Hematapoesis
Which cells provide a source of energy and synthesizes growth factors and in what compartment of the bone marrow are they found?
Adipose cells, Marrow stromal compartment.
LIst Granulocytes and Agranulocytes?
Agranulocytes = Lymphocytes and Monocytes Granulocytes = Neutrophils, Eosinophils and Basophils
Differentiate between the two lineages of cells that form the myeloid and lymphoid stem cell populations.
Agranulopoiesis = Lymphocytes and Monocytes - Heterochromatin content increases - No specific granules form - No nuclear lobulation - Cell size decreases Granulopoiesis = Neutrophils, Eosinophils and Basophils (Granulocytes) - Chromatin condenses - Cytoplasmic granules form - Nucleus become lobulated - Cell size decreases
Describe the role of stem cell factor (SCF) in hematopoiesis.
Also known as c-Kit ligand or Steel factor Produced by fetal tissues and bone marrow Weak stimulator of hematopoiesis Makes stem cells responsive to other cytokines
LIst the 5 Colony forming units (CFU) that are derived from myeloid stem cells?
BFU-E --> Proerythroblast -->RBC CFU-Mega ---> Megakaryocyte --> Platelets CFU-GM --> Monoblast or Myeloblast --> Monocyte or Neutrophil. Eosinophilic Myeloblast --> Eosinophil Basophilic Myeloblast --> Basophil
Which cells of the Neutrophil lineage are found in the blood?
Bands, Neutrophils
Identify the three major groups of hematopoietic growth factor HGFs?
Colony-stimulating factors (CSF) - G-CSF - GM-CSF - M-CSF Erythropoietin (EPO) and thrombopoietin (TPO) Cytokines (primarily interleukins) (IL-3, IL-2, IL-6)
Explain the general significance of hematopoietic growth factor (HGF)?
Control proliferative and maturational phases of hematopoiesis Used for clinical treatments Produced in bone marrow by endothelial cells, stromal cells, fibroblasts, developing lymphocytes, and macrophages
Predict the erythropoietin level during chronic kidney disease. • This would result in what condition? • How could you treat this patient? • How can you determine the effectiveness of treatment?
EO level is decreased. This would result in anemia. In order to treat you would Administer recombinant erythropoietin via IV. Remember Major regulator of erythropoiesis - 90% produced in kidney in response to hypoxia - Also produced in neurons and glial cells of the central nervous system (CNS) and retina.
What cells in the Marrow stromal compartment separates it from the Hematopoietic Cell compartment?
Epithelial cells
Which Hematopoietic cells deliver oxygen from lungs to tissues and pick up carbon dioxide from the tissues and unload it in the lungs?
Erythrocytes (RBCs)
Which Colony-stimulating factors (CSF) stimulates the formation Erythrocytes (RBC)?
Erythropoietin (EPO)
What Acts on pluripotent stems cell in synergy with TPO SCF, and Interleukins to promote proliferation and differentiation of various blood cell progenitors AND is associated with SCF?
Flt3 ligand
Which Colony-stimulating factors (CSF) is produced by endothelial cells, fibroblasts, and macrophages and stimulates an increase in neutrophils?
G-CSF
Which Colony-stimulating factors (CSF) is used in treatment for neutropenia after chemotherapy, bone marrow transplant?
G-CSF More potent than GM-SF for increasing neutrophils during neutropenia
Which Colony-stimulating factors (CSF) is produced by endothelial cells, T cells, fibroblasts, and monocytes and stimulates the formation of all leukocytes and reticulocytes?
GM-SF (granulocyte-macrophage colony stimulating factor)
Describe the progression (in terms of time) of hematopoiesis in the fetus to the adult.
Hematopoiesis activity in... Starts in Fetus: Yolk sac (3-8 weeks) Liver (6-30 weeks) Spleen (9-28 weeks) Bone Marrow (28 weeks onward) Adult Bone marrow Skull, clavicles, vertebrae, ribs, sternum, pelvis, and ends of the long bones
Which bone marrow compartment is highly vascular and contains Hematopoietic stem cells that are committed precursor cells (Maturing cells)?
Hematopoietic Cell Compartment
Identify the structure of the bone marrow compartments?
Hematopoietic Cell Compartment Marrow Stromal Compartment
Which term refers to bundles of blood cells at different stages of maturation?
Hematopoietic cords
Summarize the general characteristics of the three basic hematopoietic stem cell populations: hematopoietic stem cells (myeloid/lymphoid), committed precursor cells (CFUs) and maturing cells.
Hematopoietic stem cell: capable of self-renewal Committed Precursor cells: generation of distinct cell lineages 5 colony-forming units (CFUs) derive from the myeloid stem cell Maturing cells are committed
Which cytokine(s) act on pluripotent stems cell to develop lymphoid stem cells?
IL-1, IL-4
Which cytokine(s) are also known as T-cell growth factor?
IL-2
Which cytokine(s) are important for B-cell differentiation?
IL-2, IL-6
Which cytokine(s) Influences the replication and growth potential of hematopoietic progenitors of the myeloid lineage?
IL-3
Where is Erythropoietin (EO) primarily made?
Kidney
What is distinctive to know about Megakaryoblasts?
Large Oval or Kidney-shaped Nucleus
Where in the body is Thrombopoietin (TPO) primarily made?
Liver
What are the vascular Sinusoids?
Located between Hematopoietic cords It is Lined with endothelial cells Often have megakaryocytes discharging protoplatelets into the sinusoid
Which Colony-stimulating factors (CSF) stimulates an increase in monocytes and macrophages?
M-CSF (macrophage colony-stimulating factor)s
Moncytes differentiate into...?
Macrophages Kupffer cells = LIver (most) Osteoclast = bone Langerhans = skin Microglia = Brain In spleen think REd pulp
Which cells remove of dead cells and debris in the Marrow stromal compartment of the bone marrow?
Macrophages.
List and describe progression of Monocyte Maturation?
Monoblast - Large round euchromatic nucleus, No cytoplasmic granules, Mitotic, Identical to Myeloblast. Promonocyte - Large slightly indented nucleus, Divide several times before becoming monocytes Monocyte - Mature cell Macrophage - Emigrated blood monocytes that differentiate in tissues, Found at sites of infection
List progression of Basophil Maturation?
Myeloblast Promyelocyte Basophilic Myelocyte Basophilic Metamyelocyte Basophilic Band Basophil Mast Cell
List progression of Eosinophil Maturation?
Myeloblast Promyelocyte Eosinophilic Myelocyte EosinophilicMetamyelocyte Eosinophilic Band Eosinophil
Describe the progression of neutrophil maturation?
Myeloblast - Mitotic, Large round euchromatic nucleus, No cytoplasmic granules. Promyelocyte - Mitotic, large flattened Nucleus, Condensed chromatin, Azurophilic granules present. Myelocyte - Mitotic, indented nucleus, Specific granules accumulate, Smaller than promyelocyte Metamyelocyte - NOT MITOTIC, Meta "beyond," Deeply indented nucleus, Densely packed specific granules. Band - Horseshoe-shaped Nucleus, Chromatin condensed and lobulated, 3-5% of circulating leukocytes. Polymorphonuclear Neutrophil
Which are the major components of the erythroid lineage that are located in the periphery normally?
Polychromatic erythrocyte (reticulocyte) Erythrocyte
List the 2 Colony Forming Units that are derived from Lymphoid stem cells?
Pre B cell -->B lymphoblast --> B Lymphocyte ProThymocyte --> T lymphoblast --> T lymphocyte
Describe and identify the major components of the erythroid lineage.
Pronormoblast (Proeyrthroblast) - Mitotic, Large Nucleus, Ribosomes make hemoglobin. Basophilic Normoblast - Mitotic, smaller Nucleus, Patchy Chromatin, Basophilic Cytoplasm. Polychromatic Normoblast - Mitotic, Smaller Nucleus, Condensed Chromatin, Light blue staining clumps of polyribosomes, Light pink staining hemoglobin Orthochromic Normoblast - Not mitotic, dense, eccentric (pyknotic) nucleus, pink Cytoplasm Polychromatic erythrocyte (reticulocyte) - 1% of circulating RBCs, Nucleus was extruded(thrust out), Pink cytoplasm, Blue staining residual polyribosomes, not mitotic. Erythrocyte - Mature cell (looks like a donut - no blue stain, white in the middle)
What are the two types of marrow? Differentiate them?
Red Marrow = All bone marrow starts off as Red in newborns. Hematopoietically active. Yellow Marrow = is yellow based on the presence of adipocytes. Hematopeotically inactive. In the adult, red and yellow marrow fluctuates based on the hematopoietic needs of the individual
Where do B cell and T cells Mature?
T-Cells Mature in the Thymus B-Cells Mature in the Bone Marrow
Predict the thrombopoietin level during chronic liver disease. • This would result in what condition? • How could you treat this patient? • How can you determine the effectiveness of treatment?
TPO level low. Results in Thrombocytopenia (low platelet count). You can treat this patient by Administering TPO or receptor agonist. You determine the effectiveness of treatment by getting platelet count level.
What is Hematopoiesis?
The formation of red blood cells (RBC)
Which Hematopoietic cells secrete vasoconstrictors and stick together to form a temporary plug?
Thrombocytes (Platelets)
Which Colony-stimulating factors (CSF) stimulates an increase in megakaryocytes and platelets?
Thrombopoietin (TPO)
Which cells produce hematopoietic growth factors and in what compartment of the bone marrow do they reside?
endothelial cells, marrow fibroblasts and stromal (reticular) cells Marrow Stromal Compartment
Describe important things to know about the staining of cells that we need to identify?
haematoxylin and eosin staining DNA is stained blue. Eosin is a dye that binds protein so pink color will reflect hemoglobin.
Higher numbers Bands and Neutrophils indicate what?
may indicate infection
Adult stem cells and cord blood stem cells are considered _________.
multipotent
What is Stroma?
support or connective tissue necessary for hematopoiesis. Reticular connective tissue Adipocytes and macrophages