HEMA DAY 2 Flashcards
1
Q
This refers to a continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation, and maturation.
A
Hematopoiesis
2
Q
MESOBLASTIC or YOLK SALC PHASE
- Begins around __th day of embryonic development after fertilization
- Early in embryonic development, cells from the mesoderm migrate to the yolk sac
- Formation of _________________ in the central cavity of the yolk sac
- The first lineage produced from a developing embryo is the _____.
- Stage for ____________________
- These primitive but transient yolk sac erythroblasts are important in early embryogenesis to produce hemoglobin
1.
2.
3.
A
MESOBLASTIC or YOLK SALC PHASE
- Begins around __th day of embryonic development after fertilization
- Early in embryonic development, cells from the mesoderm migrate to the yolk sac
- Formation of primitive erythroblast in the central cavity of the yolk sac
- The first lineage produced from a developing embryo is the RBC.
- Stage for embryonic or primitive hematopoiesis
- These primitive but transient yolk sac erythroblasts are important in early embryogenesis to produce hemoglobin (Gower-1, Gower-2, and Portland)
1. Gower-1
2. Gower-2
3. Portland
3
Q
_______________ are primitive hemoglobins formed by immature erythrocytes in the yolk sac. These hemoglobins include Gower I, Gower II, and Portland types. They are found in the human embryo and persist until approximately _________ of gestation
A
Embryonic hemoglobins are primitive hemoglobins formed by immature erythrocytes in the yolk sac. These hemoglobins include Gower I, Gower II, and Portland types. They are found in the human embryo and persist until approximately 12 weeks of gestation
4
Q
GLOBIN CHAIN COMBINATION
2 epsilon + 2 zeta
A
Gower 1
5
Q
GLOBIN CHAIN COMBINATION
2 alpha + 2 epsilon
A
Gower 2
6
Q
GLOBIN CHAIN COMBINATION
2 zeta + 2 gamma
A
Portland
7
Q
This is when the RBC lineage is formed
A
Mesoblastic phase
8
Q
This is when the WBC and platelets start to form
A
Hepatic phase
9
Q
This term refers to the hematopoiesis where all blood cells are allowed to form
A
Definitive hematopoiesis
10
Q
HEPATIC PHASE
- The hepatic phase of hematopoiesis begins at ___ to ___ week of gestation
- By the second month of gestation, the _____ becomes the major site of hematopoiesis
- Characterized by recognizable clusters of developing _____________, ______________, and ______________ colonizing the ______________, __________, __________, __________, and ultimately the _____________ in the final medullary phase.
- Production of ________________ also begins during the hepatic phase
- Hematopoiesis during this phase occurs __________, with the liver remaining the major site of hematopoiesis during the second trimester of fetal life
- During the hepatic phase, ______________ is the predominant hemoglobin, but detectable levels of ______________ may be present
- Stage for the beginning of ____________ with a decline primitive hematopoiesis in the yolk sac
A
HEPATIC PHASE
- The hepatic phase of hematopoiesis begins at 5th to 7th week of gestation
- By the second month of gestation, the liver becomes the major site of hematopoiesis
- Characterized by recognizable clusters of developing erythroblasts, granulocytes, and monocytes colonizing the fetal liver, thymus, spleen, placenta, and ultimately the bone marrow space in the final medullary phase.
- Production of megakaryocytes also begins during the hepatic phase
- Hematopoiesis during this phase occurs extravascularly, with the liver remaining the major site of hematopoiesis during the second trimester of fetal life
- During the hepatic phase, fetal hemoglobin (Hb F) is the predominant hemoglobin, but detectable levels of adult hemoglobin (Hb A) may be present
- Stage for the beginning of definitive hematopoiesis with a decline primitive hematopoiesis in the yolk sac
11
Q
HEMOGLOBIN DETERMINATION
2 alpha + 2 gamma
A
Hb F
12
Q
Site of adult hematopoietic tissue
A
Bone marrow (major site), lymph nodes, spleen, liver, thymus
13
Q
Primary site of adult hematopoiesis
A
Bone marrow
14
Q
Secondary site of adult hematopoiesis
A
Liver and spleen
15
Q
Reference range for normal adult Hgb is:
__-__% HbA
__-__% HbA2
__% HbF
A
Reference range for normal adult Hgb is:
- 95- 97% Hb A
- 2 to 3% Hb A2
- ≤1% Hb F
16
Q
MEDULLARY (MYELOID) PHASE
- In the ______ of gestation or prior to the ______ of fetal development, hematopoiesis begins in the bone marrow cavity
- By the end of ________ of gestation, the bone marrow becomes the primary site of hematopoiesis.
- Occurs during the _______ and ________ trimester. It is the major hematopoiesis during 3rd trimester
- Measurable levels of erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and hemoglobins F and A can be detected
- By age ___, red marrow is found only in the vertebrae, ribs, sternum, skull bones, pelvis, and to some extent the proximal epiphyses of the femur and humerus.
- In adult hematopoiesis, the red marrow is found only in the:
1.
2.
3.
4.
• Note: ______ and other flat bones are the principal source of production in adult
A
MEDULLARY (MYELOID) PHASE
- In the 4th month of gestation or prior to the 5th month of fetal development, hematopoiesis begins in the bone marrow cavity
- By the end of 24 weeks of gestation, the bone marrow becomes the primary site of hematopoiesis.
- Occurs during the second trimester and third trimester. It is the major hematopoiesis during 3rd trimester
- Measurable levels of erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and hemoglobins F and A can be detected
- By age 18, red marrow is found only in the vertebrae, ribs, sternum, skull bones, pelvis, and to some extent the proximal epiphyses of the femur and humerus.
- In adult hematopoiesis, the red marrow is found only in the:
R-Ribs
S-Sternum, Shoulder blade, Skull
V-Vertebrae
P-Pelvic bone, Proximal end of long bones (femur and humerus)
• Note: Sternum and other flat bones are the principal source of production in adult
17
Q
Usually seen during compensatory state such in case of BM failure, certain diseases, malignancies and infection
A
Extramedullary hematopoiesis
18
Q
Hepatomegaly and splenomegaly occurs in __________
A
Hepatomegaly and splenomegaly occurs in medullary hematopoiesis
19
Q
Hepatomegaly and splenomegaly does not occur in __________
A
Hepatomegaly and splenomegaly does not occur in medullary hematopoiesis
20
Q
Cells is present in the first few hours after an ovum is fertilized; most versatile stem cell; can develop into any human cell type; development from embryo into fetus
A
Totipotential stem cell
21
Q
Cells present several days fertilization; cannot form into a fetus
A
Pluripotential stem cell
22
Q
Derived from pluripotential stem cells; can be found in adults, but are limited to specific types of cells to form tissues
A
Multipotential stem cell
23
Q
This refers to the theory that all blood cells are derived from a single progenitor stem cell — pluripotent hematopoietic stem cell; Most widely accepted theory
A
Monophyletic theory
24
Q
This theory suggests that each blood cell lineages is derived from its own unique stem cell
A
Polyphyletic theory
25
This refers to speciaized cells within the bone marrow that provide protective and nourishing environment to the hematopoietic stem cells
Stromal cells
26
Progenitor:
Mature cells developed: basophil, neutrophil, eosinophil, monocyte, macrophage
Granulocyte-Monocyte (G-M) Progenitor
27
Progenitor:
Mature cells developed: basophil, eosinophil
Basophil-Eosinophil (E-B) Progenitor
28
Progenitor:
Mature cells developed: platelets and RBCs
Megakaryocyte-Erythrocyte (M-E) Progenitor
29
Progenitor:
Mature cells developed: granulocytes, erythrocytes, monocytes/macrophages, megakaryocytes
Common Myeloid (CM) Progenitor
30
Progenitor:
Mature cells developed: lymphocytes (B cell, T cell, and NK cells), plasma cells, and dendritic cells
Common Lymphoid (CL) Progenitor
31
This hematopoiesis type usually occurs in healthy individuals
Medullary hematopoiesis
32
This type of hematopoiesis is the formation and activation of blood cells outside the bone marrow
Extramedullary hematopoiesis
33
Per Rodak's, extramedullary hematopoiesis can also occur in ___________
Lymph nodes
34
_____________ hematopoiesis
Diseases: myeloproliferative noplasms, lymphomas, leukemias, aplastic anemia, infiltration by malignant cells, over-proliferation of a cell line, hemolytic anemias
Extramedullary
35
_____ is one of the largest organs of the body, located within the cavities of the cortical bones
Bone marrow
36
This refers to the active marrow consisting of the developing blood cells and their progenitors
Red marrow
37
This refers to the inactive marrow composed primarily of adipocytes (fat cells), with undifferentiated mesenchymal cells and macrophages
Yellow marrow
38
This hematopoiesis is also known for being the primary hematopoiesis
Medullary hematopoiesis
39
HEMOGLOBIN DETERMINATION
2 ALPHA + 2 BETA
Hb A (Predominant)
40
HEMOGLOBIN DETERMINATION
2 ALPHA + 2 DELTA
Hb A2
41
This occurs when the bone marrow does not meet the body requirements for hematopoiesis
Extramedullary hematopoiesis
42
B lymphocytes ; ______________
____________ ; Cell mediated immunity
B lymphocytes ; Humoral immunity
T lymphocytes ; Cell mediated immunity
43
How do cytokines regulate hematopoietic stem cells?
They provide signals that guide stem cell differentiation and proliferation.
44
What are hematopoietic stem cells (HSCs) responsible for in the body?
Producing blood cells
45
As hematopoietic stem cells mature, what happens to their ability to self-renew?
It diminishes.
46
What role do external growth factors play in hematopoiesis?
They regulate the proliferation and differentiation of HSCs.
47
What are microRNAs and their function in hematopoiesis
MicroRNAs are small noncoding RNAs that regulate gene expression
48
This factor mobilizes stem cells to increase white blood cell production.
G-CSF
49
What role do CD34 and CD117 play in the identification of HSCs
They are markers used to identify hematopoietic stem cells.
50
Thiis hematopoiesis is usually seen during compensatory state (BM failure, certain diseases, malignancies, infection)
Extramedullary hematopoiesis
51
Splenomegaly and hepatomegaly are expected to occur in this type of hematopoiesis
Extramedullary hematopoiesis
52
According the book of Roday's, extramedullary hematopoiesis also occurs in
Lymph nodes
53
Extramedullary hematopoiesis can be found in the following cases:
Aplastic anemia, infiltration by malignant cells, overproliferation of a cell line (Leukemia, MPD), hemolytic anemias
54
This marrow is predominant in infants and young children
Red marrow
55
This marrow siginificantly increases as a person ages in time
Yellow marrow
56
M:E ratio
3:1 (Others 4:1 or 2:1)
57
M:E ratio
6:1
Infection
58
M:E ratio
25:1
Leukemia
59
M:E ratio
20:1
Myeloid hyperplasia
60
M:E ratio
3:20
Myeloid hypoplasia
61
M:E ratio
1:20
Erythroid hyperplasia
62
M:E ratio
5:1
Erythroid hypoplasia
63
This is used in evaluating hematopoietic cell production
M:E ratio
64
According to the book of Rodak's, the M:E ratio for healthy adults range from _____________, reflecting the larger proportion of myeloid cells in the bone marrow
1.5:1 to 3.3:1
65
BONE MARROW SMEAR COLLECTION AND PREPARATION
1.
2.
3.
4.
BONE MARROW SMEAR COLLECTION AND PREPARATION
1. Posterior iliac crest
2. Sternum
3. Anterior iliac crest
4. Upper and tibial bone
66
Identify the specimen
Instruments used: trephine biopsy needle, jamshidi needle, Westermann-Jensen needle
Trephine (Core) biopsy
67
Identify the specimen
Instruments used: Aspiration needle, University of Illinois sternal needle
Bone marrow Aspirate
68
Bone marrow smears should be retained for ______
10 years
69
The two most common erythrocytic stages with fried egg appearance
Polychromatophilic and orthochromic normoblast
70
The largest cell in the bone marrow
Megakaryocyte
71
The most predominant cell in the bone marrow
Metamyelocyte
72
The bone marrow differential requires at least ___, and preferrably ____ cells to be counted for a marrow differential
500, 1000
73
The bone marrow is estimated to be capable of producing the following daily for every kg of body weight:
Erythrocytes:
Platelets:
Granulocytes:
The bone marrow is estimated to be capable of producing the following daily for every kg of body weight:
Erythrocytes: 2.5 billion
Platelets: 2.5 billion
Granulocytes: 1 billion
74
- Bone forming cells
- Water-bug or comet appearance
- Mistaken as plasma cells
Osteoblasts
75
- Bone resorption or destroying cells
- Mistaken as megakaryocyte
Osteoclasts
76
This can be calculated to establish the percentage of cells in mitosis in relation to the total number of cells.
Mitotic index
77
The identification and origin of HSCs can be determined by immunophenotypic analysis using
Flow cytometry
78
Functional characterization of HSCs can be accomplished through in vitro techniques using
Culture assays
79
Cytokines that exert a negative influence on hematopoiesis
TGF-Beta, TNF-Alpha, and Interferons
80
Cytokines or hematopoietic growth factors that exert a positive influence on HSCs and progenitor cells
KIT ligand, FLT3 ligand, GM-CSF, IL-1, IL3, IL-11
81
______ is considered as the largest lymphoid organ in the body
Spleen
82
Spleen is the major site of ___________ hematopoiesis
Extramedullary
83
The spleen stores _____ of platelets
30% or 1/3
84
This lymphoid tissue contains lymphocytes, macrophages, and dendritic cells
White pulp
85
This is where the T cells reside
PALS (Periarteriolar lymphoid sheaths)
86
This is where the B cells reside
Primary follicles
87
This is where the activated B cells reside
Germinal center or Secondary follicle
88
This surrounds the white pulp and forms a reticular meshwork containing blood vessels, macrophages, memory B cells, and CD4 T cells
Marginal zone
89
This is the cord of billroth; Contains specialized macrophages for removal of the senescent RBCs
Red pulp
90
Removal of mature or senescent RBC through phagocytosis that leads to eventual degradation of cell organelles
Culling
91
This refers to the removal of RBC inclusions
Pitting
92
This leads to pancytopenia
Hyperplenism/Splenomegaly
93
This leads to pancytosis
Asplenia/Splenectomy
94
Necrosis of spleen due to entrapment of sickled RBC such as in case of sickle cell anemia
Autosplenectomy
95
This refers to the absence of splenic function
Asplenia
96
This can be caused by either surgical removal, or radiation overexposure
Asplenia
97
Hematologic results of asplenia:
1.
2.
3.
4.
5.
6.
Hematologic results of asplenia:
1. Increased susceptiibility to infection
2. Acute granulocytosis
3. Acute thrombocytosis, with occasional giant platelets
4. Chronic and absolute lymphocytosis and monocytes
5. Increased appearance of immature RBCs in circulation
6. Increased amount of circulating RBCs with cytoplasmic inclusions or abnormal forms
98
Marker for Lymphoid pan T cells
CD 2, CD 3
99
Marker for Helper/Inducer T cells
CD 4
100
Marker for Suppresor/Cytotoxic T cells
CD 8
101
Marker for Pan Myeloid
CD 13
102
Marker for Monocytes
CD 11c, CD 14
103
Marker for an Myeloid cells
CD 33
104
Marker for Hematopoietic stem cell marker
CD 34
105
Marker for NK cells
CD 16, CD 56
106
Marker for Pre-CALLA
CD 10
107
CFU for granulocyte, erythrocyte, megakaryocyte, monocyte
CFU-HEMM
108
CFU for erythrocyte
CFU-E
109
CFU for megakaryocyte
CFU-Meg
110
CFU for monocyte
CFU-M
111
CFU for granulocyte, monocyte
CFU-GM
112
CFU for myeloid to basohil
CFU-BASO
113
CFU for myeloid to eosinophil
CFU-EO
114
CFU for myeloid to neutrophil
CFU-G
115
CFU for T lymphocyte
CFU-pre-T
116
CFU for B lymphocyte
CFU-pre-B
117
Cytokine:
Primary cell source: Kidney (Peritubular interstitial cell)
EPO
118
Cytokine:
Primary cell source:Endothelial cells, placenta, monocytes, macrophages
G-CSF
119
Cytokine:
Primary cell source: T cells, macrophages, endothelial cells, fibroblasts, mast cells, mast cells
GM-CSF
120
Cytokine:
Primary cell source:CD4 T cells, NK cells, B cells
IL-2
121
Cytokine:
Primary cell source:Activated T cells, NK cells
IL-3
122
Cytokine:
Primary cell source:T cells, macrophages, fibroblasts
IL-6
123
Cytokine:
Primary cell source:CD4+ Th2 T cells, CD8+ T cells, monocytes, macrophages
IL-10
124
Cytokine:
Primary cell source:Macrophages
IL-12
125
Cytokine:
Primary cell source:Activated CD4+ T cells
IL-15
126
Cytokine:
Primary cell source:Dendritic cells, NK cells, T cells, B cells, macrophages, fibroblasts, endothelial cells, osteoblasts
IFN-a
127
Cytokine:
Primary target cell: Bone marrow erythroid progenitors (BFU-E and CFU-E)
EPO
128
Cytokine:
Primary target cell: Neutrophil precursors, fibroblasts, leukemic myeloblasts
G-CSF
129
Cytokine:
Primary target cell: Bone marrow progenitor cells, dendritic cells, macrophages, NKT cells
GM-CSF
130
Cytokine:
Primary target cell: T cells, NK cells, B cells, macrophages, monocytes
IL-2
131
Cytokine:
Primary target cell: Hematopoietic stem cells and progenitors
IL-3
132
Cytokine:
Primary target cell: T cells, B cells, liver
IL-6
133
Cytokine:
Primary target cell: T cells, macrophages
IL-10
134
Cytokine:
Primary target cell: T cells
IL-12
135
Cytokine:
Primary target cell: CD4+ T cells, CD8+ T cells, NK cells
IL-15
136
Cytokine:
Primary target cell: Macrophages, NK cells
IFN-a
137
Cytokine:
Biologic activity: Stimulates proliferation of erythroid progenitors and prevents apoptosis of CFU-E
EPO
138
Cytokine:
Biologic activity:
- Stimulates granulocyte colonies
- Differentiation of progenitors toward neutrophil lineage
- Stimulation of neutrophil maturation
G-CSF
139
Cytokine:
Biologic activity:
- Promotes antigen presentation
- T cells hemostasis
- Hematopoietic cell growth factor
GM-CSF
140
Cytokine:
Biologic activity:
- Cell growth/activation of CD4+ and CD8+ T cells
- Suppress T(reg) responses
- Mediator of immune tolerance
IL-2
141
Cytokine:
Biologic activity: Proliferation of hematopoietic progenitors
IL-3
142
Cytokine:
Biologic activity:
- Costimulation with other cytokines
- Cell growth/activation of T cells and B cells
- Megakaryocyte maturation
- Neural differentiation
- Acute phase reactant
IL-6
143
Cytokine:
Biologic activity:
- Inhibits cytokine production
- Inhibits macrophages
IL-10
144
Cytokine:
Biologic activity: T Cell, Th1 differentiation
IL-12
145
Cytokine:
Biologic activity: CD4+/CD8+ T cell proliferation, CD8+/NK cell cytotoxicity
IL-15
146
Cytokine:
Biologic activity:
- Antiviral
- Enhances MHC expression
IFN-a
147
Cytokine:
Current/Potential Therapeutic Applications:
- Anemia of chronic renal disease (In predialysis, dialysis dependent, and chronic anemia patients)
- Treatment of anemia in cancer patients on chemotherapy
- Autologous predonation blood collection
- Anemia in HIV infection to permit use of zedovudine (AZT)
- Post autologous hematopoietic stem cell transplant
EPO
148
Cytokine:
Current/Potential Therapeutic Applications:
- Chemotherapy-induced neutropenia
- Stem cell mobilization
- Peripheral/Bone marrow transplantation
- Congenital neutropenia
- Idiophatic netropenia
- Cyclic netropenia
G-CSF
149
Cytokine:
Current/Potential Therapeutic Applications:
- Chemotherapy-induced neutropenia
- Stem cell mobilization
- Peripheral blood/bone marrow transplantation
- Leukemia treatment
GM-CSF
150
Cytokine:
Current/Potential Therapeutic Applications:
- Metastatic melanoma
- Renal cell carcinoma
- Non-Hodgkin lymphoma
- Asthma
IL-2
151
Cytokine:
Current/Potential Therapeutic Applications:
- Stem cell mobilization
- Postchemotherapy/Transplantation
- Bone marrow failure states
IL-3
152
Cytokine:
Current/Potential Therapeutic Applications:
- Stimulation of platelet production, but not at tolerable doses
- Melanoma
- Renal cell carcinoma
- IL-6 inhibitors may be promising
IL-6
153
Cytokine:
Current/Potential Therapeutic Applications:
- Target lymphokine in prevention of B cell lymphoma and Epstein-Barr virus lymphomagenesis
IL-10
154
Cytokine:
Current/Potential Therapeutic Applications:
- Allergy treatment
- Adjuvant for infectious disease therapy
- Asthma
- Possible role for use in vaccines
IL-12
155
Cytokine:
Current/Potential Therapeutic Applications:
- Melanoma
- Rheumatoid arthritis
- Adoptive cell therapy
- Generation of antigen-specific T cells
IL-15
156
Cytokine:
Current/Potential Therapeutic Applications:
- Adjuvant treatment dfor stage II/III melanoma
- Hematologic malignancies: Kaposi sarcoma, hairy cell leukemia, and chronic myelogenous leukemia
IFN-a
