Y1S1 Myeloid Tissue Histology PDF

(MICRO LEC) – (MICROSCOPIC HUMAN STRUCTURAL BIOLOGY 1A) (MYELOID TISSUE HISTOLOGY & Dr. Dennis Ivan Bravo) (Y1S1_Week 7_Sept/2024) DIMAYACYAC - SALAMANCA - SALAS - SAMSON - SANCHEZ - SANTIAGO - SAROCA - SICAT - TABBILOS - TALOSIG...

(MICRO LEC) – (MICROSCOPIC HUMAN STRUCTURAL BIOLOGY 1A) (MYELOID TISSUE HISTOLOGY & Dr. Dennis Ivan Bravo) (Y1S1_Week 7_Sept/2024) DIMAYACYAC - SALAMANCA - SALAS - SAMSON - SANCHEZ - SANTIAGO - SAROCA - SICAT - TABBILOS - TALOSIG - TAWASIL - TEOPENGCO - ULANG - UMALI - VENDIVIL OUTLINE Introduction FAT STORAGE Histology and Structure ○ Yellow Marrow Storage of adipose tissue (yellow marrow) ○ Red Marrow Hematopoiesis ○ Aside from hematopoiesis, the bone marrow is also a ○ Erythropoiesis storage site for triglycerides. Adipose tissue can be ○ Thrombopoiesis found in the bone marrow particularly in the yellow ○ Granulopoiesis ○ Monocytopoiesis marrow. Clinical Relevance Summary BONE MARROW STRUCTURE REFERENCES Myeloid Tissue Histology PPT and Recorded Lecture RED MARROW: THE BLOOD-MAKING MAESTRO Active hematopoietic: stem cells, progenitor cells, and INTRODUCTION precursors: erythroblasts, myeloblasts and megakaryoblasts ○ Primarily responsible for hematopoiesis Functions of the Bone ○ Active in hematopoiesis Support for soft tissues and tendon attachment ○ Stem cells, progenitor cells, and precursor cells in ○ Protection for internal organs varying stages of development are found here. The bone is an important organ that protects vital ○ This will include the precursors: internal organs like the brain and heart. Erythrocytes or Red Blood Cells- ERYTHROBLASTS ○ Movement in combination with skeletal muscle Leukocytes or White Blood Cells- MYELOBLASTS Thrombocytes or Platelet- MEGAKARYOBLASTS It is responsible for locomotion so whenever skeletal muscles would contract by themselves, this would not YELLOW MARROW: THE FAT-STORING STEWARD create any movement unless of course that skeletal muscle is attached to the bone. Adipose cells, varies with age and activity Store and release minerals (Calcium) ○ The yellow marrow is composed of adipose so ○ Bones also have other functions aside from its its main function is to store triglycerides. mechanical function. They store and release minerals like calcium and phosphate. YELLOW MARROW & RED MARROW Functions of the Bone Marrow The blood factory ○ Deep within the bone is the bone marrow and it is actually a factory or some of the formed elements of the blood. Soft, spongy tissue found inside bones Primary site of hematopoiesis ○ The bone marrow is a soft spongy tissue found inside the core of the bone and this is their primary site for blood production which we call hematopoiesis. HEMATOPOIESIS Production of blood cells (red blood cells, white blood cells, and platelets) IMMUNE FUNCTION Yellow Marrow ○ Located in long bones of adults (Femur, Humerus) Housing of immune cells (B and T lymphocytes) in the initial ○ Highly infiltrated with adipocytes stages of development ○ NOT hematopoietic, BUT has potential to become ○ The red marrow has immune function because it houses the immune cells which include the B and the T one if necessary lymphocytes at least in the initial stages of development. PAGE 1 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Red Marrow red marrow are the erythroid precursor cells, myeloid ○ Found in flat bones (e.g., sternum, ribs, pelvis) and in precursor cells,, and lymphoid progenitors. the proximal ends of long bones (e.g., femur, humerus) ○ Highly cellular and actively involved in Schematic Histology of a Typical Red Marrow hematopoiesis Histology of the Yellow Marrow The bone marrow is highly vascular and contains sinuses through which red blood cells pass after their maturation process. These sinuses are lined by endothelial cells. Red - Bony trabechular The marrow is composed of erythroblastic cells in different Spaces - occupied largely by triglyceride by lipid droplets; stages of development. Adipocytes with signet ring appearance The myeloid area is occupied by cells that will eventually give rise to various local sinuses. Additionally, the marrow contains large adipocytes that store triglycerides. Cellular components of red marrow Hematopoietic Cells: The Stars of the Show Blood cell precursors at various stages of development Precursors include erythroid, myeloid, and lymphoid progenitors Histology of a Red Marrow It is typical to observe that 50% of the tissue should be filled with adipocytes in adults. Additionally, there are hematopoietic cells at different stages of development. Some cells are larger than others, indicating that they are in earlier stages of development. Sinus: are capillaries that would provide blood supply to the red marrow Marrow is a highly vascular organ Adipocytes / Fat cells are the normal component of the red marrow present in red marrow but the main cells in the PAGE 2 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Cellular Components of Red Marrow Red Marrow Stromal Cells: The Supporting Players Support and regulate hematopoiesis: ○ Endothelial cells that lines the sinusoids ○ Fibroblasts that produces fibers like collagen and reticular fibers ○ Adipocytes that stores triglycerides ○ Macrophages that would phagocytose defective hematopoietic cells ○ Reticular cells Histology of the Red Marrow Spaces (white circle structures) were filled with adipocytes, followed by the presence of hematopoietic cells in varying stages of development. The large cells seen are known as the megakaryocytes, which are located inside the pink circles. Bone Marrow The bone marrow is highly vascular due to the presence of numerous sinusoids that branch off from arteries to supply it. The internal environment of the marrow is lined by reticuloendothelial cells, which are depicted as green structures in the image above. The tissue is highly vascular, containing numerous ○ Hematopoietic stem cells occupy this space, and they sinusoids through which red blood cells pass. Some red are in various stages of development. blood cells are being released from the marrow. The large cells are megakaryocytes, which are responsible for producing platelets. Structural Components of Red Marrow The spaces in the tissue are occupied by different cell stacks, and the remaining cells are hematopoietic cells in Extracellular Matrix: The Set Design various stages of development. Provides structural support and regulates cell-cell interactions Components: collagen, laminin, fibronectin PAGE 3 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Microenvironment of red bone marrow HEMATOPOIESIS The Growth Factors and Cytokines: The Stagehands of Hematopoiesis ○ Substances orchestrating the production of blood cells ○ Promote cell proliferation, differentiation, and survival ○ Examples: erythropoietin (EPO), colony-stimulating factors (CSFs), thrombopoietin (TPO) Red marrow composition with age Amount of hematopoietic cells varies with patient’s age: ○ Child: Red BM is 100% hematopoietic and present in virtually every bone very few adipocyte ○ Adults: Red BM is 50% hematopoietic and 50% adipocyte and present in the sternum, ribs, pelvis and skull ○ 70 y/o: Hematopoietic cell is reduced to 30% mostly occupied by adipocytes Hematopoiesis Hematopoiesis: Process of blood cell formation Importance: Essential for maintaining a healthy blood supply and supporting various physiological functions Starts with Hematopoietic Stem Cells (HSCs) End products: Erythrocytes, leukocytes, platelets Illustration of Hematopoiesis Starts with Hematopoietic Stem Cells (HSCs) HSC gives rise to various progenitor cells Progenitors develop to precursor cells ○ Erythropoiesis: Proerythroblast to RBC ○ Thrombopoiesis: Megakaryoblast to platelet ○ Granulopoiesis: Myeloblast to neutrophil ○ Monocytopoiesis: Monoblast to monocyte Hematopoiesis gives rise to hematopoietic stem cells. These cells are capable of cellular division or mitosis to replenish itself. Then it will differentiate into progenitor cells. And those progenitor cells will develop into cells committed to develop into different cell lines, we referred to those committed cells as precursor cells. So in the erythropoiesis of the precursor, is the proerythroblast that will differentiate to become the RBCs. In thrombopoiesis the committed precursor is the Everything starts with hematopoietic stem cells and will megakaryoblast. differentiate to different progenitor In granulopoiesis the committed precursor is the myeloblast. ○ Myeloid progenitor cells —> RBC, Platelets, In monocytopoiesis the committed precursor is the Leukocytes monoblasts. ○ Lymphoid progenitor cells —> T cells and B cells So it starts with the hematopoietic stem cells. We can refer to it as the “Great granddaddy” of all the cells in the blood. PAGE 4 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Characteristics of Hematopoiesis and leukocytes (with exception of lymphocytes). While the Self-renewal: capable of producing more HSCs common lymphoid progenitor will give rise to the B and T Multipotent: can differentiate into all types of blood cells lymphocytes. DIAGRAM HEMATOPOIESIS The common myeloid progenitor (CMP) will give rise to granulocyte-monocyte progenitor, which is the daddy for both the monocyte and neutrophils. The eosinophil-basophil progenitor is the daddy for both the eosinophil and basophil. The megakaryocyte-erythrocyte progenitor is the common ancestor for both platelets and RBC. HEMATOPOIESIS Everything starts with the multipotent hematopoietic stem cell. It is characterized as capable of self renewal and it doesn’t go through mitosis and replenishes itself. Because it is multipotent and can give rise to all cell types in the bone marrow. It can be differentiated by common myeloid progenitor and also the common lymphoid progenitor. The great grand daddy HSC gives rise to progenitor cells (grand daddies): The common myeloid progenitor is the ancestor of ○ Common Myelocyte Progenitor erythrocytes, platelets, granulocytes, and monocytes. While It gives rise to erythrocytes, granulocytes, the common lymphoid progenitor is the ancestor for monocytes, and platelets B-lymphocyte, T-lymphocyte, and NK cell. We’ll only focus on ○ Common Lymphocyte Progenitor the common myeloid progenitor. Gives rise to B lymphocytes, T lymphocytes, and natural killer cells HSC will undergo division and differentiation to ultimately give rise to all the cells in the blood. This will include the reticulocytes, leukocytes, and the platelet. So everything starts with the HSC. We can refer to it as the “great granddaddy” of all the cells in the blood. It will differentiate to give rise to myeloid and lymphoid progenitors. The myeloid progenitor will give rise to the RBCs, platelets, PAGE 5 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY ERYTHROPOIESIS The common myeloid progenitor will further give rise to the granulocyte-monocyte progenitor which is the ancestor for granulocyte and monocyte. The eosinophil-basophil progenitor will give rise to eosinophil and basophil. CMP can also be differentiated to the megakaryocyte-erythrocyte progenitor which is the ancestor for erythrocyte and platelet. Process of RBC production Hematopoietic Stem Cell (HSC) to Common myeloid progenitor (CMP) to Megakaryocyte-erythrocyte progenitor (MEP) to Proerythroblast Proerythroblasts (The first committed progenitor that will give rise to RBC) mature through several stages to become erythrocytes The maturation process is characterized by volume loss, loss of organelle and nucleus, HgB synthesis Regulated by erythropoietin (EPO) Now let us take a look at the development of the megakaryocyte-erythrocyte progenitor which is the ancestor for both the RBCs and platelets. PAGE 6 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY ERYTHROPOIETIC CELLS PROERYTHROBLAST Sometimes known as Pronormoblast First committed erythroid progenitor A large, nucleated cell with an abundant cytoplasm Undergoes mitotic divisions to produce more erythroid progenitors Basophilic cytoplasm (RNA) Start of Hemoglobin synthesis But the level of hemoglobin here is still low that it doesn’t really contribute to the staining character of proeryhtroblast BASOPHILIC ERYTHROBLAST Basophilic Normoblast Intensely basophilic because of ribosomes Synthesizes hemoglobin Nucleus starting to condense Continues to undergo mitotic divisions to continue How do we distinguish erythropoietic cells? replenishing the RBC precursor cells ○ No visible granules in contrast to granulopoetic cells that do not contain granules all throughout their development POLYCHROMATIC ERYTHROBLAST ○ Round nucleus How do we determine the stage of development? Based When the level of RNA and hemoglobin are almost equal, the cell would now have A mix of red and blue staining, showing on: both hemoglobin and ribosomes so now we can refer to the ○ Cell size cell as polychromatic erythroblast or polychromatic normal ○ Condensation of nucleus blast ○ Cytoplasm color Nucleus becomes smaller Begins to expel organelles Hemoglobin synthesis has intensified (and hemoglobin synthesis will continue until orthochromatic erythroblast) ORTHOCHROMATIC ERYTHROBLAST Characterized by condensed pyknotic nucleus ○ nucleus is at its smallest size and ready to be extruded out Last stage with nucleus (we would find the nucleus) Primarily stains red due to abundant hemoglobin Continues to expel organelles Intensified hemoglobin synthesis ORTHOCHROMATIC ERYTHROBLAST When they are younger, they are larger. As they become more mature the cytoplasm becomes relatively smaller. The more mature cells are smaller until they become biconcave in shape. When they are young, they are predominantly basophilic because of the abundance of RNA, and as they continue to produce hemoglobin, the basophilic character disappears and is going to be replaced by eosinophilic character attributed to abundance of hemoglobin. PAGE 7 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY We have here an orthochromatic erythroblast, we can see that ERYTHROPOIESIS it is expelling out the condensed pyknotic nucleus after this stage the nucleus will not disappear, it will now be known as reticulocyte or polychromatic erythrocyte POLYCHROMATIC ERYTHROCYTE Reticulocyte Enucleated, residual ribosomes and organelles Hemoglobin synthesis has halted Mature into fully developed erythrocyte within 1-2 days Here some ribosomes are still present, but will eventually disappear. At this point, hemoglobin synthesis has stopped. Hemoglobin synthesis is no longer possible for this stage. So this reticulocyte will mature into a fully developed RBC within 1-2 days. orthochromatophilic POLYCHROMATIC ERYTHROBLAST Reticulocyte Number is good indicator of BM activity High number: chronic or severe loss of mature RBC Low number: chemotherapy, aplastic anemia, pernicious anemia, bone marrow malignancies The level of reticulocyte that reaches the maturation is a good clinical indicator for bone marrow activity. Excessive number of Erythropoiesis chain of events reticulocytes that reach the circulation may be indicative of ○ Proerythroblast - largest cell; As it matures, 3 things chronic or severe loss of mature red blood cells, that even the young ones being extruded out in the circulation. Like young can be observed: soldiers being called out to serve because the more experienced Cell volume begins to decrease ones have already died. Other one is the reticulocyte lower than Shift from basophilic color to eosinophilic color due the normal. This indicates depression of the bone like what to abundance of RNA to Hgb happens in chemotherapy, in aplastic anemia, pernicious anemia, The nucleus is condensing and will be ejected at or other bone marrow malignancies. the orthochromatic erythroblast The precursor initially has a high amount of ERYTHROCYTE RNA that eventually goes down. This will be replaced with hemoglobin. Final stage Primary regulator: Biconcave shape ○ Erythropoietin (EPO) Abundant hemoglobin Produced in kidneys in response to low O2 levels Circulates in the bloodstream for approximately 120 days Stimulates erythropoiesis by: before being destroyed in the spleen Promoting proliferation and differentiation of erythroid progenitor cells SUMMARY OF ERYTHROPOIESIS Increasing Hgb synthesis Other factors influencing erythropoiesis: Proerythroblast: Committed erythroid progenitor ○ Iron availability Basophilic erythroblast: Synthesizes hemoglobin; ○ Vitamin B12 and folic acid (deficiency results to halted presence of ribosomes maturation = megaloblast) Polychromatic erythroblast: Red and blue staining (due to ○ Hormones: Testosterones, cortisol, thyroid hormones the presence of both the RNA and Hgb) Orthochromatic erythroblast: Pyknotic nucleus Reticulocyte: Enucleated residual ribosomes Mature erythrocyte: Fully developed PNEMONIC: Proper Blood Needs Oxygen Really Bad! PAGE 8 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY THROMBOPOIESIS THROMBOPOIESIS Process of platelet formation. Hematopoietic stem cel to Common myeloid progenitor to Megakaryocyte-erythrocyte progenitor (MEP) to first identifiable immediate precursor Megakaryoblast MEP is the origin of both RBC and platelet precursors (they are siblings!) Thrombopoiesis is characterized by endocytosis and pseudopod fragmentation. MEGAKARYOBLAST A large, nucleated cell with abundant cytoplasm Contains granules and organelles that will eventually become platelets Megakaryoblast, the earliest identifiable immediate precursor, it is a large, nucleated cell with abundant cytoplasm. The RBC and platelets do have a common ancestor and that PROMEGAKARYOCYTE would be the Megakaryocyte-erythrocyte progenitor. Continues increase in size Undergo endomitosis (resulting polyploid chromosomes) Cytoplasm becomes filled with granules and organelles Megakaryoblast will give rise to Promegakaryocyte, which will continue to increase in size. It will undergo endomitosis where there is doubling of chromosome; it is not gonna be followed by actual cellular division and this result to polyploid chromosome. PAGE 9 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY MEGAKARYOCYTE The result of endomitosis of a promegakaryocyte Very large, multinucleated cell with a polyploid nucleus due to endomitosis Cytoplasm contains numerous granules and organelles Extends cytoplasmic processes (pseudopodia) into the bone marrow sinusoids THROMBOCYTE Platelets Formed from megakaryocytes pseudopod fragmentation Small, disk-shaped anucleated cells Diagram that shows megakaryocytes where they are extending Play a crucial role in blood clotting their pseudopods or proplatelets into the sinusoids. Pseudopods/proplatelets that would fragment to give rise to the thrombocytes/platelets. The platelets that are going to be formed from the fragmentation of megakaryocytes is a small, disk-shaped anucleated cells which play a crucial role in blood clotting. THROMBOPOIESIS - SUMMARY Promegakaryoblast: Committed thrombocyte progenitor ○ Give rise to megakaryoblast Megakaryoblast: Undergo endomitosis ○ Give rise to a large cell called megakaryocyte Megakaryocyte: Gives rise to platelets via fragmentation Platelets: Anucleated cells important for clotting ○ Initiates the process of clotting PNEMONIC: “Please Make My Tea!” THROMBOPOIESIS So, let’s look for megakaryocyte here, the large cells we see here which is considered to be larger than hematopoietic precursors is the megakaryocyte In thrombopoiesis, we start with myeloid stem cell that will give rise to megakaryoblast, undergoing endomitosis, to give rise to megakaryocyte that will fragment to give rise to platelets. The Megakaryocyte pseudopod will start to bud off and that would give rise to the platelets PAGE 10 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY THROMBOPOIESIS Primary regulator: ○ Thrombopoietin (TPO) Produced by the liver and kidney Stimulates megakaryocyte production and maturation in the bone marrow Primary stimulant Negative feedback loop: ○ Increased platelet count leads to decreased TPO production in the liver Granulocyte-monocyte progenitor is a common ancestor for both neutrophil and monocyte. GRANULOPOIESIS Common myeloid progenitor: give rise to erythrocytes, granulocytes, platelets, and monocytes Megakaryocyte-erythrocyte progenitor: give rise to RBC and platelet Process of neutrophil formation. Granulocyte-monocyte progenitor: give rise to neutrophils HSC to CMP to GMP to Myeloblast and monocytes ○ From hematopoietic stem cell to common myeloid progenitor to granulocyte-monocyte progenitor to myeloblast GMP is the origin of both neutrophil and monocyte PAGE 11 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Development characterized by change in nucleus shape Appearance of granules (primary followed by specific secondary) MYELOBLAST Earliest identifiable committed precursor Blast: young First committed granulocyte progenitor Large, nucleated cell with abundant cytoplasm Mitotic divisions to produce more granulocyte progenitors ○ Always capable of mitosis so that it replenish When the first granules appear, it is called itself and other granulocyte precursor promyelocyte. When the secondary granules start to appear, it is PROMYELOCYTE referred to as myelocyte. When the secondary granules are predominant, it is Pro: before, cyte: cell now referred to as metamyelocyte. Contains primary granules (azurophilic granules) These granules contain lysosomal enzymes and other proteins involved in phagocytosis Undergoes mitotic divisions to replenish itself and other granulocyte precursor MYELOCYTE Contains secondary granules (specific granules) Secondary granules determines the granulocyte subtype (neutrophil, eosinophil, or basophil) Aside form the appearance of the secondary granules, the Nucleus undergoes morphological changes and development from promyelocyte to band neutrophil, it is becomes indented characterized by flattening of the nucleus. it becomes horseshoe shaped until it becomes segmented. METAMYELOCYTE Summary Meta: beyond Nucleus becomes more indented, resembling a ○ Myeloblast: First committed granulocyte progenitor horseshoe shape ○ Promyelocyte: Contains primary granules Cytoplasm becomes more abundant replete with ○ Myelocyte: Contains secondary granules secondary granules (becoming predominant) ○ Metamyelocyte: Nucleus becomes indented ○ Band neutrophil: Nucleus becomes horseshoe-shaped BAND NEUTROPHIL ○ Mature segmented neutrophil: Developed neutrophil with a multilobed nucleus Nucleus becomes fully horseshoe shaped Cytoplasm contains numerous granules (secondary) PNEMONIC: Ready to enter the bloodstream “My Phone Memory Might Be MicroSoft!” MATURE SEGMENTED NEUTROPHIL Fully developed neutrophil with a multilobed nucleus Contains abundant granules for phagocytosis Circulates in the bloodstream for a few days before entering tissues to fight infections PAGE 12 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY GRANULOPOIESIS Regulators are group of proteins that stimulate the growth and differentiation of granulocytes: ○ Granulocyte-colony stimulating factor (G-CSF) ○ Granulocyte-macrophage colony-stimulating factor (GM-CSF) ○ Interleukin-3 (IL-3) Produced by various cells: macrophages, T cells, and endothelial cells Regulate granulopoiesis in response to infection or inflammation MONOCYTOPOIESIS Process of monocyte formation. HSC to CMP to GMP to Monoblast ○ From hematopoietic stem cell to common myeloid progenitor to granulocyte-monocyte progenitor to monoblast GMP is the origin of both neutrophil and monocyte PAGE 13 OF 14  MICRO LEC – MYELOID TISSUE HISTOLOGY Monocytopoiesis KEY POINTS Monoblast: First committed monocyte progenitor Bone marrow is a vital tissue involved in: ○ earliest identifiable precursor and the one committed ○ Hematopoiesis to the pathway ○ Immune function Promonocyte: A larger cell with a more indented nucleus ○ Fat storage. Mature monocyte: Fully developed monocyte with a kidney-shaped nucleus and abundant cytoplasm Hematopoiesis is the process of blood cell production, Monocytes migrate from the bone marrow into the involving hematopoietic stem cells and their differentiation bloodstream. into various blood cell lineages. Circulate in blood for a few days before entering tissues. Hematopoiesis: occurs primarily in the bone marrow. Upon entering tissues, monocytes differentiate into Hematopoietic stem cells (HSCs): progenitor cells that give macrophages. rise to all blood cell lineages. Macrophages are larger and more phagocytic than HSCs: self-renew and differentiate into various blood cell monocytes. types: ○ Common myeloid progenitor (CMP) Summary ○ Common lymphoid progenitor (CLP) Monoblast: First committed monocyte progenitor Promonocyte: Large indented nucleus Monocyte: Kidney shaped nucleus Erythropoiesis is the process of red blood cell production, Macrophage: Active phagocytic in tissues regulated by erythropoietin (EPO). ○ Proerythroblast is earliest identifiable precursor MONOCYTOPOIESIS ○ Development involves Synthesis of hemoglobin Regulation: Loss of organelles ○ Colony-stimulating factors (CSFs): Extrusion of nucleus (normoblast) ○ Granulocyte-macrophage colony-stimulating factor ○ Mature erythrocyte is extruded unto circulation (GM-CSF) ○ Macrophage colony-stimulating factor (M-CSF) Granulopoiesis is the process of white blood cell Interleukins production, regulated by colony-stimulating factors (CSFs). ○ Can also stimulate monocytopoiesis, in response to ○ Myeloblast is the earliest identifiable precursor infection or inflammation ○ Process involves appearance of secondary ○ Interleukin-3 (IL-3) specific granules and nuclear segmentation ○ Interleukin-4 (IL-4) ○ Band neutrophil migrates to the circulation ○ Interleukin-5 (IL-5) ○ Mature segmented neutrophil CLINICAL RELEVANCE Thrombopoiesis is the process of platelet production, regulated by thrombopoietin (TPO). BONE MARROW DISORDERS: ○ Megakaryoblast is the earliest identifiable precursor Anemia ○ Promegakaryocyte undergoes endomitiosis Deficiency in red blood cells, leading to fatigue, ○ Megakaryocyte undergoes proplatelet weakness, and shortness of breath fragmentation manifested in circulation, this is in general deficiency of ○ Thrombocyte/platelet RBC Leukemia Malignant proliferation of white blood cells, affecting their function and leading to various symptoms PAGE 14 OF 14