Hematopoeisis Flashcards
Where does hematopoeisis take place in the fetus during the first trimester?
There are islands of hematopoeisis in the yolk sac that develop from hemangioblasts
What are hemangioblasts?
Progenitors for both hematopoeitic and endothelial cells
Where does hematopoeisis take place in the fetus during the second trimester?
Liver and spleen
[this is extramedullary hematopoeisis, meaning outside the bone]
Where does hematopoeisis take place in the fetus in the 7th month of pregnancy?
In the bone marrow, which now becomes the primary source of hematopoeisis
Bone marrow remains the primary source of hematopoeisis into adulthood, and dominates in which skeletal areas?
Skull Clavicles Vertebrae Ribs Sternum Pelvis Ends of long bones
When in crisis, adults can reactivate previous sites of active marrow in an attempt to increase hematopoeisis. Which two extramedullary areas are targeted?
Liver and spleen
Bone marrow consists of what 2 compartments?
Hematopoietic cell compartment
Marrow stromal compartment
Which area of the bone marrow is highly vascular?
Hematopoeitic cell compartment
Which area of the bone marrow produces hematopoeitic growth factors (endothelial cells, marrow fibroblasts, and reticulocytes)
Marrow stromal compartment
What is the source of energy for the marrow stromal compartment?
Adipose cells
_________ bone marrow is not active in blood cell formation because it is made up predominantly of adipose cells
Yellow
What is the chief form of bone marrow in the medullary cavities of bones in adults, particularly long bones of the arms, legs, fingers, and toes?
Yellow bone marrow
[although hematopoeitically active bone marrow does contain some fat]
A slide showing no red in the bony trabeculae would indicate _________ anemia, meaning no production of any cells in the bone marrow
Aplastic
Stromal structure consists of:
Stroma, which contains __________ connective tissue, adipocytes, and macrophages.
Hematopoeitic _______, which are bundles of blood cells at different stages of maturation.
Vascular ___________, which lie between the above structures and ar elined with endothelial cells. Often ____________ discharge protoplatelets into this area.
Reticular
Cords
Sinusoids; megakaryocytes
What is the significance of hematopoeitic stem cells?
They are capable of self-renewal; very few cells can do this and there is a potential for malignancy.
________ stimulates the differentiation of multipotent (pluripotent) hematopoeitic stem cells into lymphoid progenitor cells, as well as proliferation of all cells in the lymphoid lineage.
IL-7
Committed precursor cells generate distinct cell lineages under the influence of 5 _________, derived from the myeloid stem cell
CFUs (colony-forming units)
What cell types are derived from the lymphoid progenitor cells?
B cells
T cells
NK cells
What cell types are derived from the myeloid stem cells?
RBCs Platelets Monocytes (macrophages) Neutrophils Eosinophils Basophils
Maturing cells in either cell lineage are considered committed. ________ _________ preserves the pool of stem cells and is critical for feeding common myeloid progenitor and common lymphoid progenitor into the differentiation or maturation pathway.
Self renewal
What is the primary control for proliferative and maturational phases of hematopoiesis, and can also be used as a clinical treatment?
Hematopoietic growth factors
These are produced in bone marrow by endothelial cells, stromal cells, fibroblasts, developing lymphocytes, and macrophages
What are the 3 major groups of hematopoietic growth factors?
Colony-Stimulating Factors (CSF’s)
Erythropoietin (EPO) and Thrombopoietin (TPO)
Cytokines (primarily interleukins)
__________ is the growth factor for neutrophils
G-CSF
__________ is the growth factor for neutrophils, eosinophils, basophils, monocytes, and dendritic cells. It acts synergistically with EPO to support RBC lineage and with TPO to stimulate megakaryocyte progenitors
GM-CSF
__________ is the growth factor for macrophages
M-CSF
__________ is the growth factor for the erythroid lineage
EPO
__________ is the growth factor for megakarycyte progenitors and hematopoietic stem cells
TPO
___________ is also known as c-Kit ligand or Steel factor. It is produced by fetal tissues and bone marrow and acts as a weak stimulator of hematopoiesis. It makes stem cells responsive to other cytokines
SCF (Stem Cell Factor)
_______ ligand is closely related to SCF. It acts on pluripotent stem cells in synergy with TPO, SCF, and interleukins
Flt3
________ is the interleukin that influences replication and growth potential of hematopoietic progenitors
IL-3
Which interleukins act on pluripotent stem cells to develop into lymphoid stem cells?
IL-1
IL-4
Which interleukins are specific to B and T cell growth and development?
IL-2 –> T cells
IL-2 and IL-6 –> B cells
True or false: GM-CSF is less potent than G-CSF for increasing neutrophils during neutropenia
True
EPO is the hematopoietic growth factor primarily produced in the ___________ in response to _________, and stimulates the formation of erythrocytes
Kidney; hypoxia
[thus EPO synthesis is severely impaired in chronic renal disease]
The effectiveness of EPO treatment can be monitored by an increase in _____________ in peripheral blood
Reticulocytes
TPO is primarily produced in the ________, but also by kidney and skeletal muscle
Liver
TPO is responsible for stimulating an increase in megakaryocytes and ___________, leading to bleeding issues in patients with chronic liver disease
Platelets
T-cell progenies are produced in the _________
B-cell progenies are produced in the _________
Thymus
Bone marrow
What is the general trend in nucleus:cytosol ratio as hematopoietic cell populations mature?
Nucleus gets smaller, cytosol increases
Thrombocytes (platelets) secrete _____________, and stick together to form a temporary platelet plug
Vasoconstrictors
What is the first cell type that begins erythropoiesis?
Proerythroblast
At what stage in erythropoeisis would you have a 14-19 micrometer cell, large central nucleus, ribosomes making hemoglobin, and active mitosis?
Proerythroblast
At what stage in erythropoiesis do you have a 13-16 micrometer cell with a smaller nucleus than a proerythroblast, patchy chromatin, basophilic cytoplasm, and active mitosis?
Basophilic erythroblast
At what stage in erythropoiesis do you have a 12-15 micrometer cell with a smaller nucleus than a basophilic erythroblast, condensed chromatin, light blue staining clumps of polyribosomes, light pink staining hemoglobin, and active mitosis?
Polychromatic erythroblast
Polychromatophilic erythroblasts have a characteristic ______________-appearance, and are ______ independent. From this point forward the cells will NOT be mitotically active.
Checkerboard
EPO
At what stage of erythropoiesis do you have an 8-10 micrometer cell with a dense, eccentric (pyknotic) nucleus, pink cytoplasm, and no active mitosis happening?
Orthochromatic erythroblast
At what stage in erythropoiesis do you have a 7-8 micrometer cell where the nucleus has been extruded, cytoplasm is pink, and there are some blue-staining residual polyribosomes?
Reticulocytes
[this is 1% of circulating RBCs]
EPO (erythropoietin) is a glycoprotein. 90% of it is produced in the _________ in response to hypoxia. EPO synthesis is severely impaired in chronic ________ disease, and the effectiveness of EPO treatment can be monitored by an increase in ______________ in peripheral blood.
Kidneys
Renal
Reticulocytes
___________ mature into erythrocytes after one day in circulation
Reticulocytes
A normal RBC has a central __________ at 1/2 - 3/5 diameter and measures 7-8 micrometers.
Pallor
While looking at a slide, you note pinkish cytoplasm with parts of it tinged blue. The nucleus is condensed, dark, and partially extruded. What stage of erythropoeisis is this cell?
Orthochromatophilic erythroblast
While looking at a slide you note that a cell has the same amount of cytoplasm as an RBC, and a supravital stain reveals a blue endoplasmic reticulum. There is no nucleus present. What stage of erythropoeisis is this cell?
Reticulocyte
While looking at a slide you note a large central nucleus. The cytoplasm is blue with deep blue clumps in pale gray-blue background. The nucleus is round with fine burgundy colored chromatin and 3-5 pale nucleoli. What stage of erythropoiesis is this cell in?
Proerythroblast
While looking at a slide you notice a smaller nucleus with patchy chromatin. The cytoplasm has bluish clumps on pale blue with a hint of gray-pink background. The nucleus is round and the chromatin appears coarse. What stage of erythropoiesis is this cell in?
Basophilic erythroblast
While looking at a slide you notice a smaller nucleus, condensed chromatin, and light blue clumps of polyribosomes. The cytoplasm is yellow-pink with a blue tinge. The nucleus is small, round, with checkerboard chromatin, without nucleoli. What stage of erythropoiesis is this cell in?
Polychromatophilic erythroblast
In chronic kidney disease, EPO production decreases. What condition would this result in?
Anemia
[treatment would include administration of recombinant erythropoeitin, effectiveness depends on increase in reticulocytes in the blood]
90% of EPO is produced in the kidneys. Where else is it produced?
Retina and CNS (neurons and glial cells)
How would you distinguish between a megakaryocyte and an osteoclast?
Megakaryocytes have a multilobed nucleus, while osteoclasts are multinucleated
_____________ rest next to sinusoids and extend protoplatelet projections between the endothelial cells into the sinusoids where they are shed.
Megakaryocytes
During what stage of hematopoiesis would you see a 15-50 micrometer cell with a large oval or kidney-shaped nucleus and basophilic cytoplasm?
Megakaryoblast
During what stage of hematopoiesis would you see a 100 micrometer cell with a unique large multilobed nucleus (polypoid)?
Megakaryocyte
What causes the megakaryocyte to have a large multilobed nucleus?
Endomitosis - nuclear divisions occur without cell division
What is the major regulator of megakaryocyte and platelet development?
TPO (thrombopoietin)
Where is the majority of TPO produced, and where else is is produced?
Mostly in the liver, in smaller amounts in kidney and bone marrow
TPO would be decreased in a condition of chronic liver disease. This would result in what condition?
Thrombocytopenia (decreased platelets)
[tx would include administration of TPO or receptor agonists, and effectiveness is based on increase in platelets in the blood]
_____________ refers to leukopoiesis where heterochromatin content increases, no specific granules form, no nuclear lobulation, and a cell size decrease
Agranulopoiesis
What cell types undergo agranulopoiesis?
Lymphocytes (from lymphoid stem cells), and monocytes (from myeloid stem cells)
____________ refers to leukopoeisis where chromatin condenses, cytoplasmic granules form, nucleus becomes lobulated, and cell size decreases
Granulopoiesis
What cell types undergo granulopoiesis?
Neutrophils, basophils, eosinophils (all from myeloid stem cells)
___________ are cells responsible for phagocytizing bacteria and releasing antimicrobial chemicals
Neutrophils
____________ are phagocytic cells that form antigen-antibody complexes, respond to allergens, and inflammatory chemicals. They also participate in antiparasitic and bactericidal responses
Eosinophils
______________ are cells that secrete histamine and heparin. They participate in inflammatory reactions during immune responses and allergies
Basophils
What is a “left-shift” when referring to hematopoiesis?
An increase in immature cell lineages and a decrease in mature cells (occurs in cancer)
What is the first cell type in leukopoiesis?
Myeloblast
At what stage in leukopoiesis would you see cytoplasm with small blue clumps on light blue background, no granules, and cytoplasmic blebs extend from periphery. The nucleus appears red blue, fine chromatin, and 2-3 pale nucleoli
Myeloblast
At what stage in leukopoeisis would you see blueish cytoplasm with many small dark azurophilic granules, as well as a red-blue nucleus, medium and increasingly coarse chromatin, and a nucleolus
Promyelocyte
At what stage in leukopoeisis would you see pale blue cytoplasm, dark azurophilic and smaller neutrophilic granules, a clear paranuclear Golgi; the nucleus is medium, somewhat flattened, eccentric, and with somewhat coarse chromatin, no distinct nucleoli?
Neutrophilic myelocyte
At what stage in leukopoeisis would you see pale cytoplasm with the golgi nestled in the indentation of the nucleus; the nucleus is indented, acentric, with dense dark chromatin, and no nucleoli?
Neutrophilic metamyelocyte
During what stage in leukopoiesis would you see blue cytoplasm, both azurophilic and neutrophilic cytoplasm, and a horseshoe shaped dark-blue nucleus with very coarse chromatin and no nucleoli?
Neutrophilic band/stab cell
What do monocytes differentiate into?
Macrophages
What type of agranulocyte has a large, round, euchromatic nucleus, no cytoplasmic granules, active mitosis, and are identical to myeloblasts?
Monoblasts
What type of agranulocyte is 18 micrometers with a large, slightly indented nucleus, and divide several times prior to becoming monocytes?
Promonocytes
What type of agranulocyte is 12-18 micrometers and is the mature cell form with an indented, U-shaped nucleus, and “foamy” weakly basophilic cytoplasm?
Monocytes
Lymphocytes include B and T cells, which cannot be distinguished by light microscopes.
_____ cells secrete antibodies
______ cells destroy cancer cells, virus infected cells, and foreign cells
B
T
How would you distinguish lymphocytes from other cell types?
12-20 micrometer cells with nucleus and 1-2 nucleoli. No cytoplasmic granules.
In a peripheral blood smear, their nucleus will be roughly the same size as a normal RBC, so they are a good marker to evaluate RBCs for type of anemia
Lymphocytes vary in size on peripheral blood smears. How do you distinguish between inactive vs. active lymphocytes?
Inactive = narrow rim cytoplasm
Active = increased cytoplasm
