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Lecture 1: Hematopoiesis Flashcards

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1
Q

What is hematopoiesis?

A

Hematopoiesis is the formation of blood cells in the bone marrow of the [Pelvis, proximal femur, skull, sternum, ribs, vertebrae].

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2
Q

What are all cells derived from?

A

A single, pluripotent HSC (hematopoetic stem cells).

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3
Q

All cells are derived from a single, pluripotent HCS. What is this theory called?

A

Monophyletic theory.

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4
Q

What is the monophyletic theory?

A

The monophyletic theory says that all cells are derived from a single, pluripotent HCS.

HCS will divide into 2 common progenitor cells (common lymphoid progenitor cells and common myeloid progenitor cells).

Common myeloid progenitor cells (CMP) then divide into MEP (megakaryocyte/erythrocyte progenitor cells) and GMP (granulocyte monocyte progenitor cells).

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5
Q

HCS will divide into what?

A
  1. CLP (common lymphoid progenitor cells)- directly divide into lymphocytes.
  2. CMP (common myeloid progenitor cells)
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6
Q

What does CMP divide into?

A
  1. Granulocyte/monocyte progenitor cells (GMP)

2. Megakaryocyte/erythrocyte progenitor cells (MEP).

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7
Q

What are the phases of hematopoeisis, at the 1st trimester, 2nd trimester and 7th month?

A
  1. Hematopoiesis begins in the fetus in the 1st trimester in the umbilical vesicle (yolk sac).via hemangioblasts (progenitors of hematopoeitic and endothelial cells)
  2. Continues in the 2nd trimester in the liver (primarily) and spleen.
  3. During 7th month, the bone marrow becomes the primary site of hematopoiesis.
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8
Q

In the first trimester, where does hematopoiesis begin?

A

Umbilical cord (vesicle sac).

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9
Q

Where do hematopoietic islands develop from?

A

Hemangioblasts

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10
Q

What are hemangioblasts?

A

Hemangioblasts make hematopoietic and endothelial cells.

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11
Q

In the 2nd trimester, where does hematopoiesis continue to occur?

A
  1. Liver (primarily)

2. Spleen

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12
Q

During month 7, what becomes the primary site of hematopoeisis?

A

Bone marrow.

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13
Q

As we age, where do we see an increase in hematopoiesis?

A
  1. . Ribs
  2. . Sternum
  3. Vertebrae
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14
Q

What is bone marrow and what is it made up of?

A

Bone marrow is the tissue in bone that makes BC.

It is made up of:

  1. blood vessels
  2. hematopoetic cells
  3. sinusoids
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15
Q

What are sinusoids?

A

Sinusoids are fenestrated capillaries that are made up of [endothelial cells and adventitial cells] and have a discontinuous basement membrane, making the bone marrow porous.

Sinusoids are a part of bone marrow that separate the [hematopoietic compartment from peripheral circulation].

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16
Q

What are adventitial cells?

A

Adventitial cells incompletely cover sinusoids. They help to support developing BC by

  1. making reticular fibers
  2. secreting cytokines (CSFs, IL-5 and IL-7].
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17
Q

What lies in between sinusoids?

A

Hematopoietic cords

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18
Q

What type of system is the [bone marrow-sinusoid system]?

A

A closed system where newly made BC must escape the sinusoid by penetrating the endothelium so that it can enter circulation.

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19
Q

If the bone marrow-sinusoid system is a CLOSED system, how do newly made blood cells escape?

A
  1. A maturing BC or megakaryocye pushes against the endothelial cells of the sinusoid membrane.
  2. Fuses and pierces through the cell and forms an opening.
  3. Each blood cell must squeeze through to enter the lumen of the sinusoid.
  4. Afterwards, the cell will “Self-repair” and the opening closes to prevent immature cells from leaving,
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20
Q

Migration of BC across the bone marrow endothelium is what kind of event?

A

A transcellular event.

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21
Q

What are the 2 types of bone marrow?

A
  1. Red bone marrow

2. Yellow bone marrow

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22
Q

What is red bone marrow?

Where is it found?
What kind of cells if it made up of?
How do the cells organize?

A

Red bone marrow is an immature form found in the medullary cavity of long bones and spongy bone in young kids.

The hematopoietic cords are mainly developing BC and megakaryocyte (with some macrophages, mast and adipose cells)

Different types of blood cells will develop in clusters.

  • erythrocytes and megakaryocytes develop in clusters near the wall of the sinusoid.
  • granulocytes develop in clusters further from the wall.
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23
Q

The hematopoietic cords in red bone marrow are mainly what types of cells?

A

Developing blood cells and megakaryocytes.

Some macrophages, mast cells and adipose cells are present.

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24
Q

In red bone marrow, in what arrangement do blood cells develop?

A

They develop in clusters.

Erythrocytes and megakaryocytes develop in clusters near the wall of the sinusoids.

Granulocytes will develop in clusters further from the wall.

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25
What is yellow bone marrow?
Yellow bone marrow is the type predominately in adults bone. - Not as hematopoietically active. - So, mainly adipose cells. Yellow bone marrow has the ability to become hematopoietic again, by becoming red bone marrow.
26
How can yellow bone marrow become hematopoietic again (red bone marrow)?
HCS can repopulate.
27
As we age, we see a decrease/increase amount of adipose tissue compared to HCS.
Increase.
28
Active bone marrow contains what ratio of adipose and hemotopoetic tissue.
50:50 Active bone marrow is found in your 1. ribs 2. vertebrae 3. pelvis 4. shoulder.
29
What is the cellularity of bone marrow?
The ratio of HCS to adipocytes.
30
How can we find the cellularity of bone marrow?
Subtract a person age from 100 and add +/- 10%. Ex. 30 years old. 100-30= 70% +/- 10%.= 60-80%
31
What is the cellularity of bone marrow important for?
It is important in looking at the fx of bone marrow BIOPSYs.
32
What is hypocellular marrow?
Small number of HCS. | High number of adipocytes.
33
What is hypocellular marrow indicative of?
Aplastic anemia or someone going through chemotherapy.
34
What is hypercellular marrow?
This bone marrow has been infected by hemopoetic cell tumors. High number of HCS. Low number of adipocytes.
35
What is hypercellular marrow indicative of?
Acute myelogenous leukemia.
36
What is a bone marrow aspirate?
A needle is inserted in the skin until it hits bone. Particularly, the posterior part of the iliac crest. It is smeared and looked at. Unfortunately, this can fuck up the morphology of the cell.
37
What is a bone marrow core biopsy?
A needed it inserted in the bone and takes out a peice of INTACT bone marrow. This allows you to look at its architecture.
38
What controls proliferation and maturation of hematopoiesis?
Hematopoietic growth factors.
39
Where are hematopoietic growth factors made?
In bone marrow by 1. Endothelial cells 2. Stromal cells 3. Fibroblasts 4. Developing lymphocytes 5. Macrophages.
40
What are the 3 major groups of hematopoietic growth factors?
1. Colony-stimulating factors (CSF) 2. EPO (erythropoietin) and TPO (thrombopoietin) 3. Interleukins (cytokines)
41
HSC--> ?
1. CLP (common lymphoid progenitors) | 2. CMP (common myeloid progenitors)
42
CMP-->
gives rise to lineage-restricted progenitors 1. GMP - granulocyte/monocyte progenitors 2. MEP--> megakaryocyte/erythrocyte progenitors MEP)
43
CLP-->
- Lymphocytes (T cells and B-cells, which will make Plasma cells) - Natural killer cells
44
MEP wil give rise to what?
1. Megakaryocyte- committed progenitor cells (MKP, CFU-Meg) | 2. Erythrocyte- committed progenitor cells (ErP, CFU-E)
45
GMP (granulocyte/monocyte progenitor) will give rise to what
1. Neutrophil progenitors (NoP- CFU-G) 2. Eosinophil progenitors (EoP, CFU-Eo) 3. Basophil progenitors (BP, CFU-Ba) 4. Monocyte progenitors (MoP, CFU-M)
46
What is erythropoiesis?
The creation of RBC, which is regulated by erythropoietin (EPO).
47
When is EPO released?
When SpO2 levels are low.
48
Erythropoeisis process
CMP--> MEP--> ErP/CFU-E (erythropoietin-sensitive erythrocyte committed progenitors) MEP needs EPO, IL-3 and IL-4 for this process to occur. GATA-1 is needed for terminal differentiation.
49
CMP--> MEP requires what
EPO IL3 IL4
50
ErP are called what?
erythropoietin-sensitive erythrocyte-committed progenitors (ErP-CFU-E)
51
What is required for the terminal differentiation of MEP--> ErP
GATA-1
52
What do ErPs differentiate into?
Proerythroblast (pronormoblast)--> basophillic erythroblasts (basophilic normoblast)--> polychromatophillic erythroblast (polychromatophilic normoblast)--> orthochromatophilic erythroblast (normoblast)--> polychromatophilic erythrocyte (reticulocyte) PBPOP
53
What is a proerythroblast (pronormoblast)? Size? Cytoplasm?
Large cell with a 1-2 large, round nuclei. | Cytoplasm is basophilic, stains v purple.
54
What is a basophilic erythroblast (basophilic normoblast)?
Small nucleus. Cytoplasm has strong basophilia because ribosomes are creating hemoglobin. Accumulation of Hb gradually will change the staining reaction of the cytoplasm with eosin.
55
What is a polychromatophillic erythroblast? (polychromatophilic normoblast)
-Cytoplasm will stain acidophilic and basophilic, creating distinct purple and pink regions. Nucleus is smaller than basophilic erythroblast and heterochromatin can have a checkered pattern.
56
What is a orthochromatophilic erythroblast (normoblast)? Cytoplasm? Size? Divide?
Acidophilic cytoplasm increases (becomes more pink) and nucleus becomes denser. - it is slightly larger than a mature RBC - Will no longer divide - Nucleus is extruded and will go into sinusoids.
57
What is a polychromatophilic erythrocyte?
Reticulocytes. When stained, you can see a few polyribosomes making Hb. Reticulocytes make up 1-2% of our total RBC count and when number of RBC increase, reticulocytes increase as well.
58
__________ make up 1-2% of our RBC count.
Reticulocytes.
59
When the number of RBC increase, ______________ increase as well.
reticulocytes.
60
What is thrombopoiesis?
The formation of platelets from CMP.
61
Thrombopoiesis process
CMP--> MEP--> [via GM-CSF and IL3]--> MKP (CFU-Meg) | --> Megakaryocyte
62
What is a megakaryocyte?
Large cell with a non-lobed nucleus. Undergoes endomitoses.
63
What process to megakaryocytes undergo?
Endomitoses- divides, but does not split.
64
How are platelets formed?
Platelets are located on the peripheral cytoplasm of the megakaryocyte. As megakaryocytes squeeze through the endothelial cells of sinusoids, pieces of their processes (called proplatelets) are broken off to create platelets.
65
Where is thrombopoetin made?
LiVeR | KiDnEy
66
What is granulopoiesis?
The formation of granulocytes and monocytes from CMPs. CMPs--> GMPs via [GM-CSF and IL-3] to create ``` neutrophil progenitor (NoP, CFU-G) eosinophils progenitor (EoP, CFU-Eo) basophils progenitor (BaPs, BMCP) and monocytes (MoP, CFU-M) ```
67
What causes GMPs to differentiate into granulocytes and monocytes?
1. GM-CSF | 2. IL-3
68
Neutrophil progenitors (NoP) has how many identifiable stages?
6
69
EoPs and BaPs have how many identifiable stages?
They also have 6 stages but we cannot idenity any of them
70
Eosinophil progenitors require what?
GM-CSF IL-3 IL-5
71
Basophil progenitors requier
GM-CSF | IL-3
72
Stages of granulopoiesis
1. Myeloblast 2. Promyelocyte 3. Myelocyte 4. Metamyelocyte MPMM
73
Myeloblast Nucleus? Granules? Stain?
1st stage; earliest precursor - Large spherical nucleus with 3-5 nucleoli - No granules - Stains intensely basophilic
74
Promyelocyte Nucleus? Granules?
- 2nd stage - Large round nucleus - Start to make azurophilic granules that are not specific. - With each division, the number per cell will reduce
75
Myelocyte Nucleus? Granules?
3rd stage - Nucleus will begin to indent - Granules will start to become specific
76
Metamyelocyte
4th stage. - Nucleus indention deeps - Specific granules > azurophillic granules - Will become banded cells.
77
Which stage of granulopoeisis do specific granules begin to form?
3rd stage: myelocyte. Thus, at this stage we can identify 1. eosinophilic myelocytes 2. basophilic myelocutes 3. neutrophilic myelocytes.
78
What is the fate of metamyelocytes?
They become banded (stab) cells.
79
Band (stab) cells.
Banded cells have an elongated nucleus that begins to become multi-lobed. This is hard to see in eosinophil and basophil lineage. From here; mature neutrophils, mature basophils and mature eosinophils will begin to form.
80
What are mature neutrophils called?
Polymorphonuclear neutrophil | Segmented neutrophil
81
What is a neutrophil shift?
When there are too many IMMATURE neutrophils in the body, they will go into a reserve pool in the bone marrow for about 5 days. From that pool, 50% of bands forms will circulate and 50% will adhere to the endothelial wall (marginated pool). Both pools will act on demand.
82
What is a marginated pool?
Marginated pools are the immature neutrophils that adhere to the endothelial wall
83
What happens during severe infections?
Reserve granulocytes drain faster than we can replace them. Thus, [band cells, metamyelocytes and myelocytes] come enter circulation, causing a LEFT shift.
84
Left shift
an increase in the number of band cells, metamyelocytes and myelocytes in circulation. In response to infection
85
Right shift
an increase number of mature blood cells in circulation
86
How do monocytes develop?
GMP--> monocyte progenitor cell (MoP/monoblast) -for this to occur, we need [PU.1, Egr-1, IL-3 and GM-CSF] MoP-->promonocyte--> monocyte
87
What is a promonocyte?
Precursor to monocytes. They are a large cell with basophilic cytoplasm and large, indented nucleus.
88
How long does monocyte formation take?
55 hours; then, it is released into circulation in the blood.
89
What does monocyte turn into?
Once in the tissue, it will become a [MACROPHAGE] via GM-CSF and M-CSF.
90
Lymphopoiesis
Formation of [NK cells] [T-cells] [B-cells] from CLP.
91
What is the first identifiable progenitor of lymphoid cells?
Lymphoblast- a large cell that can divide 2-3 times into a lymphocyte.
92
Lymphoblast--> ?
Lymphocyte. As this occurs, nuclei and size of the cell becomes smaller, nucleoli disappears.
93
T-lymphocyte
Made in bone marrow. Develop in thymus. Creation requires Ikaros, GATA-3
94
B-lymphocyte
develop in bone marrow Creation requires Ikaros and Pax5.
95
Which granulocyte do specific granules begin to form?
myelocyte
96
Which granulocyte does the nucleus begin to indent?
myelocyte
97
Which granulocyte do we begin to develop non-specific granulocytes?
promyelocyte
98
Indentation deepens specific granules outweigh the azurophilic this will then start to make band cells.
Metamyelocyte
99
Metamyelocytes will then form what?
band cells- elongated and nearly uniform

Immunology (12 decks)

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