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Hematopoiesis
Is a continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation and maturation
Hematopoietic stem cell
A ______________ (multipotential stem cell, pluripotential stem cell, multipotent stem cell) is capable of cell-renewal (i.e., replenishment) and directed differentiation into all required cell lineages.
Yolk Sac
Sites of Hematopoiesis (Fetus) #1
Aorta-Gonad Mesonephros
Sites of Hematopoiesis (Fetus) #2
Fetal liver
Sites of Hematopoiesis (Fetus) #3
Bone Marrow
Sites of Hematopoiesis (Adult)
Mesoblastic Phase
Is considered to begin around the 19th day of embryonic development after fertilization.
Gower-1,
Hemoglobin needed for mesoblastic phase #1
Gower-2
Hemoglobin needed for mesoblastic phase #2
Portland
Hemoglobin needed for mesoblastic phase #3
Hepatic Phase
Begins to happen at 5 – 7 gestational weeks.
Hepatic Phase
Extravascular hematopoiesis
spleen, thymus, kidneys and lymph nodes
The developing _________________ contribute to the hematopoietic process during this phase.
Hgb F
The predominant hemoglobin for Hepatic Phase is
Hgb A
Detectable amount of adult hemoglobin in hematic phase _______ is present.
medulla
Derived its name from its location – “__________” meaning inside the bones.
mesenchymal cells
The ___________, which are a type of embryonic tissue, differentiate into structural elements
Bone Marrow
By the end of 24 weeks gestation, the ___________ becomes the primary site of hematopoiesis.
Granulocyte colony-stimulating factor (G-CSF)
Erythropoietin (EPO), ______________, and Hemoglobins A and F can be detected.
Extramedullary Hematopoiesis
Occurs when the BM cannot meet body requirements
Bone Marrow (BM), Liver, Spleen, Thymus, Lymph Nodes
Also called the Reticulo-Endothelial System (RES)
Bone Marrow
Contains developing erythroid, myeloid, megakaryocytic and lymphoid tissue.
Primary lymphoid
___________ tissue consists of the bone marrow and thymus is where T and B lymphocytes are derived.
Secondary lymphoid
_____________ tissue, where lymphoid cells respond to foreign antigens, consist of the spleen, lymph nodes, and mucosa-associated lymphoid tissue.
Red marrow
hematopoietically active marrow consisting of the developing blood cells and their progenitors.
Yellow Marrow
hematopoietically inactive marrow composed primarily of adipocytes (fat cells), with undifferentiated mesenchymal cells and macrophages.
Newborn
80 – 90% BM is active RED Marrow.
Young adult
60% of BM is active. Hematopoiesis is confined to the proximal end of long bones, large flat bones, pelvis and sternum.
Older adult
40% is active; 60% is fat.
Normocellular
marrow has 30-70% hematopoietic cells
Hypercellular/Hyperplastic
>70% hematopoietic cells.
Hypocellular/Hypoplastic
<30% hematopoietic cells
Aplastic
marrow has few or no hematopoietic cells.
3:1 – 4:1
M:E Ratio (Myeloid: Erythroid) Ratio
Granulocyte, Erythrocyte, Megakaryocyte, Monocyte
CFU – GEMM
Erythrocyte
CFU – E
Megakaryocyte
CFU – Meg
Monocyte
CFU – M
Granulocyte, Monocyte
CFU – GM
Myeloid to Basophil
CFU – BASO
Myeloid to Eosinophil
CFU - EO
Myeloid to Neutrophil
CFU – G
T Lymphocyte
CFU – pre – T
B Lymphocyte
CFU – pre – B
Erythropoiesis
occurs in the BM and is a complex, regulated process for maintaining, adequate numbers of erythrocytes in the peripheral blood.
CFU-GEMM
The _____________ gives rise to the earliest identifiable colony of RBCs called burst-forming unit-erythroid (BFU-E). BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into colony forming unit-erythroid (CFU-E) colonies. The CFU-E has many EPO receptors and has an absolute requirement for EPO.
burst-forming unit-erythroid (BFU-E)
The CFU-GEMM gives rise to the earliest identifiable colony of RBCs called ___________. BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into colony forming unit-erythroid (CFU-E) colonies. The CFU-E has many EPO receptors and has an absolute requirement for EPO.
colony forming unit-erythroid (CFU-E) colonies
The CFU-GEMM gives rise to the earliest identifiable colony of RBCs called burst-forming unit-erythroid (BFU-E). BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into ______________. The CFU-E has many EPO receptors and has an absolute requirement for EPO.
EPO
EPO serves as differentiation factor that causes the CFU-E to differentiate into pronormoblasts, the earliest visually recognized erythrocyte precursors in the BM.
myelopoiesis
Leukopoiesis can be divided into two major categories #1
lymphopoiesis
Leukopoiesis can be divided into two major categories #2
CFU-GEMM
__________ to differentiate into neutrophils, eosinophils and basophils includes GM-CSF, G-CSF, macrophage colony-stimulating factor (M-CSF), IL-3, IL-5, IL-11 and KIT Ligand.
macrophage colony-stimulating factor (M-CSF)
CFU-GEMM to differentiate into neutrophils, eosinophils and basophils includes GM-CSF, G-CSF, ___________, IL-3, IL-5, IL-11 and KIT Ligand.
IL-3
is a multi-lineage stimulating factor that stimulates the growth of granulocytes, monocytes, megakaryocytes and erythrocytes.
Eosinophils
requires GM-CSF, IL-5 & IL-3.
Basophils
requirements for differentiation are less clear, but it seems to depend on presence of IL-3 and KIT Ligand.
LYMPHOID
_______________differentiation requires IL-2, 7, 12, 15 and to some extent IL-4, 10, 13, 14, 16.
megakaryopoiesis
Early influences on ______________ are GM-CSF, IL-3, 6, 11, KIT Ligand and TPO.
Erythron
is the term used to describe the total population of mature RBC and their precursors in blood, bone marrow and other sites.
Pronormoblast
Size: 14 to 20 um
Pronormoblast
N:C Ratio = 8:1
Pronormoblast
Nucleoli: present (1-2) usually very faint
Basophilic Normoblast
Other name for Prorubricyte
Basophilic Normoblast
Size: 12 to 17 um
Basophilic Normoblast
Nucleoli: 0-1
Basophilic Normoblast
N:C Ratio = 6:1
Basophilic Normoblast
is the last stage with a nucleolus.
Basophilic Normoblast
gives rise to 4 rubricytes.
Polychromatic Normoblast
Other name for Rubricyte
Polychromatic Normoblast
Size: 10 to 15 um
Polychromatic Normoblast
N:C Ratio = 4:1
Polychromatic Normoblast
Last stage capable of mitosis (cell division).
Polychromatic Normoblast
Each of these cells (rubricyte) gives rise to 2 metarubricytes.
Polychromatic Normoblast
First stage of Hgb synthesis (Hemoglobinizations)
Polychromatic Normoblast
Checkerboard Appearance
Muddy/Gray
Lymphocyte
Crushed Velvet
Sky Blue/Robin Egg Blue
Orthocromatic Normoblast
Orthocromatic Normoblast
Other name for Metarubricyte
NRBC
Other name for Orthocromatic Normoblast
Orthocromatic Normoblast
Size: 7 to 12 um
Orthocromatic Normoblast
N:C Ratio = 0.5:1
Orthocromatic Normoblast
Cytoplasm: Salmon pink or pale blue
Orthocromatic Normoblast
Nucleus = pyknotic (dense mass of degenerated chromatin)
Orthocromatic Normoblast
Last stage with a nucleus.
Reticulocyte
Size: 7 to 10 um
Reticulocyte
Young RBC’s containing residual RNA (last immature erythrocyte stage)
Reticulocyte
Spend 2 to 3 days in the bone marrow and 1 day in the peripheral blood before developing into a mature RBC.
Reticulocyte
Last stage of Hemoglobin synthesis (Hemoglobinazation)
SHIFT CELLS
seen in conditions with Increase RBC production.
STRESS RETICULOCYTES
n in more severe condition (e.g. Anemia)
Mature Erythrocyte
RBC
600:1
Normal ratio of RBC to WBC is approximately
15:1
normal ratio of RBC to Platelets
mitochondria
Adult RBC contains no
10%
RBC Membrane: Carbohydrates
40%
RBC Membrane: Lipids
50%
RBC Membrane: Proteins
1%
Pronormoblast % in BM
1%-4%
Basopholic Normoblast % in BM