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ICM- Hematology and Oncology
Hematopoiesis, Bone Marrow Examination, Intro to Anemias (T Pierce)
43
Medical
Professional
11/15/2009

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Term
define hematopoiesis
Definition
process by which blood cells are produced and released into peripheral blood
Term
components of hematopoiesis
Definition
  • stem cells
  • GF's
  • microenvironments

tightly regulated

Term
function of stem cells
Definition
  • self renewal
  • differentiation
Term
Sites of hematopoiesis
Definition
  • during fetal life
    • starts with yolk sac
    • then liver and spleen for second trimester
  • begining in second trimester, bone marrow hematopoiesis begins to rise and peaks at birth, then:
    • higest in vertebra
    • next highest is sternum
    • thrid highes is rib
    • lowest in tibia and femur (drop off during second decade of life)
Term
Different GF's involved in hematopoiesis
Definition
  • CSF (colony stimulating factors)
  • interleukins
  • erythropoietin
Term
kinetics of hematopoiesis
Definition
  • erythrocytes
    • 5 days to release
    • 16 progeny from each stem cell
    • survive 120 days
  • granulocytic (esp. neutrophils)
    • 14 days to release
    • 16-32 progeny from each stem cell
    • survive 1-4 days
  • megkaryocytic
    • 5 days to release
    • hundreds of progeny from each stem cell
    • survive 8-11 days
Term
bone marrow examination (specimen type, sites)
Definition
  • specimen types
    • aspirate (can smear or allow it to clot)
    • core biopsy (bone sample)
  • sites
    • posterior, superior iliac spine
    • sternum (aspirate only)
    • anterior tibia (young kids)
Term
Effect of age on cellularity of bone marrow
Definition
as you age, cellularity will decrease
Term
bone marrow aspirate smear: What do we look for?
Definition
  • marrow cellularity (estimate only)
  • myeloid:erythroid ratio- normal 3:1
  • maturation of hematopoietic lineage
  • low frequency elements- plasma cells, histiocytes, lymphocytes (found in small numbers)
  • iron stores- histiocytic and sideroblastic
  • foreign cells (metastatic neoplasm)
  • microorganism
Term
Bone marrow core biopsy: what we look for
Definition
  • cellularity- in young children, 90% or in elderly, 30%
  • general maturation of hematopoetic lineage (aspirate is better)
  • fibrosis
  • foreign cells
  • granulomas
  • microorganisms- esp. mycobact., fungi
  • bone morphology
Term
indications for bone marrow examination
Definition
  • anemia, neutropenia, thrombocytopenia
  • leukemia evaluation
  • metastatic neoplasm
  • selected infectious agents

after less invasive tests have been exhausted

Term
anemia is measured by what
Definition
  • decreased Hct
  • decrease Hb conc.
  • decrease RBC count
Term
definition of anemia
Definition
reduction in total circulating RBC mass, which results in reduction in oxygen carrying capacity of blood
Term
What kind of variables could alter Hct, Hg, RBC count
Definition
  • gender (after puberty, higher in male)
  • age (higher in newborn, low in children, then pop to adult levels in puberty)
  • high altitude living (decrease oxygen tension induce increase erythropoietin production)
  • posture (prolong bed rest decrease values)
  • stress, extreme exercise- increase values
  • dehydration- increase values (hemoconcentration)
  • overhydration (ex: IV fluids)- decrease values (hemodilation)
Term
classification of anemia
Definition

pathophys

morphologic

Term
pathophys classification of anemias
Definition
  • decrease RBC production
  • increase RBC destruction (hemolytic anemia)
  • increase RBC loss (acute hemorrhage)
Term
Ways that you can decrease RBC production
Definition
  • primarily affect stem cells
    • aplastic anemia
    • pure red cell aplasia (only RBC effected)
    • myelodysplastic syndrome
    • anemia of renal failure (EPO deficiency)
  • afect differentiating cells
    • impair DNA synthesis
      • B12 or folate deficiency
      • impair B12, folate metabolism
    • impair Hb synthesis
      • iron deficiency
      • thalassemia (decrease globin chain syn.)
      • sideroblastic anemia (defective heme synthesis)
    • multiple mechanism
      • anemia or chronic disease
      • myelophthisic anemia (space occupying disease of bone marrow)
Term
Different types of anemias with increased RBC destruction
Definition
  • extracorpuscular
    • immune mediated
    • non immune mediated
  • intracorpuscular
    • acquired
    • inherited
      • RBC membrane defects
      • RBC enzyme deficiencies (G6PDH)
      • globin chain structural defects
      • globin chain synthesis defects
Term
morphologic classification of anemias
Definition
  • normocytic
  • microcytic
  • macrocytic
Term
Examples of normocytic anemia
Definition
  • aplastic anemia
  • anemia of chronic disease (some)
  • myelophthisic anemia
  • hemolytic anemia (most EXCEPT thalessthemia)
  • acute blood loss
Term
Examples of microcytic anemia
Definition
  • iron deficiency
  • thalassemia
  • sideroblastic anemia
  • anemia of chronic disease (some)
Term
Examples of macrocytic/megaloblastic anemia
Definition
  • B12 or folate deficiency
  • certain antineoplastic drugs
Term
general symptoms of anemia
Definition
  • fatigability
  • dyspnea on exertion
  • faintness
  • vertigo
  • palpitation
  • angina pectoris
  • claudication
  • tinnitis
  • headache
Term
Clinical features of anemia
Definition
  • general features- due to reduced oxygen carrying capacity of blood
    • tissue hypoxia
    • compensatory mechanism to prevent tissue hypoxia
  • specific features
    • related to specific etiology of anemia
Term
General physical signs of anemia
Definition
  • pallor
  • tachycardia
  • hypotension
  • systolic murmor
Term
specific symptoms of anemia
Definition
  • history of GI or GU bleed- iron deficiency
  • PICA (eating unusual things like clay, starchy foods, chew ice)- iron deficiency
  • jaundice- hemolytic anemia
  • dark urine- hemolytic anemia
  • neurologic complaints- B12 deficiency
Term
specific physical signs of anemia
Definition
  • dry atrophic skin and nail changes- iron deficiency
  • jaundice- hemolytic anemia
  • red, swollen tongue- B12 deficiency
  • certain neurologic signs- B12 deficiency
Term
Factors affecting clinical features
Definition
  • rate at which anemia develops
    • ability to compensate over time
  • degree of cardiac or pulmonary compensation
    • young people tolerate better than older
  • metabolic requirements
    • increase in metabolic requirements makes anemic patietns worse (ex: pregnancy)
  • underlying disease states
Term
lab evaluation of anemia
Definition
  • Hct, Hb, RBC count (CBC)
  • RBC indices (CBC)
  • peripheral smear evaluation
  • reticulocyte count
  • iron studies
  • B12 and folate studies
  • Hb degradation products
  • specific tests for hemolytic anemia
  • bone marrow examination
Term
components of complete blood count (CBC)
Definition
  • WBC count (total)
  • WBC differential count (% and absolute counts)
  • Hct
  • Hb
  • RBC count
  • RBC indices
    • MCV
    • MCH
    • MCHC
    • RDW
  • platelet count
Term
RBC indicies: MCV (definition, purpose)
Definition
  • definition- measure of average volume (size) of individual RBC
  • used to classify anemias morphologically
Term
RBC indicies: RDW
Definition
mathematical expression of degree of variation in volume of individual RBC's within a population of RBC's
Term
RBC indices: MCH
Definition
  • measure of average total Hb content of individual RBC
  • parallel MCV and MCHC
Term
RBC indicies: MCHC
Definition
  • measure of average concentrations of Hb in individual RBC
  • decreased in microcytic anemia
Term
peripheral blood smear examination: what to look at
Definition
  • RBC morphology
    • size- variation (anisocytosis), microcytic, normocytic, macrocytic
  • Hb concentration
    • normochromic
    • hypochromic
  • number of immature RBC
    • polychromasia (just been released from bone marrow, still got a little too much RNA, so a lil larger and bluer)
    • nucleated RBC's
  • shape
    • variation (poikilocytosis)
    • specific shapes
Term
different RBC shapes
Definition
  • normal (discocyte)
  • target cell (codocyte)
  • teardrop cell (dacryocyte)
  • fragmented RBC (schistocyte)
  • sickle cell (drepanocyte)
  • ovalocyte (elliptocyte)
  • spherocyte
  • burr cell (echinocyte)
  • acanthocyte
Term
Other than RBC's, what else should we look for in smear
Definition
  • platelet number and morphology
  • WBC number and morphology
Term
purpose of reticulocyte count
Definition
  • RBC stained for RNA; immature RBC have residual RNA
  • quantitation of number of immature RBC present in peripheral blood
  • corrected reticulcyte count
    • corrected reticulocyte count (%) = raw reticulocyte % x (patients Hct/mean normal Hct)
Term
Iron studies that can be considered
Definition
  • serum iron
    • total iron present of serum
  • total iron binding capacity
    • total capacity of serum to bind iron
    • reflection of serum transferrin level
  • serum ferritin
    • reflect total body iron storages
Term
studies for megaloblastic anemias
Definition
  • serum vit B12 (cobalamin)- good reflection of body stores
  • serum and RBC folate
    • serum level is labile (reflects recent intake in diet)
    • RBC levels better measure of total body stores
  • Schilling test (not done)
    • once useful in det. cause of vit B12
    • difficult for patient and associated with analytical problems
  • IF blocking Ab
    • high specificity
    • when positive in patient of low vit B12, dx of autoimmune pernicious anemia
Term
tests specific for hemolytic anemia
Definition
  • Coombs test
  • RBC enzyme assay for G6PDH
  • test for sickeling Hb
  • Hb electrophoresis to quantify Hb A2, F
  • sucrose hemolysis, HAM's, specific red cell Ag tests for PNH
  • osmotic fragility, RBC membrane protein test for hereditary spherocytosis
Term
bone marrow examination of anemias: what do we look for>
Definition
  • amount of erythropoiesis in marrow
    • total cellularity
    • M:E ratio
  • erythrocytic maturation sequence
  • iron stores
    • histiocytes
    • sideroblastic
  • hematopoietic or metastatic neoplasms
Term
EPO mechanism of action
Definition
  1. there is a decrease in partial pressure of oxygen
  2. this is sensed by oxygen senser in kidney
  3. it will respond by increase production of EPO
  4. leads to stimulation of production of only cells committed to RBC linieage
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