Hematopoiesis Flashcards

1
Q

Where does hematopoiesis occur and what are they derived from?

A

Skull, sternum, ribs, vertebrae, pelvis and proximal femur, derived from hemopoietic stem cells

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2
Q

What two lineages come from hemopoietic stem cells?

A

Common lymphoid progentior CLP and common myeloid progenitor CMP

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3
Q

Where does hematopoiesis start during 1st trimester of development?

A

In yolk sac/umbilical vesicle, developed from hemangioblasts

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4
Q

Where does hematopoiesis continue during 2nd trimester and 7th month?

A

2nd trimester occurs in liver and then spleen, 7th month occurs in bone marrow

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5
Q

What are the main constituents of bone marrow?

A

Blood vessels, hematopoeitic cells, and sinusoids

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6
Q

Bone marrow has endothelial lining, discontinuous basement membrane and adventitial cells, what are these and what do they produce?

A

They are cells that provide support for developing blood cells and produce reticular fibers and cytokines

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7
Q

What lies in between sinusoids and what do sinusoids do in bone marrow?

A

They separate hematopoietic compartment and peripheral circulation, with cords in between

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8
Q

What are the first two steps for the bone marrow-sinusoidal system (new blood cells penetrating endothelium to enter blood circulation)? (2)

A
  1. Maturing blood cell/megakaryocyte process pushes against endothelial cell
  2. Fuses and pierce luminal plasma membrane (endothelial cell) forming a transitory opening
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9
Q

What occurs once a blood cell forms a transitory opening in an endothelial cell to enter the blood stream from a sinusoid in bone marrow? (2)

A
  1. Each blood cell/process squeezes through and enters sinusoidal lumen
  2. Endothelia cell repairs itselft and the opening closes (WHOLE PROCESS CALLED A TRANSCELLULAR EVENT)
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10
Q

What is special about red bone marrow (4)?

A

located in medullary cavity of young long bones/spongy

Hematopoietic cords are developing blood cells/megakaryocytes

Contains macrophages, mast cells and adipose cells

specific blood cells develp in their own nests/clusters

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11
Q

What is special about yellow bone marrow (4)?

A

Mainly adipose tissue

located in medullary cavity of adult bones (not active bone marrow)

In active bone marrow, you will see 50% adipose/50% hematopoietic tissue

Can always return to being red bone marrow

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12
Q

how do you calculate normal cellularity of bone marrow (ratio of hematopoietic cells to adipocytes)?

A

subtract individuals age from 100 and add -/+10%

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13
Q

What is the difference between hypo and hypercellular marrow?

A

Hypo: few blood forming cells found (like chemo)

Hyper: BM affected by hematopoietic cell tumors (leukemia)

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14
Q

What is the difference between a bone marrow aspirate and core biopsy?

A

Aspirate is not always accurate, mainly cells where core biposy scrapes bone and able to analyze bone architecture **better analyzation

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15
Q

How are hematopoietic stem cells regulated (3) and what produces the regulation (5)?

A

Regulated by
colony-stimulating factors (CSF)
Erythropoeitin (EPO) and Thrombopoietin (TPO)
Interleukins (cytokines) IL-3 IL-2 IL-6 etc
Endothelial, stromal, fibroblasts, lymphocytes, and macrophages produce these 3 groups

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16
Q

What do CMP and CLP express on their surface receptors and lineage restricted progenitors are derived from CMPs (common myeloid progenitor cells)?

A

Their receptors influence proliferation and maturation, as well as contain cytokines and colonystimulating factors CSFs

CMPs become granulocyte/monocyte progenitors (GMP) and megakaryocyte/erythrocyte progenitor (MEP/ErP)

17
Q

What cells are derived from GMPs (granulocyte/monocyte progenitor)?

A

Neutrophil progenitors
Eosinophil progenitors
Basophil progentiors
Monocyte progenitors

18
Q

What regulates erythropoiesis and what ‘influences’ or directs MEP->ErP?

A

Regulated by erythropoietin (EPO) acts on surface receptors ErP

EPO, IL-3, and IL-4 direct MEP to become ErP/CFU colony forming unit, then GATA-1 is needed

19
Q

What are the first two steps of erythropoeisis?

A
  1. ErPs become proerythroblasts, large spherical nucleus & cell, dark purple cytoplasm
  2. Proerythroblast becomes basophilic erythroblast, small nucleus, dark purple staining d/t lots of Hg
20
Q

What are the last 3 steps of erythropoiesis after proerythroblast is formed?

A
  1. Polychromatophilic erythroblast: acidophilic+basophilic/purple+pink stain cytoplasm, smaller nucleus
  2. Orthochromatophilic erythroblast (normoblast), acidophilic cytoplasm and dense nucleus, large than mature erythroblasts, **start to lose nucleus
  3. Polychromatophilic erythrocyte = reticulocyte, increased when high loss of blood, light purple stain no nucleus
21
Q

What regulates thrombopoiesis and what does the process make?

A

It makes platelets/ megakaryocytes for clotting, regulated by GM-CSF and IL-3 TPO growth factors to become MKP (progenitor) forms megakaryocyte (large nucleus and size)

22
Q

What are the steps for megakaryocyte to get into the blood in order to start platelet formation?

A

Thrombopoietin (TPO) produce in liver and kidney

  1. MKC too large cannot get to blood
  2. extends protoplatelets through opening in endothelia cells
  3. Platelet peirces through, breaking off when colliding with other things in circulation; go to site needed
23
Q

What is granulopoiesis, what growth factors make GMPs into NoP, EoP, and BaPs?

A

Granulopoiesis is the formation of neutrophils, basophils, monocytes, and eosinophils. Granulocyte/monocyte progenitor (GMP) use GM-CSF (colony stimulating factor) to make N/E/B progenitors

24
Q

What is special about eosinophil and basophil progenitors compared to neutrophil progentiros?

A

E and B have 6 steps, but only four are identifiable. E requres GM-CSF, IL3, and IL5m while B requires GM-CSF and IL3

25
Q

What are the first two steps in granulopoiesis?

A
  1. A myeloblast is formed from a progenitor large nucleus, 3-5 nucleoli, intensly basophilic
  2. Promyelocyte; large spherical nucleus w primary azurophilic granules (cytoplasm)
26
Q

What are the third and fourth steps in granulopoiesis after a promyelocyte is formed?

A
  1. Myelocyte; exhibits specific granules (pink)+azurophilic, nucelus indentation
  2. metamyelocyte; nuclear indentation deepens, pink out number azurophilic, give rise to band cells
27
Q

What is important to remember for granulopoiesis regarding the steps for neutrophil/basophil/eosinophil cells?

A

Neutrophil has 6 identifiable steps, basophil and eosinophil have only four (they all share the same 4 steps)

28
Q

What are band cells and where are they derived from?

A

In neutrophils, band cells are u-shaped nuclear cells from metamyelocytes, only identifiable in neutrophils

29
Q

What is the next indentifiable cell for eosinophils and basophils after metamyelocyte?

A

mature eosinophils and mature basophils

30
Q

Immature neutrophils enter a reserve pools in bone marrow, what comes from the reserve pool?

A

50% band forms will circulate through the endothelial wall
50% adhere to endothelial walls (marginated pool)
both provide reserve to become mature when needed

31
Q

When there is a sudden infection and the reserve granulocytes are used quicker than production, what occurs? (shift?)

A

Band forms, metamyelocytes and myelocytes enter the circulation causing a left shift! (towards immature)

32
Q

What occurs when there is a right shift in neutrophils?

A

When there is an increase of mature neutrophils due to overproduction (not commonly seen)

33
Q

What is the first step for formation of monocytes and what growth factors are needed?

A
  1. GMP differentiates into monocyte progentior cell (MoP), using PU.1, Egr-1, IL-3, GM-CSF (same as Neutrophil)
34
Q

What are the 2nd and 3rd steps for formation on monocytes?

A
  1. MoP becomes promonocyte; large cell, basophilic cytoplasm & large indented nucleus
  2. Monocyte forms from promonocyte, takes 55 hours, differentiate into macrophages using GM-CSF and M-CSF
35
Q

What is the first step of lymphopoiesis and what will be the end products?

A

Lymphopoiesis forms lymphocytes and NK cells, starting from HSC becoming CLP common lymphoid progenitor cells

36
Q

What are the final steps in lymphopoeisis?

A

lymphoblast forms; large cell divides 2/3 times

becomes lymphocyte; nuclei smaller, cell size decrease

37
Q

Where are T-lymphocytes produced and developed and what growth factors do they require?

A

Produce in bone marrow, developed in Thymus

GF: Ikaros, GATA-3

38
Q

Where are B-lymphocytes developed and what growth factors do they require?

A

Produced in bone marrow (bursa-equivalent organ) stay in bone marrow

GF: Ikaros Pax5