Hematopoetic system: platelet

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Hematopoetic system: platelet
2013-07-23 14:39:05

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  1. Blood liquid contains
    plasma and serum
  2. plasma vs serum

  3. Different type of plasma proteins
  4. blood cells embryology
    3 WEEKS: Yolk Sac (Primitive stem cells)

    • 3rd MONTH: Stem cells migrate to the  LIVER which is the chief site of blood cell
    • formation until birth.
    • 4th MONTH: Stem cells migrate to the bone
    • marrow and commence hematopoesis.

    BIRTH: Bone marrow is the sole source for hematopoesis.
  5. The main source of blood cell in adult
    the bone marrow
  6. Bone Marrow
    • nProvides
    • the microenvironment for the orderly proliferation, differentiation and release
    • of blood cells.

    • nIn
    • a normal adult the marrow cavity includes ends of long bones
  7. Blood  supply to the bone
    • Blood
    • supply.  1. Nutrient artery (enters at
    • the center of the bone) -2. Medularly artery – 3. radial artery – 4. cortical
    • capillary – 5. endosteal capillary – 6. medullary vascular sinuses – 7. central sinus – 8. efferent vein.
  8. nCommon
    Lymphoid stem cell
    • -Pro
    • T-cells

    • -Pro
    • B-cells

    • -Natural
    • Killer cells
  9. nCommon
    myeloid stem cell


    • -Granulocyte/
    • macrophage

  10. Pluripotent
    Stem Cell produces
    common lymphoid stem cell and common myeloid stem cell
  11. Hypercellular bone marrow
    inc cell in bone marrow
  12. Erythropoesis is regulated by
    • nErythropoietin , a hormone that is
    • synthesized in the kidney.
  13. Nutrients
    required for red cell production include
    • Iron,
    • B-12, Folate
  14. Red cell maturation happen in
    peripheral blood
  15. RBC morphology
    • biconcave
    • discs with an average diameter of 7.2 µm
  16. RBC composition
    • na
    • lipid bilayer  under which is the protein
    • cytoskeleton the main being spectrin.
  17. RBC fxn
    • They
    • transport oxygen to peripheral tissues
  18. RBC's termination
    • Normal  life span is 120 days and senescent red cells
    • are removed from circulation by the spleen and liver
  19. Red
    cell development
    • As the red cells mature they lose
    • the nucleus and become hemoglobinized

    • and then enter the circulation.
    • Acute blood loss in the presence of a normal

    • bone marrow can result in
    • hyperplasia of the red cell precursors and lead

    • to increased immmature
    • red cells in  the circulation  (reticulocytes)
  20. The
    • an
    • immature erythrocyte with residual ribosomal RNA
  21. reticulocyte - normal range
    • 0.5
    • to 1.5% of reticulocytes refers to a normal, healthy person
  22. If
    the patient is anemic and the marrow response is healthy, reticulocyte lvl
    • n,
    • the % should be much higher, up to 10X higher %.

    • 1 %
    • reticulocyte count would mean the marrow is not responding to the anemia
  23. RBC membrane
  24. 3 CBC value of RBC
    • Hb
    • RBC count 
    • PCV - packed cell volume or hematocrit
  25. microcytic
    small RBC
  26. macrocytic
    large RBC
  27. hypochromotic
  28. anisocytosis
  29. poikylocytosis
  30. Classification
    of Anemias
    pathology and morphology
  31. Classification
    of Anemias - pathology
    • 1.Decreased
    • red cell production

    • 2.Increased
    • red cell destruction (hemolysis)

    • 3.Blood
    • Loss , acute or chronic
  32. Classification
    of Anemias - morphology
    • 1.Microcytic
    • (iron deficiency,  thalassemia)

    • 2.Macrocytic
    • (folate or B12 deficiency)

    • 3.Normocytic
    • but with abnormal shapes (hereditary spherocytosis, sickle cell disease)
  33. RBC disorder - anemia
    • nIs defined as reduced oxygen
    • carrying capacity of blood which stems from a reduction in the total
    • circulating red cell mass to below the normal amounts. 
    • nThis results in lower hemoglobin (Hb)
    • and Hematocrit
  34. Anemia
    due to decreased red cell production
    • Nutritional
    • defects:
    • –Iron deficiency
    • –B12/ Folic Acid deficiency ( megaloblastic
    • anemia)

    • nBone
    • marrow failure: Aplastic anemia

    nErythropoetin deficiency: Renal failure

    • nDisorders
    • of globin synthesis: thalessemia
  35. Transferrin
    • Transport
    • protein for iron
  36. Ferritin
    • Storage
    • form of iron, levels reflects the iron stores in the body
  37. TIBC
    • nThe amount of iron that the
    • transferrin could bind in a fully saturated state; TIBC is high when serum iron
    • is low.
  38. nMost
    common form of nutritional deficiency
    iron deficience anemia
  39. nthe
    best indicator of the body iron stores
    • Serum
    • ferritin
  40. Iron
    Deficiency Anemia cause
    • ndietary,
    • malabsorption due
    • to sprue and
    • celiac disease, chronic blood loss

    • nResults
    • in hypochromic microcytic anemia
  41. Iron absorption
    • nIn
    • the duodenum iron is absorbed into the epithelial cells Divalent Metal
    • Transporter (DMT)
  42. Ferroportin
    • nfound
    • in the epithelial cells and macrophages releases the iron from the enterocytes
    • into hepatic portal system
  43. Hepcidin peptide hormome
    • nproduced
    • by the liver major role in iron homeostasis

    • ninhibits
    • secretion of ferroportin hence inhibits iron absorption
  44. Juvenile
    nHepcidin mutation or hemojuvelin mutation
  45. Response
    to iron deficiency in order of occurrence
    • 1.Decreased
    • serum ferritin is the first response to iron deficiency

    • 2.Decreased
    • % saturation of transferrin

    • 3.Decreased
    • serum iron

    • 4.Decreased
    • hemoglobin

    • 5.Microcytic
    • red cells (MCV <80)

    • 6.Hypochromic
    • red cells
  46. Hemosiderine - histological slide
    • a
    • visible brown
    • pigment stored in macrophages in the liver,
    • spleen and  bone marrow
  47. Lab finding - Iron deficiency
    • dec serum iron 
    • inc TIBC
    • <10% SAt
    • Ferrintin
  48. Lab finding- anemia of chronic disease
  49. Iron deficiency vs anemia of chronic disease
  50. hypochromic microcytic anemia
  51. Clinical presentation in iron deficiency
    Fatigue, breathlessness

    Pica; persistent compulsive desire to ingest certain food or non-edible items like ice, clay, plaster.

    Sore mouth, angular stomatitis, palor
  52. vitamins that are required for DNA synthesis

    Deficiency leads to...?
    Both B12 and Folic Acid 

    Megaloblastic anemia
  53. MEgaloblastic anemias - pathogenesis & hallmark
    • Deficiency leads to impairment in
    • DNA synthesis which results in delay in nuclear maturation and cell division in
    • comparision to the cytoplasmic elements hence nuclear to cytoplasmic asynchrony effecting all cell lineages. 

    Hallmark is the presence of megaloblasts
  54. MEgaloblastic anemia - bone marrow finding
    Normal cellularity in adults 40-60%. In megaloblastic anemia bone marrow is hypercellular with increased megaloblasts

    All hematopoetic lineages show nuclear to cytoplasmic dyssynchrony.
  55. Megaloblastic anemia - peripheral smear finding
    macrocytic anemia (MCV >100fL)  and  hypersegmented neutrophils
  56. Vitamin B12 -  dietary source
    • Abundant in all animal products and
    • is resistant to cooking and boiling.
  57. common cause of B12 deficiency
    pernicious anemia
  58. Dietary B12 deficiency confined to
    strict vegan
  59. Pernicious anemia - cause
    • Vitamin B12 deficiency resulting from inadequate gastric production or defective
    • function of intrinsic factor (IF).

    • Intrinsic factor  secreted from the parietal
    • cells of the stomach that forms a complex with B12 that attaches to the epithelial intrinsic factor receptors present in the ileum which leads to the absorption of Vitamin B12.

    The absorbed B12 is bound to the transport protein transcobalmin II which delivers it to the liver and other parts of the body.
  60. Causes for Intrinsic factor deficiency
    autoimmune and malabsorption
  61. Causes for Intrinsic factor deficiency - autoimmune
    antibodies against the parietal cells

    antibodies against IF-B12 complex.

    occurrence of PA in patients with other autoimmune conditions such as RA, Diabetes, Hashimoto thyroiditis.
  62. Causes for Intrinsic factor deficiency- Malabsorption
    due to gatrectomy, and other small bowel disorders such as Whipple disease, Crohn’s Disease, tropical sprue.
  63. Folic Acid
    Sources: uncooked fruits and vegetables

    Food folates are in the polyglutamate forms and must be split to monoglutamate for absorption in proximal third of the small intestine.

    Within cells the monoglutamate form is converted into tetrahydrofolate which is involved in the synthesis of purines and pyrimidines (DNA synthesis)
  64. Causes of Folic Acid deficiency
    Diets poor in fresh fruits and vegetables

    Alcoholics; alcohol interferes with folate metabolism

    Increased metabolic needs: pregnancy and lactation

    Drugs: anticonvulsants, antimicrobials, methotrexate

    Malabsorption: Celiac disease and Tropical Sprue
  65. Lab findings for B12 and Folic Acid deficiency
    Peripheral blood smear- Macrocytic anemia (MCV > 110), hypersegmented neutrophils (> 5 nuclear lobes)

    Bone marrow: Hypercellular, megaloblastic changes, erythroid hyperplasia
  66. Response to B12 treatment after therapy in a B12 deficient includes
    Increase in reticulocyte count within the first week

    Disappearance of hypersegmented neutrophils in 2-3 weeks
  67. Anemia of Chronic Disease - cause
    Chronic infections, – TB, osteomyelitis

    Chronic immune disorders- Rheumatoid arthritis, regional enteritis

    Neoplasms- lymphoma, carcinoma
  68. Anemia of Chronic Disease - pathogenesis
    Increased interleukins (IL) which inhibit the release of iron from the stores, decrease the responsiveness of the bone marrow to erythropoetin.

    In response to inflammatory cytokines liver produces Hepcidin, which suppresses ferroportin from releasing iron from the enterocytes and macrophages.

    • Inflammatorycytokines also blunts bone marrow response to erythropoetin
    • SerumFerritin levels are high, TIBC is low

    Reticulocytecount is low
  69. Red cell membrane proteins and fxn
    Ankyrin, spectrin, protein 4.2, band 3

    • Function
    • - Vertical interactions:
    • - Perpendicular to the red cell membrane
    • - Stabilize the lipid bilayer
  70. Aplastic Anemia
    • Trilineage bone marrow hypoplasia due to
    • constitutional and acquired causes.

    Presentation; Pancytopenia (peripheral blood counts for all three lineages is decreased), bone marrow hypoplasia (cellularity < 10%).

    Clinical: Anemia, bleeding, infections.
  71. Aplastic Anemia - cause
    Idiopathic: Most common

    Infections: Parvovirus, Hepatitis, HIV1, Influenza, EBV

    Drugs: Chloramphenicol, chemotherapy, sulfonamides, anticonvulsants

    Genetic: Fanconi’s anemia, Familial aplastic anemia, dyskeratosis congenita

    Others: Paroxysmal nocturnal hemoglobinuria, pregnancy, immune disorders.
  72. RBC membrane - lipid layer
    • The lipid bilayer in the red cells have an outer half that is enriched by phosphatidyl choline and sphingo myelin 
    • The inner half of the lipid bilayer is enriched by phosphatidyl serine and phosphatidyl ethanolamine
  73. Red Cell Membrane Disorders
    nHereditary Spherocytosis

    nHereditary Elliptocytosis

    nSouth Asian Ovalocytosis

    nAcanthocytosis and related disorders

    nRh deficiency syndrome
  74. Most common RBC membrane disorder
    nHereditary Spherocytosis

    nHereditary Elliptocytosis
  75. Hereditary
    Spherocytosis - etiology
    nDeficiency of one of the cytoskeleton proteins that keep the lipid bilayer intact.

    • nThe ensuing destabilisation of the lipid bilayer leads to
    • release of lipids from the membrane as microvesicles and surface area deficiency.

    nHence RBC’s become non deformable
  76. Hereditary
    Spherocytosis - favorable tx
  77. Hereditary
    Spherocytosis - genetic cause and presentation
    • nIn
    • most patients (70%) autosomal dominant inheritance

    Most prevalant in Northern European decent

    • Presents
    • as hemolytic anemia
  78. Hereditary
  79. Hereditary
    Spherocytosis - dx - clinical feature
    anemia, Jaundice, splenomegaly
  80. HereditarySpherocytosis - dx - lab finding
    • Hemoglobin-
    • Low

        MCV- Low normal

        MCHC- High

        RDW- High

    •     Hemolysis- LDH, reticulocytosis,
    • bilirubin

        Osmotic fragility test- gold standard
  81. Gold stand for hereditary spherocytosis
    Osmotic fragility test
  82. Hereditary elliptocytosis - common in ?/confer resistance to / major defect
    • nCommon
    • in African and Mediteranean
    • decent

    • nConfers
    • resistance to malaria

    • nMajority
    • of defect is due to spectrin
    • defect
  83. acanthocytosis
    spike-like projecction
  84. Stomacytosis
    elongated shaped plasma
  85. Pyropoikilocytosis
  86. Red cell Enzyme disorder - G6PD
    housekeeping  gene that is essential for basic cellular functions

    G6PD generates NADPH which is utilized for glutathione reduction. Reduced glutathione restores hemoglobin in the soluble state and prevents oxidative damage.
  87. G6PD deficiency leads to-
    • nHemolysis
    • in the presence of oxidant stress.

    • nMorphologic
    • sequel of the oxidative damage to hemoglobin is –Heinz bodies.

    • nBite
    • cells are rarely seen

    • nG6PD
    • deficiency confers protection against malaria
  88. G6PD - gene encoded/dx/tx
    Gene for G6PD is encoded on the X chromosome

    Laboratory diagnosis- Spectrometric analysis

    • Treatment:
    • Avoidance of oxidant stressors medications, fava beans and infections.
  89. Pyrimidine 5’Nucleotidase: genetic/fx
    Inherited as an autosomal recessive fashion

    Participates in the degradation of RNA in the reticulocytes
  90. the only red cell enzyme deficiency that has a specific consistent
    morphological abnormality-basophilic stippling
    • Pyrimidine
    • 5’Nucleotidase
  91. Basophilic stippling - definition and cause
    Ribosomal RNA that is precipitated during staining

    Causes heavy metal poisoning, sideroblastic anemias, thalessemia