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