Presentation on theme: "HISTOLOGY 1.8.: HEMATOPOIESIS Prenatal:"— Presentation transcript:
1HISTOLOGY 1.8.: HEMATOPOIESIS Prenatal: Blood cell generation begins in the wall of the yolk sac duringintrauterine life: primitive erythroblasts derive from mesenchyme.Later the hematopoietic cells migrate to the liver.Then the bone marrow, spleen, lymph nodes and thymus of theembryo are seeded with hematopoietic stem cells from the liverand become engaged with hematopoiesis.
2II. Postnatal hematopoiesis The major site of hematopoiesis is the bone marrow, it also persistsin the liver and spleen for a few weeks after birth (potential is retained).Early in life all the marrow is active, with age the demand forblood cells decreases: red marrow is replaced by resting yellowmarrow.Red bone marrow is present in the adult animal:sternumvertebraeribsskullpelvisepiphyses of long bones
3Structure of the bone marrow The hematopoietic compartment consists of irregularanastomosing cords that lie between vascular sinuses.The marrow lacks lymphatic vesselsInnervation: vasomotor nerves around the blood vesselsBone marrow smearBone marrow in sternumHematopoietic compartment
4Blood cells are produced in the hematopoietic compartment and reach the bloodstream by crossing the wall of vascular sinuses.Adventitial reticular cells:meshwork that support hematopoietic cells and provide specialmicroenvironment that influence the development of the variousstem cells.They may fill with fat and transform into adipose cells whenhematopoiesis decreases.Marrow hematopoiesis: is most active in areas close to the bone.Erythropoietic cells and megakaryocytes are close to vascularsinuses.Granulopoietic cells are deep within the cords, away from the vascular
5Hematopoietic stem cells: Undifferentiated cells are generally larger than mature cells,they have large euchromatic nuclei (large nuclear-to-cytoplasmic ratio).The marrow contains several types of self-replicating stem cells.Their morphology resembles that of lymphocytes, but their proliferatingcapacity differs: pluripotentmultipotent stem cellsunipotentEmbryonic yolk sac, fetal liver,spleen, bone marrow:primitive stem cells (pluripotent)Lymphoid stem cells myeloid stem cells (multipotent)Lymphocytes erythrocytic granulocytic monocytic megakaryocytic(They are all unipotent cell types)
6Hematopoietic and stromal stem cell differentiation
7CFU-E (Colony-forming unit-erythrocyte) (Rubriblast)16-22 mm(Metarubricyte)12-15 mm(Rubricyte)14-18 mm(Prorubricyte)10-12 mm
8Erythron: mass of circulating erythrocytes + marrow erythropoietic tissue Efficacy of erythropoiesis in a dog: 1 million/secondErythroblastic islands: group of erythrocytic cells within the bone marroworganized around a macrophage (more mature ones at the periphery).
92. Prorubricyte (arrowhead) 1. Rubriblast (arrow)largest, with deep blue cytoplasmand round euchromatic nucleus2. Prorubricyte (arrowhead)Similar, but smaller, no nucleoli4. Metarubricyte: the smallestnucleated erythrocyte withpicnotic nucleus4.3.3. Basophilic rubricyte: nucleus withclumped chromatin
10ReticulocyteMature mammalian erythrocytesErythrocyte kinetics:Development of rubriblasts to mature erythrocytes: 5-7 daysReticulocytes: normally 1-2 days maturation within the bone marrowRegulation of erythrocyte formation: cellular and humoral factorserythropoietin: key-molecule produced in the kidney
11GranulopoiesisOccurs in clusters away from the vascular sinuses in the midportionof the hematopoietic compartment of the marrowCFU-GM: colony-forming units-granulocyte-monocyte (bipotent)Neutrophil and /or monocyte progenitor cells15-18 mm10-15 mm18-22 mm
12Myeloblast: ovoid or spherical cell, spherical euchromatic nucleus, light blue cytoplasm.Promyelocyte: larger, similar nucleus,more cytoplasm, with azurophilicgranules.Myelocyte: spherical to slightly indented nucleus, some chromatincondensation, specific and azurophilic granules.Specific granules indicate the type of granulocyte to bedeveloped.Metamyelocyte: indented, kidney-shaped heterochromatic nucleus,specific granules have their characteristic colours.Band-form: further nuclear indentation, C,-S,-V-shaped nuclei.Mature forms: marked segmented nuclei and specific granules
13Granulocyte kinetics: Compartments of granulocytic cells:proliferative (mitotic) with myeloblasts,promyelocytes, myelocytesmaturative (postmitotic) with metamyelocytes,band neutrophilsreserve (storage) with mature neutrophilsProduction time for granulocytes: 5-7 daysCompartments of blood neutrophils: circulating (6-14 hours)marginatingTotal neutrophil pool in the blood is replaced at least twice a day.The production and kinetics of eosinophils, basophils and monocytesare similar to those of neutrophils.
14Formation of monocytes: monocytopoesis CFU-M: monocyte progenitor (common ancestor with neutrophils)Monoblast Promonocyte MonocyteAzurophilic granules Final shape and size of nucleusMonocytes reside in the blood stream for 24 hours, then enterthe connective tissue as CT macrophages.Their development is still not fully understood.
15Thrombopoiesis:CFU-MK: colony-forming unit-megakaryocyte: large sphericaleuchromatic nucleusMegakaryoblast: undergoes endomitosis, thus, only the nucleus dividesPromegakaryocyte: multilobed nucleus, lot of cytoplasmMegakaryocyte: largest hematopoietic cell in the marrow ( mm)
16Platelet kinetics:Platelets are produced by fragmentation of the megakaryocyticcytoplasm along demarcation membranes.Place of megakaryocytes in the bone marrow: against the sinus wall.They shed their platelets directly into the bloodstream, or extend theircytoplasmic projections through the endothelium into the sinus lumen.Life span of platelets: 9-12 days in domestic species.Place of storage: spleenRegulation of platelet formation: local regulatory factors andthrombopoietin produced in the kidney.
17Lymphopoiesis Stem cells derive from the bone marrow. Lymphoid stem cells: pre-B-lymphocyte B-lymphoblast B-lymphocytepre-T-lymphocyte T-lymphoblast T-lymphocyteStem cells derive from the bone marrow.Maturation process for B-lymphocytes: bone marrow, GALT(bursa-equivalent organs)Maturation process for T-lymphocytes: thymus