0325 - Haematopoiesis Flashcards
What is haematopoiesis?
The process in which blood cells are formed in the body from stem cells.
Identify 5 key differences between haematopoietic stem cells and progenitor cells
Lifespan - HSC perpetual, Progenitor cells non-perpetual, can’t maintain long-term haematopoiesis.
Proliferation - HSC extensive proliferation, Progenitor cells limited proliferation
Self-renewal - HSC capable, progenitor diminished or no capacity
Pluripotency - HSC pluripotent, Progenitor committed to lineage
Quiescence - HSC usually quiescent, progenitor cells actively cycling.
How is erythropoiesis regulated? How many RBCs produced/day?
2.5*10^11 (¼ trillion) produced each day
Regulated by erythropoietin (EPO).
Describe the EPO cycle
Low O2 tension in proximal tubule of kidney leads to EPO release.
EPO stimulates marrow progenitor and erythroid precursor cells.
EPO internalised with receptor and destroyed, receptor recycled.
Erythroferrone ensures adequate iron supply
RBC release
Increases O2 capacity, providing negative feedback on EPO.
Describe the lifecycle of RBCs
Unipotential stem cell, spends 6 days as an erythroblast in bone marrow, develops into reticulocytes.
Reticulocyte spends one day in one day in marrow, one day in blood.
Erythrocyte lives for 120 in blood.
Proerythroblast -> basophilic normoblast -> polychromatic normoblast -> orthochromatic normoblast -> reticulocyte -> erythrocyte
What is granulopoiesis? What are the initiation and completion cells?
Process by which mature granulocytes are produced in bone marrow.
Starts with a myeloid stem cell. Can differentiate into neutrophils, monocytes, eosinophils or basophils.
What are the main regulators of Granulopoiesis? How do they work?
Granulocyte colony-stimulating factor (GCSF) - produced by endothelium, macrophages, and other immune cells - internalised via GCSF receptor on myeloid progenitor.
IL-6 - produced by monocytes and fibroblasts, important in emergency (acute infection) granulopoiesis.
Describe the development of granulocytes (Neutrophils)
Unipotential stem cell.
Becomes myeloblast, promyelocyte, and myelocyte, then metamyelocyte and band cell, over around 10-14 days in the bone marrow.
Moves to blood, becomes circulating or marginated neutrophil for around 8 hours.
Becomes neutrophil in connective tissue for around 2 days.
What is thrombopoiesis? How is it regulated?
Development of platelets from megakaryocytes in bone marrow - form by budding from the surface. Production is proportional to number and size of megakaryocytes.
Regulated by thrombopoietin - produced by the liver, levels inversely proportional to platelet counts (so should stimulate it). TPO receptor (target for drug therapy) is internalised.
What is an easy way of categorising blood cell disorders?
Think of the type of cell, then too much, too little, or poor quality.