Haematopoiesis Flashcards
What does blood plasma contain?
- Water
- Small organic compounds (eg glucose) and electrolytes (sg. Sodium)
- Proteins: Albumin, Globulins (α, β, γ), Fibrinogen – involved in clotting
What type of cells give rise to all blood cells and where are they found?
Haemopoietic stem cells (HSCs) in the bone marrow give rise to all haemopoietic cell lineages
What are the general stages of haematopoiesis?
1) Proliferation – mitosis, making more cells
2) Differentiation – which lineage will the cell go down?
3) Maturation – after a cell has committed to being a certain type, it will develop
These processes overlap.
The process is dependent on glycoprotein growth factors produced mainly by bone stromal cells – exceptions being erythropoietin (kidneys) and thrombopoietin (liver).
List the different types of potency from most potent to least potent
Totipotent cells can differentiate into any cell type, including embryonic and extraembryonic
Pluripotent cells can differentiate into any cell type of the embryo
Multipotent cells can differentiate into several different, but related cell types
Oligopotent cells can differentiate into a small number of very closely related cell types
Unipotent cells can produce more cells of identical cell type
What cell types can arise from the common myeloid progenitor?
- Megakaryocyte
- Erythrocyte
- Mast cell
- Myeloblast
What cell type can arise from a megakaryocyte?
thrombocytes
What cell type can arise from myeloblasts?
- Basophil (granulocyte)
- Neutrophil (granulocyte)
- Eosinophil (granulocyte)
- Monocyte -> Macrophage
What cell type can arise from the common lymphoid progenitor?
- Natural killer cell
- Small lymphocyte
What cell types can arise from the small lymphocyte?
- T lymphocyte
- B lymphocyte -> plasma cell
Describe the characteristics of the 3 types of granulocytes
Neutrophils are phagocytic, with lytic enzymes within granules, including peroxidase and lysozyme - very effective in killing ingested bacteria
Eosinophils are most important in defence against larger parasites
Basophils are non-phagocytic and release active substances from their granules
Describe the differences between monocytes and macrophages
Monocytes circulate in the blood
Macrophages are formed by differentiation of monocytes are 5-10x bigger and found in the tissues
Macrophages ingest small pathogens and other material by phagocytosis
Describe the stages in thrombopoiesis
Thrombopoiesis = production of platelets
Megakaryoblast → Promegakaryocyte
→ Megakaryocyte → Thrombocytes (Platelets)
Megakaryocytes in the bone marrow are situated adjacent to blood sinusoids.
Segments of megakaryocyte cytoplasm protrude into the blood sinusoids.
The blood flow splits off cytoplasmic fragments, which become platelets.
Platelets circulate in the blood for 7 -10 days.
40% are located in the spleen.
What is leukocytosis?
High white cell count
What is leukopenia?
Low white cell count
What is lymphocytosis?
High lymphocyte count
What is lymphocytopenia?
Low lymphocyte count
What is neutrophilia?
High neutrophil count
What is neutropenia?
Low neutrophil count
What is thrombocytosis?
High platelet count
What is thrombocytopenia?
Low platelet count
Describe erythropoiesis
Proerythroblast → Erythroblast → Reticulocyte → Erythrocyte
What are the 4 characteristics of erythrocyte maturation?
1) Decrease in cell size
2) Haemoglobin production
3) Loss of organelles (inc. nucleus)
4) Acquisition of biconcave disc shape
It is controlled by erythropoietin (EPO) and requires Iron, Folic acid and Vitamin B12
What is the purpose of the biconcave shape in erythrocytes?
1) Maximises surface area
2) Minimises distance from surface
3) Increases flexibility
Structural proteins to maintain shape
Simplified internal structure (lack organelles)
Simplified metabolism
What vitamins etc. are required for erythropoiesis and why?
Folic acid (B9), Cobalamin (B12) and Intrinsic factor are required for DNA synthesis
Vitamin B6 and Iron are needed to make the globin chains and haem for haemoglobin synthesis
What can cause megaloblastic/pernicious anaemia?
Folic acid (folate; vitamin B9) is required for DNA synthesis and therefore cellular proliferation
Cobalamin (vitamin B12) is involved in the recycling of folic acid
Lack of either can lead to megaloblastic anaemia, although plentiful folic acid can ameliorate the effects of vitamin B12 deficiency
Intrinsic Factor (IF) is a glycoprotein produced by the parietal cells of the stomach. It binds to vitamin B12 and is essential for it’s absorption in the ileum. Lack of Intrinsic Factor, most often due to an autoimmune response to parietal cells, leads to pernicious anaemia (megaloblastic anaemia)
Where in the body are folic acid and cobalamin absorbed and how long are they stored for?
Folic acid (B9) is absorbed in the duodenum and jejunum. Normal stores of folic acid last about 3-7 months. Folic acid deficiency can arise from inadequate intake, malabsorption, increased demand, drugs (e.g. alcohol).
Cobalamin (B12) is absorbed in the terminal ileum.
Normal stores of cobalamin last about 3-4 years.
Cobalamin deficiency is usually due to malabsorption (rarely inadequate intake).
Name some inherited disorders of the globin chains
α or β thalassemia, sickle cell anaemia
How are haem groups synthesised?
Synthesis of haem groups occurs by a metabolic pathway, with steps in the mitochondria and cytoplasm.
Vitamin B6 is an essential co-enzyme in this pathway
What are inherited disorders in heme synthesis called?
Porphyrias
Where is iron stored?
Most of the absorbed iron is transported to the bone marrow where it is used to make haem.
The remainder is stored in the liver and spleen or used by other tissue cells in enzymatic processes.
Iron absorption is regulated by the hormone hepcidin, which is released by the liver when iron levels are too high.
Hepcidin inhibits iron absorption by decreasing ferroportin activity on the basolateral membrane of intestinal epithelial cells.
Define anaemia
A deficiency of red cells or haemoglobin in the blood
Define macrocytic anaemia
Involves large erythrocytes, but in low number and/or with low Hb content per cell
Define microcytic anaemia
Involves small erythrocytes and usually low Hb content per cell
Define normocytic anaemia
Involves erythrocytes of normal size, but usually present in inadequate number
Describe iron deficiency anaemia and its causes
Deficiency of iron leads to decreased amounts of haemoglobin; low levels of haemoglobin in turn decreases the production of RBCs
Caused by blood loss, diet low in iron, poor absorption of iron
Describe pernicious anaemia and B vitamin deficiency
RBCs do not develop as they normally would because of a lack of B vitamins (B9, B12), which leads to decreased production of RBCs
Causes: Lack of intrinsic factor, diet low in B vitamins, decreased absorption of B vitamins
Describe aplastic anaemia and its causes
Bone marrow is unable to produce enough blood cells; a life threatening condition
Causes: Cancer therapy, exposure to toxic substances, autoimmune disorders, viral infections
Describe haemolytic anaemia and its causes
RBCs are destroyed faster than the bone marrow can replace them
Inherited causes include sickle cell and thalassemia
Describe anaemia of chronic diseases and its causes
Various illnesses over a long time can reduce the production of RBCs
Causes: Rheumatoid arthritis, kidney disease, diabetes, tuberculosis or HIV
What is erythropoietin (EPO)?
Erythropoietin (EPO) is released by fibroblasts in the kidneys in response to cellular hypoxia and stimulates erythropoiesis in the bone marrow. It binds to a specific receptor on proerythroblasts / basophilic erythroblasts and promotes cell survival.
What is thrombopoietin?
Thrombopoietin is produced in the liver and elsewhere and primarily stimulates the differentiation of megakaryocytes and thrombocytes (platelets). There is a negative feedback loop in which thrombocytes reduce thrombopoietin levels.
