Hematology Exam 2

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mawilburn
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Hematology Exam 2
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2010-05-13 14:38:59
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Blood Heme Melissa
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Exam 2 heme
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  1. ET Essential Thrombocythemia
    Rare CMPD characterized by marked thrombocytosis and abnormal platelet functions.
  2. Rare CMPD with thrombocytosis and abnormal platelet function.
    ET Essential thrombocythemia
  3. ET Causes and symptoms:
    • Clonal multipotential stem cell, mostly megakaryocytes
    • Hypersensitivity of megakaryocytes to cytokines and thrombopoietin
    • Absence of identifiable causes of reactive thrombocytosis
    • Absence of Philadelphia chromosome
    • Hgb no higher than 13 g/dL
    • Absence of significant marrow fibrosis
    • Consumption of coag factors- Acute hemorrhage
    • Presence of stainable iron in BM
  4. Myelofibrosis With Myeloid Metaplasia symptoms
    • bone marrow fibrosis
    • proliferation of megakaryocytic and granulocytic cells
    • extramedullary hematopoiesis-splenomegaly
    • Chromosomal abnormalities (no philly)
  5. Bone Marrow fibrosis, splenomegaly, anemia
    Myelofibrosis with Myeloid Metaplasia
  6. Myofibrosis with myeloid metaplasia- smear signs
    • Teardrop RBCs
    • Normochromic normocytic anemia
    • Leukoerythroblastosis
    • Giant platelets
    • Many nRBCs
  7. Teardrop RBCs
    Normochromic normocytic anemia
    Leukoerythroblastosis
    Giant platelets
    Many nRBCs
    Myelofibrosis with myeloid metaplasia
  8. 7 Lymphoproliferative disorders
    • Chronic Lymphocytic Leukemia (CLL)
    • Hairy Cell Leukemia
    • Sezary Syndrome
    • Prolymphocytic Leukemia- younger lymphs
    • Hodgkin’s and Non- Hodgkin’s lymphoma
    • Multiple Myeloma
    • Waldenstrom’s Macroglobulinemia
  9. CLL Cause
    Clonal B proliferation-chromosomes 11, 12, and 13, especially trisomy 12
  10. Clonal B proliferation
    CLL
  11. CLL Signs
    • Lymphadenopathy
    • Many white counts are >100,000 x 109/L
    • Peripheral smear shows exclusively small lymphocytes intermixed with few lymphoblasts
    • Smudge cells
    • nRBCs and spherocytes may be present if autoimmune hemolytic
    • CLL Fragile small lymphocytes
    • Smudge cells
  12. CLL Symptoms
    • Splenomegaly & Lymphadenopathy- lymphs accumulating in nodes and spleen
    • Anemia, Neutropenia, & Thrombocytopenia-Lymph production crowds out other cell proliferation
    • Autoimmune hemolytic anemia- caused by altered immune function
  13. Splenomegaly
    Lymphadenopathy
    Anemia
    Neutropenia
    Thrombocytopenia
    Autoimmune hemolytic anemia
    CLL
  14. Hairy Cell Leukemia Cause
    B-cell malignancy
  15. Hairy Cell Signs and diagnosis
    • Fragile mononuclear cell
    • Hair-like projections of the cytoplasm
    • Spongy appearance of chromatin
    • Stain with TRAP- tartrate-resistant acid phosphatase
    • Thrombocytopenia
    • Pancytopenia
    • Massive spleen
    • Infection
  16. Hairy Cell Leukemia
  17. Sezary Syndrome Causes
    • T-cell lymphoma with mycosis fungoides
    • Infiltration of Lymphocytes on skin
  18. Sezary Cell Description
    • Large cells (8 - 20 mm)
    • Ovoid, convoluted, cerebriform nucleus
    • May be mistaken for monocytes
    • Folded, brain-like
    • Clefted
    • Clover pattern
    • Blue cytoplasm
  19. Sezary Syndrome-cutatneous T-cell lymphoma
  20. Prolymphocytic Leukemia (PLL)- Causes
    Variant of chronic lymphocytic leukemia
  21. PLL- Signs/Symptoms
    • Splenic enlargement
    • Liver involvement
    • Escalating white counts
    • Prolymphocytes have more abundant cytoplasm than mature lymphocytes
  22. PLL
  23. Hodgkin’s Lymphoma-Causes
    People exposed to EBV or environmental hazards are at increased risk.
  24. Hodgekin's Lymphoma Signs/Symptoms/Diagnosis
    • Single cervical lymph node becomes firm to the touch and does not disappear
    • Low-grade fever
    • Weight loss
    • In lymph nodes - Presence of Reed-Sternberg cell
    • Diagnosis via lymph biopsy
    • Reed-Sternberg Cell
    • Hodgekin's Lymphoma
  25. Reed-Sternberg Cell in Lymph nodes
    Hypermetabolism
    Cervical lymph node swollen
    Hodgekin's Lymphoma
  26. Non-Hodgkin’s Lymphoma Causes/Symptoms
    • May present as painless cervical lymph node involvement
    • Lymphoma cells may be seen in peripheral smear
    • Disease can spread
    • Plasma Cells-Evolve from B-lymphocytes
    • Medium-sized cell
    • Have an eccentric nucleus
    • Have well-defined Golgi apparatus
    • Cytoplasm has distinct sea blue/cornflower color
    • Chromatin organized in a pinwheel structure
    • Make immunoglobulins
  27. Multiple Myeloma Cause
    • Disorder of Plasma Cells
    • Accumulation of plasma cells in BM and other locations
    • Exposure to atomic radiation
    • Work involving organic solvents
    • Toxins within the textile industry
    • Occupations with exposure to chemicals, pesticides, or herbicides
    • Chromosome 13 abnormalities
    • Caused by cytokine IL-6
  28. Disorder of Plasma Cells
    Multiple Myeloma
  29. 3 pathways of multiple myeloma
    • Acceleration of plasma cells in the bone marrow
    • Activation of bone resorption factors or osteoclasts
    • Production of an abnormal monoclonal protein
  30. Mulitple Myeloma Signs
    • Inclusions called Russell bodies or other crystalline inclusions
    • Flame cells may be seen in IgA myeloma -Deep pink cytoplasm
    • Monoclonal gammopathy
    • Increased osteoclast activity -Serum calcium increased
    • Rouleaux formation
    • Bence-Jones protein found in urine of patients with multiple myeloma
    • ESR usually elevated due to increased settling
    • "Punched-out” lesions on initial radiography
  31. Russell Body in Multiple Myeloma
  32. Multiple Meyloma Symptoms
    • Anemia
    • Thrombocytopenia
    • Neutropenia
    • Can Spread in body as plasmacytomas
    • Fatigue
    • Bone Fractures
  33. Waldenstrom’s Macroglobulinemia Cause
    Overproduction of IgM caused by abnormal B lymphocytes
  34. Waldenstrom’s Macroglobulinemia
    Signs/Symptoms
    • IgM interferes with coagulation factors by coating platelets and impeding their function
    • Peripheral smear may show rouleaux and plasmacytoid lymphocytes
    • Cryoglobulins-May lead to Raynaud’s phenomenon(Cold, tingeling, fingers and toes); Causes bleeding; Cold agglutenins
  35. RBC Maturation Series
    • Pronormoblast
    • Basophilic Normoblast
    • Polychromatophilic normoblast
    • Orthochromic normoblast (NRBC)
    • Reticulocyte (requires stain)
    • Erythrocyte
  36. Secondary RBC Maturation Series
    • Rubriblast
    • Prorubricyte
    • Rubricyte
    • Metarubricyte
    • Diffusely Basophilic Erythrocyte
    • Erythrocyte
  37. Target Cells
  38. Target Cells
    Excessive plasma chol. can lead to excessive membrane chol. and cause cell to become heavier and thicker, displacing the Hgb. Surface area to volume ratio increases, cell is less fragile.
  39. RBC Membrane protiens
    • Glycophorin A (Glycophorins are proteins
    • containing carbohydrates)
    • Spectrin
    • Ankyrin
  40. Spherocytes
  41. 3 RBC Metabolism Pathways
    • Embden-Meyerof
    • Hexose Monophosphate Shunt
    • Methemoglobin Reductase
  42. Embden-Meyerhoff Pathway
    • Glycolytic
    • Generates 2,3 diphosphoglycerate-unloading of Oxygen
    • 90% of cell metabolism
    • Anareobic
  43. Generates 2,3-DPG
    • Embden-Meyerhoff pathway
    • Aids in unloading of oxygen
  44. Hexose Monophosphate Shunt
    • Produces NADPH
    • Protects against oxidative damage
  45. Produces NADPH, Protects against oxidative damage
    Hexose Monophosphate shunt
  46. If Hexose Monophosphate Shunt inaccurate:
    • Then - Heinz Bodies
    • Bite Cells
    • Cause- G6PD deficiency
  47. Heinz Bodies
    Caused by Denaturing of Hgb- precipitation in form of Heinz Bodies. HMS-G6PD deficiency
  48. Heinz Bodies
  49. Bite Cell
  50. Methemoglobin Reductase Pathway
    • Keeps heme in ferrous (+2) state
    • If deficient, cannot bind oxygen
  51. RBC Size
    • –Normal 6-8µm
    • –MCV 80- 100 fL
    • –MCHC 32% -36%
  52. Microcytic Anemias
    • Iron Def Anemia -IDA
    • Anemia of Inflammation-AoI
    • Thalassemia
    • Iron Overload Disorders
  53. Macrocytic Anemias
    • Megaloblastic-Folic acid or Vit. B-12 def
    • Liver Disease
    • MCV > 110fL
  54. Polychromasia
    • Gray/Blue Color
    • Retic released - BM response to anemic stress
  55. Polychromatic RBC
  56. MCV
    • Mean Corpuscular Volume
    • 80-100fL, HCT/RBC x10
  57. MCH
    • Mean Corpuscular Hgb
    • 27-31pg
    • Hgb/RBC x10
  58. MCHC
    • Mean Corpuscular Hgb Concentration
    • 32-36%
    • Hgb/HTC x100
  59. RDW
    • RedCell Distribution Width
    • 11.5-14.5%
    • Anisocytosis
  60. Hgb
    • 14-18 Males
    • 12-16 Females
    • g/dL
  61. HCT
    • 42-52% Males
    • 37-47% Females
  62. WBC Count
    4-11 x10^9g/L
  63. RBC Count
    • 4.7-6.1 Males
    • 4.2-5.4 Females
    • x10^12/L
  64. RBC Color Classification
    • MCHC
    • Normochromic- 32-36%
    • Hypochromic- <32%
  65. RBC Size Classification
    • MCV
    • Microcytic- <80fL
    • Normocytic- 80-100fL
    • Macrocytic- >100fL
  66. Target Cell
    • Seen in
    • Hemoglobin C disease
    • Liver Disease
    • Iron Deficiency
    • Hgb abnormalities
    • Thalassemia
    • or artifact
  67. Spherocytes
    • Increased MCHC, no central pallor
    • Loss of RBC membrane
    • Ab and complement coated cells get their membranes shreard in splenic circulation
    • Also hereditary
  68. Stomatocytes
    • Slit like central pallor
    • Increased fragility
  69. Ovalocytes and Elliptocytes
    • ATP and 2,3-DPG decreased
    • Ovalocytes-myelodysplastic syndromes, thalassemias, megaloblastic processes
    • Eliptocytes-seen in hereditary elliptocytosis, ideopathic myelofibrosis and iron deficiency
  70. Ovalocytes and Elliptocytes
  71. Acnthocytes
    • Seen in:
    • abetalipoproteinemia (a lipid disorder)
    • anorexia nervosa
    • lecithin cholestrol acyltransferase deficiency
    • alcohol intoxication
    • pyruvate kinase deficiency
    • vit E deficiency
    • post splenectomy
    • MCHC normal
  72. Acanthocytes
  73. Tear Drops
    • RBC inclusion is “pitted” as cell passes through the spleen. A “tail” is left and RBC membrane does not reform discocyte shape.
    • Large cells have to squeeze through microvasculature of the spleen
    • Seen in ideopathic myelofibrosis with myeloid metaplasia, thalassemia syndromes, iron deficiency, inclusion bodies (the things that get “pitted” see later in lecture)
  74. Tear Drop Cells
  75. Fragmented Cells
    • Helmet Cells
    • Burr Cells
    • Shistocytes
  76. Red Cell Inclusions
    • •Howell Jolly Bodies–remnants of DNA
    • •Siderotic Granules/ Pappenheimer bodies–iron
    • •Basophilic stippling–RNA and mitochondrial remnants
    • •Heinz Bodies–denatured hemoglobin
  77. Heinz Bodies
    • Denatured and precipitated Hgb
    • Use crystal violet or brilliant cresyl blue stain.
    • α thalassemic syndromes, G6PD, unstable Hgb syndromes, RBC injury from chemical insult
  78. Cabot Rings
    • figure 8 shaped stippling
    • Made of arginine-rich histones and non-hemoblobin iron
    • Seen in megaloblastic anemias, homozygous thalassemic syndromes, post splenectomy
  79. Cabot Ring
  80. Siderotic Granules (Prussian Blue)
    and
    Pappenheimer Bodies (Wright Stain)
    • •Granules of non-heme iron
    • •Seen in iron excess, sideroblastic anemia, hemochromatosis, hemosiderosis, sickle cell, thalassemia, post splenectomy
  81. Pappenheimer bodies
  82. Rouleaux Formation
    • Multiple myeloma
    • Waldenstrom’s macroglobulinemia
    • Chronic inflammatory disorders
    • Some lymphomas
  83. Microcytic Anemias
    • Iron deficiency anemia
    • Sideroblastic anemia
    • Thalassemia
    • Anemia of inflammation
  84. Iron Deficiency Anemia
    • Decreased red count
    • Decreased hemoglobin
    • Decreased hematocrit
    • Decreased MCV
    • Decreased MCHC
    • Decreased serum iron
    • Decreased serum ferritin
    • Increased TIBC
    • Decreased transferrin sat.
  85. Anemia of Chronic Disease/Anemia Inflammation (AOI)
    • Red cell count, hemoglobin, and hematocrit all borderline
    • MCHC normal
    • MCV slightly low
    • Serum iron low
    • Serum ferritin normal or increased
    • TIBC decreased-holding onto iron
  86. Sideroblastic Anemia
    • 5-aminolevulinic synthetase is deficient, Protoporphyrin ring cannot be formed
    • Iron accumulates in the mitochondria, because it cannot be incorporated into heme
    • Dimorphic blood picture
    • Pappenheimer bodies
    • Siderocytes and ringed sideroblasts with Prussian blue (BM)
    • Increased serum ferritin
    • Increased serum iron
    • TIBC is normal or low
  87. Iron Overload and Hemochromatosis
    • (NOT AN ANEMIA!)
    • accumulation of excess iron in reticuloendothelial cells in various
    • tissues
    • Causes tissue damage
    • Increase in intestinal iron absorption due to mutation in the HFE gene on chromosome 6
  88. Hereditary Hemochromatosis
    • increased % transferrin saturation is a hallmark
    • presence of HFE gene
    • Elevated serum iron
    • Elevated serum ferritin
    • Elevated transferrin saturation
    • Normal serum transferrin
    • Normal TIBC
  89. Thalassemia
    • Globin chain disorders
    • Microcytic process
    • Hemolytic anemias
    • Normal iron status
    • Not enough Hgb A chains produced
  90. Alpha Thal
    • 0, 1 or 2 functional genes.
    • Also a carrier state with 3 functional genes
    • Gene Deletions
  91. Beta Thal
    • Inherit defective beta genes
    • Heterozygotes or homozygotes
    • Many mutations
  92. H-Bodies w. supravital stain
  93. Osmotic Fragility
    • Used to screen for carrier states of thalassemia
    • (and also hereditary spherocytosis)
    • Normal RBC’s lyse at .45% NaCl
    • HE spherocytes (decreased SA:volume) lyse at .65% NaCl
    • Beta thal and alpha thal trait lyse at < .45% NaCl
  94. Beta thalassemia major
    Cooley’s Anemia
    • Little or no beta-chains (therefore little or nohemoglobin A)
    • Low hemoglobin levels (6 - 9 g/dl)
  95. Beta thalassemia minor/trait
    • 1 abnormal beta gene
    • Microcytic, hypochromic anemia
    • Hemoglobin A2 increased to 5-10% Alpha/Delta combos
  96. Kleihauer-Betke acid elution test
    • Hb F
    • Normal cells = ghost
    • HGB F cells-stained
  97. Macrocytic Anemias
    • Macrocytic Megaloblastic Anemias
    • –Vit B 12 or Folic Acid Deficiencies
    • Macrocytic Non-Megaloblastic Anemias
    • –Liver Dz. or drug induced
  98. Megaloblastic Anemia
    • Macrocytic normochromic anemia
    • Defective nuclear maturation due to impaired DNA synthesis
    • N:C asynchrony
    • Cause -Vit B 12 or Folic acid deficiency
    • MCH is increased, but MCHC is normal
  99. Megaloblasts
    • Megaloblasts = large RBC precursors
    • Large granulocyte precursors including large bands and giant metamyelocytes
    • “sievelike“ chromatin
  100. Megaloblastic Smear
    • Macrocytes and macro-ovalocytes
    • Schistocytes, tear drops, spherocytes, targets
    • HJ bodies, Cabot rings, basophilic stippling
    • Absolute retic is low, RPI is <2 indicating ineffective erythropoeisis
  101. Reticulocyte
    Corrected retic% = (retic% X Patient hct)/Normal hct* based on age and sex
  102. RPI
    • Reticulocyte Production Index
    • RPI = corrected retic / maturation time in days

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