Hemopoiesis Flashcards
Hemopoiesis aka as
Hematopoiesis
RBC production
Erythropoiesis
WBC production
Leukopoiesis
Hemopoiesis talks about how:
✓ blood cells are formed in the body
✓ how they mature
✓ what are the precursor cells needed for
differentiation
is initiated in early embryonic development
Hemopoiesis
3RD WEEK OF GESTATION:
Yolk Sac Phase
Hematopoietic cells are generated in: the Yolk Sac as blood islands (cell aggregates) in the
3rd week of gestation
are the first blood cells formed during the first 2 to 8 weeks of life
Primitive RBC (Erythroblasts)
2ND MONTH – 5TH MONTH OF GESTATION
Hepatic Phase
By the second month to fifth month of gestation, the ______ becomes the major site of hematopoiesis
liver
have made their initial appearance in the second month to fifth month of gestation
Granular Leukocytes (NEB)
In the ________________, the bone marrow begins to function in the production of blood cells
fourth month of gestation
After _________, the function of liver and spleen in production of blood cell declines and the bone marrow assumes the role of hemopoiesis
7-9 months
5TH FETAL MONTH:
Medullary Hematopoiesis
After the fifth fetal month, the bone marrow begins to assume its ultimate role as the
primary site of hematopoiesis
Hematopoiesis outside the bone marrow is called
Extra-medullary hematopoiesis
Hematopoiesis in the bone marrow
Medullary Hematopoiesis
AFTER BIRTH
* The bone marrow will assume the function of hemopoiesis:
✓ Vertebrae
✓ Sternum
✓ Ribs
✓ Femur – stops at age of 25
✓ Tibia – stops at age of 20
As we age, we will have a declining hemopoiesis in
ribs, sternum and vertebrae
are involved in differentiation and proliferation for maturation.
Growth Factors
trigger maturation of cells into its mature form
promote differentiation and proliferation of cells to become their mature counterparts.
Growth Factors
States that our blood cells came from a single type stem cell which is the hematopoietic stem cell.
Monophyletic Theory
The hematopoietic stem cell (Pluripotent Stem Cells) can differentiate to be become either a
Myeloid Stem Cell or a Lymphoid Stem Cell
can become RBC, Platelets, Granulocytes, and Monocytes
Myeloid Stem Cells
can become Beta-Lymphoblast or T-Lymphoblast that will give rise to T-lymphocyte and B-lymphocyte
Lymphoid Stem Cell
Maturation is affected by the different GROWTH FACTORS:
- Erythropoietin = erythrocyte
- Thrombopoietin = platelets
- Colony stimulating factors (GM-CSF)
▪ Granulocyte CSF = eosinophil. Basophil, neutrophil
▪ Monocyte CSF = monocyte
- Bone marrow stem cell believed to be where all blood cells arise
Pluripotent Stem Cells
- Can produce all blood cell types
- Proliferate and form two major cell lineages:
Pluripotent Stem Cell
two major cell lineages:
✓ lymphoid cells (B and T lymphocyte)
✓ myeloid cells (RBCs, platelets, granulocytes,
Monocytes)
daughter cells with restricted potentials that came from myeloid stem cells
Progenitor Cells or Colony forming Units (CFUs)
FOUR TYPES OF PROGENITORS/CFUS
Myeloid stem cell gives rise to:
1. CFU-erythrocytes (CFU-E) = ERYTHROCYTE
2. CFU-megakaryocytes (CFU-Meg) = PLATELET
3. CFU-granulocytes-monocytes (CFU-GM) = BEN & MONOCYTES
Lymphoid stem cell gives rise to:
4. CFU-lymphocytes of all types (CFU-L) = T & B LYMPHOCYTE
✓ Increased Potentiality (has increased potential to become
any of the progenitor cell depending on the demand of
body)
✓ Decreased Mitotic Activity
✓ Increased Self-Renewing Capacity
✓ Decreased susceptibility to Growth Factors
STEM CELLS
✓ Decreased Potentiality
✓ Increased Mitotic Activity (has the ability to
proliferate)
✓ Decreased Self-Renewing Capacity
✓ Highly Influenced by Growth Factors
PROGENITOR CELLS
✓ Increased Mitotic Activity
✓ Highly Influenced by Growth Factors
PRECURSOR CELLS (blast cells/young cells)
✓ Typical Morphologic Characteristics
✓ Differentiated Functional Activity
MATURE CELLS
- also called as hematopoietins (poietins)
- highly influences the progenitor and precursor cells
Hemopoietic Growth Factors (CSF)
Hemopoietic Growth Factors (CSF) has overlapping FUNCTIONS in:
✓ Stimulating Proliferation (mitogenic activity) of immature (mostly progenitor and precursor) cells
✓ Supporting Differentiation of maturing cells
✓ Enhancing The Functions of mature cells
Given to patients with low blood cell count (Patients undergoing chemotherapy and those who have malignancy) or patients who are immunocompromised
HEMOPOIETIC GROWTH FACTORS
TWO TYPES OF BONE MARROW:
RED and YELLOW bone marrow
- blood-forming red bone marrow
Red bone marrow
filled with adipocytes
→ Can revert back to red bone marrow when needed
Yellow bone marrow
In the newborn, ________________________________________ in blood cell production
all bone marrow is red and active
As we age, other areas like in __________________________ will have a decreased activity of blood cell production
vertebrae, sternum, rib, femur, and tibia
In conditions like ____________________, where there is demand for more red blood cells, yellow marrow reverts to red
severe bleeding or hypoxia
Components of the Red Bone Marrow
Stroma
Hemopoietic cords
Sinusoidal capillaries
Matrix of bone marrow (collagen type 1, proteoglycans, fibronectin, and laminin)
→ Meshwork of reticular or adventitial cells and a delicate web of reticular fibers supporting hemopoietic cells and macrophages
Stroma
island of cells (blood islands)
Hemopoietic cords
→ This is where blood exits if they are already mature
Sinusoidal capillaries
Matrix of bone marrow also contains:
collagen type I, proteoglycans, fibronectin, and laminin
stabilizes the cell attached to the marrow
Laminin
In certain abnormal circumstances, the spleen, liver, and lymph nodes revert back to producing immature blood cells
There is resulting
splenomegaly and hepatomegaly
CLINICAL SIGNIFICANCE
When the bone marrow becomes dysfunctional in cases such as
aplastic anemia, infiltration by malignant cells, or over proliferation of cell line (e.g., leukemia)
CLINICAL SIGNIFICANCE
When the bone marrow is unable to meet the demands placed on it, as in the
hemolytic anemias
→ specialized niches in which erythroid
precursors proliferate, differentiate, and enucleate (expel nucleus)
Erythropoietic Islands
Erythroid cells account for ___% - ____ % of nucleated cells in normal bone.
5% to 38%
MATURATION SERIES (RBC)
- Proerythroblast (Rubriblast)
- Basophilic Erythroblast (Prorubricyte)
- Polychromatophilic Erythroblast (Rubricyte)
- Orthochromatophilic Erythroblast (Metarubricyte)
- Reticulocyte (Polychromatophilic Erythrocyte)
- Erythrocyte
As nucleus is expelled, the capacity of the erythrocyte to carry hemoglobin ____________ (thus it is important to expel the nucleus)
increases
▪ First recognizable cell in the erythroid series
▪ a large cell with loose, lacy chromatin, nucleoli, and basophilic cytoplasm
Proerythroblast
▪ With more strongly basophilic cytoplasm and a condensed nucleus with no visible nucleolus.
▪ Basophilia of these two cell types is caused by the large number of polyribosomes synthesizing hemoglobin
Basophilic Erythroblast
▪ cell volume is reduced
▪ show regions of both basophilia and acidophilia in the cell
▪ Heterochromatin granules form a checkerboard pattern
Polychromatophilic Erythroblast
▪ After the last mitosis, the nucleus becomes small and dense (pyknotic), and the ___________________ stage is reached
▪ mitosis is no longer possible
Orthochromatophilic Erythroblast
▪ smaller than the polychromatophilic erythroblast
▪ contains more abundant hemoglobin and fewer polyribosomes and remains slightly polychromatophilic
Orthochromatophilic Erythroblast
▪ the nucleus and a small rim of cytoplasm are ejected from the orthochromatophilic erythroblast
▪ On air-dried films with Romanowsky-type stains, the reticulocyte is polychromatophilic as a result of the retention of RNA in reticulocytes
Polychromatophilic Erythrocyte / Reticulocyte
Reticulocyte constitute __% - ___% of the the total RBC count, lose the polyribosomes and quickly mature as erythrocytes
1% to 2%
Reticulocyte matures to form
Erythrocyte
- formation of BEN (basophil, eosinophil, neutrophil)
Granulopoiesis
- Myeloid cells account for __% - __% of the nucleated cells in normal bone marrow
23% to 85%
(MYELOID) Early cells are located in the
cords and around the bone trabeculae
Neutrophils in the bone marrow reside in the:
✓ Proliferating Pool - where cells spend an average of 3 to 6 days and released in:
✓ Maturation Storage Pool
If needed, cells from the storage pool can exit into the circulation rapidly and will have an average life span of ________ hours
If there is an infection, cells from storage pools are ______
6 to 10 hours; released
MATURATION SERIES (GRANULOPOIESIS)
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
– no cytoplasmic granule
Myeloblast
– first azurophilic granules being secreted in Golgi apparatus
Promyelocyte
moderate number of azurophilic granules and initial production of specific granules in Golgi zone
Myelocyte
abundant specific granules and dispersed azurophilic granules; Golgi apparatus reduced
Metamyelocyte
▪ most immature recognizable cell
▪ has finely dispersed chromatin, and faint nucleoli
▪ can be seen in bone marrow
Myeloblast
▪ characterized by its basophilic cytoplasm and azurophilic granules containing lysosomal enzymes and myeloperoxidase
▪ produce lineages for the three types of granulocytes
Promyelocyte
▪ with gradual increase of specific granules
Myelocytes
▪ specific granules eventually occupy most of the cytoplasm
▪ mature with further condensations of the nuclei
Metamyelocyte
▪ stage at which granulocytes are clearly identified if it is eosinophil, basophil or neutrophil
Metamyelocyte
▪ Mature basophil, eosinophil, neutrophil
Mature Granulocyre
cells that are capable of undergoing mitosis
Granulopoietic compartment
acts as a buffer system (releases cells when needed)
Storage compartment
FUNCTIONAL COMPARTMENTS OF NEUTROPHILS in Bone Marrow
Granulopoietic and Storage Compartment
FUNCTIONAL COMPARTMENTS OF NEUTROPHILS inBlood
Circulating cells
Marginating Cells
they circulate throughout the blood
Circulating cells
they try to adhere to endothelial cells
Marginating cells
(TRUE OR FALSE)
Increase in the number of neutrophils in the circulation, does not necessarily imply an increase in neutrophil production
TRUE
▪ can cause neutrophils in the marginating compartment to move into the circulating compartment
▪ those cells attached to endothelial cells detach and move to the circulation = increase in neutrophil count
INTENSE MUSCULAR ACTIVITY OR THE
ADMINISTRATION OF EPINEPHRINE
▪ increase the mitotic activity of neutrophil precursors in the marrow
ADMINISTRATION OF GLUCOCORTICOIDS (ADRENAL GLAND HORMONES)
▪ is due to an increase in production of neutrophils and shorter duration cells in the medullary storage compartment
BACTERIAL INFECTIONS NEUTROPHILIA
▪ Immature cells may appear in the bloodstream
→ Examples are band neutrophils
BACTERIAL INFECTIONS NEUTROPHILIA
- Formation of monocytes
Monocytopoiesis
MATURATION SERIES (Monocytopoiesis)
Monoblast
Promonocyte
Monocyte
▪ is a committed progenitor cell
▪ identical to the myeloblast in its morphologic
characteristics
Monoblast
▪ a large cell (up to 18 m in diameter) with basophilic cytoplasm and a large, slightly indented nucleus
▪ chromatin is lacy and nucleoli are evident
▪ divide twice as they develop into monocytes
Promonocyte
▪ rich in RER, has extensive Golgi apparatus in which granule condensation occurs
▪ no specific granule, only azurophilic granule
Monocyte
observed as fine azurophilic granules in blood monocytes
– function for several months as macrophages as they enter tissues
Primary Lysosomes
LYMPHOPOIESIS
* arose from
Lymphoid Stem Cell
lymphocytes and plasma cells are produced in
lymphoid follicles
Lymphoid cells typically account for __% - __% of the nucleated cells in the normal bone marrow
1% to 5%
all lymphocyte progenitor cells originate in the
bone marrow
Circulating lymphocytes originate mainly in the:
✓ Thymus (t-lymphocytes)
✓ peripheral lymphoid organs (B-lymphocytes)
→ from the word “bursa”
MATURATION SERIES (Lymphopoiesis)
Lymphoblast
Prolymphocytes
Lymphocytes (T-Lymphocyte or B-Lymphocyte)
▪ the first identifiable progenitor of lymphoid cells
▪ divides two or three times
Lymphoblast
▪ are smaller and have relatively more condensed chromatin but none of the cell-surface antigens that mark T or B lymphocytes.
Prolymphocytes
▪ acquire their full attributes in the thymus
▪ mature in thymus
▪ predominant lymphocyte in the lymphoid organs
T-Lymphocyte
▪ lymphocytes that have differentiated in the bone marrow
▪ acquire their full attributes in the bursa
▪ migrate to peripheral lymphoid organs, where they inhabit and multiply in their own special compartments
B-Lymphocyte
To distinguished this two (T-Lymphocyte or B-Lymphocyte), _________________________________________ are required.
Cluster differentiation markers are present
(T-Lymphocyte or B-Lymphocyte)
- are malignant clones of leukocyte precursors
- blast cells became malignant or tumor cells
Leukemias
General groups of leukemias:
Lymphocytic leukemias
Myelogenous and Monocytic leukemias
→ involves blast cell of lymphocytes
Lymphocytic leukemias
→ Involve blast cells of BEN or monocytes
Myelogenous and Monocytic leukemias
- shift in cell proliferation
- patient with leukemia is usually ________________________ because WBCs in the circulation are the blast cells.
anemic and prone to infection
Clinical technique used in the study of leukemias
BONE MARROW ASPIRATION
specific to membrane proteins of precursor blood cells aids in identifying cell types derived from these stem cells
labeled monoclonal antibodies
- Also known as thrombocytopoiesis
- Platelet production
Megakaryopoiesis
MATURATION SERIES (Megakaryopoiesis)
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Platelet
▪ are the largest cells found in the bone marrow
▪ Protrude through the vascular wall as small cytoplasmic processes to deliver platelets into the sinusoidal blood
Megakaryocytes
Megakaryocytes develop into platelets in approximately
5 days
▪ Metabolically active cell fragments.
▪ cytoplasmic fragments of megakaryocytes
Mature platelets
▪ These anuclear cells circulate in the peripheral blood after being produced from the cytoplasm of bone marrow megakaryocytes
▪ Appear as aggregates in blood smear.
Mature platelets
- Disease characterized by decreased number of platelets
- Indicating a defect in the liberation mechanism of these corpuscles
THROMBOCYTOPENIC PURPURA
- Life span of platelets: 9 days
- Excessive bleeding is expected when there is wound
THROMBOCYTOPENIC PURPURA