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WEEK 5 RBCS ppt ash.ppt

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    Blood and Bone Marrow

    Histology Dr. ashraf

    mahmoud

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    Blood is a specialized type of connective tissue.

    It is composed of:

    A-Blood cells 45 %which include the following:1-Red blood corpuscles (erythrocytes).

    2-White blood cells (leucocytes).

    3- Platelets (Thrombocytes).B-Plasma55%(fluid intercellular substance).

    -In man, blood volume is about 5 liters.

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    The blood plasma-Plasma is an aqueous solution containingplasma proteins,inorganic salts and severalorganic compounds such as vitamins, aminoacids and hormones.

    -Plasma is in constant exchange with the extracellular fluids of the body.

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    -Plasma proteins are of threecategories:

    1-Albumins.2-Globulins.

    3-Fibrinogens.

    -Albumins can bind with insoluble fattyacids helping in their transport,

    -globulins form antibodies of the immune

    system and-fibrinogensform fibrin of the blood clot.

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    A- In the embryothey are:1-Yolk sac mesoderm during the first twomonths.

    2-Liver and spleen from the second to the fifthmonth.

    3-Bone marrow from the fifth month onwards.

    B- In the adult, haemopoiesis occurs in:

    1-Bone marrow ( myeloid tissue) mainly ofthe skull, ribs,sternum, vertebrae, pelvis andproximal ends of long bone.

    2-Lymphoid tissue.

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    Types of bone marrow1-Red bone marrow

    Red bone marrow is present in all bones ofthe foetus and in certain bones of adults

    ( mentioned above ).

    2-Yellow bone marrow

    yelloow bone marrow is present in adult

    long bonesand is characterized by a high fat

    content.

    Yellow marrow can be changed into red one

    in times of need.

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    Examinationof bone marrow

    Can be done by:

    1-Bone marrow sections.

    2-Bone marrow smears.

    3-Marrow films.

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    Structure of bone marrow

    (myeloid tissue)

    The myeloid tissue consists of:

    I-Connective tissue stroma

    II-The fixed stromal cells include:

    III-Free haemopoietic cells:

    f

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    Structure of bone marrow

    (myeloid tissue)

    The myeloid tissue consists of:

    I-Connective tissue stroma: containing bloodsinusoids.

    The stroma is made up of reticular networkcontaining blood sinusoids, venules and arterioles.

    The blood sinusoids have fenestrated endothelialcells with occludent junctions in between these cells.

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    II-The fixed stromal cells include:

    1-Reticular cells

    They are branched cells with pale nucleus and palecytoplasm. They produce reticular fibres, secreting

    type III collagen.Reticular cells have some phagocytic activity andmay have a role in immunological response.

    2-Fibroblasts

    Secretes collagen that supports the blood vessels andthe stroma.

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    3-Macrophages

    They are derived from monocytes.

    These macrophages have pseudopodia whichare able to extend between endothelial cells toengulf any foreign body in the blood.

    4-Fat cells.

    5-Osteogenic cellslining the bone trabeculae.

    6-Endothelial cells lining the blood sinusoids,venules and arteriole

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    III-Free haemopoietic cells:

    All types of developing blood cells are

    present in the meshes of the reticular

    stroma.

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    The pluripotential stem cells

    -They are present in a pool and are able toproduce all types of blood cells.

    These stem cells resemble lymphocytes with adiameter of 7 m and a large rounded nucleushaving prominent nucleoli. Their cytoplasm

    contains many ribosomes but few mitochondriaand rER.

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    The pluripotential stem cells proliferate and form:

    I-Myeloid multipotential cells:which will become:

    -Erythrocytes.

    - Granulocytes.-Monocytes.

    -Megakaryocytes.

    II-Lymphoid multipotential cells: which willbecome: -Lymphocytes.

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    II-Lymphoid multipotentialcells

    which will become:

    -Lymphocytes.

    -These stem cells proliferate and form lesspotential cells (progenitor cell)

    -Progenitor cellsare unipotential or bipotential

    -Precursor cells( e.g. lymphoblasts anderythroblasts ) produce mature cells

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    RED BLOOD CORPUSCLES

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    RED BLOOD CORPUSCLES

    RBC d Bl di Di d

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    RBC and Bleeding Disorders

    NORMAL

    Anatomy, histology

    Development

    Physiology

    ANEMIAS

    Blood loss: acute, chronic

    Hemolytic

    Diminished erythropoesis

    POLYCYTHEMIA

    BLEEDING DISORDERS

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    Peripheral Blood: Erythrocytes

    RBCs constitute thelargest number ofcells in the blood

    Biconcave discs

    NO NUCLEUS

    ContainHemoglobin

    I RED BLOOD CORPUSCLES

    http://www.jdaross.mcmail.com/images/erythrocytes.jpghttp://www.jdaross.mcmail.com/images/erythrocytes.jpg
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    I-RED BLOOD CORPUSCLES(ERYTHROCYTES)

    1-Shape

    -It is round biconcavecorpuscle in side view, known

    as a dumb bell shape bell shape.-Thebiconcave shape provides a large surface area

    for gas exchanges.

    -In the human it is round non-nucleated-Such corpuscles may coalesce together by their sideforming the rouleaux appearance.

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    Abnormalities in the shape

    A-Crenation:-it means loss of the water contents

    from the R.B.C.resulting in decreasing itssize and irregularities in its shape.

    B Heamolysis:

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    B-Heamolysis:

    -It means loss of the corpuscularhemoglobin as result of its rupture.

    -The main causes of heamolysis are:

    1-Hyponotic solutions.

    2-Incompatible blood transfusion.3-Toxins.

    C-Poikilocytosis:

    The R.B.C takes the pear shape.D-Sickle shaped cell:

    The corpuscle takes the shape of a crescent.

    RBC

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    RBC

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    2-Size

    -Diameter:7.5 micrometers with a rangebetween (6-8um).

    -Thickness: 1.9 microns.

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    Abnormalities in the size

    A-Macrocyte:The diameter is more than 8

    micrometers.

    B-Microcyte:

    The diameter is smaller than 6micrometers.

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    C-Spherocyte:

    The thickness of the corpuscle is morethan 1.9 micrometers.

    D-Anisocytosis:It is variation in the size of the R.B.C. in theblood of the

    same person. Such variation is detected byPrice Jones curve.

    3 C t

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    3-Count

    -The normal count of the red blood corpuscleis always done in one cubic millimeter of

    blood.

    *In the male it is about 5-5.5 million /1 ul *In the female it is about 4.5 millions /1 ul.

    -The red blood cells count is done by special

    apparatus called heamocytometer or by the

    automated methods.

    Abno malities in the co nt

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    Abnormalities in the count

    A-Increase in the number

    ( Polycythaemia)

    Causes: -Primary, without a definite cause.

    -Secondary due to low oxygen tension.Muscular exercise.

    Pregnancy.

    High altitude.Heart disease.

    Cold bath.

    Heavy meals.

    B-Decrease in the number

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    B-Decrease in the number(oligocythaemia)

    Causes: Hemorrhage.Heamolysis.

    Idiopathic.

    Aplastic due to bone marrow defect.Deficiency of one of the major factors forRBCs development e.g iron or B12.

    4 C l

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    4-Color-Fresh blood when spreaded appear yellowish

    greenin color but thick drop of blood appearredin color due to condensation of large

    number of the R.B.C. over each other.

    -The color of the blood is due to the red

    pigment hemoglobin which appear deeper in

    the peripheral part of the corpuscle and pale inits central part due to reduced thickness of the

    corpuscle.

    -The normal color is called Normochromic.

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    Abnormalities in the color

    A-Hypochromic:

    The amount of the hemoglobin is less than the

    normal concentration.B-Hyperchromic:

    The amount of the hemoglobin is more than

    the normal concentration.C-Stippling:

    Bluish dots considered as precipitation of the

    the stain.

    D-Polychromasia:

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    D Polychromasia:

    The corpuscle contains undiffused heam-oglobin, so double colors can be seen, the theblue color of the cytoplasm and the red color ofthe HB.

    E-Cabot ring:

    It is a remnant of the nuclear membrane.

    F-Howel jolly bodies:

    They are remnants of the chromatinof the nucleus.

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    5-Structure

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    5-Structure

    -Erythrocytes have flexible cell membranes, which

    contain lipids, proteins and carbohydrates.

    -The membrane peripheral proteins (spectrins) are

    responsible for the shape of the erythrocyte and help intheir flexibility on passing through capillaries.

    -Erythrocytes contain haemoglobin 33%,water 66%and some enzymes needed for glucose metabolism.Haemoglobin is aconjugated protein formed of globinand haematin.

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    -By EM, erythrocytes are highly electron densedue to their iron content.

    -Haemoglobin can combine with O2 oxyhaemoglobin or CO2

    carbaminohaemoglobin.

    These combinations are reversible.-Haemoglobin may combine with CO carboxyhaemoglobin which is irreversible.

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    6-Fate

    -Normally, the life span of human erythrocytes is 120days.

    - erythrocytes are removed from the circulation by

    macrophages of the spleen and bone marrow.-Haemoglobinis destructed to globin and haematin.

    -Haematin is furtherly broken into haemosidrin

    (which is reused to form haemoglobin in the liver )and haematoidin ( bilirubin ) which is excreted in

    bile.

    R ti l t

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    Reticulocytes

    -They are immature form of erythrocytes in theblood released from the bone marrow.

    -Their normal percentage in blood is about 1 %

    of the circulating red blood cells.-Microscopically, they cannot be differentiatedfrom ordinary erythrocytes in a blood film.They need special incubation (supravital

    staining) by brilliant cresyl blue.

    -

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    -Reticulocytes increase in cases ofincrease demand for erythrocytesformation from bone marrow as inhaemorrhages.

    EM, their cytoplasm appears less electrondense due to less haemoglobin content.

    -Reticulocytes show remnants ofribosomes, mitochondria and Golgi.

    MATURATION OF RED BLOOD CELLS

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    MATURATION OF RED BLOOD CELLS1-pluripotential stem cell

    myeloid multipotentialcells.2- erythrocyte- colony forming cells

    3-Proerythroblas

    4-basophilic erythroblasts ts

    5-polychromatophilic erythroblasts

    6-normoblasts

    7-reticulocyte

    8-er throc te

    ERYTHROPOIESIS

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    ERYTHROPOIESISMATURATION OF RED BLOOD CELLS

    1-Thepluripotential stem cellsof the bonemarrow proliferate and form myeloidmultipotentialcells.

    2-These cells form the progenitor daughtercells, erythrocyte- colony forming cells

    (ECFC) which differentiate intoproerythroblasts.

    3-Proerythroblasts are the first recognizable

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    3 Proerythroblasts are the first recognizable

    cells of the erythrocytic series.

    They are large cells ( 12-15 m ) with large

    moderately stained nuclei having prominent

    nucleoli and their cytoplasm is basophilic.

    4-Proerythroblasts differentiate into basophilic

    erythroblasts which is smaller ( 10-12 m )

    than proerythroblast having a smaller

    condensed nucleus and basophilic cytoplasm.

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    5-Basophilic erythroblasts differentiateinto polychromatophilic erythroblasts

    which is smaller than basophilic erythroblastswith a small more condensed nucleus.

    The cytoplasm is polychromatophilic due tothe presence of polysomes ( basophilic ) andhaemoglobin ( acidophilic ).

    Mitosis occurs in proerythroblasts,basophilicand polychroma- tophilic erythroblasts.

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    6-Polychromatophilic erythroblasts

    differentiates tonormoblasts

    which are smaller in diameter ( 8-10 m )having darkly stained eccentric nuclei.

    The cytoplasm is acidophilic due to thepresence of haemoglobin.

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    7-The nucleus of normoblast

    is extruded to the outside to be phagocytosed bymacrophages and the cell now is calledreticulocyte. Reticulocytes are slightly largerthan mature erythbrocutes. Their number is

    1-2 % of blood erythroblasts.

    They have blue network which is the remnants

    of polysomes.They stain positively with the supravital stainbrilliant cresyl blue.

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    8-The reticulocyteloses its polyribosomes and becomes mature

    erythrocytebeing a biconcave disc-shaped full ofhemoglobin. Mature erythrocytes pass through theendothelium of blood sinusoids to the generalcirculation.

    -The development of erythrocytes is under the

    control of erythropietin and it needs iron, folic acidand vit. B12.

    -Erythropoiesis takes about 7 days to produce

    mature cells.

    RBC Development

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    RBC Development

    Proerythroblast

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    Proerythroblast

    Biggest in lineage Large central nucleus

    with one or two

    nucleoliBasophilic cytoplasm

    b/c ribosomes

    Look for Golgi ghost

    Basophilic Erythroblast

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    Basophilic Erythroblast

    Smaller thanproerythroblast

    Checkerboardnucleus(heterochromatic)

    Intense basophilia(lots of ribosomes!)

    Proerythroblast vs Basophilic

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    y pErythroblast

    Polychromatophilic Erythroblast

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    Polychromatophilic Erythroblast

    Smaller than basophilicerythroblast

    Smaller intensely

    heterochromaticnucleus

    Purple/lilac cytoplasm

    mix of basophiliafrom ribosomes andgrowing eosinophilia

    from hemoglobin

    Normoblast

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    Normoblast

    Smaller thanpolychromatophilicerythroblast

    Small, compact,

    intensely stainingnucleus that is gettingready to be extruded

    Eosinophilic cytoplasm

    due to abundanthemoglobin

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    Reticulocyte

    Immature RBC thathas polyribosomes

    Appear as polychrom-atophilic erythrocyteon blood smear

    When stained with aspecial (supravital)stain Reticulocyte

    Erythrocyte

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    Erythrocyte

    Smallest

    Eosinophilicdue tohemoglobin

    NONUCLEUS!

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    Sickle Cell Disease

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    Sickle Cell Disease Classic hemoglobinopathy

    Normal HGB is 2 2: -chain defects(Val->Glu)

    Reduced hemoglobin sickles inhomozygous

    8% of American blacks are heterozygous

    THALASSEMIAS

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    THALASSEMIASA WIDE VARIETY of diseases involving GLOBIN

    synthesis, COMPLEX genetics

    Alphaor betachains deficient synthesis

    involved Often termed MAJOR or MINOR, depending on

    severity, silent carriers and traits are seen

    HEMOLYSIS is uniformly a feature, a microcyticanemia

    A crew cut skull x-ray appearance may beseen

    RBC LAB

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    RBC LAB