What is haemopoiesis?
- Haemopoiesis is the process by which blood cells are formed
- It involves the specification of blood cell lineages and proliferation to maintain an adequate number of cells in the circulation
Where does haemopoiesis occur before and after birth?
- Early embryo – process begins in the vasculature of the yolk sac before shifting to the embryonic liver by ~week 5-8 gestation
- After birth – sole site of haemopoiesis is in bone marrow
Describe bone marrow production in infants and adults respectively
- Infant – extensive throughout the skeleton
- Adult – limited distribution (pelvis, sternum, skull, ribs, vertebrae)
Which cells drive haemopoiesis?
Haemopoietic stem cells
Five major lineage pathways arise from the haemopoietic stem cells in bone marrow.
Describe the process of thrombopoiesis
- Thrombopoiesis results in the ultimate formation of platelets involved in clot formation
- Platelets have no nuclei and are membrane bound fragments of cytoplasm that bud off from megakaryocytes
What is another name for platelets?
Which substance drives thrombopoiesis?
Thrombopoietin (TPO) drives megakaryocyte formation, and hence thrombopoiesis
Describe the process of granulopoiesis
Granulopoiesis is the process by which granulocytes arise from myeloblast cells which in turn arise from common myeloid progenitor cells
Identify the three granulocytes
Describe the process of monocytopoiesis
Monocytopoiesis is the process which leads to the production of monocytes (and subsequently, macrophages)
What do monocytes do?
Monocytes circulate in the blood for ~1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells
Describe the process of lymphopoiesis
Lymphopoiesis is the process in which lymphocytes develop from a common lymphoid progenitor cell
Identify some lymphocytes
- B cells
- T cells
- Natural killer cells
Compare and contrast B cell and T cell lymphopoiesis
- B cell lymphopoiesis commences in the foetal liver and is completed in the bone marrow
- T cell lymphopoiesis begins in the foetal liver but mainly occurs in the thymus
T cell maturation occurs in the thymus gland.
Describe this process
T cell receptor genes rearrange in immature T cells to be able to produce a vast array of different T cell receptors which recognise a wide range of antigens presented to them by APCs
B cell maturation occurs in the bone marrow.
Describe this process
- Immunoglobulin genes rearrange in immature B cells to allow production of antibodies with a wide array of specificities
- Final maturation requires exposure to antigen in the lymph nodes in to to gain the capacity to recognise non-self antigens and produce large quantities of specific antibodies
Describe the process of erythropoiesis
Erythropoiesis is the process by which red blood cells are produced from a common myeloid progenitor cell in the bone marrow
What is another name for red blood cells?
Why is erythropoiesis a continual process?
Red blood cells have a finite lifespan of approx. 120 days in the bloodstream and lack the ability to divide
Which substances drives erythropoiesis?
Erythropoietin (EPO), secreted from the kidneys
How does EPO increase erythropoiesis?
EPO promotes the expansion of the erythroid precursors in the bone marrow by inhibiting apoptosis in CFU-E progenitor cells
When is erythropoietin production by the kidneys increased?
EPO production increases in response to a decrease in the oxygen level in the bloodstream (hypoxia) thereby stimulating more red blood cell production
The main function of EPO is to inhibit apoptosis of CFU-E progenitor cells.
In four steps, describe how this process occurs
⇒ Activation of the erythropoietin receptor on CFU-E progenitor cells allows them to develop, proliferate and differentiate
⇒ Nucleated erythroblasts extrude their nucleus and most of their organelles
⇒ Reticulocytes (immature red blood cells) are formed
⇒ Reticulocytes are released into the circulation
Describe the maturation of reticulocytes into erythrocytes
Once in the bloodstream reticulocytes extrude their remnants of organelles, e.g. mitochondria and ribosomes, and take ~1 to 2 days to mature into red blood cells
Explain the clinical relevance of reticulocyte count
The reticulocyte count from a blood sample therefore provides a good diagnostic estimate of the amount erythropoiesis occurring in a patient’s bone marrow
Erythrocytes, once matured in the bloodstream, lack both nuclei and mitochondria.
Respectively, explain the consequences of this
- Lack of nuclei – susceptible to oxidative damage e.g. G6PDH deficiency
- Lack of mitochondria – reliance on glycolysis for energy production e.g. pyruvate kinase deficiency
What is the reticuloendothelial system and what does it do?
- The RE system is a network of cells located throughout the body and is part of the larger immune system
- Its role is to remove dead/damaged cells and to identify and destroy foreign antigens in blood and tissues
The cells which compose the RE system are phagocytic and include monocytes in blood and different types of macrophages in various tissues.
Identify some of these macrophages and their associated tissues
The spleen has a prominent role in the RE system in filtering blood to remove deformed and old cells from the circulation.
In 4 steps, describe this process
⇒ Haemoglobin is removed from senescent erythrocytes
⇒ The globin portion is degraded to its constitutive amino acids
⇒ The haem portion is metabolised to bilirubin
⇒ Bilirubin is removed in the liver, conjugated and secreted in bile