Haemopoiesis Flashcards
Where does hemopoiesis occur?
Pluripotent stem cells for blood cell formation (hemopoiesis) occur in the bone marrow of children and adults.
What are progenator cells and what do they do?
Progenitor cells are committed to forming each type of mature blood cell.
They proliferate and differentiate within microenvironmental niches of stromal cells, other cells and ECM with specific growth factors.
These progenator cells are also known as colony forming units (CFUs) and the growth factors are also called colony stimulating factors (CSFs) or cytokines.
What are the different types of bone marrow?
Red bone marrow is active in hemopoiesis.
Yellow bone marrow consists mostly of adipose tissue.
What are erythropoietic islands?
Erythropoietic islands or cords within marrow contain the red blood cell lineage
- Proerythroblasts
- Erythroblasts with succeeding developmental stages called:
- Basophilic
- Polychromatophilic
- Orthochromatophilic
That reflect the cytoplasmic transition from RNA-rich to harmoglobin-filled.
What occurs at the last stage of erythropoiesis?
At the last stage of erythropoiesis, cell nuclei are extruded, producing reticulocytes that still contain some polyribosomes but are released into the circulation.
What does granulopoiesis involve?
Granulopoiesis includes
- myeloblasts, which have large nuclei and relatively little cytoplasm;
- promyelocytes, in which lysosomal azurophilic granules are produced;
- myelocytes, in which specific granules for one of the three types of granulocytes are formed;
- And metamyelocytes, in which the characteristic changes in nuclear morphology occur.
What are band cells?
Immature neutrophilic metamyelocytes called band (stab) cells are released prematurely when the compartment of circulating neutrophils is deleted during bacterial infections.
When are monocytes and lymphocytes procuced and from what?
Monoblasts produce monocytes in red marrow.
Lymphoblasts give rise to lymphocytes primarily in the lymphoid tissues in processes involving acquired immunity.
What are megakaryocytes and what do they do?
Megakaryocytes are large polyploid cells of red bone marrow.
They produce platelets or thrombocytes by releasing them from the ends of cytoplamic processes called proplatelets.
How do blood elements enter into the circulation?
All formed elements of blood enter the circulation by crossing the discontinuous endothelium of sinusoids in the red marrow.
Describe where hematopoiesis occurs at different stages of life.
Blood islets - yolk sac mesoderm - since third week.
Liver, spleen - starts at the second month.
Bone marrow - since the third month.
Describe bone marrow.
Red bone marrow and yellow bone marrow.
Red (hematogenous) bone marrow.
Stroma, hematopoietic cords and sinusoidal capillaries.
Stroma - reticular connective tissue - reticular cells, reticular fibres and macrophages.
Bone marrow is found in the medullary canals of long bones and in the small cavities of cancellous bone, with two types based on their appearance at gross examination:
- Blood-forming red bone marrow ,
- whose color is produced by an abundance of blood and hemopoietic cells
- Yellow bone marrow ,
- which is filled with adipocytes that exclude most hemopoietic cells.
In the newborn all bone marrow is red and active in blood cell production.
As the child grows, most of the marrow changes gradually to the yellow variety.
Under certain conditions, such as severe bleeding or hypoxia, yellow marrow reverts to red.
Red bone marrow contains
- a reticular connective tissue stroma,
- hemopoietic cords or islands of cells, and
- sinusoidal capillaries.
The stroma is a meshwork of:
- Specialized fibroblastic cells called stromal cells (also called reticular or adventitial cells)
- A delicate web of reticular fibers supporting the hemopoietic cells and macrophages
The matrix of bone marrow also contains:
- Collagen type I
- Proteoglycans
- Fibronectin
- Laminin
The latter glycoproteins interacting with integrins to bind cells to the matrix.
Red marrow is also a site where older, defective erythrocytes undergo phagocytosis by macrophages, which then reprocess hemebound iron for delivery to the differentiating erythrocytes.
What does the hematopoietic niche in marrow include?
The hematopoietic niche in marrow includes:
- The stroma
- Osteoblasts
- Megakeryocytes
Between the hematopoietic cords run:
- The sinusoids - which have discontinuous endothelium, through which newly differentiated blood cells and platelets enter the circulation.
Describe hemopoietic stem cells.
All blood cells arise from a single major type of pluripotent stem cell in the bone marrow that can give rise to all the blood cell types.
These pluripotent stem cells are rare, but they proliferate and form two major lineages of progenitor cells with restricted potentials (committed to produce specifi c blood cells):
- one for lymphoid cells (lymphocytes)
- The lymphoid progenitor cells migrate from the bone marrow to the thymus or the lymph nodes, spleen, and other lymphoid structures, where they proliferate and differentiate.
- another for myeloid cells (Gr. myelos, marrow) that develop in bone marrow.
- Myeloid cells include granulocytes, monocytes, erythrocytes, and megakaryocytes.
How is bone marrow examined?
Sternal punture
Trepanobiopsy:
- Bone marrow and bone tissue taken from the iliac bone.
- 2mm diameter.
- 15 mm length.
Explain the changes that occur during erythropoiesis.
Several major changes take place during erythropoiesis.
- Cell and nuclear volumes decrease
- 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)
- Simultaneous increase in the amount of hemoglobin (a highly eosinophilic protein)
- Mitochondria and other organelles gradually disappear
Explain the cell divisions during erythropoiesis.
There are three to five intervening cell divisions between the proerythroblast and the mature erythrocyte.
The development of an erythrocyte from its first recognizable progenitor cell to the release of reticulocytes into the blood takes approximately 1 week.
The glycoprotein erythropoietin, a growth factor produced by cells in the kidneys, stimulates production of mRNA for globins, the protein components of hemoglobin, and is essential for the production of erythrocytes.
The distinct progenitor cell of the erythroid series is the proerythroblast (~20um):
- Large cell
- Loose, lacy chromatin, nucleoli
- Basophilic cytoplasm.
The next stage is represented by the basophilic erythroblast (~10-16um), with:
- More strongly basophilic cytoplasm
- Condensed nucleus with no visible nucleolus
The basophilia of these two cell types is caused by the large number of polysomes synthesizing hemoglobin.
During the next stage:
- 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
- Now called a polychromatophilic erythroblast (~10-12um).
In the next stage:
- Cell and nuclear volumes continue to condense
- No basophilia is evident
- Highly condensed chromatin
- Resulting in a uniformly acidophilic cytoplasm—the orthochromatophilic erythroblast (~8-10um) (also called a normoblast ).
Late in this stage, this cell ejects its nucleus which is then phagocytosed by macrophages.
The cell still has a small number of polyribosomes that, when treated with the dye brilliant cresyl blue, form a faintly stained network and the cell is called the reticulocyte.
Reticulocytes pass to the circulation (where they may constitute 1% of the red blood cells), quickly lose the polyribosomes, and mature as erythrocytes.
Explain the process of granulopoiesis.
Granulopoiesis involves cytoplasmic changes dominated by synthesis of proteins for the azurophilic granules and specific granules.
These proteins are produced in the rough ER and the prominent Golgi apparatus in two successive stages.
Made initially are the azurophilic granules, which contain lysosomal hydrolases, stain with basic dyes, and are basically similar in all three types of granulocytes.
Golgi activity then changes to produce proteins for the specific granules, whose contents differ in each of the three types of granulocytes and endow each type with certain different properties.
In sections of bone marrow, cords of granulopoietic cells can be distinguished from erythropoietic cords by their granule-filled cytoplasm.
- Myeloblast
- 15-20um
- Spherical nucleus
- Nucleoli
- Promyelocyte I
- 22-25um
- Azurophilic granules
- Promyelocyte II
- First specific granules form (neutrophilic, eosinophilic, basophilic)
- Myelocyte
- 15-20um
- Oval nucleus
- Coarser chromatin clumps
- Metamyelocyte
- Horse shoe shaped nucleus
- Postmitotic
Explain the process of monocytopoiesis.
Monoblast:
- The monoblast is a committed progenitor cell that is virtually identical to the myeloblast morphologically
Promonocyte:
- Further differentiation leads to the promonocyte ,
- Large cell (up to 18 μ m in diameter)
- Basophilic cytoplasm
- Large, slightly indented nucleus
- The chromatin is lacy
- Nucleoli are evident
- Promonocytes divide twice as they develop into monocytes .
Monocyte:
- Extensive RER
- Large Golgi complexes forming lysosomes, which are observed as fine azurophilic granules at maturity
- Monocytes circulate in blood for several hours and enter tissues where they mature as macrophages (or other phagocytic cells)
- Function for up to several months
Explain the process of lymphopoiesis.
Lymphocytes are the smallest and the second most common type of white blood cell.
They are known as the cells of immunity.
Lymphocytes have large round/oval nuclei that occupies most of the cell with little cytoplasm.
The nucleus will stain dark purple or blue when it is exposed to a certain stain called Wright’s stain.
Lymphocytes function to provide a specific response to invading organisms.
There are two types of lymphocytes:
- T lymphocytes
- B lymphocytes
They are derived from the hematopoietic stem cell (HSC).
Lymphopoiesis or lymphocyte development occurs in the marrow and in the lymphoid organs to which precursor cells migrate from marrow.
- Pluripotent stem cell
- Lymphoid stem cell
- Lymphoblast (B or T)
- Prolymphocyte (B or T)
- Lymphocyte (B or T)
Describe the process of thrombopoiesis (megakaryocytopoiesis).
Megakaryocytes are produced from stem cells in the bone marrow by a process called thrombopoiesis.
Platelets have an average life span of 5–10 days.
Platelets are destroyed by phagocytosis.
