Haemopoiesis

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What is Haemopoiesis

Process that forms blood cells

Name the 3 types of Haemopoiesis

(1) Erythropoiesis-RBCs (2) Thrombopoiesis- Platelets (3) Leucopoiesis- WBCs

Where does Haemopoiesis take place?

(Adults)- Bone marrow( intra medullary) of vertebrae, ribs, sternum, skull, sacrum & pelvis, proximal ends of femur (Infants)- Bone marrow (Foetus): 0-2 yolk sac of embryo, 2-7 liver, spleen ( extra medullary), 5-9 bone marrow.

Where does Haemopoiesis begin?

Pluripotent stem cell- independently replicate, proliferate and differentiate= rise of mature blood cells. Signup and view all the answers

Describe the bone marrow

(1) hollow, contains connective tissues & where Haemopoiesis occurs (2) Haemopoietic tissues: - stem cells, erythroblasts, myoblasts, sinuses, non Haemopoietic cells (3) Adhesion molecules in the extracellular matrix (4) Extracellular matrix. Signup and view all the answers

Function of sinuses ?

Vascular spaces of pools of blood lining the endothelial cells & regulate the release of mature and immature cells in the blood Signup and view all the answers

Function of non- Haemopoietic cells

Support the bone marrow & produce growth factors e.g stromal cells like fibroblasts that produce collagen that support other cells, macrophages that produce growth factors, promote RBC production, iron storage and rids debris and Adipocytes that store energy as fat. Signup and view all the answers

What retains immature blood cells in the bone marrow, ensuring they’re not released prematurely?

Adhesion Molecules Signup and view all the answers

Function of Extracellular matrix of bone marrow

Controls stem cell mobilisation ( Extracellular matrix releases haemopoietic stem cells in response to stimuli e.g injury) and stem cell homing( attracts circulating Haemopoietic stem cells & keeps them in the bone marrow until optimal proliferation can occur) Signup and view all the answers

What is the role of stem cell factor( SCF) growth factor in Haemopoiesis?

SCF acts on pluripotent stem cells = differentiation into either: (1) common myeloid progenitor cells or (2) common lymphoid progenitor cells. Signup and view all the answers

What is the role of colony stimulating factor GM-CSF ?

Can non specifically stimulate the differentiation of blood cells into RBCs, WBCs & Platelets Signup and view all the answers

What is the role of Erythopoietin in Haemopoiesis?

Acts in erythroid precursors= stimulation of RBC production. Signup and view all the answers

What is the function of Thrombopoietin in Haemopoiesis?

Stimulates platelet production Signup and view all the answers

What is the function of Granulocyte colony stimulating factor (G-CSF)?

Stimulates production of granulocytes Signup and view all the answers

What is the function of M-CSF?

Stimulates the production of monocytes Signup and view all the answers

Describe Apoptosis

Tightly regulated process of physiological cell death, individual cells are triggered to activate intracellular proteins= death of cell. Characterised morphologically by: 1.Cell shrinkage 2.Condensation of nuclear chromatin 3.Fragmentation of the nucleus 4.Cleavage of DNA at internucleosomal sites Apoptosis results from the action of caspases, these are activated due to cleavage=endonuclease digestion of the DNA and disintegration of the cell skeleton Signup and view all the answers

Describe the red blood cell

3.9-6.5X10^12/ L is the normal concentration Transport lung O2→tissue Highly specialised cell- no nucleus or mitochondria Red due to haemoglobin Flat, biconcave disc shape Centre of pallar- lighter part of the cell, takes up ⅓ of the cell Approx 3 microns in diameter. Produced in the bone marrow, circulate for 120 days and removed by the liver or spleen Signup and view all the answers

How does erythropoeisis occur? RBC formation.

→ Earliest stem cell in the RBC pathway= common myeloid progenitor cell-CFU-GEMM. → CFU-GEMM can give rise to other stem cells, however erythropoietin is specific to red blood cell formation. → Erythropoietin acts on common erythroid and megakaryocyte progenitor cells(CFU-EMK)= committed erythroid specific progenitor cells( CFU-E)= pronormoblast= erythroblast= nucleated red blood cells. Approx 0.5-1.5% of reticulocytes is normal, 2.5%+ of reticulocytes= pathological condition. → As the pathway proceeds, the cells become smaller , and haemoglobin synthesis becomes prominent. → Nucleated red blood cell loses nucleas( nuclear extravasation), as it becomes a reticulocyte. → Some reticulocytes will remain in the bone and some will pass from the bone marrow and mature into RBCs or erythrocytes. → Transformation from reticulocyte→ erythrocyte can take about 3-4 days and can occur in the bone marrow or in the blood. Signup and view all the answers

How does erythripoeisis regulated?

By Erythropoeitin 90% of erythropoeitin is produced in the peritubular interstitial cells of the outer cortex of the kidney; 10% in the liver and elsewhere. Erythroporetin is produced only in response to O2 tension(hypoxia) in the tissues of the kidneys. Hypoxia occurs= hypoxia inducable factors: HIFa & HIFb to stimulate erythropoeitin production. So erythropoetin production increases in conditions such as aneamia, atmospheric O2 is low, defective cardiac or pulmonary function, damage to the renal circulation, affecting delivery of O2 to the kidney. Signup and view all the answers

Describe Thrombopoeisis-platelet production

Small blood cells that lack nuclei-approx 1-4 micrometers long Main function= produce platelet plug in response to vascular injury Shortest lifespan of all the bloodcells- 7-10 days circulation before being removed by macrophages. Generated at a rate of 10^11 daily and are fragments of megakaryocytes. Produced in the bone marrow from fragments of the cytoplasm of megakaryocytes-driven by thrombopoeitin synthesised in the liver. Megakaryocytes mature via endomitotic replication- DNA replication without cell division- platelets bud off the cytoplasm of megakaryocytes. Blood and bone marrow levels of threombopoeitin is directly related to platelet count- due to thrombopoeitin only being produced when platelets are required. Signup and view all the answers

Describe Granulocytes

4 Main types of cells differentiated depending on the set of granules they have in their cytoplasm: 1- basophils: have between 2-5 lobes, their granules will stain a lilac colour- last 6-10 hours in the bloodstream before moving from the capillaries to the tissue-phagocytosis of bacteria and inflammation function. 2- eosinophils: bi-lobed nucleus, paler cytoplasm with orange granules- protects against parasitic infections and participates in the allergic response. 3- neutrophils: lobulated nucleus , with large purple staining granules, circulate in the blood in tiny numbers and then migrate to the tissue-involved in hypersensitivity reactions and release histamine and heparin. 4-monocytes: largest of all the blood cells, kidney shaped nuclues, circulate for 24 hours before migrating to tissues such as the lungs and the liver and then they become macrophages- involved in phagocytosis of bacteria and releasing cytokines. Signup and view all the answers

Describe T-lymphocyte

B & T cells are the 2 main lymphocytes-both arise from haemopoeitic stem cells( IL-7)- Common lymphoied progenitor cells. T cells: develop from cells that have migrated to the thymus: the maturation of T cells is recognised by the presence of certain molecules on the surface of the cell & the arrangement of genes leading to the T cell receptor. They recognise antigens by surface expressed, highly variable T cell receptors.Two types of T cells: Helper T cells; Cytotoxic T cell. → T cell receptors cannot bind to antigens directly so peptides of the antigen are presented on APC’s e.g MHC 1 OR MHC 2. MHC1 presents to cytotoxic T cells; whereas MHC2 presents to Helper T cells. T cells cooperate in antibody production and also recognise and destroy cells infected with viruses. Signup and view all the answers

Describe B lymphocyte

B cells: mature in the bone marrow and circulate in peripheral blood until antigen recognition on pathogens occurs. They are at the centre of the adaptive immune response and they are responsible for mediating the production of antigen specific immunoglobulins( Ig(GAMED)) against invasive pathogens. Signup and view all the answers

Describe bone marrow aspiration

<ol> <li>bone marrow aspiration( small amount of liquid taken from the bone & pulled into the syringe); the aspiration is smeared onto a slide & stained using Romanowsky stain- provides cell population & morphology of cells or Pearls stain- common but specific stain and detects the presence of ion in biopsy specimens e.g deposits of ferritin iron in the bone marrow biopsy sample,</li> </ol> Signup and view all the answers

Describe the M/E ratio

Cellularity alters throughout life: a normal adult will have 50:50 haemopoetic cells: fat cells; in kids it's 70:30 and older people it’s 30:70. → In a healthy individual the myeloid white blood cell precursors exceed the number of erythroid red blood cell precursors in a ratio of 3:1( M/E ratio)- important in disease diagnosis. Signup and view all the answers

What is fluorescence flow cytometry?

Assess cell population depending on their size and granularity. It can be modified with fluorochrome linked to these antibodies to probe for the presence of different types of molecules that are present on the surface of a cell. It can also be modified to look at molecules that are within the cytoplasm. This technique uses monoclonal antibodies that are conjugated to fluorochromes to define cell surface glycoproteins e.g CD34 ( a marker of stem cells). Signup and view all the answers