INTS2 - The Haematopoietic System Flashcards
Define the haematopoietic system
System of organs and tissues involved in the production and maintenance of cellular blood components, including the bone marrow, spleen, thymus and lymph nodes.
Define embryonic development.
Beginning of cell and tissue development during embryonic life which covers conception to birth.
Define foetal development.
Organ formation within an embryo.
Define stem cells.
Undifferentiated cells that can differentiate into specialised cells but also main the ability to divide, through mitosis, to form more stem cells. Found in multicellular organisms.
Define bone marrow.
Tissue located in the cavity of some bones. Location of haematopoietic tissue and cell development. Commonly located in large bones e.g. femur and pelvic bones.
Define peripheral blood.
Fluid circling in veins and arteries which carries main cells allowing oxygen distribution by red cells, immunity provided by lymphocytes, antibacterial defence provided by granulocytes and fluid distribution.
Define what lymphocytes are.
Cells originating in bone marrow and are transferred to lymphoid tissues e.g. thymus, spleen and lymph nodes.
Define terminology for low and high levels of lymphocytes.
Low - lymphocytosis.
High - lymphocytopenia.
Define what granulocytes are.
Granule containing cells - include eosinophils, basophils and neutrophils. Involved in bacterial and parasite defence.
Define terminology for low and high levels of granulocytes.
Low - granulocytosis.
High - granulocytopenia.
What are the two main cell lineages from a HSC.
Myeloid and lymphoid.
Where does HSC proliferation occur in embryos.
Foetal liver.
What are the three layers of the yolk sac.
Ectoderm, mesoderm, endoderm.
Which layer of the yolk sac, results in the development of the haematopoietic system.
Mesoderm.
What cells are produced by the ectoderm.
Epidermis (skin)
Brain neurons
Pigment cells
What cells are produced by the mesoderm
Muscle - cardiac and skeletal (smooth in gut)
Tubule cells of kidney
Red blood cells
What cells are produced by the endoderm.
Lung cells.
Thyroid cells.
Pancreatic cells.
Define embryogenesis.
First 8 weeks of development following fertilisation .
What are osteoblasts
Bone forming cells.
What are Chondrocytes.
Cartilage cells.
Discuss the AGM system
Aorta-gonad-mesonephorns are a region of the mesoderm constituting the dorsal aorta and the gonad regions.
What are the first two sites of haematopoiesis in a developing foetus.
Yolk sac and dorsal aorta.
Discuss the process by which haematopoiesis occurs in different locations
First sites in embryo are dorsal aorta - part of AGM, and the yolk sac.
Develops to the foetal liver which then migrated to the bone marrow upon bone formation.
What are hemogenic endothelial cells.
Cells in dorsal aorta with ability to differentiate into haematopoietic cells.
What is the primary haematopoietic organ.
Foetal liver.
Discuss formation of embryonic stem cells from the endothelial cells of dorsal aorta.
Cells start to ‘bud’ off which is a type of asexual reproduction.
Can adult liver be a site of haematopoiesis.
Only under stress or leukaemia. Works with the spleen.
What are progenitors in cell differentiation.
More differentiation than a stem cell however not fully differentiated yet. Will always differentiate into its specific target.
What are the possible sites where HSCs (differentiated or not) from the foetal liver go to.
Spleen. Thymus. Bone marrow.
Discuss primitive or primary haematopoiesis.
HSCs originating in the yolk sac the dorsal aorta of embryos.
Discuss definitive/secondary haematopoiesis.
Liver is colonised as site of haematopoiesis by circulation of cells from dorsal aorta and yolk sac. Eventually, bone marrow is established as definitive site of haematopoiesis
What are immature early versions of cells called.
End in -blasts
What are mature versions of cells called.
End in -cytes or -phils
How can cells in bone marrow and peripheral blood be differentiated in a normal healthy human.
Bone marrow has homogeneity. Contains early immature versions of cells which are similar. Peripheral blood has heterogeneity. Contains fully differentiated haematopoietic cells. Will not contain immature cells.
Define common name for leukocytes. What are the two main type song leukocytes.
White blood cells. Granular and non-Granular.
What are the granular leukocytes.
White blood cells containing granules. Eosinophils. Basophils. Neutrophils. Mast cells.
What are the non granular leukocytes.
B and T lymphocytes. Natural killer cells. Monocytes.
Discuss appearance of red blood cells under a microscope. Provide explanation for appearance.
Light in the middle, dark on periphery. Haemoglobin, giving the red colour, is concentrated on periphery, therefore appears darker.
Discuss appearance of neutrophil.
Segmented nucleus. Neutral staining granules.
Discuss appearance of basophils.
Blue staining granules. Kidney bean shaped nucleus.
Discuss appearance of eosinophils.
Nucleus in two pieces. Red granules found in cytoplasm.
Discuss link between megakaryocytes and thrombocytes.
Megakaryocytes are large cells. Cytoplasms breaks off the form thrombocytes e.g. platelets.
Discuss nucleus in a monocyte.
One large kidney bean shaped nucleus.
What two types of growth factors stimulate HSC differentiation.
Cytokines and interleukins.
What types of cells are in the bone marrow.
HSCs. Adipose tissue. Stromal cells. Endothelial cells of blood vessels. Bone matrix.
Why is bone marrrow highly vascularised.
Contains many blood vessels to aid movement of differentiated HSCs into circulation.
What is the role of stromal cells in bone marrow,
Source of growth factors which aid HSC differentiation.
What is a bone marrow aspirate and when is it carried out.
Extraction of bone marrow sample for observation if abnormal blood cells are observed in blood sample.
Give examples of potential diseases that may require bone marrow aspirates to be done as diagnosis
Leukaemia. Anaemia. Blood cell conditions. Hemochromatosis.
How are bone marrow aspirates collected in adults and children.
Adults require local anaesthetic whereas children require full anaesthetic. Obtained from iliac crest (hip bone).
Discuss self renewal aspect of HSCs.
HSCs undergo differentiation as well as self renewal to ensure constant supply of HSCs is present.
Where do hormones that control HSC differentiation come from.
Liver or kidney.
Discuss role of EPO in HSC differentiation.
Erythropoietin is hormone secreted by kidney increasing production of RBCs. Increased secretion during low oxygen Odofin to increase RBC production, increasing oxygen supply.
Discuss role of GCSF in HSC differentiation,
Granulocyte colony stimulating factor ifs a glycoprotein hormone produced by the endothelium, macrophages and other immune cells. Stimulates production of granulocytes and myeloid stem cells by bone marrow. Cells produced are released into circulation.
Discuss role of TPO in HSC differentiation.
Thrombopoietin is glycoprotein hormone produced by liver and kidneys which stimulates megakaryocyte production and differentiation, aiding the formation of thrombocytes I.e. platelets.
Discuss lymphocyte stimulation during HSC differentiation,
Lymphocytes receive stimulatory signals, not in the form of hormones. Difficult to stimulation growth of lymphocytes as they can only develop from precursor lymphoid cells.
What is the normalRBC count in men and women.
- 7-6.1 million cells per micro litre of blood - men.
4. 2-5.4 million cels per micro litre of blood - women
Average life span of RBCs.
90-120 days
What is heme in haemoglobin.
Part that attaches one by one to each of globin tetramers. Carries iron allowing oxygen to bind to the molecule, aiding its transportation around the body.
What is globin In haemoglobin.
Protein part which the heme attaches itself to behaving as a scaffold.
Which part of a haemoglobin is not recycled.
Heme - metabolism to form bilirubin and then removed was waste either as bile in gall bladder or urine.
What parts of the RBC are recycled and how.
Iron and proteins. Iron recycled back into bone marrow. Proteins are broken down into amino acids and used in varying processes.
Discuss full process of RBC break down once old.
Haemoglobin broken down into heme and globin. Amino acids transported through plasma and used again for protein synthesis. Iron removed form heme and passes into blood plasma to re enter bone marrow until needed for new RBC synthesis. Heme recycled through liver and converted to bilirubin.
Which two organs are involved in recycling of RBCs.
Spleen and liver.
Define haematocrit.
Percentage of red blood cells in comparison to tutorial blood volume, following centrifugation.
How are the final stages of maturation in red blood cells distinguish.
Enucleated structures only - lacking nucleus.
Name for RBC maturation.
Erthyropoiesis.
Discuss reasons for low oxygen levels in blood.
Reduced number of RBCs due to blood loss. Reduced haemoglobin production due to limited haemoglobin gene availability. Increased oxygen demand e.g. low oxygen available at high altitude.
Where does erythropoiesis occur.
Bone marrow and liver.
When does erythropoiesis occur in the liver and what is this called.
Extramedullary erythropoiesis which can be triggered in adult life if issues arise.
Which organ detects low blood oxygen
Kidney
What is the name of a premature stage of erythropoiesis that can be found in peripheral blood.
Reticulocytes.
Where does erythropoiesis occur in embryos and how long until
Occurs in yolk sac until end of first trimester.
Hepatic erythropoiesis occurs in liver during foetal development until start of third trimester (can continue until a few days after birth)
Bone marrow RBC maturation occurs during end of pregnancy and thereafter.
Which bones stop carrying out haematopoiesis at age 25.
Tibia and femur.
Discuss blood doping and the role of EPO in sport.
Increasing blood in the body in order to increase blood and oxygen availability. EPO taken to increase red blood cell production,
What is granulopoiesis and where does it occur. What is it controlled by.
Formation of granulocytes. Occurs in bone marrow. GCSFs. Granulocyte colony stimulating factor.
What is the life span for granulocytes and how are they removed when dead.
5-90 hours. Tissue macrophages are signalled which phagocytose dead granulocytes, clearing them from tissues.
What is the nucleated component of the blood.
Granulocytes and lymphocytes.
What are mononuclear cells.
Cells with one nucleus only.
What are polymorphonuclear leukocytes.
Neutrophil granulocytes.
Give general overview of role of granulocytes
Bacterial and parasitic infection fighting.involved in innate immunity.
Discuss morphology of neutrophils
Multi segmented nucleus held by chromatin filaments. Contain neutral staining granules, when stained with Wrights stain.
Discuss the role of neutrophils
Recruited for sites of infection immediately/quickly. Pass through small gaps in endothelial cells to get to site of infection. Contain granules which contain anti microbial degradative substances. To break down infectors. Pass out of body as pus or in blood plasma.
What are the granules present in neutrophils
Primary/azurophilic
Secondary
Tertiary
Discuss role of primary granules of neutrophils .
Contain cationic proteins - kill bacteria.
Proteolytic enzymes and cathepsin G - break down bacterial proteins.
Lysozymes - break done bacterial cell walls.
Myeloperoxidases - generation of bacteria killing toxic substances
What are myeloperoxidases.
Substances that produced toxic bacteria killing substances. Found in primary granules of neutrophils.
Discuss role of secondary granules in neutrophils.
Specific granules found in mature cells that form lactoferrin which removes iron from bacteria. Also produced lysozymes.
Discuss role of tertiary granules in neutrophils
Contain phosphatases and mrtalloproteinases aiding movement through connective tissue of the neutrophil
Discuss which granules are found in which neutrophils
Primary - found in immature cells.
Seoncdary - found In mature cells.
Tertiary found in all.
What are the strategies by which neutrophils attack pathogenic micro organisms.
Engulf and digest by phagocytosis. Release anti microbial substances from granules. Produce neutrophil extracellular traps (NETs) which comprises of a web of chromatin and anti microbial proteins from primary and secondary granules.
Discuss morphology of eosinophils
Kidney shaped nucleus with 2-4 Containing red staining granules
What is a normal eosinophils count.
30-350 eosinophils per micro litre of blood.
Define eosinophilia.
Increased eosinophils count in blood.
Discuss granule count in eosinophils.
Contain many granules however varies as granules can degranulate in the bloodstream.
Which disease can occur in eosinophils accumulate in the nasal mucosa.
Allergic rhinitis or various nasal allergies.
Discuss immune functions of eosinophils.
Destruction of tumour cells. Repair damaged tissue. Sometimes participate in phagocytosis.
Discuss role of eosinophils In allergic responses.
Work alongside basophils and mast cells to produce allergic responses.
How do eosinophils cause inflammation.
If interleukin 5 is expressed in high levels, it regulates adhesion molecules which then facilitate eosinophils binding to endothelial cells which causes inflammation.
How are eosinophils involved in fighting parasites.
Contain unique toxic protein immunoglobulin E which is toxic to parasites.
Discuss morphology of basophils.
Lobed nucleus with no visible chromatin filaments (thicker sections between nuclei lobes). Blue staining granules which are numerous in the cell.
Discuss immune responses of basophils, in terms of molecules produced by basophils.
Histamines - increase blood flow.
Serotonin - induces inflammation.
Heparin - prevents blood clotting too quickly
Discuss role of basophils and how they can carry this role out.
Involved in inflammation and allergic responses. Contain receptors that bind to antibodies and histamines.
Discuss formation of platelets.
Of myeloid cell lineage. Megakaryocyte formed whose cytoplasm breaks off forming platelets/thrombocytes.
How are platelets destroyed.
By phagocytosis in liver and spleen.
What are the two zones of cytoplasm in platelets, and how are they distinguished.
Hyalomere - outer region which Hardly stains.
Granulomere - inner region which stains mor.e
What is the granulomere and discuss its features.
Inner region of cytoplasm in platelets. Contains granules that are not individually visible. Contain molecules for blood coagulation e.g platelet growth factors used in repair of damaged tissues. Also contains most organelles.
What is the hyalomere and discuss its features.
Inner region of cytoplasm in platelets. Contains cytoskeletal elements.
Define haemostasis.
Blood clotting.
Discuss role of platelets in blood clotting in detail.
Serotonin released from platelets which stick damaged vessels, causing them to vasoconstrict. Collagenous fibres and von Willebrand factors bind to platelets causing them to swell and become sticky. Platelets are activated into dendritic form. Platelet plug/thrombus formed. Other activating substances mediate conversion of prothrombin to thrombin in plasma which aids aggregation and clogging of damage. Thrombin catalysed conversion of fibrinogen into fibrin which polymerises into fibrils forming a fibrous net as part of the blood clot. Platelets are captured in fibrous net further aiding clotting.
Discuss role of fibrinogen and prothrombin in blood clotting.
Prothrombin is converted into thrombin. Thrombin catalyses conversion of fibrinogen into fibrin which forms filamentous fibrils forming a fibrous net which catches further platelets aiding blood clotting.
Where are lymphocytes matured.
B - bone marrow
T - thymus
Discuss morphology of lymphocytes.
Indistinguishable by morphology between two types of lymphocytes. Sparse amount of cytoplasm which appears as small rim around periphery. Large nucleus which stains blue/purple.
What is the primary role of lymphocytes.
Immune response.
How are lymphocytes transported.
Blood circulation and lymph system
Discuss B lymphocytes and their role.
Production of antibodies, which are released into blood, and neutralise complementary foreign antigens. Form memory cells which circulate in blood for many years.
Discuss T lymphocytes and their role.
Produced in thymus. Helper cells produce cytokines which direct immune responses. Cytotoxic cells produce toxic granules which contain enzymes that can kill pathogens or pathogenic infected cells. Form memory cells which circulate in blood for long times.
Discuss role of natural killer cells.
Cells in immune system which act to kill pathogenic cells by recognising changes to surface molecules e.g. major histocompatibility complexes.
How do natural killer cells work - general overview.
Produce cytotoxic granules which destroy cells.
Discuss effects of aplastic anaemia.
Reduced platelets - lack of clotting so bruising can occur.
Reduced RBC - reduced oxygen so shortness of breath.
Reduced leukocytes - reduced immune reponses so infections common.
How can aplastic anaemia be treated.
Stem cell transplants - rebuilds bone marrow aiding haematopoiesis, increasing numbers of haematopoietic cells.
Blood transfusions. Increase numbers of haematopoietic cells.
