.png){kind=icon}
1 Name the different types of cell found in peripheral blood and provide a brief explanation of the functions of each.
Red blood cells – contain haemoglobin and carry oxygen to metabolizing tissues.
Platelets – are responsible for forming a primary platelet plug and as such are involved in the initial stages of blood clotting.
Neutrophils – phagocytic cells involved in fighting infections.
Eosinophils – involved in allergy and release antihistamine. Also involved in the body’s response to helminth infections.
Basophils – involved in allergy and secrete histamine.
Monocytes – are an intermediate stage of maturation, eventually forming tissue macrophages. Monocytes and macrophages are phagocytic.
Lymphocytes – are involves in fighting infection. B cells secrete antibodies, T cells regulate the B-cell response and can interact with cells infected by viruses. Large granular lymphocytes are important in suppressing and killing infected and cancerous cells.
2 Name the main haemopoietic sites associated with the embryonic stage of development.
Liver, spleen and yolk sac.
3 Using the equation P=M/L outlined above, state the volume of red cells that would need to be produced each day if the red cell lifespan reduced to 75 days.
2250/75 = 30 mL per day.
4 Provide a brief comparison between red and yellow marrow.
Red marrow is haemopoietic marrow. The elements required for blood cell production can be found in this area. The yellow marrow is composed of adipose (fatty) tissue. Bone marrow is found within the long bones of adults, and there is a dynamic relationship between red and yellow marrow. As we age, the amount of red marrow decreases allowing yellow marrow to increase. As demands for haemopoiesis increase, so yellow marrow is replaced by red marrow.
5 Define cellularity and explain the consequences of haemolysis on bone marrow cellularity in terms of both red and yellow marrow.
Cellularity describes the proportion of haemopoietic cells in the bone marrow. Cellularity decreases as we age. During embryonic development, cellularity is approximately 100%. This means that all of the bone marrow is haemopoietic. By the time we reach 70 years of age, only 30% of the bone marrow is haemopoietic red marrow, the remainder being composed of yellow marrow.
Haemolysis describes a reduction in red cell lifespan. In cases of haemolysis, we typically would expect to see an expansion of red marrow and a concurrent reduction in yellow marrow. This process facilitates the production of red cells to compensate for the reduced red cell lifespan.
6 Explain the differences between the two different forms of cell division associated with stem cells.
Asymmetric cell division describes the production of two dissimilar daughter cells from a single stem cell, whereas symmetric cell division describes the production of two identical daughter cells.
7 Outline the role of EPO in red cell production.
Erythropoietin (EPO) is important for ensuring adequate red cell production. It interacts primarily with CFU-E and pronormoblasts, both expressing the EPOR. EPO increases cell proliferation and inhibits apoptosis.
8 Explain how a low platelet count can facilitate thrombopoiesis.
Platelets, like their precursors, express the thrombopoietin receptor Mpl. Thrombopoietin interacts with receptors both on platelets and their precursors; as the platelet count decreases, there is a greater concentration of bioavailable thrombopoietin to interact with Mpl receptors on platelet progenitors, thereby increasing thrombopoiesis.
9 List the main characteristics of blast cells, and provide a brief explanation of each.
High nuclear:cytoplasmic ratio – the nucleus of the cell takes up the majority of the cell volume.
Open chromatin configuration – chromatin is open, enabling DNA transcription and translation to occur.
Prominent nucleoli – regions of the nucleus containing genes encoding ribosomal RNA that aid in DNA transcription and translation.
10 Provide a description of the role of erythroblastic islands, and state how the central macrophage may be intrinsically involved in iron control.
Erythroblastic islands contain a central macrophage with pseudopodia. Red cell precursors interact with this central macrophage and start to mature. As the red cell nucleus is extruded, phosphatidylserine expressed on the nuclear membrane facilitates uptake and degradation of the nucleus by the macrophage. Macrophages are also important in iron storage. It has been suggested that these central macrophages control the release of iron to red cell precursors, enabling the synthesis of haemoglobin to occur.
11 Compare and contrast reticulocytes with mature red blood cells.
Reticulocytes are larger than mature red blood cells and are not of a biconcave disc shape. Reticulocytes stain with a bluish tinge (termed polychromasia) when exposed to Romanowsky stain, due to their relatively higher mRNA content. Red cells stain a pink/red colour. Using a supravital stain, reticulocytes appear striated due to the presence of ribosomes. Red cells do not possess this feature. Neither red cells nor reticulocytes contain a nucleus. Reticulocytes are capable of carrying oxygen in the same manner as red cells.
12 Explain the value of measuring reticulocytes in the evaluation of bone marrow function.
Reticulocytes can easily be measured within the peripheral blood and can be used as an indication of bone marrow function. In cases of haemolysis or blood loss, a reticulocytosis is expected. This reticulocytosis represents bone marrow compensation. Conversely, in cases of iron, vitamin B12 or folate deficiency, we tend not to see a reticulocytosis because the raw materials required to produce blood cells are unavailable. Failure of a reticulocyte response may indicate an aplastic marrow (ie one that cannot produce cells).
13 Explain the role of endomitosis in thrombopoiesis.
Endomitosis ensures that megakaryocytes increase in size and content to facilitate the production of granular platelets.
14 List the key maturational stages in the development of granulocytes. For each stage, state whether or not mitosis occurs, and confirm the presence or absence of granules.
Myeloblast (mitotic): some final granules may be seen in late myeloblasts, otherwise granular content increases within the promyelocyte stage and begins to drop as cells divide. Myeloblasts are followed by promyelocyte (mitotic), myelocyte (mitotic), metamyelocyte (non-mitotic) and effector cell (non-mitotic) stages.
15 List the common causes of anaemia.
Iron deficiency, vitamin deficiency (including B12 and folate), haemolysis, bleeding, bone marrow suppression and abnormal haemoglobin production.
16 Briefly compare and contrast erythrocytosis with polycythaemia.
Both are associated with an increased red cell count. Erythrocytosis describes an EPO-dependent mechanism of red cell production to compensate for a reduced oxygen carrying capacity of the blood. The stimulus for increased EPO secretion will be the reduced oxygen carrying capacity of the blood through either physiological or environmental causes. Conversely, polycythaemia describes an EPO-independent increase in red cell production, usually as a consequence of a cancer of the red cell precursors. Care must be taken as the terms erythrocytosis and polycythaemia historically have been used interchangeably.
Discussion Questions
- Discuss the application of haemopoietic growth factors in the treatment of named haematological diseases.
- Based on your understanding of the genesis of blood cells, provide an overview of the role of a diagnostic haematology laboratory.
- Two important clinical procedures used to determine bone marrow function include the bone marrow aspirate and bone marrow trephine biopsy. Investigate each of these procedures and write brief notes on the merits of each.