2) Origin of blood cell Flashcards
Define haematopoiesis
It is the production of RBC, WBC and platelets from HSC (Haemoatopoietic Stem Cells). Highly regulated to maintain constant cell numbers. Requires enormous less replication and maintains between self renewal, terminal differentiation and migration of cell death.
Describe the anatomy of haematopoiesis
In foetal development, during the 1st trimester - in yolk sac. 2nd - liver and spleen. 3rd - central peripheral skeleton. In adulthood - restricted to bone marrow.
Describe the cellular pathways haematopoiesis
There are pluripotent/ multipotent stem cells. These become either lymphoid or myeloid stem cells. Both differentiate into progenitors, precursors then the final mature blood cell.
Going down the lymphoid pathway, they differentiate to T-cells or B-cells to plasma cells.
Myeloids can split to make erythrocytes, neutrophils, monocytes (turns into macrophages) , eosinophils, basophils and megakaryocyes, which becomes platelets.
Describe the specific differentiation pathways.
RBC = Erythropoeisis:
Multipotential Hemotopoietic SC - Common myeloid progenitor- proerythroblast - basophilic erythroblast - polychromatic erythroblast - orthochromatic erythroblast - polychromatic erythroblast - erythrocyte
Neutrophils = Granulopoiesis:
Mulitipotential hemotopoigetic SC - Common myeloid progenitor - granulocyte monocyte progenitor - myeloblast - promyelocyte - myelocyte - metamyelocyte - band - segmental neutrophil
Platelets = Thrombopoeiesis:
Mulitipotential hemotopoigetic SC - Common myeloid progenitor - Megakaryocyte erythrocyte progenitor - megakaryoblast MK-I - Promegakaryocyte MK-II - Megakayocyte MK-III- Platelets
Eiosinophils = Granulopoiesis:
Mulitipotential hemotopoigetic SC - Common myeloid progenitor - Eiosinophi-basophil progenitor - myelopblast - promyelocyte - eosinophillic myelocyte - eosinophillic band - eosinophil
Monocyte = Monopoiesis:
Mulitipotential hemotopoigetic SC - Common myeloid progenitor - Granulocyte-monocyte progenitor - mono blast - promonocyte - monocyte - macrophage
Lymphocyte = lymphopoiesis
Stem cell - lymphoid progenitor - B-lymphocytes and T-lymphocytes
There is an antigen independent phase, antigen dependent phase and a memory phase.
Describe the haematopoietic growth factors for blood cells formation
There is a polypeptide growth factor. HSC come in contact with stromal cells. There is cell-cell communication by binding via cell-surface transmembrane receptors to secrete cytokines to growth factor. This stimulates the growth and survival of progenitors
Understand the formation of blood cells
All formed elements of the blood derive from a common progenitor – the hematopoietic stem cells, HSCs. HSCs are multipotent, meaning they can differentiate to all types of blood cells. They also have the ability to multiply constantly to maintain their numbers in the bone marrow. Formation of blood cells from hematopoietic stem cells is a multi-step process, involving several intermediate progenitors, and is regulated by a network of signaling molecules, known as cytokines. These cytokines control the proliferation, differentiation and survival or death of the various progenitors. By doing so, they maintain steady-state levels of blood cells in normal situations; and, in response to certain stimuli, induce production of a particular cell type. For example, in response to blood loss, production of red blood cells is accelerated.
Differentiation starts when progenitor cells develop surface receptors for a specific stimulating factor. Once this happened, the cells lose their potency and become committed to a certain cell type.
Production of red blood cells, RBC, or erythrocytes, is stimulated by erythropoietin, EPO. During the differentiation process, the cells reduce in size, increase in number, start making hemoglobin, and lose their nucleus. EPO is produced predominantly by the liver during fetal development and by the kidneys in adulthood. Low levels of EPO are constitutively secreted and are sufficient to compensate for normal red blood cell turnover. When RBC count drops, such as during blood loss, the resulting oxygen-deficiency state, hypoxemia, is detected by the kidneys. The kidneys respond by increasing their EPO secretion, which leads to increased red blood cell production by the end of 3 to 5 days. People living at high altitudes usually have higher RBC count as a response to lower oxygen levels. Athletes whose demand for oxygen is more elevated, also have higher RBC counts.
Production of granulocytes and macrophages, the key players of the body’s innate immune response, is controlled by several colony-stimulating factors, CSFs. Normally, these cells are kept at a more or less constant number, by relatively low levels of CSFs, but their production can increase greatly and quickly upon infection. CSFs are commonly secreted by mature lymphocytes and macrophages, but can be produced, if needed, by virtually any organ or cell type. CSF production may increase a thousand-fold in response to indicators of infection, such as bacterial endotoxins.
Production of platelets is stimulated by thrombopoietin, TPO, a hormone secreted by the kidneys and liver. TPO is responsible for formation of megakaryocytes – the gigantic cells that develop as a result of multiple rounds of DNA replication without cell division. A megakaryocyte gives rise to tens of thousands of platelets, which are essentially broken fragments of its cytoplasm. Production of platelets is subject to a classic negative feedback loop: reduced platelet levels in the blood promote their production, while elevated levels inhibit it.
