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Hematology%20Physiology%201%20Erythropoiesis

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Title: Hematology%20Physiology%201%20Erythropoiesis


1
Hematology Physiology 1 Erythropoiesis
  • Brenda Beckett, PA-C

2
Terms to Understand
  • Hematopoiesis
  • Erythropoiesis
  • Pluripotent hematopoietic stem cell (PHSC)
  • Committed stem cell (progenitor cell)
  • Differentiation
  • Maturation
  • Self-renewal
  • Proliferation
  • Reticulocyte
  • Polychromasia
  • Normocyte
  • Erythropoietin
  • Adult hemoglobin
  • Fetal hemoglobin
  • Apotransferrin
  • Transferrin
  • Apoferritin

3
Terms, continued
  • Ferritin
  • Hemosiderin
  • Serum iron
  • Total iron binding capacity
  • ?-thalassemia
  • ?-thalassemia
  • Hemoglobinopathy
  • Anemia
  • Porphyria
  • A,B,O,Rh blood types

4
Red Blood Cell
  • Transports hemoglobin
  • Carries oxygen from lungs to tissues
  • Carries CO2 back to lungs
  • Biconcave disc
  • Able to change shape
  • Has excess membrane

5
Red Blood Cell
  • Mature RBC has no nucleus
  • 5,200,000 (males), 4,700,000 (females) per cubic
    milliliter
  • Lifespan of 100-120 days
  • Derived from pleuripotent hematopoietic stem
    cells (PHSC)

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PHSC
  • Retained in bone marrow
  • Reproduction controlled by growth inducers
  • Differentiation controlled by differentiation
    inducers
  • Will become committed stem cell (progenitor cell)

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11
Erythropoiesis
  • Decreased O2 in tissues causes increased
    production of erythropoietin
  • Hormone
  • Formed in kidney (80-90) and liver
  • Occurs in fetal liver and spleen, then shifts to
    fetal bone marrow
  • Occurs in axial skeleton and proximal end of long
    bones in adults

12
Reticulocytes
  • Final cell produced in marrow before release
  • Basophilic remnants of endoplasmic reticulum
    remain, becomes mature RBC (normocyte) within one
    day
  • Normally 1 of total RBCs

13
Reticulocyte Count
  • Can differentiate between anemias due to
    decreased production and those of increased
    destruction
  • Will see polychromasia on Wrights stain, need to
    order separate test for reticulocyte count

14
Hemoglobin Formation
  • Begins at proerythroblast stage, continues until
    reticulocyte (before leaving bone marrow)
  • Heme molecule combines with globin (long peptide
    chain) to form hemoglobin chain.
  • 4 chains bind together to form hemoglobin
    molecule.

15
Hemoglobin
  • Binds loosely and reversibly with O2
  • Oxygen atom binds loosely with iron atom in
    hemoglobin
  • Bound as O2, released as dissolved O2

16
Iron Metabolism
  • Iron important part of hemoglobin, myoglobin and
    other structures
  • 65 of total iron in hemoglobin
  • 4 myoglobin
  • 1 various heme compounds
  • 0.1 in plasma combined with transferrin
  • 15-30 stored in liver as ferritin

17
Iron Transportation Storage
  • Absorbed in small intestine
  • Binds with apotransferrin (?globulin) to form
    transferrin loosely bound
  • Excess deposited in liver and bone marrow
  • In liver, combines with apoferritin to form
    ferritin.
  • Also stored as insoluble hemosiderin iron
    overload

18
Iron Usage
  • If plasma iron low, iron removed from ferritin,
    transported as transferrin in plasma
  • Transferrin binds strongly with cell membranes on
    erythroblasts in marrow
  • Ingested, delivered to mitochondria
  • Heme synthesized

19
Globin chains
  • 4 globin chains combine with heme to make
    hemoglobin molecule
  • 95-97 of adult hgb has 2 ?-chains and 2 ?-chains
    (?2?2) aka Hgb A
  • Fetal hgb (Hgb F) has ?2?2. High O2 affinity,
    mostly changes to HgbA by birth
  • Hgb A2 (?2?2), 3-5 of adult

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Abnormal Hemoglobins
  • Hemoglobinopathies hemoglobin chains are
    abnormal
  • Thalassemias hemoglobin chains normal in
    structure but decreased or absent. Named for
    which chain is affected.
  • Genes are on chromosomes 11 16

22
Anemia
  • Qualitative or quantitative deficiency of
    hemoglobin
  • Significant blood loss
  • Plasma replaced in 1-3 days
  • RBCs replaced in 3-4 weeks
  • Hemolysis
  • Deficient RBC production

23
Vitamin B12/Folate
  • Important for final maturation of RBCs
  • Essential to synthesize DNA
  • Decrease in either leads to failure of nuclear
    maturation and division
  • RBCs also become larger, irregular shape, flimsy
    membrane
  • Carry O2 normally, have short lifespan

24
Vitamin B12/Folate Deficiency
  • Macrocytic or megaloblastic anemia
  • Pernicious anemia inability to absorb Vitamin
    B12 from GI tract
  • Gastric mucosa secretes Intrinsic Factor (IF),
    combines with B12, available for absorption
  • B12 stored in liver and bone marrow

25
Iron deficiency
  • When iron stores are depleted, stored iron is
    mobilized
  • When iron stores drop, hemoglobin synthesis is
    affected iron deficient erythropoiesis.
    (hypochromic)
  • More severe, leads to decreased erythropoiesis,
    smaller cells (microcytic)

26
Iron Deficiency Anemia
  • Low iron stores low Ferritin
  • Low circulating iron (transferrin) low Serum
    Iron
  • Leads to increased Total Iron Binding Capacity
    (TIBC)
  • Hypochromic, microcytic anemia

27
Anemia of Chronic Disease
  • Most likely due to inflammation
  • Iron stores arent released
  • Decreased erythropoiesis
  • Upregulation of WBC production causes decreased
    erythropoiesis
  • Normocytic or microcytic

28
Hemolytic anemias
  • RBCs are fragile, shorter lifespan
  • Rupture as pass through capillaries and spleen
  • Hereditary or acquired (immune mediated)
  • Increased destruction leads to increased
    bilirubin (jaundice)

29
Hemolytic anemias
  • Hereditary spherocytosis (and others)
  • Cells are spherical, cant withstand compression
    easily ruptured
  • Sickle cell anemia
  • Abnormal Hgb S (on ? chain)
  • Exposed to low O2, forms crystals, elongates cell
    sickle
  • Sickle trait protective against malaria

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Thalassemias
  • Autosomal recessive, Mediterranean
  • Reduced synthesis of one globin chain, leads to
    microcytic anemia
  • ? or ? chain affected
  • Can coexist with hemoglobinopathies
  • Carrier state can be protective against malaria

32
G6PD Deficiency
  • Hereditary
  • Low levels of G6PD (enzyme)
  • Certain triggers lead to hemolysis, anemia,
    jaundice
  • Foods, medications, infection
  • Protective against malaria

33
Polycythemia
  • Increased number of RBCs primary or secondary
  • High altitude physiologic polycythemia
  • Cardiac failure, smoking, tumors
  • Polycythemia vera blast cells continue to
    produce RBCs even though there are too many in
    circulation. Viscous blood. Treatment phlebotomy

34
Porphyria
  • Inherited or acquired
  • Disorder of enzymes in heme pathway
  • 7 different types
  • Different combos of elevated porphyrins (heme
    precursors) in tissues
  • Excreted in urine and stool
  • Sx photosensitivity, abd pain, port wine urine,
    muscle weakness, behavior changes

35
RBC/Hemoglobin destruction
  • Changes to plasma membranes as cell ages
  • Recognized by phagocytes
  • Phagocytosis in spleen
  • Heme broken down into iron biliverdin
  • Biliverdin converted to bilirubin
  • Iron bound to transferrin

36
Effects of anemia
  • Lack of oxygen in tissues
  • Symptoms can be vague
  • Weakness, fatigue, malaise
  • Dyspnea
  • Pallor
  • Increased cardiac output plapitations, heart
    failure

37
Blood Groups ABO
  • AB antigens agglutinogens on RBC
  • Anti-A /or Anti-B develop in absence of antigens
  • Will agglutinate RBCs, lyse, leads to renal
    failure, death

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Rh Typing
  • Other antigens can be present on RBCs
  • Antibodies develop if exposed to antigen
  • D (Rh), d, C, c, E, e
  • Erythroblastosis fetalis

40
WBC
  • The overall concentration of white blood cells of
    all types in the blood, expressed as thousands of
    cells per cubic millimeter (mm3) of blood. The
    terms used to describe a decreased and an
    increased WBC are leukopenia and leukocytosis,
    respectively.

41
RBC
  • The concentration of erythrocytes in the blood,
    most commonly expressed as millions of cells per
    cubic millimeter (mm3). The terms describing a
    decreased and an increased RBC are
    erythrocytopenia and erythrocytosis,
    respectively, or, more commonly, anemia and
    polycythemia.

42
HGB/HCT
  • The overall concentration of hemoglobin in the
    blood, expressed as grams of hemoglobin per 100
    milliliters of blood.
  • The hematocrit, the percentage of the blood
    volume consisting of red cells, expressed as a
    percent ().

43
MCV
  • mean corpuscular volume, the average volume of
    individual erythrocytes in a blood sample,
    expressed as femtoliters (fl) per cell. One
    femtoliter is the equivalent of 10-15 liters.
    The terms used to describe an erythrocyte with a
    normal, decreased, or increased cell volume are
    normocyte, microcyte, and macrocyte,
    respectively.

44
MCHC
  • mean cell hemoglobin concentration, the average
    concentration of hemoglobin within erythrocytes,
    expressed as grams of hemoglobin per dL of cells.
    Because the intracellular hemoglobin
    concentration determines the density of color
    (suffix -chromia) of erythrocytes on a stained
    blood smear, the morphological descriptions
    associated with a normal, increased or decreased
    MCHC are normochromia, hyperchromia and
    hypochromia, respectively.

45
MCH
  • mean cell hemoglobin, the average quantity of
    hemoglobin in individual erythrocytes, expressed
    as picograms (pg) per cell. One picogram is the
    equivalent of 10-12 grams.

46
RDW
  • red cell distribution width, expressed as the
    coefficient of variation around the mean cell
    volume (MCV). The larger the value for RDW, the
    greater the variability in size within the
    erythrocyte population. The morphological
    correlate of an increased RDW is variation in the
    diameters of individual erythrocytes seen on the
    peripheral smear, or anisocytosis.

47
PLT/MPV
  • the concentration of platelets in the peripheral
    blood, expressed as thousands of platelets per
    cubic millimeter (mm3) of blood.
  • mean platelet volume, the average volume of
    individual platelets, expressed as cubic microns
    per platelet or as femtoliters per platelet.

48
RETIC
  • the reticulocyte percentage, or the percentage of
    immature erythrocytes in a peripheral blood
    sample. These immature cells usually constitute
    from 0.5 to 1.5 of the circulating red blood
    cell population. An absolute reticulocyte count,
    expressed as millions of cells per cubic
    millimeter (mm3), can be obtained by multiplying
    the RBC by the reticulocyte percentage.

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