dr. Tariq Aladily • Echinocytes: circumferential small cytoplasmic
projections, seen in uremia
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Faculty of Medicine Dr. Tariq Aladily
Hypothyroidism
• Thyroxin is essential for cell metabolism
• morphology: macrocytic anemia
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Faculty of Medicine Dr. Tariq Aladily
Chronic liver disease
• Bleeding is common
• Lipid synthesis is impaired, cell membrane defects
• RBCs show long projections (acanthocytes)
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Faculty of Medicine Dr. Tariq Aladily
• Acanthocyte: long membrane projections
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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
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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
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Faculty of Medicine Dr. Tariq Aladily
• Left: PB shows macrocytes
• Right: ring sideroblasts in BM smear (iron stain)
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Faculty of Medicine Dr. Tariq Aladily
THE END