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Endocrine Exam 2 > 26 - Hematopoiesis > Flashcards

26 - Hematopoiesis Flashcards

1
Q

What is hematopoiesis?

A

The formation of blood cells

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2
Q

What are the functions of hematopoiesis?

A
  • Provides the cellular elements (RBC’s and leukocytes) of the peripheral blood
  • This takes place in the bone marrow
  • Delivery of oxygen to the tissues + providing host cell defense
  • Replaces of 0.5 X 1012 cells/day (half trillion cells/day)
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3
Q

What are the different cells that hematopoiesis produces?

A
  • Lymphocytes
  • RBCs
  • Platelets
  • Granulocyes
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4
Q

What is the life span of the cells produced from hematopoiesis?

A
  • Lymphocytes – years
  • RBCs – 120 days
  • Platelets – 7 to 10 days
  • Granulocytes – 6 to 8 hours

Hematopoiesis needs to be tightly controlled due to distinct cell life spans ***

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5
Q

Describe the conundrum of highly produced cells and high population of cells

A

Given the fact that most of the cells you will see in peripheral blood will be RBCs, what would you think the most common cells would be in bone marrow? You would think RBCs, but this is not the case

Precursor cells of granulocytes will be the main cell type you will see being produced in the bone marrow because granulocytes turn over so much more frequently than RBCs do (a couple times each day!)

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6
Q

What are the characteristics of hematopoietic stem cells?

A

Characteristics

  • 0.1 - 0.01% of bone marrow cells (VERY small population in BM)
  • Gives rise to progenitor cells of all lineages
  • Highest proliferative potential of any hematopoietic cell type ***
  • Capable of self-renewal and differentiation ***
  • Multipotential
  • Can’t be identified morphologically
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7
Q

What are the two main processes that hematopoietic stem cells undergo?

A

Self-renewal and differentiation

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8
Q

What are bone marrow stromal cells?

A
  • Cell that have an important role in the maintenance and differentiation of hematopoietic cells
  • Examples: adipocytes, fibroblastoid cells and reticuloendothelial cells
  • All of these cells are connective tissue cells and create a different microenvironment for the hematopoietic cells to differentiate
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9
Q

How does the cell determine whether or not it binds to stromal cells?

A

If the hematopoietic cell is primitive (less differentiated), it will bind tightly to stromal bone marrow cells

If the hematopoietic cell is mature, there will be less binding to stromal cells

This phenomenon is due to the differential expression of cell adhesion molecules which regulate its binding activity

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10
Q

How important are bone marrow stromal cells?

A

VERY important

- Bone marrow stromal cells are one of the two things you NEED in order to have proliferation and differentiation

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11
Q

What is the purpose of cytokines in hematopoiesis?

A
  • Cytokines drive specific cell differentiation pathways
  • Progenitor cell cytokines (i.e. stem cell factor) act on immature cells
  • End-stage cytokines act on more differentiated cell types in order to induce lineage-specific differentiation
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12
Q

Which cytokines do you need to know?

A

There are three you need to memorize

1 - Granulocyte colony stimulating factor (G-CSF)
2 - Ereythropoietin (EPO)
3 - TGF-beta

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13
Q

How is granulocyte colony stimulating factor (G-CSF) used for the purpose of hematopoiesis?

A
  • G-CSF is released by macrophages at inflammatory sites
  • G-CSF will then enter the circulation and reach the bone marrow
  • Once G-CSF reaches the bone marrow, it induces the production and release of neutrophils to participate in the inflammatory process
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14
Q

How is erythropoietin (EPO) used for the purpose of hematopoiesis?

A
  • EPO is produced and released by “pretubular interstitial cells” found in the kidney in response to hypoxia
  • EPO then enters the circulation and reaches the bone marrow
  • Once in the bone marrow, EPO induces the production and release of RBCs
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15
Q

What inhibits EPO?

A

Erythropoietin (EPO) is inhibited by an increased oxygen partial pressure

When oxygen is high, there is not a need for more RBCs to deliver oxygen to the tissues

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16
Q

How is TGF-beta used for the purpose of hematopoiesis?

A

TGF-beta is actually used for the DOWNREGULATION of stem cell growth and differentiation

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17
Q

How does TGF-beta downregulate stem cell growth and differentiation?

A

TGF-beta decreases the number of cell surface receptors in the bone marrow which respond to cytokines which will induce growth and differentiation

TGF-beta does not directly block cytokines, but it downregulates the receptors so the cytokines are less effective in inducing growth and proliferation

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18
Q

How else are cytokines used (other than by the body’s natural regulation of hematopoiesis)?

A

They can be used CLINICALLY to manipulate hematopoiesis

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19
Q

How is granulocyte colony stimulating factor (G-CSF) used clinically?

A

G-CSF may sometimes be used before high-dose chemotherapy to stimulate the bone marrow to make more stem cells. Stem cells are a special type of blood cell from which all other blood cells are made. The stem cells are collected from the blood and stored. They can then be given back to you after high-dose chemotherapy treatment and will make new blood cells to replace those you have lost.

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20
Q

What are the basics for harvesting stem cells before chemotherapy by giving G-CSF?

A

Basics

  • Giving G-CSF mobilizes stem cells to blood
  • Harvest stem cells from blood
  • This is less invasive than taking bone marrow
  • There is a low chance of getting stem cells contaminated with tumor cells
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21
Q

What is the purpose of returning stem cells following chemotherapy?

A

Basics

  • Following chemo, returning stem cell swill stimulate granulopoiesis
  • This is useful because of chemotherapy-induced marrow suppression
  • This lowers the risk of infection and allows the patient to withstand more frequent chemotherapy
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22
Q

How can granulocyte monocyte colony stimulating factor (GM-CSF, another cytokine) be used clinically?

A
  • GM-CSF functions to increase myeloid cell (projenitor cell) recovery in bone marrow transplant patients
  • Myeloid cell = progenitor cell for granulocytes, monocytes, erythrocytes, or platelets
  • GM-CSF treatment is given to patients who receive a bone marrow transplant
  • It is more toxic than G-CSF because it can increase the risk of thrombosis (DVT) and capillary leak syndrome (edema and hypotension)
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23
Q

How is erythropoeitin (EPO) used clinically?

A

EPO can be used to treat anemia caused by renal insufficiency

EPO treatment can increase RBC mass in these patients

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24
Q

What are the two forms of bone marrow?

A
  • Yellow marrow

- Red marrow

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25
Q

Describe yellow bone marrow

A

Normally inactive and mainly found in adipose tissue

26
Q

Describe red marrow

A

Active and participating in hematopoiesis

27
Q

Describe the progression of bone marrow in terms of where it is located in the body throughout life

A
  • In the first few years of life, all bone marrow is red
  • By the age of 18, red marrow is found in the ribs, sternum and pelvis
  • Extramedullary hematopoiesis is possible
28
Q

What is extramedullary hematopoiesis?

A

Extramedullary hematopoiesis takes place in the spleen and liver when bone marrow is dysfunctional or unable to meet the demands of the body
- When the body is in dire need of some cells (i.e. RBCs), the body can actually make it in other places than the bone marrow - liver and spleen

29
Q

Describe an immature RBC

A

Rubriblast

  • Large cell size
  • High nucleus to cytoplasm ratio (lots of nucleus, little cytoplasm)
  • Nucleoli is present
  • Basophilic cytoplasm
30
Q

Describe a mature RBC

A

Erythrocyte

  • Smaller cell size
  • Lower nucleus to cytoplasm ratio (little nucleus, lots of cytoplasm)
  • No nucleoli
  • Larger cytoplasm
31
Q

What happens as a RBC matures?

A
  • Cell size decreases
  • Nuclear: the cytoplasmic ratio goes down because they get rid of some nuclei
  • Nucleoli go down in number and eventually disappear
  • The cytoplasmic staining will go from darker blue (immature) to lighter blue (mature) due to the decrease in RNA found in the mature erythrocyte
32
Q

What is the definition of erythropoiesis?

A

The formation or production of RBCs

33
Q

Describe when and where erythropoiesis occurs

A
  • Erythropoiesis starts in primitive RBCs in the embryonic yolk sac
  • Erythropoiesis continues in extrameduallary organs (i.e. liver, spleen)
  • Erythropoiesis predominates in the red marrow during late fetal development
34
Q

Describe the maturation sequence of RBCs

A
  • Stem cell
  • Rubriblast
  • Prorubricyte
  • Rubricyte
  • Metarubricyte
  • Reticulocyte
  • Mature erythrocyte
35
Q

What is granulopoiesis?

A

Production of cells in the granulocytic lineage, including neutrophils, eosinophils and basophils

36
Q

What is the sequence of development of granulopoiesis?

A
  • Stem cell
  • Myeloblast
  • Promyelocyte
  • Myelocyte
  • Metamyelocyte
  • BAND CELL ***
  • Granulocyte
37
Q

What is a band cell?

A

An “almost” but “not quite” mature granulocyte

- Remember granulocytes are cells like neutrophils eosinophils and basophils

38
Q

What do we call the situation where we will see more band cells in the circulation?

A

A “shift to the left”

39
Q

What accounts for a “shift to the left”?

A
  • A shift to the left means that we are seeing less mature neutrophils in the peripheral blood and more immature neutrophils (band cells)
  • This may signify that the bone marrow is having a problem keeping up with the demand of making granulocytes
  • This can happen in infection
  • The bone marrow is on overdrive and they are just trying to get them out as quickly as possible so they send them out as band cells knowing that by the time they reach the target site, they will be mature neutrophils
40
Q

What is the life span and life cycle of a granulocyte?

A
  • After release, granulocytes circulate for a few hours and then die
  • In the circulation, neutrophils will evenly distribute between two pools: circulating pool (in circulation) and marginating pool (in tissues)
  • A dynamic equilibrium is maintained between these two pools
41
Q

What is the role of splenic phagocytes?

A

They remove dead and dying granulocytes from the circulation

42
Q

What are monocytes?

A

Baby macrophages

“I want to be a macrophage when I grow up!”

43
Q

Describe the life of a macrophage

A
  • Macrophages develop from monocytes and are distributed throughout the body
  • The specific name of the macrophage is dependent upon the part of the body it is in
  • Monocytes circulate for approximately 8 hours then they enter the tissues and differentiate into macrophages
  • The lifespan of a macrophage is from months to years
44
Q

What are the names of different macrophages based on the tissue they are found in

A
  • Histiocytes = loose connective tissue
  • Kupffer cells = liver
  • Osteoclasts = bone
  • Microglial cells = nervous system
45
Q

What are the developmental stages of monocytes?

A
  • Stem cell
  • Monoblast
  • Promonocyte
  • Monocyte
  • Macrophage
46
Q

What is the definition of lymphopoiesis?

A

The production of cells in lymphocytic lingeage, including T lymphocytes, B lymphocytes or natural killer cells (NK cells)

47
Q

What are the maturation stages of lymphocytes?

A
  • Stem cell
  • Lymphoblasts
  • Prolymphocyte
  • Lymphocyte
48
Q

Describe the development of B lymphocytes and NK cells

A

B lymphocytes and NK cells develop entirely in the bone marrow and are released into the peripheral blood

49
Q

Describe the development of T lymphocytes

A

T lymphocytes take a different path
- T cells start out in the bone marrow, but they need the thymus to fully mature
- In the bone marrow, they exist as prothymocytes
- Prothymocytes are released into the peripheral blood to migrate to the thymus
- Once in the thymus, they are called thymocytes
- Within the thymus, these cells mature and differentiate into T lymphocyte subsets
- The vast majority of thymocytes that want to become mature T cells die in the thymus, only 2-5% actually become mature T cells
(due to positive and negative selection)
- Once T lymphocytes leave the thymus, most of them populate lymphatic organs ***

50
Q

What is thrombopoiesis?

A

The production of platelets (AKA thrombocytes)

Platelets are anuclear cytoplasmic remnants of magacaryocytes

51
Q

What is the role of platelets in hemostasis?

A
  • Limit bleeding

- Repair endothelium

52
Q

How are platelets (throbocytes) formed?

A
  • Megakaryocytes undergo endomitosis (nuclear mitosis without cytoplasmic division)
  • This mitosis process creates a large polyploid (32N) cell
  • This cell can undergo thrombopoiesis
53
Q

Describe the process of thrombopoiesis

A
  • Thrombopoiesis is stimulated by thrombopoietin
  • Thrombopoietin promotes the production of magakaryocyte precursor production
  • Thrombopoietin also stimulates endomitosis
54
Q

What is the maturation sequence of thrombocytes (platelets)?

A
  • Stem cell
  • Megakaryoblast
  • Promegakaryocyte
  • Megakaryocyte
  • Platelet
55
Q

Describe megakaryocytes

A
  • Megakaryocytes have long cytoplasmic extensions (really long) which constrict at various points and divide into fragments
  • There is a pinching off and breaking off to form platelets
  • This process has the potential to produce a LOT of platelets
  • Each magakaryocyte can form 100-1000 platelets
56
Q

Describe platelets

A
  • The lifespan of platelets is about 9 days
  • When platelets die they are phagocytized in the liver or spleen
  • There is an EMERGENCY reserve of platelets in the spleen ***
57
Q

What is an “absolute” cell count?

A
  • Provides the quantity of each cell type per unit volume

- This is the ACTUAL cell count

58
Q

What is a “differential” cell count?

A
  • A RELATIVE percent of each cell type
  • You will get a report with the percentage of each cell type
  • This means it is relative to the rest of the cell population
  • You will NOT know how many RBCs there are total
59
Q

What do you need to look at when assessing a patient?

A

LOOK AT BOTH ABSOLUTE AND DIFFERENTIAL COUNT ***

60
Q

How can you calculate the absolute cell type?

A

Absolute = total WBC count x % cell type

61
Q

What are the most common cell type in bone marrow?

A

Granulocytes

This is because the turnover rate is so high

RBC precursors are very low because they last a long time

62
Q

What percent of circulating RBCs are in the form of immature reticulocytes (precursor cells)?

A

1% *******

KNOW 1% for reticulocytes –> typically only 1 % of the RBCs in the periphery will be the immature form of reticulocytes ***

Endocrine Exam 2 (18 decks)

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