HEMATOPOIESIS Flashcards
is the continuous, regulated process of renewal, proliferation, differentiation and maturation of all blood cell lines.
Hematopoiesis
this process result in the formation and specialization of all functional blood cells which are released from the bone marrow into the circulation
Hematopoiesis
mature blood lives has a limited life span , the cell population must be capable of ________ that will sustain the system
self-renewal
what are the phases or sites of hematopoiesis?
Mesablastic, hepatic and myeloid
hematopoiesis is considered to begin around the ___________ of embryonic development after fertilization
nineteenth day
early in embryonic development, cells from the __________ migrate to the ________.
mesoderm, yolk sac
these primitive but _______________ are important in early _________ to produce _________.
transient yolk sac erythroblasts, embryogenesis, hemoglobin
____________ differs from hematopoiesis that occurs later in the fetus and adult in that it occurs ________ (or within developing blood vessels)
Yolk sac hematopoiesis, intravascularly
what are the three types of hemoglobin?
Gower-1, Gower-2 and portland
they are needed for delivery of oxygen to rapidly developing embryonic tissues?
Hemoglobin (Gower-1, gower -2 and portland)
what phase of hematopoiesis does the description fit into?
“it begins around the nineteenth day of embryonic development”
mesoblastic phase
what phase of hematopoiesis does the description fit into?
“ Early in embryonic development, cells from the mesoderm migrate to the yolk sac.”
Mesoblastic phase
it also known as within developing blood vessels
Intravascularly
what phase of hematopoiesis does the description fit into?
“begins at 5-7 gestational weeks and is 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.”
Hepatic phase
what phase of hematopoiesis does the description fit into?
“Hematopoiesis during this phase occurs extravascularly, with the liver remaining the major site of hematopoiesis during the second trimester of fetal life.”
Hepatic phase
the hepatic phase begins in _____________ (weeks )and is 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.”
5 -7 gestational weeks
in the hepatic phase, hematopoiesis occurs __________, with the liver remaining the major site of hematopoiesis during the __________ of fetal life.
extravascularly, second trimester
in the hepatic phase the _______, first fully developed organ in the fetus becomes the major site of T cell production whereas the _________ (organ) produce B cells.
Thymus, kidney and spleen
what phase of hematopoiesis does the description fit into?
“the thymus, the first fully developed organ in the fetus, becomes the major site of T cell production, whereas the kidney and spleen produce B cells.”
Hepatic phase
the ______________ signals the beginning of a definitive hematopoiesis with a decline in the primitive hematopoiesis in the yolk sac. In addition the ________ now begin to appear
developing erythroblasts, lymphoid cells
what organ produces T cells in the fetus stage?
Thymus
What organ produces B cells
kidney and spleen
what phase begins between the fourth and fifth month of fetal development?
Medullary phase or myeloid phase
in what phase does the description fit? “the hematopoietic activity of this stage is apparent of development and the myeloid-to-erythroid ratio gradually approaches 3:1 to 4:1 (normal adult levels)”
medullary phase (myeloid phase)
“by the end of 24 weeks’ gestation, the bone marrow becomes the primary site of hematopoiesis” what phase does the description fit?
Medullary (myeloid) phase
in what month does the medullary (myeloid) phase begin during fetal development?
fourth and fifth month
hematopoietic activity, especially ___________, is apparent during this stage of development and the ____________ ratio gradually approaches 3:1 to ________ (normal adult levels)
myeloid activity, myeloid-erythroid ratio, 4:1
myeloid-to-erythroid ratio of normal adult levels
4:1 ratio
in what week of gestation does the bone marrow become the primary site of hematopoiesis?
24 weeks’ gestation
what happens during the 24 weeks’ gestation period?
the bone marrow becomes the primary site of hematopoiesis
in adults, where does the hematopoietic tissue located?
bone marrow, lymph nodes, spleen, liver and thymus.
what does the bone marrow contain?
Developing erythroid, myeloid, megakaryocytic and lymphoid cells
where does the lymphoid development occur?
in the primary and secondary lymphoid tissue
the primary lymphoid tissue consists of the?
bone marrow, thymus and is where the t and b lymphocytes are derived
the secondary lymphoid tissue where lymphoid cells responds to foreign antigens consists of the?
spleen, lymph nodes and mucosa associated lymphoid tissues
a theory where it describes the origin of the hematopoietic progenitor cells
Stem cell theory
a theory where it suggests that all blood cells are derived from a single progenitor stem cell called pluripotent hematopoietic stem cell
monophyletic theory
the two theories of the stem cell theory?
Monophyletic theory
polyphyletic theory
a theory where it suggests that each of the blood cell lineages is derived from its own unique stem cell. it is also noted as the most widely accepted theory among experimental hematologists.
polyphyletic theory
what does the monophyletic theory suggests?
a theory where it suggests that all blood cells are derived from a single progenitor stem cell called pluripotent hematopoietic stem cell
what does the polyphyletic theory suggests?
a theory where it suggests that each of the blood cell lineages is derived from its own unique stem cell. it is also noted as the most widely accepted theory among experimental hematologists.
in the monophyletic theory, what do you call the single progenitor stem cell that suggest the derivation of the all blood cells?
pluripotent hematopoietic stem cell
(of an immature or stem cell) capable of giving rise to several different cell types.
pluripotent
what are the two major types of morphologically unrecognizable progenitor cells?
uncommitted and committed hematopoietic stem cells
it occurs in the bone marrow and is a complex, regulated process for maintaining adequate number of erythrocytes in the peripheral blood.
Erythropoiesis
what are the two erythroid progenitors?
Burst forming unit - erythroid (BFU-E)
Colony forming Unit - erythroid (CFU-E)
it is the earliest morphologically recognizable erythrocyte precursor in the bone marrow?
pronormoblast
meaning of CFU-GEMM?
Colony Forming Unit Granulocyte, Erythrocyte, Monocyte and Megakaryocyte
the CFU-GEMM gives raise to the earliest colony of RBCs called the _________.
Burst forming unity - Erythroid (BFU-E)
BFU-Es under the influence of interleukin GMCSF, PPO and Kitlygan will develop into?
Colony Forming Unit - Erythroid
serves as a differentiation factor for the CFU-Es and BFU-Es?
Erythropoiesis
they are named for their ability to form colonies on semi solid medium in culture experiments that enable the study of their characteristics and development.
Erythroid progenitors (BFU-E and CFU-E)
they are the earliest committed progenitor gives rise to the large colonies as they are capable multi subunits called burst
Burst forming unit - Erythroid (BFU-E)
what do you call the multi-subunits of a BFU-E?
burst
it gives rise to smaller colonies?
Colony forming unit - Erythroid
How many estimated days does the BFU-E to mature to become CFU-E and the CFU-E to become a pronormoblast?
1 week
it is derived from the BFU-E and CFU-E from pluripotent hematopoietic stem cells.
Pronormoblast
is similar to the other proliferation of the other cell lines. It is the process of encompassing replication, for example division, that increases cell numbers and development from immature to mature cell stages.
Normal blast proliferation
the pronormoblast can be divided to _______ and then it will be divided to the next stage ______.
basophilic, polychromatic normal blasts
What are the criteria used in identification of Erythroid Precursors?
diameter of the cell decreases
diameter of the nucleus decreases more rapidly than the diameter of the cell
nuclear chromatin pattern becomes coarser, clumped and condensed developing a rasp berry appearance
The nucleus becomes quite condense with no parachromatin evident at all
The nucleus is also said to be pyknotic
nucleoli disappears
cytoplasm changes from gray-blue to salmon pink
major function of the red blood cell?
carry oxygen from the lungs to the tissues
acid base buffer
Appearance and characteristic of the RBC
biconcava in shape and distensible
is the first microscopically recognizable precursor cell in erythropoiesis
it is aka Proerythroblast
pronormobalst
after mitosis the pronormoblast forms ?
two basophilic normoblast
is present only in the bone marrow in healthy states
pronormoblast
in the pronormoblast the nucleus to cytoplasm ratio is ?
8:1
describe the nucleus of the pronormoblast?
the nucleus is round to oval, containing one or two nucleoli. Has a purple red chromatin which is open and contains few, if any, fine clumps
describe the nucleus of the basophilic normoblast
the chromatin begins to condense, revealing clumps along the periphery of the nuclear membrane and a few in the interior
describe the nucleus of the basophilic normoblast
the chromatin begins to condense, revealing clumps along the periphery of the nuclear membrane and a few in the interior
describe the appearance of the cytoplasm of the pronormoblast
basophilic
describe the appearance of a basophilic normoblast?
deeply basophilic. Cytoplasm is dark blue because of the concentration of ribosomes and RNA
Ratio of NC of the Basophilic Normoblast
Moderate 6:1
when the basophilic normoblast undergoes mitosis it gives rise to _____________.
two daughter cells
what is detectable in the basophilic normoblast?
hemoglobin synthesis
the basophilic normoblast is present only in the _________________ during healthy states
bone marrow
describe the nucleus of the polychromatic normoblast?
the condensation of chromatin reduces the diameter of the nucleus considerably
describe the appearance of the polychromatic normoblast’s cytoplasm
first stage in which the pink color can be seen as it is associated with the stained hemoglobin
NC ratio of polychromatic normoblast
Moderate
the last stage of polychromatic normoblast contains and is capable of ?
contains nucleus and is capable of mitosis
what is the orthromatic normoblast known as?
Metarubicyte
describe the appearance of the nucleus’ metarubicyte?
the nuclues is completely condensed or pyknotic
describe the cytoplasm of the orthrochromatic normoblast?
pink gray (more pinkish) associated with nearly complete hemoglobin
what is the NC ratio of the othrochromatic normoblast ?
Low
it no longer is capable of division?
Orthochromatic normblast
what is the polychromatic erythrocyte is known as?
Reticulocyte
what is the polychromatic erythrocyte first precursor appearance?
anucleated
this erythropoiesis phase is where RNA synthesis stops while heme synthesis continues
Polychromatic erythrocyte
what does the polychromatic erythrocyte loses?
it loses its RNA and mitochondria
describe the appearance of the nucleus of the polychromatic erythrocyte
none
describe the cytoplasm of the reticulocyte?
pink gray or salmon pink. This stage is where the cell is the same color with the mature cell
where does the polychromatic erythrocyte reside? and how many days and where does it move?
resides in the bone marrow for about 1-2 days and moves into peripheral blood for about 1 day
what is the lifespan of the erythrocyte?
120 days
what is final phase of the erythropoiesis?
erythrocytes
it has no nucleus,mitochondira and endoplasmic reticulum
erythrocytes
describe the appearance of an erythrocyte
biconcave disc measuring in 7 - 8 “m in diameter with a thickness of 1.5 to 2.5 “m
describe the appearance of an erythrocyte when it is on a wright-stained blood film.
salmon pink stained cell with a central pale area that responds to the concavity of the cell. The central pallor is about one-third the diameter of the cell
what does the erythrocyte contain?
contains cytoplasmic enzymes capable of metabolizing glucose
it is the term describing the dynamics of the RBC production and destruction
erythrokinetics
it is the primary oxygen-sensing system of the body that is located in the peritubular fibroblasts.
kidney
it is the too little tissue oxygen which is detected by the peritubular fibroblasts.
hypoxia
it is the major stimulatory cytokine for RBC
erythropoietin
it directly stimulates erythropoiesis, which partially explains the higher hemoglobin concentration in men than in women.
testosterone
is a thermostable, nondialyzable, glycoprotein hormone with a molecular weight of 34 kD
Erythropoietin
is a true hormone, being produced at one location _________ and acting at a distant location __________.
kidney and bone marrow
initiates an intracellular message to the developing erythroid cells; this process is called __________
signal transduction
what are the three effects of the Erythropoietin?
early release of reticulocytes
preventing apoptotic
reducing the time
how many days in total if erythropoietin (reduction of time) is being activated in the blood ?
4 days in total
is the process of generating white blood cells from the pluripotent hematopoietic stem cells of the bone marrow.
Leukopoiesis
what are the two generate various types of leukocytes?
myelopoieisis and lymphopoiesis
it is where leukocytes in the blood are derived from MYLOID STEM CELLS
myelopoiesis
it is where lymphatic system (lymphocytes) are generated from lymphoid stem cells
lymphopoiesis
what are the factors that promote differentiation of the CFU-GEMM into neutrophils, monocytes, eosinophils and basophils?
GM-CSF (Granulocyte macrophage colony-stimulating factor), G-CSF , macrophage colony-stimulating factor (M-CSF), IL-3, IL-5 IL-11 and KIT ligand.
stimulates the proliferation and differentiation of the neutrophil and the macrophage colonies from the colony forming unit granulocyte and monocyte
GM-CSF
stimulates neutrophil differentiation and monocyte differentiation from the colony forming granulocyte or CFU-M
G-CSF and M-CSF (Macrohage colony-stimulating factory)
a multilineage stimulating factor, stimulates the growth of granulocytes, monocytes, megakaryocytes and reituring cells (?)
IL-3 (interleukin = IL)
what does the eosinophil require for differentiation?
GM-CSF, IL-3 and IL-5
the basophil differentiation requires?
IL-3 and KIT Ligand
growth factors that promote lymphoid differentiation requires?
IL -2, IL-7, IL -12, IL-15
occurs in the bone marrow where it shares a common progenitor with monocytes and distinct from eosinophils and basophils, known as the granulocytemonocyte progenitor
Neutrophil development
it is the major cytokine responsible for the stimulation of neutrophil production
granulocyte colony-stimulating factor
what are the three stem pools of developing neutrophils in the bone marrow
stem cell, proliferation, maturation
one of the three pools of the developing neutrophils in the bone marrow where it consists of HSCs that are capable of self-renewal and differentiation
stem cell pool
one of the three pools of the developing neutrophils in the bone marrow where it consists of cells that dividing and includes common myeloid progenitors (CMPs), CFUGEMMs, and granulocyte-monocyte progenitors
proliferation pool
one of the three pools of neutrophil development where consisting cells are undergoing nuclear maturation that form the marrow researve and are available for release: metamyelocytes, band neutrophils and segmented neutrophil.
maturation pool
it makes up to 0 to% to 3% of nucleated cells in the bone marrow and measure 14 to 20” m in diameter.
myeloblast
what makes up the percentage of the myeloblast of the nucleated cells in the bone marrow and what is its measurement in diameter?
0%- 3%, 14-20”m diameter
it is the first recognizable cell that begin the process of granulpoiesis or leukopoeisis
myeloblast
it is the earliest microscopically recognizable neutrophil precursor cell in the bone marrow
myeloblast
describe the myeloblast’s nucleus?
large euchromatic spherical nucleus with three to five nucleoli
what is the volume of the myeloblast of nucleus to cytoplasmic?
Large
describe the staining characteristic of a myeloblast
the small amount of agranular cytoplasm stains intensely basophilic
the promyelocyte comprises _____________ of the nucleated cells in the bone marrow. it is relatively larger than the myeloblast cells and measure ______ in diameter. The nucleus is ______ and is often eccentric.
1-5% , 16-25”m in diameter. round to oval
what does the promyelocyte only produce?
azurophilic granules
what are the primary granules of the promyelocyte in the cytoplasm?
azurophilic granules
they are the first to exhibit specific granules
myelocytes
they are the last stage capable of mitosis in the leukopoiesis
myelocytes
the recognition of the myelocytes can be possible in the lines of? (3 types)
neutrophil, eosinophil and basophil
they are patches of grainy pale pink cytoplasm representing secondary granules begin to be evident in the area of the golgi apparatus.
neutrophil
what does the neutrophil been referred to as?
reffered to as the dawn of neutrophilia
is characterized by the presence of large pale, reddish orange secondary granules, along with azure granules in blue cytoplasm
eosinophil
the nucleas of the eosinophil is similar to the ________.
neutrophil myelocytes
it constitutes to 3% to 20% of nucleated marrow cells
metamyelocytes
this stage the cells are no longer capable of division and the major morphologic change is in shape of the nucleus
metamyelocyte
what is the shape of the nucleus of a meatmyelocyte and what is the appearance of its chromatin and nucleoli
indented (kidney bean shape) chromatin is clumped and nucleoli are absent
what synthesis may begin during the stage of the metamyelocyte?
synthesis of tertiary granules (aka gelatinase granules)
what is the size of the metamyelocyte?
14-16”m
what does the metamyelocyte’s cytoplasm contain and what is the appearance of its basophilia?
very little residual of RNA and therefore little or no basophilia
it makes up 9% to 32% of nucleated marrow cells and 0% to 5% of the nucleated peripheral blood cells
band (stab) cells
all evidence of RNA (cytoplasmic basophilia) is absent and tertiary granules continue to be formed during this stage
band (stab) cell
in the band (stab) cell what may begin to form during this stage?
secretory granules
describe the appearance of the band (stab) cell’s nucleus.
nucleus is highly clumped and nuclear indentation began in the metamyelocyte now exceeds one hald the diameter of the nucleus.
what percentage makes up the the band (stab) cell of the nucleated marrow cells?
9 - 32%
what percentage makes up the band (stab) cell of the nucleated peripheral blood cells
0-5%
what are the two mature granulocyte?
segmented neutrophils and mature eosinophils
in the mature granulocyte the segmented neutrophil makes up _________ of the nucleated cells in the bone marrow.
7-30%
what is the different between the segmented neutrophil and bands?
the presence of two and give nuclear lobes connected by a thread-like filaments
in the mature granulocyte, describe the appearance of its nucleus and cytoplasm.
segmented granulocyte has a presence of two to five nuclear lobes connected by a thread-like filament
Mature eosinophils displayes a bilobed nucleos, its cytoplasm contains refractile, orange-red secondary granule
in the mature granulocyte, it usually displays a bilobed nucleus. Their cytoplasm contains characteristic refractile of orange-red secondary granules.
mature eosinophils
what are the functions of a neutrophil?
phagocytosis
bactericidal activity
move in a zigzag pattern in the presence of chemoattractant
phagocytose a foreign particle
bactericidal activity mediated by H2O2 superoxide anion, myeloperoxidase and free halogen
important in the defense against infectious agents
can cause tissue necrosis, tissue injury and inflamation
what are the functions of Eosinophils
modulate inflammatory response
anthelmintic activity - generating oxidants and release cationic proteins
granules contain major basic proteins
functions of the basophil
immediate hypersensitivity reactions
they appear to be larger than neutrophils (diameter of 15 to 20”m) because they tend to stick and spread out on glass or plastic
monocytes
what is the goal of the slightly immature monocytes?
their ultimate goal is to enter the tissues and mature into macrophages, osteoclasts or dendritic cells
describe the nucleus of the monocyte?
round, oval or kidney shaped or indented horsesshoe shaped
what is the chromatin pattern of a monocyte?
lace-like or stringy
describe the cytoplasm of the monocyte
ground glass appearance
how many days does the monocyte remain in circulation?
3 days
what is the other term of the mononuclear phagocyte system
reticuloendothelial system
what is the purpose of monocytes?
defense against microorganism, mycobacteria, fungi, protozoa and viruses
what do you call the monocyte when it migrates to the tissue?
histocytes or macrophages
what are the three divisions of lymphocytes?
t cellls, be cells and natural killer cells (NK)
they are the major players in adaptive immunity
T and B cells
makes up a small percentage of lymphocytes and are part of innate immunity
NK cells
what are the subdivisions of lymphocytes immunity?
humoral immunity and cellular immunity
is a subdivision of the lymphocyte where they are the producing antibodies
humoral immunity
is a subdivision of the lymphocyte where they respond by attacking foreign organisms or cells directly
cellular immunity
they are the antibody-producing lymphocytes and they develop in the bone marrow.
B- lymphocytes or B cells
cellular immunity is accomplished by two types of lymphocytes what are they?
T cells and NK cells
they are cells that are developed in the thymus?
t cells
they are developed in the bone marrow? it is a type of lymphocyte.
NK cells
where are the NK cells developed?
bone marrow and thymus
they are part of the innate immunity and are capable of killing certain tumor cells and virus infected cells without prior sensitization
NK lymphocytes
what is the function of the NK Lymphocytes?
capable of killing tumor cells and virus -infected cells without prior sensitization and it modulate the functions of other cells including macrophages and T cells
when stimulated the lymphocyte becomes?
they undergo mitosis and produce both memory and effector cells
lymphocytes _______ from the blood to the tissues and back to the blood
recirculate
they are capable of rearranging antigen receptor gene segments to produce a wide variety of antibodies and surface receptors.
B and T lymphocytes
where does the T and NK lymphocytes mature?
outside the bone marrow
what is the life span of the T-cells
months to years
what is the immunity of the T-cells possess?
cell mediated immunity
what is the immunity of the B-cells called?
humoral immunity
What cell does the B Cells produce?
plasma cells and produce antibodies
what is the population percentage of B-cells
10-20%
it is the process by which megakaryocytes and platelets develop?
megakaryopoiesis
it is the main site of production of TPO?
liver
it controls the production and release of platelets?
Hormonal factor TPO
in the megakarypoiesis, megakayocyte progenitors arise from the common myeloid progenitor under the influence of the transcription gene product called
GATA-1
in the megakaryopoiesis the GATA-1 is regulated by the____
FOG 1
megakaryocyte differentiation is suprressed by another transcription gene product ______
MYB
what is the order of differentiation of the megakaryopoiesis of the three megakaryocyte lineage-committed progenitor stages?
Least mature Burst-forming unit (BFU-Meg)
intermediate Colonyforming unit (CFU-Meg)
More mature progenitor, Light-density CFU (LD-CFU-Meg)
they are under the megakaryopoeisis where all three prgenior stages resemble lymphocytes. What are they?
Burst-forming unity
Colony forming unit
Light-density CFU
thrombocytopoiesis is also known as the?
platelet shedding
a single megakaryocyte may shed around how many platelets?
2000-4000 platelets
the platelet lifespan is over ?
8-9 days
