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What does hematopoiesis refer to?

It refers to the ongoing production of RBCs, WBCs, and Platelets.


How many red blood cells are produced every day?

~175 Billion


Where are blood cells produced?

In the early embryo, they are produced in the yold sac. In the fetal stages, they are produced in the liver and spleen.   By the time of birth, they are produced in the bone marrow.   If the bone marrow is severely compromised in life, the liver and spleen may begin making them again.   In young children, blood cells are produced inmost of the marrow cavities throughout the body. In adults, they are mostly produced in vertebrae, pelvis, sternum, ribs, and calvarium.


What is the general structure of bone marrow?

Marrow space is encased in cortical bone and interspersed with trabecular bone.   It is highly, highly vascular with leaky endothelial capillaries, such that the space is effectively continuous with the rest of the plasma compartment.   Marrow stromal cells are bound to the non-luminal side of the endothelial cells and produce the protein framework of the marrow (type IV collagen) and the regulatory factors/adhesion molecules that maintain hematopoiesis.


What are the earliest hematopoietic cells in the process?

The hematopoietic stem cells are the earlist precusors of the process.   They are not very common and cannot be recognized morphologically.   Can be identified by binding CD34 and CD117.   Their unique function is ASYMMETRIC CELL DIVISION, giving rise to one daughter cell and one multipotent PROGENITOR cell.


What are the stages of progenitor cells?

Multipotent progenitor cells - capable of differentiating into all lymphoid and myeloid cells.     Oligopotential progenitor cells - either common myeloid progenitor cells OR common lymphoid progenitor cells.   Lineage-restricted progenitor cells 


How many cells will a lineage-restricted progenitor cell give rise to, and how does this influence the concentration of hematopoietic stem cells?

One lineage restricted progenitor cell may give rise to 2000 red or white blood cells.   Thus, there cannot be too many hematopoietic stem cells around due to the severe amplification that results from their lineage.


At what point in their development do RBCs lose their nucleus?

After they have made all of their hemoglobin.   At that point, they do not need to produce anything else.   Staining-wise, this means that the Wright stain will be blue while there are many ribosomes present in the cell to red at there is more hemoglobin and fewer ribosomes.


What are the first cells in the red cell lineage that are identifiable in a smear, and what is their morphology?

Pronormoblasts.  14-20 um in diameter.   Cytoplasm stains deep blue (basophilic), Nucleus is large and round to slightly oval, 1-3 nucleoli (help indicate that the nucleus is immature), 1% of nucleated cells in bone marrow.


What is the order of cells leading to the production of erythrocytes?

Pronormoblast, Basophilic Normoblast, Polychromic Normoblast, Orthochromic Normoblast (last stage with nucleus), Polychromatic Erythrocyte, Reticulocyte (still has residual RNA), Erythrocyte.     (PBPOPE)



What is the typical timeline for erythrocyte creation?

3-5 mitotic divisions between pronormoblast and polychromatophilic normoblast stage.  2-7 days for propnormoblasts to mature into orthochromic normoblast.  1 more day to extrude the nucleus, and the reticulocyte spends 2-3 days maturing in the marrow.


What hormone stimuates RBC development and what triggers its activation?

Erythropoietin (EPO) stimulates the production of RBCs.  It is produced in response to hypoxia.   EPO acts to:   Activate stem cells of bone marrow to divide into pronormoblasts, increase the rate of mitosis and the maturation process, increase rate of hemoglobin production, causes increased rate of reticulocyte release into the peripheral blood.


What are the granulocytes and what differentiates them?

Neutrophils, basophils, & eosinophils.   They are differentiated by the staining properties of the compounds in their granules. ( red, blue, nuetral)


What is the order of cell precursors of granulocytes?

Myoblast, Promyelocyte, Myelocyte (secondary granules that differentially bind stain appear; myelocyte also refers only to neutrophil myelocytes b/c eosinophils and basophils are very rare in comparison), Metamyelocyte, Band (after the indentation in the nucleus is more than 1/2 the thickness of the nucleus), Segmented Granulocyte (totally segmented nucleus, usually 3 parts).


What are the stimulating hormones and timeline for granulocyte development?

Granulocyte colony stimulating factor (G-CSF) initiates granulocyte development.   Myeloblasts, Promyelocytes, and Myelocytes undergo cell division in the mitotic pool (4-5 cell divisions, 3-6 days).  Metamyelocytes, Bands, and Segs do not divide. (5-7 days in maturation and storage pools)


How do neutrophils circulate in the blood and how much time do they spend there?

50% of neutrophils circulate freely (circulating pool), 50% adhere to the walls of blood vessels (marginal pool) and these cell trade places rapidly.   Average time spent in peripheral blood is 10 hours before leaving the blood stream.


Three characteristics of neutrophils

Their granules contain destructive enzymes used to destroy microorganisms.   They also have phagocytic activity.   Mature segmented neutrophil granulocytes are called PMNs for polymorphonuclear leukocytes, or "segs" and "polys".


How many nuclear lobes do eosinophils have and how long do they live?   What are they specialized for?

Generally 2 lobes, and live for 8-12 days.   Their granulocytes are used to fight organisms too large to phagocytoze (parasite, fungi, worms). Also involved in mast cell modulation. IL-5 is the main cytokine responsible for their production.


What stimulates the production of monocytes and how long do they circulate in the blood?

Production is stimulated by monocyte-colony stimuating factor (M-CSF).   Timeline of their maturation in marrow is not well understood.   Mature monocytes will circulate in the blood for about 20 days before entering tissues to become macrophages, some reside in the marrow.


What are teh stages of monocyte development?

Promonocyte, monocyte


How many platelets are produced every day, how many can be produced, and what initiates their production?

Around 100 Trillion platelets are produced per day, and that can be increased 20-fold if needed.   Their production is initiated by by the cytokine thrombopoietin acting on a megakaryocyte/erythroid progenitor cell.


Where are most marrow biopsies taken in adults?

Posterior, superior iliac spine