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RED BLOOD CELLS

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RED BLOOD CELLS by Mary Yvonnette C. Nerves, MD, FPSP Erythropoiesis A process by which early erythroid precursor cells differentiate to become the mature RBCs ... – PowerPoint PPT presentation

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Title: RED BLOOD CELLS


1
RED BLOOD CELLS
  • by
  • Mary Yvonnette C. Nerves, MD, FPSP

2
Erythropoiesis
  • A process by which early erythroid precursor
    cells differentiate to become the mature RBCs
  • Primary regulator ERYTHROPOIETIN
  • - stimulates red cell precursors at all levels
    of maturation to hasten the maturation process
  • - responsible for stimulating the premature
    release of reticulocytes into the bloodstream.

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Erythropoiesis
  • Total erythropoiesis
  • - total number of red blood cells (RBCs)
  • - measured by the myeloid-erythroid (ME)
    ratio from aspirate smears plus the estimate
    of cellularity from biopsy sections

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  • Effective erythropoiesis
  • - number of viable and functional RBCs
    available for physiologic needs
  • - reflects the balance between the number
    of cells produced and their life span
  • - measured by the reticulocyte count, which is
    normally 1 of the total RBC count

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Stages of Maturation
  • Pronormoblast (Rubriblast)
  • Basophilic Normoblast (Prorubriblast)
  • Polychromatophilic Normoblast (Rubricyte)
  • Orthochromatic Normoblast (Metarubricyte)
  • Reticulocyte
  • Erythrocyte

9
Pronormoblast
  • Earliest recognizable and largest cell of
    the erythrocyte series
  • Morphology
  • - Size 12 20 um
  • - Nucleus large round, oval, dark violet
    fine chromatin 1 2 nucleoli
  • - Cytoplasm deep blue spotty, basophilic
    w/ a perinuclear halo
  • - N/C Ratio 81
  • - BM () 1

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Basophilic Normoblast
  • Hemoglobin synthesis begins at this stage
  • Morphology
  • - Size 10 15 um
  • - Nucleus large round to sl oval
    condensed, coarse chromatin 0 1 nucleoli
  • - Cytoplasm deeply basophilic clusters of
    free ribosomes
  • - N/C Ratio 61
  • - BM () 1-4

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Polychromatic Normoblast
  • Increased production of hemoglobin pigmentation
    and decreasing amounts of RNA
  • Last stage in which the cell is capable of
    mitoses
  • Morphology
  • - Size 10 - 15 um
  • - Nucleus round nucleus, deep staining, may
    be centrally or eccentrically located
    coarse clumped chromatin
  • - Nucleoli 0

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  • Morphology
  • - Cytoplasm abundant blue-gray (RNA) to
    pink-gray (hemoglobin)
  • - N/C Ratio 41
  • - BM () 10-20

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Orthochromatic Normoblast
  • The last nucleated stage
  • Cannot synthesize DNA and cannot undergo
    cellular division
  • The NRBC sometimes seen in the
    peripheral circulation

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  • Morphology
  • - Size 8 - 10 um
  • - Nucleus small pyknotic nucleus dense
    chromatin 0 nucleoli
  • - Cytoplasm abundant red-orange
    cytoplasm uniform in color
  • - N/C Ratio 12
  • - BM () 5-10

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Reticulocyte
  • Slightly larger than the mature RBC with
    residual amts of RNA
  • Reticulocyte count an index of bone marrow
    activity or effective erythropoiesi
  • Morphology
  • - Size 8 - 10 um
  • - Nucleus anucleate cell containing small
    amt of basophilic reticulum (RNA)
  • - Nucleoli 0
  • - Cytoplasm large amt of blue-pink
    staining hemoglobin cytoplasm

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Erythrocyte
  • A biconcave 6 8 um disc
  • Life span 120 days
  • Main function to transport hemoglobin,
    a protein that delivers oxygen from the lungs to
    tissues and cells
  • Contains 90 hemoglobin and 10 H2O
  • normal conc of RBCs varies w/ age, sex
    geographic distribution

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  • Morphology
  • - Size 7 - 8 um
  • - Nucleus anucleated cell
  • - Nucleoli 0
  • - Cytoplasm pink staining, zone of
    central pallor is 1/3 of cell diameter
    devoid of hemoglobin
  • - N/C Ratio NA

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Hemoglobin Structure Function
  • A conjugated protein that serves as the vehicle
    for the transportation of O2 and CO2
  • When fully saturated, each gram of Hgb can hold
    1.34 mL of O2
  • A molecule of Hgb consists of 2 pairs of
    polypeptide chains (globin) and 4
    prosthetic heme grps each contg 1 atom of ferrous
    iron

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DESCRIPTION of TERMS
  • SIZE DESCRIPTORS
  • Anisocytosis variation in the sizeof the RBCs
    due to a pathologic condition

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  • Normocytic normal sized biconcave disc RBC
  • - normal MCV

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  • Microcytic Smaller RBCs less than 6 um
  • - MCV lt 80 fl
  • - Defect / Change abn size due to failure
    of hgb synthesis
  • - Dse IDA, Thalassemia, Chronic dse
  • Macrocytic Larger RBCs greater than 9um
  • - MCV gt 90 fl
  • - Defect / Change impaired DNA synthesis /
    stress erythropoiesis
  • - Dse Megaloblastic anemia / liver dse /
    MDS / Alcoholism / Malaria

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Macrocytic
Microcytic
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  • CHROMICITY DESCRIPTORS
  • Normochromic normal in color pale central
    area occupies less than 1/3
  • - Defect / Change normal amt of Hgb
  • - Normal indices
  • Hypochromic an RBC that has a decreased Hgb
    complement
  • - central pallor exceeds 1/3 of diameter
    of cell
  • - Defect / Change reduced Hgb content
    ( MCHC)
  • - Assoc conditions IDA / Thalassemia

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  • Hyperchromic no central pallor
  • - Defect / Change greater than normal
    MCHC
  • - Assoc condition Spherocytosis

Hyperchromic
Hypochromic
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  • Polychromasia blue-gray coloration
  • - Defect / Change presence of RNA
  • - Assoc condition increased erythropoietic
    activity / hemorrhage / hemolysis

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  • SHAPE DESCRIPTORS
  • Poikilocytosis variation in shape of the RBC
  • - Defect / Change irreversible alteration
    of membrane
  • - Assoc conditions Anemia / Hemolytic
    states

41
  • Discocyte normal biconcave erythrocyte - 6 8
    um diameter 0 2 um thickness
  • - Aka Normocyte

Normal Red Cells (SEM)
42
  • Acanthocyte spheroid w/ 3 12 irreg
    spikes or spicules
  • - Aka spur cell
  • - decreased cell volume
  • - Defect / Change inc ratio of chole to
    lecithin
  • - Assoc conditions
  • end-stage liver dse
  • Pyruvate kinase def
  • Hemolytic anemia
  • Abetalipoproteinemia

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  • Blister cell contains 1 or more vacuoles
  • - Aka Bite cells
  • - thinned periphery
  • - Defect / Change formed by removal of
    Heinz bodies
  • - Assoc conditions
  • Hemolytic episodes
  • G6PD def
  • Hemoglobinopathies

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  • Codocyte peripheral rim of Hgb surr by
    clear area central hemoglobinized area
    (bulls eye)
  • - Aka target cell
  • - Defect / Change excess of surface to
    volume ratio
  • - Assoc conditions
  • Hemoglobinopathies
  • Thalassemia
  • Liver dse
  • Postsplenectomy

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  • Dacryocyte teardrop or pear-shaped w/ single
    elongated point or tail
  • - Aka tear drop cell
  • - Defect / Change squeezing fragmentation
    during splenic passage
  • - Assoc conditions
  • Myeloid metaplasia
  • Thalassemia
  • Megaloblastic anemia
  • Hypersplenism

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  • Drepanocyte crescent-shaped cell that lacks
    zone of central pallor
  • - Aka Sickle cell
  • - Defect / Change polymerization
    of deoxygenated Hgb
  • - Assoc conditions
  • Sickle cell anemia
  • SC disease
  • S-thalassemia

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  • Echinocyte regular 10-30 scalloped
    short projections evenly distributed / spiny-like
  • - Aka Burr cell / crenated RBC
  • - Defect / Change Depletion of ATP
  • Exposure to hypertonic soln
  • Artifact in air drying
  • - Assoc conditions
  • Uremia
  • Cirrhosis / Hepatitis
  • Chronic renal dse

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  • Ovalocyte egglike or oval-shaped cell
  • - Defect / Change
  • Hgb has bipolar arrangement
  • Reduction in membrane chole
  • - Assoc conditions
  • Megaloblastic BM
  • Myelodysplasia
  • Sickle cell anemia

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  • Elliptocyte rod or cigar shape,
    generally narrower than ovalocytes
  • - Defect / Change polarization of Hgb
  • - Assoc conditions
  • Thalassemia
  • Iron def
  • Hereditary elliptocytosis

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  • Schistocyte Fragmented RBCs varying in
    size shape
  • - Aka Helmet cells
  • - Defect / Change extreme fragmentation produc
    ed by damage of RBC by fibrin, altered vessel
    walls, prosthetic heart valves
  • - Assoc conditions
  • DIC / TTP / Burns
  • Microangiopathic hemolytic anemia

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  • Spherocyte smaller in diameter than normal
    RBC w/ concentrated Hgb content no visible
    central pallor
  • - Defect / Change
  • lowest surface area to volume ratio
  • defect of loss of membrane
  • - Assoc conditions
  • Hereditary spherocytosis
  • Iso- autoimmune hemolytic anemia
  • Severe burns
  • Hemoglobinopathies

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  • Stomatocyte normal sized cell w/ slitlike
    area in center
  • - Defect / Change
  • artifact of slow drying
  • known to have inc permeability to Na
  • - Assoc conditions
  • Hereditary stomatocytosis
  • Acute alcoholism
  • Liver dse

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RED CELL INCLUSIONS
  • Basophilic Stippling
  • - cytoplasmic remnants of RNA
  • - Fine thin round dark blue granules
    uniformly distributed
  • - Defect/Change represents polychromasia
    (reticulocyte)
  • - Coarse medium sized uniformly
    distributed
  • - Defect/Change represents impaired
    erythropoiesis

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  • Basophilic Stippling
  • - Assoc conditions
  • Thalassemia
  • Lead Poisoning
  • Increased reticulocytosis

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  • Cabot Ring
  • - rings, loops, or figure eights red to purple
  • - Defect / Change remnants of
    microtubules of mitotic spindle
  • - Assoc conditions
  • Megaloblastic anemia
  • Dyserythropoiesis

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  • Heinz bodies
  • - deep purple irregularly shaped
    inclusions found on RBC inner surface of
    membrane
  • - Defect / Change represent precipitated,
    denatured Hgb due to oxidative injury
  • - Assoc conditions
  • Hereditary defects in HMS
  • G6PD def
  • Unstable Hgbs
  • Splenectomized pts
  • Thalassemia

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  • Howell-Jolly bodies coarse round
    densely stained purple 1-2 um granules
    eccentrically located on periphery of membrane
  • - Defect / Change nuclear remnants
    contain DNA
  • - Assoc conditions
  • Megaloblastic anemia
  • Severe hemolytic process
  • Thalassemia
  • Accelerated erythropoiesis

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  • Pappenheimer bodies small, 2-3 um irregular
    basophilic inclusions that aggregate in small
    clusters near periphery w/ Wrights stain
  • - Defect / Change unused iron (nonheme)
    deposits
  • - Assoc conditions
  • Sideroblastic anemia
  • Defective erythropoiesis
  • MDS
  • Hemolytic anemia
  • Thalassemia

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  • Ringed Sideroblasts
  • - Nucleated RBC that contains nonheme
    iron particles (siderotic granules) arranged in
    ring form
  • - Defect / Change excessive iron overload in
    mitochondria of normoblasts
  • - due to defective heme synthesis
  • - Assoc conditions
  • Sideroblastic anemia
  • MDS

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Ringed Sideroblasts Prussian blue iron stain
showing excess accumulation of iron as ferritin
in mitochondria ringing nucleus.
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  • Siderocyte non-nucleated cell containing
    iron granules
  • - Defect / Change excessive iron overload in
    mitochondria of normoblasts
  • - due to defective heme synthesis
  • - Assoc conditions
  • Sideroblastic anemia
  • MDS

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  • Autoagglutination clumping of RBCs
  • - Defect / Change presence of antibody
  • - Assoc conditions
  • Cold agglutinin
  • AHA

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  • Rouleaux Formation alignment of RBCs linear
    appearing as stacks of coins
  • - Defect / Change concentration of
    fibrinogen immunoglobulin
  • - Assoc conditions
  • MM / Waldenstroms macroglobulinemia

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Red Cell Studies
81
  • Hematologic tests used to measure several
    important parameters that reflect rbc structure
    and function
  • 1) Hemoglobin determination
  • 2) Erythrocyte count
  • 3) Hematocrit
  • 4) Erythrocyte Indices MCH, MCHC, MCV
  • 5) Reticulocyte Count
  • 6) Osmotic Fragility Test
  • 7) Erythrocyte Sedimentation Rate (ESR)

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Adult Reference Ranges for Red Blood Cells
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  • Hemoglobin
  • - involves lysing the erythrocytes, thus
    producing an evenly distributed solution of
    hemoglobin in the sample
  • - Hemiglobincyanide Mtd blood is diluted in
    a soln of K3Fe(CN6). The K3Fe(CN6) oxidizes Hgbs
    to hemiglobin (metHgb) and K cyanide provides
    cyanide ions to form HiCN, w/c has a broad
    absorption max at a wl of 540 nm

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  • Erythrocyte Count
  • - involves counting the number of rbcs per
    unit volume of whole blood.
  • - expressed as number of cells per unit
    volume, specifically cells/µL
  • - NV Female 4.2 - 5.4 x 106/µL
  • Males 4.7 - 6.1 x  106/µL

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  • Hematocrit
  • - sometimes referred to as the Packed
    Cell Volume (PCV) or volume of packed red cells
  • - is the ratio of the volume of RBCs to that of
    the whole blood
  • - varies with age and sex
  • - expressed as a percentage or as a decimal
    fraction

Plasma
Buffy coat
Red cells
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  • Erythrocyte Indices
  • 1) Mean Cell Volume (MCV)
  • - average volume of red cells
  • - calculated from the Hct and RBC count
  • MCV Hct x 1000
  • RBC (in millions/uL)
  • - expressed in femtoliters (fl) or cubic
    micrometers

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2) Mean Cell Hemoglobin (MCH) - content
(weight) of Hgb of the average red cell -
calculated from the Hgb and RBC count MCH
Hgb (in g/L) RBC (/L) - value
is expressed in picograms (pg)
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  • 3) Mean Cell Hemoglobin Concentration (MCHC)
  • - the average conc of Hgb in a given volume of
    packed red cells
  • - calculated from the Hgb conc the Hct
  • MCHC Hgb (in g/dL)
  • Hct
  • - expressed in g/dL

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  • Reticulocyte Count
  • - Principle Reticulocytes are immature
    non- nucleated red cells that contain RNA
    and continue to synthesize Hgb after the loss
    of the nucleus
  • - Supravital staining blood is briefly
    incubated in a soln of new MB or BCB, the RNA
    is precipitated as a dye-ribonucleoprotein compl
    ex ? dark blue network (reticulum or
    filamentous strand)
  • - NV 0.5 1.5 or 24 84 x 109/L

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  • Osmotic Fragility Test (OFT)
  • - a measure of the ability of red cells to take
    up fluid without lysing
  • - Red cells are suspended in a series of tubes
    contg hypotonic solns of NaCl solns varying
    from 0.9 to 0.0, incubated at room temp for
    30 mins and centrifuged
  • - the percent hemolysis in the supernatant solns
    is measured plotted for each NaCl conc.

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  • - The larger the amount of red cell
    membrane (surface area) in relation to the size
    of the cell, the more fluid the cell is capable
    of absorbing before rupturing
  • - Cells that are more spherical, w/ a decreased
    surface/volume ratio, have a limited capacity
    to expand in hypotonic solns lyse at a higher
    conc of NaCl than do normal biconcave cells ?
    OFT

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  • - Cells that are hypochromic flatter have a
    greater capacity to expand in hypotonic solns,
    lyse at a lower conc than do normal cells, are
    said to have decreased osmotic fragility
  • - Cells with increased surface/volume ratio are
    osmotic resistant ? IDA, thalassemia, liver dse,
    reticulocytosis

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  • Erythrocyte Sedimentation Rate (ESR)
  • - detect and monitor an inflammatory response
    to tissue injury (an acute phase response) in
    which there is a change in the plasma conc of
    several proteins
  • - Principle When well-mixed venous blood is
    placed in a vertical tube, RBCs will tend to
    fall toward the bottom. The length of the fall
    of the top of the column of RBCs in a given
    interval of time is called the ESR

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  • - ESR is affected by (3) FACTORS
  • a) erythrocytes
  • b) plasma composition
  • c) mechanical / technical factors
  • - Red Cell Factors
  • Anemia increases ESR (change in RBC plasma
    ratio favors rouleaux fotn)
  • ESR is directly proportional to the weight of
    the cell aggregate inversely proportional to
    the surface area
  • Microcytes sediment slower than macrocytes
  • Rouleaux accelerate the ESR
  • Red cells w/an abnormal or irregular shape
    hinder rouleaux fotn lower the ESR

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  • - Plasma Factors
  • Elevated levels of fibrinogen accelerate ESR
  • Albumin lecithin retard ESR
  • Cholesterol accelerate ESR
  • - Mechanical / Technical Factors
  • A tilt of 3o can cause errors up to 30 ? ESR
  • ESR increases as the temp increases
  • ESR tubes with a narrower than standard
    bore will generally yield lower ESR
  • ESR stands fro gt 60 mins ? falsely elevated ESR
  • Greater conc of EDTA ? falsely low ESR
  • - Methods Westergren Mtd / Wintrobe Mtd

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ERYTHROCYTE DISORDERS
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  • Two main disorders affecting RBCs
  • 1. Polycythemia (Erythrocytosis)
  • - an elevated Hct level above the normal
    range
  • 2. Anemia
  • - a reduction below normal limits of the
    total circulating red cell mass

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Pathophysiologic Classification of Polycythemia
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POLYCYTHEMIA
  • May be classified into (2) major conditions
  • 1) Relative Polycythemia
  • - an increase in the Hct or red cell count as
    a result of decreased plasma volume
  • - total red cell mass is NOT increased
  • - Assoc conditions acute dehydration or
    hemoconcentration / pts on diuretic therapy /
    Gaisbocks syndrome (psedopolycythemia or
    stress erythrocytosis)
  • - BM Normal

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  • 2) Absolute (or Secondary) Polycythemia
  • - an erythropoietin mediated increase in RBCs
    and Hgb due primarily to a hypoxic situation
  • - increase in the total red cell mass in the
    body assoc w/ normal or sl increased plasma
    volume
  • - Assoc conditions tumors / anabolic
    steroids / renal dso such as cystic dse,
    hydronephrosis / adrenal cortical
    hyperplasia
  • - BM Erythroid hyperplasia

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3) Polycythemia rubra vera (Primary
Erythrocytosis) - an absolute increase in all
cell types, RBCs, WBCs and platelets - not
dependent on erythropoietin levels - BM all
three cell lines increased (panhyperplasia)
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ANEMIA
  • Decreased oxygen carrying capacity of the blood
  • Anemia may also be "defined" in terms of the Hb
    content
  • Hb lt 12 g/dL in an adult male
  • Hb lt 11 g/dL in an adult female

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  • ANEMIAS SECONDARY TO BLOOD LOSS
  • Acute e.g., hemorrhage due to trauma,
    massive GI bleeding, or child delivery. Usually
    the iron stores remain normal.
  • Chronic e.g., bleeding peptic ulcer or
    excessive menstrual bleeding.

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HYPOPROLIFERATIVE ANEMIAS (Impaired Production)
  • reduced production of red cells can be subdivided
    into
  • deficiency of haematinics
  • iron deficiency
  • B12 and folate deficiency
  • dyserythropoiesis (production of defective cells)
  • anaemia of chronic disorders (AOCD)
  • myelodysplasia
  • sideroblastic anaemia
  • marrow infiltration (myelophthisic anemia)
  • aplasia (failure of production of cells)
  • aplastic anaemia
  • red cell aplasia

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Iron Deficiency Anemia
  • Normal forms of iron (Fe) and iron metabolism
  • Functional iron is found in Hb, myoglobin, and
    enzymes (catalase cytochromes)
  • Ferritin physiological storage form
  • Hemosiderin degraded ferritin lysosomal debris
    (Prussian blue positive)
  • Iron is transported by transferrin

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  • causes
  • Dietary deficiency elderly, children and poor
  • Increased demand children pregnant women
  • Decreased absoprtion
  • generalized malabsorption
  • after gastrectomy
  • Chronic blood loss
  • GI bleeding (e.g. peptic ulceration, carcinoma
    of stomach or colon)
  • menorrhagia
  • urinary tract bleeding
  • Hook worm (Ancylostoma duodenale adult worm
    sucks 0.2 ml blood/day)

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  • Lab Findings
  • Microcytic, hypochromic anemia. Low serum iron
  • BM show absence of iron
  • Ferritin Low serum ferritin indicates low body
    stores of iron
  • Transferrin These carrier proteins will be
    unsaturated and available to bind iron, hence the
    Total Iron Binding Capacity (TIBC) is increased
    with anemia.

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Anemia of Chronic Disease (AOCD)
  • Char by iron being trapped in BM macrophages
  • Can be grouped in 3 categories
  • - chronic microbial infections (eg.
    Osteomyelitis)
  • - chronic immune disorders (eg. RA)
  • - Neoplasms (eg. lymphoma, breast/lung CA)
  • Chronic inflamm dso ?inc IL-1, TNF, IF-Gamma ?
  • - reduction in renal erythropoietin ? marrow
    erythroid precursors do notproliferate
  • - hepcidin synthesis in liver ?inhibits release
    of iron

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  • Labs low serum iron
  • increased serum ferritin
  • decreased TIBC
  • normochromic, normocytic anemia or
    hypochromic, microcytic anemia

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Megaloblastic Anemia
  • A group of dso in which the blood and BM
    hematopoietic cells display changes
  • Pathogenesis impaired DNA synthesis (delayed
    mitoses) while RNA is not impaired this produces
    nuclear-cytoplasmic asynchrony
  • Megaloblastic anemias can be divided into groups
  • - anemia caused by B12 deficiency
  • - anemia caused by folate deficiency
  • - anemias nonresponsive to either therapy

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  • important background knowledge
  • B12
  • vitamin B12 is required for DNA replication and
    inhibition of transcription of DNA to RNA
  • B12 is normally absorbed from gut by the
    following mechanism
  • secretion of intrinsic factor by parietal cells
    in stomach
  • binding of intrinsic factor and vitamin B12 in
    lumen
  • intrinsic factor- B12 complex is absorbed in
    terminal ileum through pinocytotic vesicles
  • Folate
  • folate is required for DNA replication and
    inhibition of transcription of DNA to RNA
  • lack of B12 or folate means that RNA builds up
    and the cells become too large

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  • Causes
  • causes of vitamin B12 deficiency (pernicious
    anaemia)
  • lack of intrinsic factor
  • atrophic gastritis - parietal cells are destroyed
  • gastrectomy
  • malabsorption of B12 not related to lack of
    intrinsic factor
  • tropical sprue or bacterial overgrowth of
    terminal ileum
  • ileal disease (e.g. Crohn's disease affecting the
    terminal ileum)
  • fish tape-worm (these attach to intestinal wall,
    and therefore in large enough numbers, may
    prevent B12-intrinsic factor complex absorption
    in terminal ileum)
  • poor diet - rare

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  • causes of folate deficiency
  • poor diet - especially in alcoholics
  • malabsorption - coeliac disease
  • increased cell turnover (e.g. leukaemia, chronic
    haemolysis, pregnancy)
  • antifolate drugs (e.g. phenytoin)

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  • Peripheral Blood Findings

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  • Morphologic Abnormalities
  • Large RBC's with nuclear-cytoplasmic dyssynchrony
  • Ovalocytes The large RBC's tend to have an
    oval-shape.

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  • Hypersegmented Neutrophils One of the earliest
    signs of disease. 5 or 6 lobes
  • Howell-Jolly Bodies Nuclear fragments seen in
    Megaloblastic anemia.

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Aplastic Anemia
  • pancytopenia associated w/ a severe reduction in
    the amt of hematopoietic tissue that results in
    deficient production of blood cells
  • Etiology
  • Acquired
  • idiopathic
  • Chemical agents
  • Physical agents
  • Viral infections
  • Inherited
  • Fanconis anemia

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  • Pure red cell aplasia erythrocyte stem cells are
    suppressed, but the other formed elements of
    blood are unaffected
  • Anemia due to isolated depletion of erythroid
    precursors in the marrow, and may be acute or
    chronic.
  • Lab Findings
  • - Normochromic, normocytic or macrocytic anemia
  • - Reticulocytes are decreased or absent because
    it is hypoproliferative.
  • - BM hypocellular or dry tap
  • reduction in all cell lines

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HEMOLYTIC ANEMIAS (Increased Destruction)
  • Grp of dso that can be inherited, acquired,or
    drug-induced
  • Char by an increased red cell destruction or
    shortened survival of the RBC
  • Char by increased BM activity, polychromasia,
    nucleated RBCs and an increased reticulocyte
    count w/ stress reticulocytes

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  • Hemolytic anemias share the ff. features
  • 1. shortened red cell life span, that is,
    premature destruction of red cells
  • 2. elevated erythropoietin levels and
    increased erythropoiesis in the marrow other
    sites
  • 3. accumulation of products of Hgb
    catabolism, due to an increased rate of red
    cell destruction

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  • HEMOLYTIC ANEMIAS
  • Acquired
  • Immune-mediated
  • - Autoimmune
  • - Alloimmune (Transfusion)
  • - Drug-induced
  • Microangiopathic
  • Infection
  • Hereditary
  • Enzymopathies
  • Membranopathies
  • Hemoglobinopathies

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  • INTRINSIC DEFECTS
  • Hereditary Spherocytosis
  • abnormal cell membrane assoc cytoskeleton causing
    red cells to be spherical and fragile
  • principle defect is an abnormality of the
    membrane protein ankyrin
  • Lab findings Normocytic, hyperchromic anemia
    (normal MCV and increased MCHC)
  • - increased pigment catabolism, erythroid
    hyperplasia, reticulocytosis
  • - red cells with increased OFT

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  • Glucose-6-Phosphate Dehydrogenase Deficiency
  • Normal G6PD metabolises glucose, and
    forms small amounts of ATP (which maintains
    the cell cytoskeleton and membrane) and NADPH
    (which mops up free radicals)
  • G6PD def renders the cell susceptible to
    damage by free radicals
  • an X-linked recessive condition, in which
    haemolytic crises are precipitated by
    infections or certain drugs
  • Lab findings poikilocytes spherocytes,
    Heinz bodies (stain w/ methyl violet)

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  • HEMOGLOBINOPATHIES
  • Normal Hgb
  • HbA / HbF / HbA2 (adult)
  • Hb Gower-1 and 2 / Hb-Portland (embryonic)

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  • THALASSEMIA
  • Caused by impaired production of one of the
    polypeptide chains of the Hb molecule
  • Epidemiology Mediterranean, African Asian
    ancestry
  • autosomal recessive disease
  • Types according to clinical severity
  • thalassaemia major homozygote
  • thalassaemia minor heterozygote
  • Types according to molecular defect
  • beta thalassaemia
  • alpha thalassaemia

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  • Beta-Thalassemia
  • Major (Homozygous state)
  • - severe hypochromic, microcytic anaemia,
    hepato- splenomegaly, marrow hyperplasia causing
    skeletal deformities, haemochromatosis develops
    with repeated transfusions
  • Minor (Heterozygous states)
  • - reduction in HbA, but increase in HbA2 mild
    anaemia with hypochromia

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  • Alpha-Thalassemia
  • note that there are 4 copies of the alpha globin
    gene (not 2), and therefore four possible degrees
    of alpha thalassaemia exist
  • 3 good copies - silent carrier
  • 2 good copies - mild anaemia with microcytosis
  • 1 good copy - moderate haemolytic anaemia with
    hypochromia and mycrocytosis HbH (tetramer of
    beta)
  • 0 good copies - lethal in utero (hydrops fetalis)

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Thalassemia Major Patient with thalassemia major
due to heterozygous hemoglobin E/B thalassemia.
Note prominent target cells, anisopoikilocytosis,
and three nucleated red cells (normoblasts)  
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  • Sickle Cell Disease
  • Endemic to Sub-saharan Africa, due to
    heterozygous advantage conferred against
    Falciparum Malaria (infected RBC's preferentially
    sickle and are thus taken to the spleen and
    sequestered, limiting the spread of infection)
  • PATHOGENESIS Point-mutation of Glu ? Val at 6th
    position of beta-globin chain
  • Pathophysio abn Hgb polymerises at low O2
    saturation causing abnormal rigidity and
    deformity of red cells and become abnormality
    fragile (and undergo haemolysis and sludge in
    small vessels)
  • autosomal recessive, with a point mutation in
    beta gene forming an abnormal HbS more common
    in Negroes

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  • Lab. Findings
  • Smear normochromic, normocytic anemia,
    increased polychromasia, normoblasts are present,
    numerous target cells, Howell-Jolly and
    Pappenheimer bodies are present, sickle cells
  • OFT decreased
  • BM normoblastic hyperplasia w/ increased iron
    storage
  • Electrophoresis no HbA, 80 HbS (SCD)

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Sickle Cells (SEM) Scanning electron micrograph
(SEM) showing sickle cells obstructing small
vessel.  
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  • EXTRINSIC DEFECTS
  • Immune Hemolytic Anemias
  • Dso in w/c erythrocyte survival is reduced
    because of the deposition of Ig /or
    complement on the red cell membrane
  • Classification
  • 1. Autoimmune Hemolytic Anemia
  • 2. Isoimmune Hemolytic Anemia
  • 3. Drug-induced Hemolytic Anemia
  • LAB () direct indirect antiglobulin tests

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Agglutination of erythrocytes is seen on this
peripheral blood smear
Coombs Test
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  • Traumatic Hemolytic Anemia
  • Char by striking morphologic abn of the red
    cells, w/c include fragments (schistocytes)
    irregularly contracted cells (triangular cells,
    helmet cells)
  • MICROANGIOPATHIC HEMOLYSIS RBC's being damaged
    by intravascular fibrin-clots, in small vessels.
    DIC, TTP, HUS.
  • MACROANGIOPATHIC HEMOLYSIS Damage by artifical
    heart valves.

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