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Flashcards in Hematopoiesis Deck (32):
1

The marrow cavity houses the ....

developing blood cells

2

What is the cellular composition of the bone marrow?

  • composed of adipocytes and differentiating hematopoietic cells
    • present in varying proportions depending on age, during which cellularity declines
  • also contains “stromal” cells = mesenchymal stem cells (MSCs)
    • thought of as specialized fibroblasts
    • contribute physical support for hematopoietic cells in the marrow
    • nurture marrow processes by secreting growth factors

3

  • What can MSCs differentiate into?
  • What is their stem cell role?

  • MSCs are multipotent stem cells and differentiate into:
    • endothelial cells 
    • osteocytes  
    • bone marrow adipose tissue
    • hematopoietic cells (controversial)
  • In their stem cell role: 
    • MSCs may enter the circulation
    • taking up residence as multipotent adult stem cells in organs to mediate regeneration

4

  1. In the early embryo, hematopoiesis occurs first in the blood islands of the ____ ___, followed by the ____
  2. Blood production begins in the __________ of long and flat bones during the 5th month of prenatal life
  3. By age 20, fat infiltration causes the marrow of long bones to be referred to as ____________

  1. In the early embryo, hematopoiesis occurs first in the blood islands of the yolk sac, followed by the liver
  2. Blood production begins in the “red marrow” of long and flat bones during the 5th month of prenatal life
  3. By age 20, fat infiltration causes the marrow of long bones to be referred to as “yellow marrow

5

  1. Where is blood production after the age of 20?
  2. Where is a bone marrow biospy typically taken from?

  1. Hematopoiesis after age 20 ⇒ flat bones
  2. BMBx ⇒ posterior iliac crest

6

  1. How much of the body mass comes from blood cells? 
  2. What is the daily demand for: 
    • Erythrocytes
    • Granulocytes
    • Platelets

  1. 5% of total body mass 
  2. Daily demand: 
    • Erythrocytes ⇒ 1011 (100 billion)
    • Granulocytes ⇒ 1010 (10 billion)
    • Platelets ⇒ 1011 (100 billion)

7

A single, Go multipotent master stem cell in the bone marrow stroma gives rise to ....

  • hematopoietic stem cells (HSCs; syn = hemocytoblast) 
  • endothelial progenitor cells (EPCs)
  • mesenchymal stem cells (MSCs)

8

HSCs comprise only about _:_____ marrow cells

1:10,000

9

What is the hematopoeisis differentiation pathway?

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10

What is the CD for hemangioblasts?

CD34+

11

What are the immunohisto markers for HSCs?

  1. CD34+
  2. c-kit+ (CD117)
  3. Lin-

12

What is the marker for endothelial cells?

CD34+

13

  • What comes from the lymphoid progenitor?
  • What are the markers for these cells?

  • B cell (CFU-B; CD45+)
  • T cell (CFU-T; CD45+)

14

Which blood cells do not have CD45?

erythrocytes and megakaryocytes (platelets)

15

  • What comes from the myeloid progenitor?
  • What are the markers for these cells?

  • erythroid (CFU-E; CD45-)
  • granulocyte (CFU-G; CD45+)
  • monocyte (CD45+)
  • megakaryocyte (CFU-meg; CD45-)

16

What is the technique used to type and isolate cluster differentiation (CD) markers?

fluorescent-activated cell sorter (FACS)

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17

Definition of myeloid:

  1. "Pure" definition:
  2. Definition for heme/lymph course:
  3. M/E ratio:

  1. "Pure" definition:
    • any cell arising from the bone marrow
  2. Definition for heme/lymph course:
    • ​​cells arising from the granulocytic, monocytic, and megakaryocytic lineages
      • note that erythroid cells could be considered as well
  3. M/E ratio (myeloid to erythroid ratio):
    • Myeloid = non-lymphoid leukocytes

18

What are Colony Forming Units (CFUs) & Colony-Stimulating Factors (CSFs)?

  • CFUs are progenitors, which undergo colonial expansion under the influence of one or more protein factors termed CSFs
  • CSFs can be:
    • unipotent (induce 1 CFU)
    • mulitpotent (induce more than 1 CFU)

19

  • Pleuripotent CSFs ⇒
  • Unipotent CSFs ⇒ 

  • Pluripotent CSFs ⇒
    • Stem cell factor (SCF; syn = steel factor) 
  • Unipotent CSFs ⇒
    • Erythropoietin (epo)
    • Thrombopoietin (tpo)
    • Granulocyte Colony-Stimulating Factor (G-CSF)
    • Macrophage or monocyte colony-stimulating factor (M-CSF) 

20

Erythropoietin

  • What produces Epo?  
  • What is its function?
  • What is its clincal use?

  • secreted by kidney and liver cells
  • induce the erythroid colony- forming unit (CFU-E)
  • epo is used to treat many forms of anemia
    • most commonly in association with renal failure
  • also used as a performance-enhancing drug (PED) by athletes

21

Thrombopoeitin

  • What is its function?
  • What is its clinical use?

  • induces the proliferation and differentiation of the colony-forming unit for megakaryocytes (CFU-meg),
    • increased platelet production.
  • Recombinant forms are available for therapeutic use in patients with low platelet counts secondary to immune-mediated platelet destruction processes

22

Granulocyte Colony-Stimulating Factor (G-CSF):

  • What is its function?
  • What is its clincal use?

  • promotes differentiation of the neutrophil lineage (CFU-G)
  • clinically used to mobilize the release of CFU-G into the peripheral circulation in patients who have low neutrophil counts secondary to infection or chemotherapy

23

Macrophage or monocyte colony-stimulating factor (M-CSF or GM-CSF):

  • What is its function?

  • stimulates the production of approximately 1010 monocytes daily
  • monocytes enter the tissue spaces and differentiate into macrophages
  • M-CSF also induces macrophages to differentiate into osteoclasts, which are cells that degrade bone

24

What do you look for when determining WBC differentiation?

  1. Decreasing Cell Size
  2. Changes in (Cytoplasmic) Color
  3. Decreased Nuclear Size in Erythroid Cells
  4. Changes in Nuclear Morphology in Granulocytes
  5. Development of Specific Granules
  6. Condensation of chromatin

25

What happens to cell size during differentiation?

As differentiation ensues, the cells become smaller

26

Why are changes in cytoplasmic color significant?

  • Peripheral blood and bone marrow aspirate slides are stained with Wright-Giemsa 
  • Intense basophilia (blue) in the cytoplasm of early differentiating:
    • erythroid cells – proerythroblasts and basophilic erythroblasts
    • indicative of high nucleic acid concentration (i.e. globin mRNA) in the cytoplasm
  • As differentiation continues: 
    • mRNA diminishes
    • protein (hemoglobin) accumulates
      • causing the stain to become red (eosinophilic)

27

What happens to the nuclear size in erythroid cells?

  • Differentiation ensues, nuclei become smaller
  • Eventually, the nucleus is extruded prior to release of RBCs to the peripheral circulation

28

What are the changes in nuclear morphology in granulocytes as differentiation progresses?

Nuclear changes is granulocytes:

  1. Nuclei are initially round 
  2. Become progressively segmented
    • kidney-shaped (in metamyelocytes) ⇒ deeply indented (in band cells)
  3. Ultimately turn into multiple nuclear lobes
    • held together by nuclear segments as seen in segmented neutrophils
    • poly-morpho-nuclear leukocytes (PMNs)

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29

Describe the morphologic development of specific granules:

  • In the granulocytic series, primary granules (dark purple granules which are actually lysosomes) are present at the promyelocyte stage
  • As differentiation ensues, these primary lysosomal granules become obscured by secondary (specific granules)
  • Specific granules present at the myelocyte stage and beyond
    • Erythroid cells have no granules

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30

Describe the condensation of chromatin:

  • Nuclei in the most immature cells of the erythroid and granulocytic lineages have euchromatic (“open”) chromatin
  • As these cells mature, their chromatin becomes more condensed or heterochromatin (“closed”) 

31

Describe the general process of granulopoeisis:

Common myeloid progenitor ⇒ myeloblast ⇒ promyelocyte ⇒ myelocyte ⇒ metamyelocyte ⇒ band cell ⇒ granulocyte

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32

Describe the general process of erythropoeisis:

common myeloid progenitor ⇒ proerythroblast (pronormoblast) ⇒ basophilic erythroblast ⇒ polychromatic erythroblast ⇒ orthochromatic erythroblast (normoblast) ⇒ polychromatic erythrocyte (reticulocyte) ⇒ erythrocyte