Haematopoiesis Flashcards
what is haematopoiesis and erythropoiesis?
Hematopoiesis is the process of producing new blood cells, which includes various types of blood cells, such as red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Erythropoiesis specifically refers to the production of new red blood cells, which are important for transporting oxygen throughout the body. This process occurs primarily in the bone marrow, where hematopoietic stem cells differentiate into various blood cell types, including red blood cells, under the influence of specific growth factors and hormones.
what is fetal haematopoiesis?
Fetal hematopoiesis is the process of blood cell formation that occurs during the development of a fetus. It goes through various stages and occurs in different anatomical locations as the fetus develops. The progression of hematopoiesis in a developing fetus often follows the sequence of yolk sac, liver, spleen, and finally bone marrow.
Yolk Sac (3 - 8 weeks): In the early stages of fetal development, the yolk sac is one of the first sites where hematopoiesis occurs. During this phase, the yolk sac produces primitive red blood cells that are essential for the developing fetus.
Liver (6 weeks to birth): As the fetus continues to develop, the liver becomes a significant site for hematopoiesis. It produces a variety of blood cells, including red blood cells, white blood cells, and platelets.
Spleen (8 weeks - 28 weeks): The spleen also plays a role in fetal hematopoiesis, primarily during the mid-fetal development stage. It assists in blood cell production, especially in generating red blood cells.
Bone Marrow (18 weeks - adult): As the fetus approaches full-term development, hematopoiesis begins in the bone marrow. The bone marrow eventually becomes the primary site for blood cell production in postnatal life.
Lymphocytes, specifically T cells and B cells, are critical for immune responses. T cells are responsible for cell-mediated immunity, while B cells are involved in the production of antibodies and humoral immunity. The development and maturation of these lymphocytes occur in specific organs during fetal development, but the bone marrow remains an essential site for their production and maturation in postnatal life.
what is a mnemonic for the progression of haematopoiesis in a developing fetus?
Yellow Leaves Soft Breeze (Yolk sac, Liver, Spleen, Bone marrow)
what is extramedullary haematopoiesis?
Hematopoiesis typically occurs primarily in the bone marrow after birth. However, in certain circumstances, such as in response to increased demand for blood cells or when the bone marrow is compromised, extramedullary hematopoiesis can occur. This term refers to the production of blood cells outside the bone marrow.
In extramedullary hematopoiesis, other tissues and organs, such as the liver, spleen, and lymph nodes, can contribute to blood cell production to compensate for the decreased or compromised function of the bone marrow. This process is the body’s way of adapting to situations where there is an urgent need for more blood cells, such as in cases of severe anemia or bone marrow disorders.
explain how all blood cells derive from one type of haematopoietic stem cell
All blood cells, including red blood cells, white blood cells, and platelets, originate from a single type of hematopoietic stem cell. These multipotent hematopoietic stem cells have the capacity to differentiate into various specialized blood cell types, depending on the signals and microenvironment they encounter.
As these stem cells divide and differentiate, they give rise to a series of progenitor cells that become progressively more specialized, leading to the production of specific blood cell types. This process is tightly regulated to maintain the balance and composition of blood cells in the body. The hematopoietic stem cells in the bone marrow are responsible for the continuous production and replenishment of the entire blood cell population throughout an individual’s life.
explain the hierarchy of haematopoietic stem cells (HSCs) and their differentiation potential
Long-term hematopoietic stem cells (LT-HSCs) have the capacity to either self-renew, giving rise to more LT-HSCs, or differentiate into short-term hematopoietic stem cells. This decision is influenced by the presence of specific growth factors and the body’s demand for various blood cell types.
The presence of growth factors, such as Interleukin-3, erythropoietin, and G-CSF, can direct the differentiation of HSCs into specific blood cell lineages. For example:
Interleukin-3 promotes the growth of stem cells and their proliferation.
Erythropoietin stimulates the production of red blood cells (erythropoiesis).
G-CSF (Granulocyte colony-stimulating factor) promotes the production of neutrophils, a type of white blood cell.
The number of HSCs made during a lifetime is indeed difficult to calculate precisely. However, it’s known that the initial pool of HSCs, which is relatively small and established during fetal development, gives rise to all the blood cells an individual will produce throughout their lifetime. The process of self-renewal and differentiation continues to maintain and replenish the blood cell populations as needed to support the body’s functions and respond to various physiological demands and challenges.
explain the differentiation process of hematopoietic stem cells (HSCs) into various progenitor cells and their subsequent specialization into specific blood cell lineages
Short-term hematopoietic stem cells (ST-HSCs) can either give rise to more ST-HSCs or differentiate into multipotent progenitors (MPPs), which have the potential to become either:
Common Myeloid Progenitors (CMPs): CMPs are responsible for the development of all myeloid cells. This includes cells such as neutrophils, monocytes, macrophages, eosinophils, basophils, and megakaryocytes (which produce platelets). CMPs are also referred to as CFU-GEMM (Colony-Forming Unit-Granulocyte, Erythrocyte, Monocyte, Megakaryocyte).
Common Lymphoid Progenitors (CLPs): CLPs give rise to all lymphoid cells. Lymphoid cells include T cells, B cells, and natural killer (NK) cells. CLPs are also known as CFU-L (Colony-Forming Unit-Lymphoid).
what is CFU, CMP and CLP
CFU stands for “colony-forming unit,” and CMP and CLP are indeed multipotent progenitor cells. Each of them has the capacity to give rise to multiple different cell types, making them pluripotent in nature.
CMP (Common Myeloid Progenitor) can differentiate into a range of myeloid cell types, encompassing granulocytes, monocytes, macrophages, eosinophils, basophils, and megakaryocytes. CLP (Common Lymphoid Progenitor) has the potential to develop into various lymphoid cell types, including T cells, B cells, and natural killer (NK) cells. This pluripotent nature is a fundamental aspect of hematopoiesis and is crucial for the body to generate a diverse array of blood cell types to support different physiological functions and immune responses.
explain the common myeloid progenitor (CMP)
The Common Myeloid Progenitor (CMP) is also known as CFU-GEMM because it has the capacity to give rise to various blood cell types, including granulocytes, erythrocytes (red blood cells), monocytes, and megakaryocytes (which produce platelets).
Furthermore, within the myeloid lineage, there are additional differentiations. The CFU-GM (Colony-Forming Unit-Granulocyte, Macrophage) can further differentiate into CFU-G, which gives rise to neutrophils (common granulocytes), and CFU-M, which produces monocytes. Monocytes, in turn, can differentiate into macrophages, which are essential cells involved in the body’s immune response, phagocytosis, and tissue maintenance.
explain the erythroid burst-forming units (BFU-E)
Erythroid Burst-Forming Units (BFU-E) and their characteristics is accurate and informative. BFU-E represent a relatively early stage in the development of erythroid cells (red blood cells). They have limited self-renewal capacity, and their morphology, including the presence of pseudopods, moderately basophilic cytoplasm, fine nuclear chromatin, and large nucleoli, is distinctive.
BFU-E play a crucial role in the process of erythropoiesis. Under the influence of the hormone erythropoietin (Epo) and other cytokines, they differentiate and undergo several cell divisions, eventually giving rise to a large number of more mature erythrocytes (red blood cells). This process usually takes about 14 to 16 days and can result in the production of thousands of erythrocytes from a single BFU-E.
explain the erythroid colony-forming units (CFU-E)
Differentiation and Epo Sensitivity: CFU-E is very sensitive to low concentrations of Epo, and their differentiation is primarily initiated by the presence of this hormone. After this initial Epo-dependent phase, CFU-E can continue to produce pro-erythroblasts without the need for additional Epo. This responsiveness to Epo is what makes CFU-E the most Epo-sensitive blood cell.
Morphology: Under the microscope, CFU-E appears as immature cells with fine nuclear chromatin, a well-defined large nucleolus, and a perinuclear clear zone. They exhibit pseudopods and have a basophilic cytoplasm.
Production of Erythrocytes: CFU-E has the capacity to give rise to mature erythrocytes, and under the influence of low Epo concentrations, they can produce 8 to 32 erythrocytes in 5 to 8 days.
Abundance in Bone Marrow: In the bone marrow, you mentioned that for every million nucleated cells, there can be 500 to 4,000 CFU-E, indicating their presence and importance in the erythropoietic process.
Apoptosis: If Epo is absent during the development of CFU-E, they will undergo apoptosis, highlighting the crucial role of Epo in their survival and differentiation.
explain the staining process with romansky dye and the morphological characteristics of proerythroblasts
Roman Sky Dye: Roman Sky Dye, such as Wright-Giemsa stain, is utilized to stain blood cells for microscopic examination. It helps distinguish different stages of blood cell development based on their color and staining patterns.
Proerythroblast Characteristics:
Size and Shape: Proerythroblasts are round or oval cells of moderate to large size, typically measuring between 14 to 19 µm.
Nucleus: The nucleus of a proerythroblast is relatively large, occupying around 80% of the cell. This large nucleus contains chromatin, and condensation of chromatin begins at this stage.
Cytoplasm: The cytoplasm of a proerythroblast has a rim of basophilic (blue) staining. At this stage, there is very little hemoglobin present in the cytoplasm.
RNA Content: The deep blue color, as indicated by Romansky dye, signifies a high RNA content in immature cells like proerythroblasts.
Ribosomes: Proerythroblasts have the highest number of ribosomes, which play a role in producing hemoglobin. This process makes the cytoplasm more acidic over time.
The gradual decrease in cell size and the transition from a high RNA content to a predominance of red hemoglobin are part of the normal maturation process of erythrocytes (red blood cells).
explain the transition from proerythroblasts to polychromaticophilic erythroblasts
Appearance of Haemoglobin: As the erythroblast matures, it begins to accumulate faint blushes of hemoglobin in the cytoplasm. These pink areas, along with the continued presence of the blue (basophilic) staining from the earlier stages, give the cell a polychromaticophilic appearance.
Chromatin and Nucleus: The chromatin within the nucleus continues to condense and become denser. Additionally, the nucleus becomes smaller, measuring 7 to 9 µm in diameter, while the overall cell size ranges from 8 to 12 µm.
Polychromaticophilic Erythroblasts: The term “polychromaticophilic” describes the cell’s ability to stain with both blue (basophilic) and pink (acidophilic) dyes due to the presence of both RNA and early forms of hemoglobin. This is a transitional stage as the cell progresses toward becoming a mature red blood cell (erythrocyte).
explain the orthochromatic erythroblast stage in erythropoiesis
Orthochromatic Erythroblast: At this stage, the cell is referred to as an orthochromatic erythroblast. It’s characterized by possessing almost its full complement of hemoglobin in the cytoplasm, making it appear pinkish.
Size: Orthochromatic erythroblasts are the smallest among nucleated erythrocytes, with a diameter ranging from 8 to 12 µm.
Nucleus Changes: The nucleus undergoes significant changes during this stage. It becomes pyknotic, meaning it becomes smaller, more condensed, and shrinks. This process is part of the preparation for the eventual extrusion of the nucleus from the cell.
Morphological Variations: As the nucleus condenses, it may take on various shapes, such as buds, rosettes, or clover leaves, before it is eventually expelled from the cell.
explain reticulocytes and the maturation process of these young red blood
Reticulocytes: Reticulocytes are the stage following the expulsion of the nucleus from orthochromatic erythroblasts. They are considered young red blood cells and have a volume that is about 20% greater than mature red blood cells.
Retention of Organelles: Reticulocytes initially retain certain organelles, including ribosomes, mitochondria, and the Golgi complex. These organelles are important for the final stages of maturation.
Maturation Process: As reticulocytes mature, they undergo changes in organelle content. Typically, mitochondria disappear first, and ribosomes are retained longer. Some ribosomes may appear as bilaterally-indented discs during the maturation process.
Staining and Identification: In hospital and research labs, various stains and techniques are used to identify and classify different stages of erythropoiesis. Flow cytometric analysis, which relies on the binding patterns of antibodies to cell surface antigens, is one such method. The expression of markers like CD71 (transferrin receptor) can help distinguish between different stages of erythroid precursors and identify differences between BFU-E and CFU-E.
