Hematopoiesis (Part I) Flashcards
What does hematopoiesis begin with?
the pluripotent stem cell
What is the first split off of the pluripotent stem cell?
it will become either a myeloid stem cell or a lymphoid stem cell
What stems from the myeloid stem cell?
erythroblasts, megakaryoblasts, monoblasts, and myeloblasts
what is derived from erythroblasts?
RBCs
what is derived from megakaryoblasts?
platelets
what is derived from monoblasts?
monocytes
What is derived from myeloblasts?
neutrophils, eosinophils, and basophils
What stems from the lymphoid stem cell?
a pre-B cell and a Prothymocyte
what is derived from the prothymocyte?
a T lymphocyte
What are the different sites of hematopoiesis in chronological order?
yolk sac, liver, spleen, and then finally the bone marrow
What happens to hematopoiesis shortly after puberty?
prior to puberty, hematopoiesis occurs throughout all bones in the body; however, shortly after puberty, hematopoiesis occurs in more of an axillary location including the skull, sternum, ribs, vertebrae, pelvis, and proximal femur
Within the bone marrow, there are two principal compartments. What are they?
the hematopoietic cell compartment and the marrow stromal compartment
What does the hematopoietic cell compartment of the bone marrow consist of?
an erythroblastic area, a myeloid area, megakaryocytes
What does the marrow stromal compartment consist of?
endothelial cells, adipocytes, stromal cells and fibroblasts, and macrophages
what is the purpose of the endothelial cells in the marrow stromal compartment?
they are fenestrated, so they allow the mature cells to come out into the circulation and become our peripheral blood
what is the main role of all of the stromal compartment cells?
they are responsible for helping us produce the hematopoietic growth factors
how can you calculate the percentage of cellularity a person should have in their bone marrow? and what does this tell us?
you subtract their age from 100; this helps us calculate to see if someone’s bone marrow is hypocellular or hypercellular
How is the process of hematopoiesis regulated?
hematopoietic growth factors
where are hematopoietic growth factors produced?
in bone marrow by endothelial cells, stromal cells, fibroblasts, developing lymphocytes, and macrophages
what are the chief hematopoietic growth factors?
colony-stimulating factors (CSF), cytokines (interleukins), erythropoietin (EPO), Thrombopoietin (TPO)
what is the first potentiator of hematopoietic differentiation?
stem cell factor (SCF)
what is stem cell factor produced by?
fetal tissues and bone marrow
what is the main role of stem cell factor (SCF)?
it makes stem cells responsive to other cytokines
What interleukins act as hematopoietic growth factors?
IL-3, IL-6, IL-2
what is the role of IL-3 as a hematopoietic growth factor?
it influences the replication and growth potential of hematopoietic progenitors (non-lymphoid stimulator)
what is the role of IL-6 as a hematopoietic growth factor?
it stimulates megakaryocytes and neutrophil production; it is a key factor in leukemoid reaction; it acts as a B-cell growth factor
what is the role of IL-2 as a hematopoietic growth factor?
it acts as a B and T cell growth factor
What is G-CSF?
granulocyte colony-stimulating factor
what is G-CSF produced by?
endothelial cells, fibroblasts, and macrophages
what is the role of G-CSF?
it stimulates an increase in neutrophils
why is G-CSF important to know about?
it has a direct therapeutic application; it is utilized in severe neutropenia after chemotherapy or bone marrow transplant ; it is also utilized for mobilization of hematopoietic stem cells and progenitor cells in bone marrow transplant donors in order to collect enough stem cells for transplantation
Where is erythropoietin primarily produced?
in the kidney in response to low pO2 levels
what is the role of erythropoietin?
it stimulates the formation of erythrocytes
what is erythropoietin used for for treatment purposes?
erythropoietin stimulating agents are used in clinical treatment for anemia
where is thrombopoietin produced?
in the liver
what is the role of thrombopoietin?
it stimulates an increase in megakaryocytes and platelets
What are the different steps of erythropoiesis?
- Pronormoblast (proerythroblast) 2. Basophilic normoblast (erythroblast) 3. polychromatic normoblast (erythroblast) 4. orthochromic normoblast (erythroblast) 5. polychromatic erythrocytes (reticulocyte) 6. Erythrocyte
what are 2 general features of proerythroblasts?
they have a large central nucleus and 3-5 pale nucleoli
what are the general characteristics of basophilic erythroblasts?
smaller nucleus, patchy chromatin, basophilic cytoplasm, bluish clumps
what are the general characteristics of polychromatophilic erythroblasts?
smaller nucleus, condensed chromatin, light blue clumps of polyribosomes, light pink HGB; CHECKERBOARD
what are the general characteristics of orthochromatophilic erythroblast?
dense chromatin (pyknotic) nucleus, pink cytoplasm
how does the cytoplasm appear in the orthochromatophilic erythroblast?
pinkish with slight tinge of blue
how does the nucleus appear in the orthochromatophilic erythroblast?
dark, condensed, round
what are the general characteristics of reticulocytes?
the nucleus is extruded; there are blue polyribosomes
how does the cytoplasm appear in reticulocytes?
same as the circulating RBCs, but a supravital stain reveals blue reticulum
how does the nucelus appear in reticulocytes?
there is no nucleus
what percentage of our blood composition is reticulocytes?
2%
in hemolytic anemias, what is the blood composition like (speak specifically of reticulocytes)?
the reticulocyte count or index will be increased
what are 2 examples of hemolytic anemias that will cause an increase in the reticulocyte count or index?
sickle cell or beta thalassemia
what happens when the reticulocyte count is increased?
there is an increase in red cell distribution width (since the reticulocytes are larger than normal erythrocytes
what can be seen in reticulocytes when they are stained with supravital dye?
they contain remnant endoplasmic reticulum and ribosomes
What are the 2 different types of Leukopoiesis?
agranulopoiesis and granulopoiesis
what are the four characteristics of agranulopoiesis?
heterochromatin content increases; no specific granules form; no nuclear lobulation; cell size decreases
what are the four characteristics of granulopoiesis?
chromatin condenses; cytoplasmic granules form; nucleus becomes lobulated; cell size decreases
what cells form via agranulopoiesis?
lymphocytes and monocytes
what cells form via granulopoiesis?
neutrophils, basophils, eosinophils
what are the steps in the maturation process of neutrophils?
- myeloblast 2. promyelocyte 3. myelocyte 4. metamyelocyte 5. Band cell 6. Polymorphonuclear neutrophil
during leukopoiesis of granulocytes, how does the cytoplasm appear during the myeloblast stage?
there are small blue clumps on a light blue background; NO GRANULES YET
during leukopoiesis of granulocytes, how does the nucleus appear during the myeloblast stage?
red-blue, round, fine chromatin, 2-3 PALE NUCLEOLI
during leukopoiesis of granulocytes, how does the cytoplasm appear during the promyelocyte stage?
bluish with MANY SMALL DARK AZUROPHILIC GRANULES
during leukopoiesis of granulocytes, how does the nucleus appear during the promyelocyte stage?
red-blue, round, chromatin is more coarse, there is a nucleolus
during leukopoiesis of granulocytes, how does the cytoplasm appear during the neutrophilic myelocyte stage?
pale blue, dark azurophilic and smaller neutrophilic (specific) granules, with a CLEAR PARANUCLEAR GOLGI
during leukopoiesis of granulocytes, how does the nucleus appear during the neutrophilic myelocyte stage?
round, somewhat FLATTENED, no distinct nucleoli
during leukopoiesis of granulocytes, how does the cytoplasm appear during the neutrophilic metamyelocyte stage?
paler, the GOLGI IS NESTLED IN INDENTATION OF NUCLEUS
during leukopoiesis of granulocytes, how does the nucelus appear during the neutrophilic metamyelocyte stage?
INDENTED, acentric, dark dense chromatin, no nucleoli
during leukopoiesis of granulocytes, how does the cytoplasm appear during the neutrophilic band/ stab cell stage?
increased blue appearance, there are BOTH AZUROPHILIC AND NEUTROPHILIC GRANULES
during leukopoiesis of granulocytes, how does the nucleus appear during the neutrophilic band/stab cell stage?
HORSESHOE-SHAPED, dark blue, very coarse chromatin, no nucleoli
what is the main roles of eosinophils?
they phagocytize antigen-antibody complexes, allergens, and inflammatory chemicals; they have antiplastic and bactericidal activity
what is the main role of basophils?
they secrete histamine and heparin; inflammatory reactions during immune responses and allergies
What occurs during lymphocytic leukopoiesis?
B and T lymphoblasts are created in the bone marrow
what are plasma cells created from?
activated B cells which have encountered antigenic stimuli after help from T cells
how do plasma cells appear?
they have an eccentrically placed nucleus and perinuclear hoff (golgi)
where do plasma cells arise?
in secondary lymphoid organs such as the spleen and lymph nodes
what are the steps of hematopoiesis: platelets?
- megakaryblast 2. megakaryocyte 3. platelets
how do megakaryblasts appear?
as a large oval or kidney shaped nucleus; basophilic cytoplasm
how do megakaryocytes appear?
large multilobed nucleus; DNA replication without cell division–> endomitosis (polyploid nucleus); plasma membrane invaginations
how are thousands of platelets released from a single megakaryocyte?
through a process of plasma membrane invagination
what are the steps to macrophage formation?
stem cell–> monoblast–> monocyte–> macrophage–> tissue specific macrophages
what are the macrophages of the bone?
osteoclasts
how can monocytes be recognized on a blood smear?
by their characteristic nuclear appearance
what color are the first granules to appear in the developing neutrophils?
dark red/ purple
what color are the secondary granules to appear in the developing neutrophils?
lilac or light purple
what color granules do mature basophils contain?
purple/blue specific granules
what color granules do eosinophils contain?
refractile orange specific granules
