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62052
Haemopoiesis
Descrição
Blood Science Mapa Mental sobre Haemopoiesis, criado por maisie_oj em 29-04-2013.
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blood science
blood science
Mapa Mental por
maisie_oj
, atualizado more than 1 year ago
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maisie_oj
mais de 11 anos atrás
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Resumo de Recurso
Haemopoiesis
What is it?
Refers to the production of all the cells of the blood
Can be further split into
Erythropoiesis (RBCs)
Leukopoiesis (WBCs)
Thrombopoiesis (thrombocytes, aka platelets)
Begins during the 20th week of life in the foetal liver and spleen - this role is then taken over by the bone marrow in the young on into adulthood
The bone marrow
i.e. the site of haemopoiesis (in adults) - restricted to the proximal regions of long bones and the support skeleton
Develops in the embryo - from hollowing out of the long bones (forming a central cavity)
In the cavity a primitive, undifferntiated cell (haemocytoblast), or stem cell develops
All other blood cells are derived from this precursor (multipotent stem cell)
Totipotent (omnipotent) = embryonic blastocyst cells that can form ALL cells of the body and cells of the placental (not body) required for viability
Pluripotent = can form ALL cells of the body only
Multipotent = limited to produce ALL cells of a particular lineage (e.g. blood cells)
A combination of two tissues
The highly vascular red marrow (50%) is the site of blood cell production
The fatty yellow marrow (50%) - no blood production function
The 50:50 ratio can change and is measured as the level of marrow activity (marrow cellularity)
Blood cell development in the marrow
Immature cells are the largest and posses nucleoli (artefacts seen within the nucleus - mainly RNA in structure and are involved in mitosis)
In granulated cells (WBCs - neutrophils, basophils, eosinophils) the granules are acquired later in maturation
Erythrocyte nuclei are lost later in development
Developing cells are retained within the marrow until they are developed sufficiently and functionally capable
They are then released into the circulating bloodfor the remainder of their lifespan
Mechanism of haemopoiesis
Stem cells
All blood cells are produced by the bone marrow
They all come from a multipotent stem cell (haematopoietic stem cell, HSC)
Give rise to...
Myeloid cell lineage (RBCs, thrombocytes, granulocytes)
Lymphoid cell lineage (lymphocytes - B and T)
Self renewal / commitment into a commited cell lineage progenitor
Commitment -> progenitor cell 1 (e.g. common lyphoid progenitor)
Colony forming unit (CFU)
Division and differentiation
Morphologically distinct intermediate blast cell
Maturation
Mature blood cell type B
Morphologically distinct intermediate blast cell
Maturation
Mature blood cell type A
Renewed HSC (stem cell renewal)
->
Commitment -> progenitor cell 2 (e.g. comon myeloid progenitor)
Production of lineage blood cells
The bone marrow and spleen form a supportive environment (called the haemopoietic microenvironment)
Pluripotent stem cell (from developing blastocyst)
Multipotent stem cell (HSC in bone marrow)
Diameter 18-23um (large)
Give rise to myeloid and lymphoid progenitors
(Common) Myeloid progenitor
RBCs, granulocytes (PMNs, eosinophils, basophils) and thrombocytes
(Common) lymphoid progenitor
Lymphocytes only
Progenitor cells
= irreversibly commited stem cell (cannot self-renew)
Regulated by certain hormones or substances so that they can proliferate and undergo maturation
Growth factors (GFs)
Haemopoiesis occurs in a suitable microenvironment provided by a stromal matrix on which stem cells grow and divide
There are probably specific recognition and adhesion sites sites
Extracellular glycoproteins and other compounds are involved in the binding
Microenvironment (adhesion and growth factors) provided by local macrophages, ECM, adipocytes, fibroblasts etc.
E.g. granulocyte colony stimulating factor (G-CSF) - in the development and maturation of neutrophils (from myeloid progenitor)
Stimulates proliferation of early bone marrow cells
Causes direct differentiation to one or other cell type
Stimulates cell maturation (in neutrophil single nucleus beomces lobed; normal = 3-5 lobes)
Supress apoptosis or affect the function of mature non-dividing cells
Binds to cells expressing the correct receptor
Signalling via ...
JAK/STAT
JAK/Ras -> myc/fos pathway
JAK/PI3K -> Akt (blocks apoptosis)
Regulators
Important in the differentiation of colony forming unit lineages
Burst promoting activity
(Erythroid) BFU-E cell line
Erythropoietin
(Erythroid) CFU-E cell line
A glycoprotein hormone (produced in the kidneys) - stimulates the production of RBCs by stem cells i bone marrow
Secretion is stimulated in response to low O2 (by the juxtaglomerular O2 sensor)
Secreted to balance RBC production with RBC loss
Colony stimulating factor (CSF)
(Granulocyte-monocyte) CFU-GM cell line
Megakaryocytic stimulating activity
(Megakaryocytes) CFU-M cell line
Thrombopoietin
Megakaryocytes
(TPO) - the major cytokine (glycoprotein hormone) that determines the proliferation of megakaryocytes (produce platelets)
Produced in liver and kidneys
Blood cell development
Primitive stem cell (haemacytoblast)
Erythrocyte series
Erythrocyte development
HSC
Common myeloid progenitor
Burst promoting activity
+
BFU-E
CFU-E
Rubriblast (proerythroblast)
First identifiable RBC precursor
Prorubricyte
Rubricyte (normoblast)
Looks like a monocyte - but much smaller
Metarubricyte (loses nucleus at this stage)
Reticulocyte (aka diffusely basophilic erythrocyte)
Erythrocyte (mature red cell)
Erythropoietin (EPO)
+
Leukocyte series
Thrombocyte series
Different blood cell types
Erythrocytes
Biconcave disc
Approximately 7um in diameter
Non-nucleated
Contains haemoglobin (Hb)
Major function is O2/CO2 transport
Leukocytes
Granulocytes (Myeloid)
Neutrophils
12-15um diameter
characterised by segemented nucleus (2-5 lobes = normal)
Dense chromatin with regions of parachromatin (lighter areas) = lobes and nodes
Slightly eosinophilic (pinky) cytoplasm
Important in inflammatory processes (phagocytes and mediators)
Eosinophils
Most readily reconisable - due to orange granules
12-15um diameter
2-3 lobes to nucleus
Normally represent 0-6% of WBCs in blood
Granules contain; major basic protein (MBP) - toxic to parasites
Basophil
Contain purple/black large granules (may obscure the nucelus)
2-3 lobes to nucleus
12-15um diameter
Contain; heparin and large amaounts of histamine (involved in hypersensitivity reactions - mediated inflammation to antigen responses)
Monocyes
Largest cells in peripheral blood (12-20um)
Abundant blue/grey (sometimes pinky) cytoplasm, with small granules
Fine reddist granules may be seen
Phagocytes - frequently contain vacuoles
Can migrate into tissues (where they are called macrophages)
Central role in the inflammatroy process - replace neutrophils during chronic inflammation
Lymphocytes (Lymphoid)
Vary in size (7-20um) and nuclear:cytoplasmic ratio
Small lymphocytes (7-12um) have rounded nucleus with dense chromatin and little cytoplasm
Can appear much larger (15-20um) with more cytoplasm and irregularly-round nucleus
Represent 15-60% of peripheral blood
Bone marrow sampling and analysis
Myeloid:erythroid (ME) cell ratios
Provides information on the relative numbers of WBCs, RBCs and their precursors
In a healthy adult the number of WBC precursors exceeds the number of RBC precursors by 3 or 4 to 1
This ratio changes in disease (increased in infection, dominated by myelocytes and other WBC precursors in leukaemia)
Cytochemistry, flow cytometry, electronic resistance and lightscattering
Cytochemistry - chemical stains that react with cytoplasmic components and define different cells in blood and bone marrow
Blood cells contain multiple enzymes, fats and other substances that can be detected (important in the diagnosis of myelocytic leukaemias)
FAB( french-american-british) classification of acute leukaemias is based on morphology and cytochemistry
Most important cytochemical studies in the study of acute leukaemia are
Myeloperoxidase (MPO)
Lysosomal enzyme in myelocytes
Staining can reveal acute leukaemias (of myeloid lineage)
Non-specific esterase
Acid phosphatase (AP)
Stains lysosomal acid phosphatase - can detect hair cell leukaemia
Periodic acid schiff (PAS) stain
Stains polysaccharides (e.g. glycogen)
Flow cytometry - allows identification of blood cells according to different molecules on the cells
Electronic resistance
Cells pass through aperture with electric current across it (changes in current due to differernt cell sizes detected) - automated counting
Light scattering
Cells counted as they pass through a focused laser
Results sum of
Diffraction - bending of light around corners
Refraction - bending due to change in speed
Reflection - light rays reflected back by obstructive structures
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