Hematopoiesis Flashcards
1
Q
____ is the controlled, continuous, regulated process of blood cell production.
A
Hematopoiesis
2
Q
Hematopoiesis deals with the following: ____.
A
- Cell renewal
- Proliferation
- Differentiation
- Maturation
3
Q
____ result in the formation, development, and specialization of all functional blood cells.
A
Hematopoiesis
4
Q
Blood cells produced through Hematopoiesis are released from the ____.
A
bone marrow
5
Q
A ____ is capable of self-renewal and directed differentiation into all required cell lineages.
A
Hematopoietic Stem Cell (HSC)
6
Q
Hematopoiesis in the developing human can be characterized as a ____ in specific sites that rapidly changes during development.
A
select distribution of embryonic cells
7
Q
Hematopoiesis in healthy adults is restricted primarily to the ____.
A
bone marrow
8
Q
During fetal development, the restricted, sequential distribution of cells is initiated in the ____ and then progresses in the ____, then to the ____, and finally resides in the ____.
A
- Yolk sac
- Aorta Gonad Mesonephros (AGM) region (mesoblastic phase)
- Liver (hepatic phase)
- Bone marrow (medullary phase)
9
Q
Stages of Hematopoiesis
A
- Mesoblastic Phase
- Hepatic Phase
- Medullary Phase
10
Q
Mesoblastic Phase
Hematopoiesis is considered to begin around ____.
A
19th day of gestation
11
Q
Mesoblastic Phase
Chief site
A
Yolk sac
12
Q
Mesoblastic Phase
Cells from the mesoderm migrate to the ___.
A
Yolk sac
13
Q
Mesoblastic Phase
Cells from the ____ migrate to the yolk sac.
A
mesoderm
14
Q
Mesoblastic Phase
Some of the cells form ____ in the central cavity of the yolk sac.
A
primitive erythroblasts
15
Q
Mesoblastic Phase
Type of cell produced
A
Erythroblast
immature or primitive RBC
16
Q
Mesoblastic Phase
____ surround the cavity of the yolk sac and eventually form blood vessels.
A
Angioblasts
17
Q
Mesoblastic Phase
The transient yolk sac erythroblasts are important in early embryogenesis to produce ____.
A
Hemoglobin
18
Q
Mesoblastic Phase
____ is needed for the delivery of oxygen to rapidly developing embryonic tissues.
A
Hemoglobin
19
Q
____ is a protein made up of 4 units of heme that is paired with a globin.
A
Hemoglobin
20
Q
Hemoglobin is made up of ____ units of heme and globin.
A
4
21
Q
What differentiates the mesoblastic phase from all the different phases of hematopoiesis?
A
It occurs intravascularly (within the developing blood cells)
22
Q
Mesoblastic Phase
The yolk sac can remain active up to ____ of gestation.
A
8 to 12 weeks
23
Q
____ are only present during the mesoblastic stage or embryonic life.
A
Embryonic hemoglobins
24
Q
Embryonic hemoglobins
A
- Gower I
- Gower II
- Portland
25
# **Which Embryonic Hemoglobin?**
2 epsilon + 2 zeta globin chains
Gower I
26
Gower I globin contents
* 2 Epsilon globin chains
* 2 Zeta globin chains
27
# **Which Embryonic Hemoglobin?**
2 alpha + 2 epsilon globin chains
Gower II
28
Gower II globin contents
* 2 Alpha globin chains
* 2 Epsilon globin chains
29
# **Which Embryonic Hemoglobin?**
2 zeta + 2 gamma globin chains
Portland
30
Portland globin contents
* 2 Zeta globin chains
* 2 Gamma globin chains
31
Cells of mesodermal origin migrate to the ____ and give rise to HSCs for definitive or permanent adult hematopoiesis during embryonic development.
Aorta-Gonad-Mesonephros (AGM) Region
32
The ____ was previously considered to be the only site of definitive hematopoiesis during embryonic development.
Aorta-Gonad-Mesonephros (AGM) Region
33
# **Hepatic Phase**
The hepatic phase of hematopoiesis beings at ____.
5 to 7 weeks of gestation
34
# **Hepatic Phase**
Types of cell produced
* Erythroblasts
* Granulocytes
* Monocytes
* Lymphoid cells
* Megakaryocytes
35
The ____ phase is characterized by recognizable clusters of developing erythroblasts, granulocytes, and monocytes.
Hepatic
36
# **Hepatic Phase**
Chief site
Liver
37
# **Hepatic Phase**
The peak production of cells occur at the ____.
3rd month of pregnancy
38
# **Hepatic Phase**
The decline phase occurs ____.
After the 6th month
39
# **Hepatic Phase**
Other active sites
Spleen, kidneys, thymus, and lymph nodes
40
# **Hepatic Phase**
The ____ is the predominant hemoglobin.
Hemoglobin F or Fetal Hemoglobin (HbF)
41
HbF globin content
* 2 Alpha globin chains
* 2 Gamma globin chains
42
# **Hepatic Phase**
Hemoglobins present
* Hemoglobin F or Fetal Hemoglobin (HbF)
* Hemoglobin A or Adult Hemoglobin (HbA)
43
2 Types of Hemoglobin A
* HbA1
* HbA2
44
# **Which type of HbA?**
95%
HbA1
45
# **Which type of HbA?**
2 alpha + 2 beta globin chains
HbA1
46
# **Which type of HbA?**
2-3%
HbA2
47
# **Which type of HbA?**
2 alpha + 2 delta globin chains
HbA2
48
% content of HbF in adults
1-2%
49
Medullary phase is also known as the ____.
Myeloid phase
50
# **Medullary (Myeloid) Phase**
Time
5 to 6 month of gestation
| **Rodak's:** Between fourth and fifth month
51
# **Medullary (Myeloid) Phase**
Chief site
Bone marrow
52
Why is hematopoiesis in the bone marrow termed as medullary hematopoiesis?
Because it occurs in the inner part of the bone cavity, which is the *medulla*.
53
# **Medullary (Myeloid) Phase**
Types of cell produced
* Hematopoietic stem cells
* Mesenchymal cells
54
During the myeloid phase, HSCs and mesenchymal cells migrate to the ____.
core of the bone
55
____, a type of embryonic tissue, differentiate into structural elements that support developing hematopoietic elements.
Mesenchymal cells
56
Measurable levels of growth factors are evident in ____ phase.
medullary
57
# **Medullary (Myeloid Phase)**
The principal source of production are the ____.
Flat bones (e.g. sternum)
58
At the end of the 24th week of gestation, the ____ will be the main site of hematopoiesis.
Bone marrow
59
When will the bone marrow be the main site of hematopoiesis?
At the end of 24th week of gestation
60
The ____ is responsible for the synthesis or production of cells.
Adult Hematopoietic Tissue
61
____ is where Lymphoid Development occurs.
Adult Hematopoietic Tissue
| Primary and Secondary Lymphoid Tissue
62
Primary Lymphoid Tissues
* Bone marrow
* Thymus
63
Secondary Lymphoid Tissues
* Lymph nodes
* Spleen
* Liver
* MALT
64
____ is where B cells and T cells are derived.
Primary Lymphoid Tissue
65
____ is where lymphoid cells respond to foreign substances.
Secondary Lymphoid Tissue
66
The ____ develops in the embryo by the hollowing out of the skeletal bone forming a central cavity.
bone marrow
67
The soft tissue inside the central cavity is called ____.
bone marrow
68
The bone marrow contains ____.
* Hematopoietic cells
* Stromal cells
* Blood vessels
69
Main function of bone marrow
Production and proliferation of blood cells
70
All blood formed elements ultimately develop from the undifferentiated and primitive precursor called ____.
Hematopoietic Stem Cell (HSC)
71
Hematopoietic stem cell developed from ____.
Hematopoietic cell
72
The bone marrow is ____ at birth.
red
73
In young adults, the marrow is about ____ active.
60-70%
74
The cell production usually happens in the ____.
flat bones
75
____ is the replacement from red to yellow bone marrow.
Retrogression
76
____ regulate the microenvironment of hematopoietic tissue so that we can produce cells.
Stromal cells
77
Kinds of Bone Marrow
* Red
* Yellow
78
# **Which Kind of Bone Marrow?**
Active
Red
79
# **Which Kind of Bone Marrow?**
Composed of hematopoietic cells, and macrophages
Red
80
The red marrow is composed of ____.
* Hematopoietic cells (developing blood cells and their progenitors)
* Macrophages
81
# **Which Kind of Bone Marrow?**
Components are arranged in extravascular cords
Red
82
The components of red bone marrow is arranged in ____.
extravascular cords
83
Hematopoietic cells will later on develop and mature in ____ within the cords.
niches
84
Usually at birth, the bone marrow is 100% ____.
red
85
Main functions of Red Bone Marrow
* Production of blood cells
* Iron storage
* B-cell development
86
# **Which Kind of Bone Marrow?**
Inactive (not capable of producing cells)
Yellow
87
# **Which Kind of Bone Marrow?**
Composed of adipocytes and undifferentiated mesenchymal cells
Yellow
88
The yellow marrow is composed of ____.
* Adipocytes
* Undifferentiated mesenchymal cells
89
# **Bone Marrow Cellularity**
Normal bone marrow in a stained smear
Normocellular
90
# **Bone Marrow Cellularity**
30-70% hematopoietic cells
Normocellular
91
# **Bone Marrow Cellularity**
____ is the abnormal increase in the production of cells.
Hypercellular (Hyperplasia)
92
# **Bone Marrow Cellularity**
More than 70% hematopoietic cells
Hypercellular (Hyperplasia)
93
# **Bone Marrow Cellularity**
____ is the abnormal decrease in the production of cells.
Hypocellular (Hypoplasia)
94
# **Bone Marrow Cellularity**
Less than 30% hematopoietic cells
Hypocellular (Hypoplasia)
95
# **Bone Marrow Cellularity**
There is very few or a total absence of hematopoietic cells
Aplastic (Aplasia)
96
The ____ supplies blood only for the bone marrow.
Nutrient Artery
97
The ____ provides nutrients both for the bone and for the bone marrow.
Periosteal Artery
98
Hematopoietic Microenvironment is also called ____.
Hematopoietic Inductive Microenvironment or Niche
99
____ functions in nurturing and protecting HSCs.
Hematopoietic Microenvironment
100
____ functions in the balance in quiescence, self-renewal, and differentiation of HSCs.
Hematopoietic Microenvironment
101
____ is responsible for supplying semifluid matrix.
Stromal Cells
102
The ____ is the semifluid matrix supplied by stromal cells.
Stroma
103
____ secrete extracellular matrix that serves as an anchor for the developing HSCs.
Stromal cells
104
The extracellular matrix secreted by stromal cells functions in ____.
* Anchoring
* Promote cell adhesion
* Regulate HSCs
* Maintenance of proteins
105
____ play critical roles in the regulation of HSCs for them to surive and be differentiated.
Stromal Cells
106
Stromal Cells
* Endothelial cells
* Adipocytes
* Macrophages
* Osteoblasts
* Osteoclasts
* Reticular cells
107
____ regulate the flow of particles, entering and leaving the hematopoietic spaces.
Endothelial cells
108
____ are essential for the secretion of various steroids that influence erythropoiesis, maintain bone integrity, and regulate the volume of bone marrow.
Adipocytes (fat cells)
109
Adipocytes (fat cells) secrete ____.
steroids
110
____ are important for phagocytosis and the removal of unwanted materials.
Macrophages
111
____ secrete cytokines which later on regulate hematopoiesis.
Macrophages
112
Macrophages secrete ____.
cytokines
113
____ are referred to as the bone-forming cells.
Osteoblasts
114
____ are mistaken as plasma cells.
Osteoblasts
115
Osteoblasts are sometimes mistaken as ____.
plasma cells
116
____ are referred to as the bone-resorbing cells or bone-destroying cells.
Osteoclasts
117
____ support the vascular sinuses and hematopoietic cells.
Reticular cells
118
Components of the Extracellular Matrix of the Marrow
* Fibronectin
* Collagen
* Laminin
* Thrombospondin
* Tenascin
* Proteoglycans
119
Between ___ years of age, adipocytes become more abundant and begin to occupy the spaces in the long bones.
5 to 7
120
Active red marrow sites in adult skeleton
* Skull
* Proximal ends of large bones
* Sternum
* Vertebrae
* Axial skeleton
* Iliac crest
121
____ is a comparison or numerical expression of the distribution of myeloid precursor *(granulocytes)* and erythroid precursor *(RBCs)*.
Myeloid to Erythroid Ratio (M:E)
122
Normal M:E Ratio
2:1 - 4:1
123
# **TRUE OR FALSE.**
In M:E ratio, myeloid precursors should be less than erythroid precursors.
False
| Myeloid > Erythroid
124
RBCs can survive in the body for ____.
120 days
125
WBCs stay in the blood for ____.
1 - 2 days
126
M:E ratio of infection
6:1
127
M:E ratio of leukemia
25:1
128
M:E ratio of myeloid hyperplasia
20:1
129
# **Marrow Differential**
**Cell Type:** Erythroblasts
**Range:**
18-24%
130
# **Marrow Differential**
**Cell Type:** Myeloblasts Type I
**Range:**
0-1%
131
# **Marrow Differential**
**Cell Type:** Myeloblasts Type II
**Range:**
0-2%
132
# **Marrow Differential**
**Cell Type:** Promyelocytes
**Range:**
1-4%
133
# **Marrow Differential**
**Cell Type:** PMNs and precursors
**Range:**
53-63%
134
# **Marrow Differential**
**Cell Type:** Monocytes
**Range:**
0-2%
135
# **Marrow Differential**
**Cell Type:** Eosinophils and precursors
**Range:**
1-3%
136
# **Marrow Differential**
**Cell Type:** Basophils and precursors
**Range:**
0-1%
137
# **Marrow Differential**
**Cell Type:** Lymphocytes
**Range:**
8-12%
138
# **Marrow Differential**
**Cell Type:** Plasma cells
**Range:**
0-2%
139
Medical practitioners usually count at least ____ in the bone marrow.
500 cells
140
Other Normal Marrow Cells
* Macrophages
* Mast cells
* Osteoblasts
* Osteoclasts
141
____ specimens are collected when there are hematologic disorders.
Marrow
142
Preferred site for marrow specimens
Posterior iliac crest
143
Occasionally preferred sites for marrow specimens
* Anterior iliac crest
* Spinal processes
* Vertebral bodies
* Sternum
144
Preferred sites for bone marrow specimen in newborns
Upper end of tibia
145
____ are used to check cellularity.
* Trephine biopsy
* Aspiration
146
____ is the needle used for Trephine biopsy.
Jamshidi needle
147
Jamshidi needle gauge
11
148
____ is the needle used for aspiration in bone marrow specimens.
University of Illinois Sternal Needle
149
____ is the blood cell production in hematopoietic tissue other than the bone marrow.
Extramedullary Hematopoiesis
150
____ occurs whenever the bone marrow cannot meet the physiologic needs of the body.
Extramedullary Hematopoiesis
151
When does extramedullary hematopoiesis occur?
* Whenever the hyperplasia cannot meet the physiological needs of the body.
* When there are infectious agents or pathologic myelofibrosis in the bone marrow.
152
Sites of Extramedullary Hematopoiesis
* Liver
* Spleen
* Lymph nodes
* Thymus
153
The ____ serves as the major site of cell production in the second trimester of fetal development.
Liver
154
The liver serves as the major site of cell production in the ____.
second trimester of fetal development
155
The ____ stores essential minerals and vitamins that are needed in the synthesis of DNA and RNA.
Liver
156
The liver stores essential minerals and vitamins that are needed in the synthesis of ____.
DNA and RNA
157
The ____ is often involved in blood-related diseases such as Porphyria.
Liver
158
____ is the defect in the enzymes involved in the synthesis of heme.
Porphyria
159
# **Extramedullary Hematopoiesis**
Functions of the Liver
* Protein synthesis & degradation
* CHO and Lipid metabolism
* Drug and toxin clearance
* Iron recycling and storage
* Hemoglobin degradation
160
The ____ is the largest lymphoid organ in the body.
Spleen
161
The ____ is essential for lymphopoiesis and phagocytosis.
Spleen
162
The spleen is essential for ____.
lymphopoiesis and phagocytosis
163
____ is known as the **"graveyard of the body"**.
Spleen
164
The ____ removes old and damaged blood cells.
Spleen
165
What can happen when the spleen is enlarged?
It can affect even the young and healthy cells
166
When does the spleen become enlarged?
When there is an increased need for the removal of unwanted cells
| **Ex.** Leukemia
167
Two methods of RBC removal by spleen
* Culling
* Pitting
168
During ____, the cells are phagocytized and all organelles are degraded.
Culling
169
During ____, macrophages of the spleen will remove RBCs as well as its inclusions.
Pitting
170
Functions of the Spleen
* Sequesters platelets (stores in case of emergency)
* Removal of unwanted/abnormal cells
171
Rate of blood received by the spleen
350 mL/min
172
Types of Splenic Tissue
* White pulp
* Red pulp
* Marginal zone
173
The ____ are follicles with germinal centers that contains lymphocytes and macrophages.
white pulp
174
The ____ are primarily composed of vascular sinuses that contains specialized macrophages.
red pulp
175
The ____ surrounds the white pulp and contains blood vessels, macrophages, and some hematopoietic cells.
marginal center
176
The ____ are bean-shaped structures located along the lymphatic capillaries.
Lymph nodes
177
Functions of Lymph Nodes
* Lymphocyte proliferation
* Initiation of specific immune response
* Filter unwanted substances
178
Regions of the lymph nodes
* Cortex
* Medulla
179
In which region of the lymph nodes are T-cells found?
Medulla
180
In which region of the lymph nodes are B-cells found?
Cortex
181
____ originated from endodermal and mesenchymal tissue.
Thymus
182
____ is responsible for the conditioning, maturation and development of T-cells.
Thymus
183
Function of Thymus
Conditioning, maturation and development of T-cells
184
Lobules of Thymus
* Cortex (peripheral zone)
* Medulla (central zone)
185
Two Cell Theories
* Monophyletic Theory
* Polyphyletic Theory
186
The ____ states that all blood cells are derived from a single progenitor cell called *Pluripotential Hematopoietic Stem Cell*.
Monophyletic theory
187
The monophyletic theory states that all blood cells are derived from a single progenitor cell called ____.
Pluripotential Hematopoietic Stem Cell
188
The ____ is the most widely accepted theory.
Monophyletic Theory
189
The ____ states that each blood cell is derived from its unique stem cell.
Polyphyletic Theory
190
The ____ states that all cells are derived from a pool of stem cells that are self-renewing.
Stem Cell Theory of Hematopoiesis
191
____ give rise to committed stem cells for each cell line.
Pluripotential and Multipotential Stem Cells
192
Characteristics of HSCs
* Self-renewing
* Pluripotent
* Capable of apoptosis
193
# **Which characteristic of HSC?**
They differentiate into one or another type of committed cell.
Self-renewing
194
# **Which characteristic of HSC?**
Multiple cells can be produced in one stem cell
Pluripotent
195
# **Which characteristic of HSC?**
Can reconstitute the hematopoietic system of a lethally irradiated host
Apoptosis
196
Pluripotent stem cell gives rise to two progenitor cells, the ____.
* Lymphoid stem cell
* Myeloid stem cell
197
Progenitor cells need ____ in order for them to be committed in producing a specific cell.
Growth factors (stimulants)
198
____ are formed after progenitor cell has been stimulated by a growth factor.
Colony-Forming Units (CFUs)
199
____ promote proliferation and differentiation of cells.
Colony-Forming Units (CFUs)
200
# **Identify the cell line based on the abbreviation**
CFU-GEMM
* Granulocyte
* Erythrocyte
* Megakaryocyte
* Monocyte
201
# **Identify the cell line based on the abbreviation**
CFU-E
Erythrocyte
202
# **Identify the cell line based on the abbreviation**
CFU-Meg
Megakaryocyte
203
# **Identify the cell line based on the abbreviation**
CFU-M
Monocyte
204
# **Identify the cell line based on the abbreviation**
CFU-GM
* Granulocyte
* Monocyte
205
# **Identify the cell line based on the abbreviation**
CFU-BASO
Myeloid to basophil
206
# **Identify the cell line based on the abbreviation**
CFU-EO
Myeloid to eosinophil
207
# **Identify the cell line based on the abbreviation**
CFU-G
Myeloid to neutrophil
208
# **Identify the cell line based on the abbreviation**
CFU-pre-T
T-lymphocyte
209
# **Identify the cell line based on the abbreviation**
CFU-pre-B
B-lymphocyte
210
Stem Cell Cycle Kinetics
* 2.5 billion erythrocytes
* 2.5 billion platelets
* 1 billion granulocytes
* 1:1000 nucleated blood cells
211
Earliest identifiable stem cells
* CD34+
* CD38-
* HLA-DR
* Thy1
* Lin-
212
loss of "stemness"
CD38 and HLA-DR
213
committed myeloid progenitors
CD33 and CD38
214
T-lymphoid progenitor cells and natural killer cells
CD7
215
B-lymphoid progenitors
CD19
216
Cytokine with positive influence
* Erythropoietin (EPO)
* Thrombopoietin (TPO)
* Granulocyte CSF (G-CSF)
* Granulocyte-macrophage CSF (MG-CSF)
* Interleukins (1,3,6,7,9,11)
* KIT Ligands (KITLG)
* Tyrosine kinase 3 (FLT3 TG)
217
Cytokines with negative influence
* Transforming Growth Factor-β
* Tumor Necrosis Factor-α
* Interferons
218
Cytokine functions
* Prevent precursor cell from dying by inhibiting apoptosis
* Stimulate stem cells to divide
* Stimulate cell production
* Regulate differentiation
