HEMATOPOIESIS
A lecture by: Maximo B. Axibal, Jr. MD FPSP
HEMATOPOIESIS
DEF: Process of ____ of cellular elements of the blood
Production, Differentiation, Maturation & Proliferation
Stages: Fetal or adult?
HEMATOPOIESIS Types of Maturation
Synchronous Asynchronous
Medullary Extramedullary
Introduction
BM largest tissue in the body Adult: 4 L; Child: 1. 6 L BM 1 site for blood cell formation
2.5 billion RBCs / kg / day 2.5 billion platelets / kg / day 1 billion granulocytes / kg / day
Introduction
# of circulating blood cells depends on:
Rate of production Rate of release Survival
Production & destruction occur simultaneously & constantly
INTERRELATIONSHIP OF BLOOD CELLS: Theories
Monopheletic (Downey, Ferat & Pappenheim) Polypheletic (Piney, Naegali, Schilling, Rosenthal, Osgood, Sabin, Cunningham & Doan) Naegali Modification of Schilling Sabin & her co-workers
HEMATOPOIESIS
HEMATOPOIESIS: Mesenchymal period
Start: 4th wk AOG End: 2nd mon AOG
Products: Nucleated megaloblastic RBC's (2 wks AOG) Minor production of MKs
HEMATOPOIESIS: Mesenchymal (Yolk Sac) period
Mesoblastic(19-20 d): Erythropoietic Islands PNRBCs
Mesodermal (8-12 w): Extraembryonic 3 Embryonic Hgbs Megakaryopoiesis
HEMATOPOIESIS: Hepatic period
Start: End of 11th wk AOG End: 6th mon AOG Products: Extravascular erythroblasts & anucleated macrocytic RBC's Megakaryocytes- 6th wk AOG Granulocytes6th wk AOG Lymphocytes4th mon AOG Monocytes5th mon AOG
HEMATOPOIESIS: Medullary period
Start: 10th wk AOG (6th mon AOG- predominant) End: Lifetime Products: RBC's- 10th wk AOG Thrombocytes Granulocytes/ monocytes Lymphocytes- w/ contributions from thymus, L.N. & spleen (Ag independent)
HEMATOPOIESIS: Medullary period
RBC - Alpha 1 & alpha2 beta2 3 wks postpartum BM (Medullary) 4th y - rate of BM production exceeds need for blood cells
MATURATION FEATURES: NUCLEUS (DNA)
DEC N:C CHROMATIN: HETEROGENOUS HOMOGENOUS (WBC) to CLUMPED (RBC) NUCLEOLI (RNA): PRESENT DISAPPEARS
INDENTATION APPEARS (GRANULOCYTES) LOBULATIONS APPEAR (GRANULOCYTES) SOMETIMES DISAPPEAR (RBC)
MATURATION FEATURES: CYTOPLASM (RNA)
DEC N:C DEEP BLUE LIGHT BLUE (WBC) sometimes PINK (RBC) GRANULES APPEAR CELL SIZE DECREASES IN SIZE
Bone Marrow Morphology (Erythropoiesis)
HEMATOPOIESIS
Hematopoietic Regulatory Factors
Cytokines: Regulate proliferation, differentiation, function Glycoproteins Multilineage or lineage specific Redundant & complex specificities Both positive & negative feedback mechanism
Colony Stimulating factors (CSF) Interleukins (IL) Stem Cell Factor (SCF) Tumor Necrosis Factor (TNF) Transforming growth factors (TGF) Interferon (IF)
GF (1o TARGET) CHR (SOURCE)
IL 1 (STEM CELLS, LYMPHOCYTES, ENDOTHELIAL CELL)
2 (MONOCYTE)
IL 3 (STEM CELLS, MYELOID, ERYTHROID, MK)
5 (T CELL)
GF (1o TARGET) CHR (SOURCE)
IL 4 (BASOPHIL, B/ T LYMPHOCYTE)
5 (T CELL)
5 (T CELL) 7 (WBC, FIBROBLAST)
IL 5 (EOSINOPHIL, B LYMPHOCYTE)
IL 6 (STEM CELLS, B/T LYMPHOCYTE)
GF (1o TARGET) CHR (SOURCE)
IL 7 (LYMPHOCYTE)
? (WBC)
? (WBC) ? (LYMPHOCYTE) 17 (MONO, EC, FIBROBLAST)
IL 8 (GRANULOCYTE)
IL 9 (GRANULOCYTE)
G- CSF (ERYTHROID CELLS, MK)
GF (1o TARGET) CHR (SOURCE)
M- CSF (MONOCYTE)
5 (MONO, EC)
GM- CSF (GRANULOCYTE, MONOCYTE, MK)
5 (T CELL, MONO, EC)
EPO (RBCs)
7 (KIDNEY, LIVER)
Hematopoietic Cell Release
Cellular migration:
Cords through endothelial cells circulation
Normally only mature cells released Immature cells released under abnormal circumstances: Immature RBCs- hypoxia, hemolytic anemias Immature granulocytes- severe infections, sepsis Marrow replacement- fibrosis, neoplasm
LYMPHOPOIESIS
LYMPHOBLAST PROLYMPHOCYTE MATURE LYMPHOCYTE
Lymphopoiesis
BM & lymphatic organs: T-cells
BM Thymus Mature T-cells PB
B cells
BM LN (educated) PB gut lymphoid tissue, spleen Plasma Cells
Lymphopoiesis (Lymphoblasts)
THROMBOPOIESIS
MEGAKARYOBLAST PROMK MK PLATELET
Megakaryopoiesis
MONOPOEISIS
MONOBLAST PROMONOCYTE MONOCYTE
Monopoiesis
Monoblast
Promonocyte
Mature Monocytes
GRANULOPOIESIS
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
GRANULOPOIESIS
Granulopoiesis (Myeloblast)
Granulopoiesis (Promyelocyte)
Granulopoiesis (Myelocyte)
Granulopoiesis (Metamyelocyte)
Granulopoiesis (Band)
Granulopoiesis (Segmented Neutrophil)
Granulopoiesis (Kinetics)
Stage/s capable of mitosis?
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
Stage where azurophilic granule formation begin?
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
Stage where specific granule formation begin?
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
Stage where nuclear indentation begin?
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
1st stage where granulocytes can be classified as N E or B?
MYELOBLAST PROMYELOCYTE MYELOCYTE METAMYELOCYTE (JUVENILE) STAB (BAND; STAFF) MATURE NEUTROPHIL (PMN/ SEG); EOSINOPHIL; BASOPHIL
ERYTHROPOIESIS
PRONORMOBLAST BASOPHILIC NB POLY- CHROMAT NB ORTHO- CHROMAT NB POLYCHROMATOPH ILIC NORMOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
ERYTHROPOIESIS
RUBRIBLAST PRORUBRICYTE RUBRICYTE METARUBRICYTE RETICULOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
Erythrocytic Series
Rubriblast, Pronormoblast, Erythroblast, E1 Prorubricyte, Early NB, Basophilic NB, E2 Rubricyte, Intermediate NB, Polychromatic NB, E4 Metarubricyte, Late NB, Orthochromatic NB, E5 Reticulocyte, Polychromatic Normocyte Erythrocyte (Normocyte, Akaryocyte, Erythroplastid, Discocyte)
Stages capable of mitosis?
PRONORMOBLAST BASOPHILIC NB POLY- CHROMAT NB ORTHO- CHROMAT NB POLYCHROMATOPH ILIC NORMOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
Stages capable of hgb synthesis?
PRONORMOBLAST BASOPHILIC NB POLY- CHROMAT NB ORTHO- CHROMAT NB POLYCHROMATOPH ILIC NORMOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
Stage where chromatin is clumped?
PRONORMOBLAST BASOPHILIC NB POLY- CHROMAT NB ORTHO- CHROMAT NB POLYCHROMATOPH ILIC NORMOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
Stage where nucleus is extruded out of the RBC?
PRONORMOBLAST BASOPHILIC NB POLY- CHROMAT NB ORTHO- CHROMAT NB POLYCHROMATOPH ILIC NORMOCYTE MATURE RBC; ERYTHROCYTE; DISCOCYTE
Erythropoiesis (Pronormoblast)
Erythropoiesis (Basophilic Normoblast)
Erythropoiesis (Polychromatophilic Normoblast)
Erythropoiesis (Orthrochromic Normoblast)
Erythropoiesis (Polychromatophilic Erythrocyte/Reticulocyte)
Erythropoiesis (Mature Erythrocyte/RBC)
Erythropoiesis
Proerythroblast Basophilic erythroblast
Polychromatophilic erythroblast
Orthochromatophilic erythroblast
Reticulocyte
Mature RBC
Erythropoiesis (Kinetics)
Bone Marrow Differentiation
Myeloid Stem Cell
Pluripotent Stem Cell Lymphoid Stem Cell
Erythroblast
Megblast
Myeloblast
Monoblast
Tlympho blast
Blympho blast
T-cell RBC Platelet PMN Eos Baso Mono
B-cell Plasma cell
