3.1, 3.3 & 3.4 - Red Blood Cells Flashcards
1
Q
Origin of blood cells - haemopoiesis
A
- blood cells of all types originate in the bone marrow
- derived from pluripotent haemopoietic stem cells (HSCs) throughout life - HSC = hemocytoblast
- HSCs give rise to lymphoid stem cells (give rise to T, B, NK lymphocytes) and myeloid stem cells (give rise to erythrocytes, platelets, granulocytes, monocytes, eosinophils, mast cells, basophils) - common lymphoid and myeloid progenitor
- haemopoiesis - the formation and development of blood cells
2
Q
Functions and life span of blood cells
A
- erythrocyte - 120 days - oxygen transport
- platelet - 10 days - haemostasis
- monocyte - several days - defence against infection by phagocytosis + killing of microorganisms
- neutrophil - 7 to 10 hours - defence against infection by phagocytosis + killing of microorganisms
- eosinophil - little shorter than a neutrophil - defence against parasitic infection
- lymphocyte - variable - humoral and cellular immunity
3
Q
Essential characteristics of HSCs
A
HSCs have the ability to both:
1) self renew
- some daughter cells remain as HSCs
- pool of HSCs not depleted
2) differentiate to mature progeny
- other daughter cells follow a differentiation pathway
4
Q
Sites of haemopoiesis
A
- yolk sac - in embryo within mesoderm
- liver - takes over at 6-8 weeks gestation, is principal source of blood in foetus until shortly before birth
- bone marrow - starts developing haematopoietic activity at 10 weeks gestation
- haemopoiesis in children occurs in almost all bone
- in adults it mainly occurs in the bone marrow, especially the pelvis, femur and sternum
5
Q
Haemopoietic progenitor cells
A
- pluripotent HSC –> common lymphoid progenitor + common myeloid progenitor
- HSCs and progenitor cells are distributed in an ordered fashion within the bone marrow amongst mesenchymal cells, endothelial cells and the vasculature with which the HSCs interact
- haemopoiesis is regulated by a number of genes, transcription factors, growth factors and the microenvironment
- disruption of this regulation can disturb the balance between proliferation and differentiation, and may lead to leukaemia or bone marrow failure
6
Q
Haemopoietic growth factors
A
- glycoprotein hormones which bind to cell surface receptors
- regulate proliferation and differentiation of HSCs
- regulate function of mature blood cells
- erythropoiesis (RBC production) - erythropoietin
- granulocyte and monocyte production - G-CSF, G-M-CSF, cytokines e.g. interleukins
- megakaryocytopiesis and platelet production - thrombopoietin (TPO)
7
Q
Lymphoid differentiation
A
pluripotent HSC –> common lymphoid progenitor –>
- B cell progenitors in bone marrow –> mature B cells (antibody-producing)
- T cell progenitors in thymus -> bone marrow –> mature T cells (cytokine-producing)
- NK cell progenitors in bone marrow –> mature NK cells (cytokine-producing)
8
Q
Myeloid differentiation
A
pluripotent HSC –> common myeloid progenitor –>
- MEP –> erythroid + megakaryocyte
- granulocyte-monocyte
9
Q
Development of RBCs - erythropoiesis
A
- the common myeloid progenitor can give rise to a proerythroblast
- this in turn gives rise to erythroblasts and then erythrocytes (continue to divide and mature, losing nuclei and organelles)
- as the differentiation progresses, self-renewal and lineage plasticity decrease
- polychromatic RBC (young RBC with high RNA content seen using methylene blue stain - reticulocyte) –> RBCs
- erythropoiesis requires iron, folic acid, vitamin b12, erythropoietin (EPO)
10
Q
Development of anaemia
A
low iron / b12 / folic acid –> anaemia
- microcytic (small RBCs) - iron deficiency due to blood loss, reduced intake, increased requirement. Low iron availability leads to anaemia of chronic disease/inflammation
- macrocytic (large RBCs) - b12 / folic acid deficiency - megaloblastic anaemia
11
Q
Erythropoietin (EPO)
A
- normal erythropoiesis requires the presence of the growth factor EPO
- EPO is a glycoprotein that is synthesised in response to hypoxia/anaemia so there is a demand-supply feedback loop
- stimulates bone marrow to produce more RBCs
- EPO is produced in the kidney
12
Q
Development of RBCs - iron
A
Iron has two major functions:
- oxygen transport in haemoglobin
- mitochondrial proteins cytochrome a, b and c - for production of ATP, and cytochrome P450 for hydroxylation reactions (e.g. drug metabolism)
13
Q
Iron absorption
A
- iron is absorbed in the duodenum
- haem iron (animal derived) is in ferrous (Fe2+) form - best absorbed form
- non-haem iron is present in ferric (Fe3+) form in food and requires action of reducing substances (e.g. ascorbic acid, vitamin C) for absorption - sources often contain phytates which reduce absorption
14
Q
Iron homeostasis
A
- excess iron is potentially toxic to organs and there is no physiological mechanism by which iron is excreted, therefore iron absorption is tightly controlled
- absorption in the gut is carefully regulated according to body stores by hepcidin, secreted by the liver in response to high storage iron
- high iron levels stored = increased hepcidin = reduces absorption
- low iron levels stored = decreased hepcidin = increases absorption
- hepcidin synthesis is suppressed by erythropoietic activity - ensures iron supply by increasing ferroportin in the duodenum enterocyte, increasing absorption
15
Q
What does hepcidin do?
A
- decreases Fe absorption
- decreases Fe transport
- decreases Fe availability
- hepcidin binds to ferroportin and induces its internalisation = prevents efflux of iron from duodenal enterocyte
- iron lost when enterocyte dies and is shed into gut lumen
- when iron stores (ferritin) are full, upregulation of hepcidin expression = iron absorption limited
- requirement for increased erythropoiesis (needs iron for Hb) = reduction in hepcidin = increased iron absorption
16
Q
What is transferrin?
A
- the transport protein in plasma that delivers iron to bone marrow for erythropoiesis and for its use in enzymes and muscles
