College aantekeningen
Hemopoiesis
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Summarized notes from Junqueira's basic histology
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Hematopoiesis HISTOLOGYOUTLINE ■ lymphoid progenitor cells migrate from the bone marrow to
the thymus or the lymph nodes, spleen, and other lymphoid
I. HEMOPOIESIS structures, where they proliferate and differentiate.
II. STEM CELLS, GROWTH FACTORS
○ 2. Myeloid cells (develop in bone marrow)
III. BONE MARROW
■ Include granulocytes, monocytes, erythrocytes, and
IV. MATURATION OF ERYTHROCYTES
V. MATURATION OF GRANULOCYTES megakaryocytes
VI. MATURATION OF AGRANULOCYTES
VII. ORIGIN OF PLATELETS Progenitor & Precursor Cells
● Often called colony-forming units (CFUs)
○ give rise to colonies of only one cell type when cultured in vitro
HEMOPOIESIS
or injected into a spleen
● Blood cell formation ● Four major types of progenitor cells/CFUs:
● A continuous process by which the cellular elements of blood are ○ Erythroid lineage of erythrocytes
replenished ○ Thrombocytic lineage of megakaryocytes for platelet
● Also called hematopoiesis formation
● Form from stem cells in the bone marrow ○ Granulocyte-monocyte lineage of all granulocytes and
● Occurs in the bone marrow of adults and children monocytes
● Shifting locations of hemopoiesis during development: ○ Lymphoid lineage of B lymphocytes, T lymphocytes, and
○ 1. Yolk sac - first trimester natural killer cells
○ 2. Liver - second trimester ● Each progenitor cell lineage produces precursor cells (or blasts)
■ Primary organ of hemopoiesis ○ gradually assume the morphologic characteristics of the
■ Spleen plays a minor role mature, functional cell types they will become
○ 3. Bone marrow - third trimester ● Stem and progenitor cells cannot be morphologically
■ Major hemopoietic organ distinguished and simply resemble large lymphocytes.
● Stem cells divide at a rate only sufficient to maintain their
relatively small population
● Progenitor and precursor cells divide more rapidly, producing
large numbers of differentiated, mature cells
● Hemopoiesis depends on a microenvironment, or niche, with
specific endocrine, paracrine, and juxtacrine factors.
○ These requirements are provided largely by the local cells and
extracellular matrix (ECM) of the hemopoietic organs,
● Hemopoietic growth factors
○ often called colony-stimulating factors (CSF) or cytokines
○ are glycoproteins that stimulate proliferation of progenitor and
precursor cells and promote cell differentiation and maturation
within specific lineages.
MEDICAL APPLICATION
● Hemopoietic growth factors
○ important products of biotechnology companies
○ used clinically to increase marrow cellularity and blood cell
counts in patients with conditions such as severe anemia or
during chemo- or radiotherapy, which lower white blood cell
counts (leukopenia).
○ Such cytokines may also increase the efficiency of marrow
transplants by enhancing cell proliferation, enhance host
defenses in patients with infectious and immunodeficient
diseases, and improve treatment of some parasitic diseases.
STEM CELLS, GROWTH FACTORS, & DIFFERENTIATION
● Stem cells BONE MARROW
○ pluripotent cells capable of asymmetric division and self-
renewal ● found in the medullary canals of long bones and in the small
○ Some of their daughter cells form specific, irreversibly cavities of cancellous bone
committed progenitor cells ● Two types based on their appearance at gross examination:
○ Other daughter cells remain as a small pool of slowly dividing ○ Blood-forming red bone marrow
stem cells. ■ color is produced by an abundance of blood and
hemopoietic cells
Hemopoietic Stem Cells ■ contains a reticular connective tissue stroma, hemopoietic
● All blood cells arise from a single type of pluripotent hemopoietic cords or islands of cells, and sinusoidal capillaries
stem cell in the bone marrow that can give rise to all the blood ■ Stroma
cell types ● meshwork of specialized fibroblastic cells called
● Rare, proliferate slowly stromal cells (also called reticular or adventitial cells)
● give rise to two major lineages of progenitor cells with restricted and a delicate web of reticular fibers supporting the
potentials (committed to produce specific blood cells) hemopoietic cells and macrophages
○ 1. Lymphoid cells (lymphocytes) ■ The matrix of bone marrow also contains collagen type I,
proteoglycans, fibronectin, and laminin, the latter
1 of 16
,Hemopoiesis
glycoproteins interacting with integrins to bind cells to the
matrix. MATURATION OF ERYTHROCYTES
■ Red marrow is a site where older, defective erythrocytes ● Erythropoiesis
undergo phagocytosis by macrophages, which then ○ an example of terminal cell differentiation involving
reprocess heme-bound iron for delivery to the hemoglobin synthesis and formation of a small, enucleated,
differentiating erythrocytes. biconcave corpuscle.
○ Cell and nuclear volumes decrease, while the nucleoli
diminish in size and disappear.
○ Chromatin density increases until the nucleus presents a
pyknotic appearance and is finally extruded from the cell.
○ There is a gradual decrease in the number of polyribosomes
(basophilia), with a simultaneous increase in the amount of
hemoglobin (a highly eosinophilic protein).
○ Mitochondria and other organelles gradually disappear
○ requires approximately a week and involves three to five cell
divisions between the progenitor cell stage and the release of
functional cells into the circulation
● Erythropoietin - a growth factor produced by cells in the kidneys,
stimulates production of mRNA for the protein components of
hemoglobin
○ Essential for erythrocyte production
● Erythrocytic maturation
○ 1. Proerythroblast
○ 2. Basophilic erythroblast
○ 3. Polychromatophilic erythroblast
○ Yellow bone marrow ○ 4. Orthochromatophilic erythroblast
■ filled with adipocytes that exclude most hemopoietic cells ○ 5. Reticulocyte
○ In the newborn all bone marrow is red and active in blood cell ○ 6. Erythrocyte
production
○ As the child grows, most of the marrow changes gradually to ● Proerythroblast
the yellow variety. ○ Distinct erythroid progenitor cell
○ Under certain conditions, such as severe bleeding or hypoxia, ○ large cell with loose, lacy chromatin, nucleoli, and basophilic
yellow marrow reverts to red. cytoplasm
● Basophilic erythroblast
○ slightly smaller with cytoplasmic basophilia and a more
condensed nucleus
○ The basophilia is caused by the large number of free
polysomes synthesizing hemoglobin
● Polychromatophilic erythroblast
○ cell volume is reduced
○ polysomes decrease
○ some cytoplasmic areas begin to be filled with hemoglobin,
producing regions of both basophilia and acidophilia in the cell
● Orthochromatophilic erythroblasts
○ Normoblasts
○ Cell and nuclear volumes continue to condense and
basophilia is gradually lost, producing cells with uniformly
acidophilic cytoplasm
○ Late in this stage the cell nucleus is ejected and undergoes
phagocytosis by macrophages
● Reticulocyte
○ The cell still retains a few polyribosomes which, when treated
with the dye brilliant cresyl blue, form a faintly stained network
○ enter the circulation (where they may constitute 1% of the red
blood cells), quickly lose all polyribosomes
○ Mature as erythrocytes.
MEDICAL APPLICATION
● Red bone marrow
○ contains stem cells that can produce other tissues in addition
to blood cells
● Stem cells
○ These pluripotent cells may make it possible to generate
specialized cells that are not rejected by the body because
they are produced from stem cells from the marrow of the
same patient.
○ The procedure is to collect bone marrow stem cells, cultivate
them in appropriate medium for their differentiation to the cell
type needed for transplant, and then use the resulting cells
to replace defective cells.
● These studies in regenerative medicine are at early stages, but
results with animal models are promising.
HISTOLOGY 2 of 16
, Hemopoiesis
● Granulopoiesis:
○ Myeloblast
■ most immature recognizable cell in the myeloid series
■ have finely dispersed chromatin, and faint nucleoli
○ Promyelocyte
■ characterized by basophilic cytoplasm and azurophilic
granules containing lysosomal enzymes and
myeloperoxidase
■ Different promyelocytes activate different sets of genes,
resulting in lineages for the three types of granulocytes
○ Myelocyte
■ first visible sign of this differentiation appears
■ specific granules gradually increase in number
○ Metamyelocyte
■ Specific granules occupy most of the cytoplasm
■ These neutrophilic, basophilic, and eosinophilic
metamyelocytes mature with further condensation of their
nuclei.
○ Band cell
■ Intermediate stage for neutrophilic granulocyte before its
complete maturation
■ The nucleus is elongated but not yet polymorphic
MEDICAL APPLICATION
● “Shift to the left”
○ The appearance of large numbers of immature neutrophils
(band cells) in the blood
○ clinically significant, usually indicating a bacterial infection
● The vast majority of granulocytes are neutrophils
● Total time required for a myeloblast to produce mature,
circulating neutrophils : ranges from 10 to 14 days
● Five mitotic divisions normally occur during the myeloblast,
promyelocyte, and neutrophilic myelocyte stages.
● developing and mature neutrophils exist in four functionally and
anatomically defined compartments:
○ (1) the granulopoietic compartment in active marrow
○ (2) storage as mature cells in marrow until release
MATURATION OF GRANULOCYTES ○ (3) the circulating population
● Granulopoiesis ○ (4) a population undergoing margination
○ involves cytoplasmic changes dominated by synthesis of ■ a process in which neutrophils adhere loosely and
proteins for the azurophilic granules and specific granules. accumulate transiently along the endothelial surface in
○ These proteins are produced in the rough ER and the venules and small veins.
prominent Golgi apparatus in two successive stages ■ Margination of neutrophils in some organs can persist for
■ 1. Formed first are the azurophilic granules, which several hours and is not always followed by the cells’
contain lysosomal hydrolases, stain with basic dyes, and emigration from the microvasculature.
are generally similar in all three types of granulocytes.
■ 2. Golgi activity then changes to package proteins for the
specific granules, whose contents differ in each of the
three types of granulocytes and endow each type with
certain different properties
HISTOLOGY 3 of 16
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