Human Histology Chapter 10 - Hemopoiesissssssssssssssss ssss PDF

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MT56: Human Histology Lesson 10: Hemopoiesis Medical Laboratory Science | Cagayan State University - Andrews CampusBSMLS - 2E | 2ndSemester A. Y. 2020-’21 Padayon, RMT 1Hemopoiesis● is initiated in early embryonic development ● hematopoietic cells are generated in the yolk sac as blood islands in th...

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MT56: Human Histology

Lesson 10: Hemopoiesis Medical Laboratory Science | Cagayan State University - Andrews Campus

A. B. C. D. E. F. G. H.

TOPIC OUTLINE Hemopoiesis

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Stem Cells, Growth Factors, & Differentiation

Bone Marrow Erythropoiesis Granulopoiesis Monocytopoiesis Lymphopoiesis Megakaryopoiesis

Hemopoiesis ● is initiated in early embryonic development ● hematopoietic cells are generated in the yolk sac as blood islands in the 3 rd week of gestation ○ primitive red blood cells (erythroblasts) are the first blood cells formed during the first 2 to 8 weeks of life ● By the second month to fifth month of gestation, the liver becomes the major site of haematopoiesis ○ granular types of leukocytes have made their initial appearance ● In the fourth month of gestation, the bone marrow begins to function in the production of blood cells ● After the fifth fetal month, the bone marrow begins to assume its ultimate role as the primary site of hematopoiesis (medullary hematopoiesis)

Stem Cells, Growth Factors, & Differentiation

BSMLS - 2E | 2nd Semester A. Y. 2020-’21

Pluripotent Hemopoietic Stem Cells ● bone marrow stem cell believed to be where all blood cells arise ● Can produce all blood cell types ● proliferate and form two major cell lineages: 1. lymphoid cells 2. myeloid cells Progenitor & Precursor Cells ● Pluripotent stem cells give rise to daughter cells with restricted potentials called progenitor cells or colonyforming units (CFUs) ● Four types of progenitors/CFUs: 1. CFU-erythrocytes (CFU-E) 2. CFU-megakaryocytes (CFU-Meg) 3. CFU-granulocytes-monocytes (CFU-GM) 4. CFU-lymphocytes of all types (CFU-L) ● Changes in properties of hematopoietic cells during differentiation.

Hemopoietic Growth Factors (CSF) ● also called as hematopoietins (poietins) ● has overlapping functions in: ○ stimulating proliferation (mitogenic activity) of immature (mostly progenitor and precursor) cells ○ supporting differentiation of maturing cells ○ enhancing the functions of mature cells Growth Factor Cellular Source Mature Cell Main Biologic Target Activity Erythropoietin Peritubular cells None •Stimulates red of the kidney, blood cell Kupffer cells formation in vivo and cells (outer cortex) in vitro •Stimulates production of mRNA for globin IL-3 Activated T Eosinophils, •Stimulates in lymphocytes monocytes vivo and in vitro production of all myeloid cells. G-CSF Monocytes, Granuocytes •Stimulates fibroblasts, formation (in endothelial cells vitro and in vivo) of granulocytes. •Enhances metabolism of granulocytes. •Stimulates malignant (leukemic) cells M-CSF Monocytes, fi Monocytes •Stimulates broblasts, formation of endothelial cells macrophages in vitro. •Increases antitumor activity of macrophages. GM-CSF T lymphocytes, Granulocytes •Stimulates in monocytes, vitro and in vivo eosinophils, production of monocytes, granulocytes fibroblasts, and endothelial cells macrophages

Padayon, RMT

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MT56: Human Histology

Lesson 10: Hemopoiesis Medical Laboratory Science | Cagayan State University - Andrews Campus

Bone Marrow ● Two types of bone marrow: 1. Red bone marrowblood − forming red bone marrow 2. Yellow bone marrow − filled with adipocytes ● In the newborn, all bone marrow is red and active in blood cell production ● In conditions like severe bleeding or hypoxia, yellow marrow reverts to red

Erythropoiesis ● Erythropoietic islands − specialized niches in which erythroid precursors proliferate, differentiate, and enucleate ● Erythroid cells account for 5% to 38% of nucleated cells in normal bone.

Components of the Red Bone Marrow ● Stroma − meshwork of reticular or adventitial cells and a delicate web of reticular fibers supporting hemopoietic cells and macrophages ● Hemopoietic cords or islands of cells ● Sinusoidal capillaries ● Matrix of bone marrow also contains collagen type I, proteoglycans, fibronectin, and laminin,

Clinical Significance ● In certain abnormal circumstances, the spleen, liver, and lymph nodes revert back to producing immature blood cells − there is resulting splenomegaly and hepatomegaly ● This situation occurs under the following conditions: − When the bone marrow becomes dysfunctional in cases such as aplastic anemia, infiltration by malignant cells, or overproliferation of a cell line (e.g., leukemia) − When the bone marrow is unable to meet the demands placed on it, as in the hemolytic anemias

● Proerythroblast − first recognizable cell in the erythroid series − a large cell with loose, lacy chromatin, nucleoli, and basophilic cytoplasm ● Basophilic erythroblast − with more strongly basophilic cytoplasm and a condensed nucleus with no visible nucleolus. − basophilia of these two cell types is caused by the large number of polyribosomes synthesizing hemoglobin ● Polychromatophilic erythroblast − cell volume is reduced − show regions of both basophilia and acidophilia in the cell − Heterochromatin granules form a checkerboard pattern ● After the last mitosis, the nucleus becomes small and dense (pyknotic), and the orthochromatophilic erythroblast stage is reached − mitosis is no longer possible − smaller than the polychromatophilic erythroblast − contains more abundant hemoglobin and fewer polyribosomes and remains slightly polychromatophilic ● Polychromatophilic erythrocyte − the nucleus and a small rim of cytoplasm are ejected from the orthochromatophilic erythroblast − On air-dried films with Romanowsky-type stains, the reticulocyte is polychromatophilic as a result of the retention of RNA − constitute 1% to 2% of the the total RBC count, lose the polyribosomes and quickly mature as erythrocytes Granulopoiesis ● Myeloid cells account for 23% to 85% of the nucleated cells in normal bone marrow − Early cells are located in the cords and around the bone trabeculae ● Neutrophils in the bone marrow reside in the ○ proliferating pool − where cells spend an average of 3 to 6 days ○ maturation storage pool ● If needed, cells from the storage pool can exit into the circulation rapidly and will have an average life span of 6 to 10 hours

BSMLS - 2E | 2nd Semester A. Y. 2020-’21

Padayon, RMT

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MT56: Human Histology

Lesson 10: Hemopoiesis Medical Laboratory Science | Cagayan State University - Andrews Campus

● Monocyte − rich in RER, has extensive Golgi apparatus in which granule condensation occurs − primary lysosomes: observed as fine azurophilic granules in blood monocytes − function for several months as macrophages as they enter tissues

● Myeloblast − most immature recognizable cell − has finely dispersed chromatin, and faint nucleoli ● Promyelocyte − characterized by its basophilic cytoplasm and azurophilic granules containing lysosomal enzymes and myeloperoxidase − produce lineages for the three types of granulocytes ● Myelocytes − with gradual increase of specific granules ● Metamyelocyte − specific granules eventually occupy most of the cytoplasm − mature with further condensations of the nuclei − stage at which granulocytes are clearly identified ● Mature granulocyte Functional Compartments of Neutrophils

Clinical Significance ● Increase in the number of neutrophils in the circulation, does not necessarily imply an increase in neutrophil production ○ Intense muscular activity or the administration of epinephrine − can cause neutrophils in the marginating compartment to move into the circulating compartment ○ Glucocorticoids (adrenal gland hormones) − increase the mitotic activity of neutrophil precursors in the marrow ● Bacterial infections neutrophilia − is due to an increase in production of neutrophils and shorter duration cells in the medullary storage compartment − Immature cells may appear in the bloodstream − Neutrophilia is of longer duration than that which occurs as a result of intense muscular activity Monocytopoiesis ● Monoblast − is a committed progenitor cell − identical to the myeloblast in its morphologic characteristics ● Promonocyte − a large cell (up to 18 m in diameter) with basophilic cytoplasm and a large, slightly indented nucleus − chromatin is lacy and nucleoli are evident − divide twice as they develop into monocytes BSMLS - 2E | 2nd Semester A. Y. 2020-’21

Lymphopoiesis ● lymphocytes and plasma cells are produced in lymphoid follicles ● Lymphoid cells typically account for 1% to 5% of the nucleated cells in the normal bone marrow ● All lymphocyte progenitor cells originate in the bone marrow ● Circulating lymphocytes originate mainly in the: ○ thymus ○ peripheral lymphoid organs ● Lymphoblast − the first identifiable progenitor of lymphoid cells − divides two or three times ● Prolymphocytes − are smaller and have relatively more condensed chromatin but none of the cell-surface antigens that mark T or B lymphocytes ● T lymphocytes − acquire their full attributes in the thymus − predominant lymphocyte in the lymphoid organs ● B lymphocytes − lymphocytes that have differentiated in the bone marrow − migrate to peripheral lymphoid organs, where they inhabit and multiply in their own special compartments ● To distinguished this two immunocytochemical techniques using cell-specific markers are required Clinical Significance ● Leukemias − are malignant clones of leukocyte precursors − lymphocytic leukemias − myelogenous and monocytic leukemias − shift in cell proliferation − patient is usually anemic and prone to infection ● bone marrow aspiration − clinical technique used in the study of leukemias − labeled monoclonal antibodies specific to membrane proteins of precursor blood cells aids in identifying cell types derived from these stem cells Megakaryopoiesis ● the largest cells found in the bone marrow ● protrude through the vascular wall as small cytoplasmic processes to deliver platelets into the sinusoidal blood ● Megakaryocytes develop into platelets in approximately 5 days ● Mature platelets − metabolically active cell fragments. These anuclear cells circulate in the peripheral blood after being produced from the cytoplasm of bone marrow megakaryocytes, Clinical Significance ● Thrombocytopenic purpura − disease characterized by decreased number of platelets − indicating a defect in the liberation mechanism of these corpuscles. − Life span of platelets: 9 days References:  Hizon, C. (2021). Hemopoiesis powerpoint presentation. Cagayan State University.

Padayon, RMT

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