Hematopoetic System
Peripheral Blood
I. Composition
§ Blood is fluid connective tissue
§ 7% of body weight (5 liters)
Plasma
§ liquied which peripheral blood cells are suspened
§ composed of water, electrolytes, plasma proteins, hormones, fats, amino acids, vitamins, carbohydrates, lipoproteins
Formed Elements (blood cells)
§ erythrocytes (RBC)- 40-45% of total blood volume
§ leukocytes (WBC and platelets)- 1-2% of total blood volume
§ freshly drawn blood is red blud
§ form jelly-like mass if allowed to clot
§ clot is formed by conversion of fibrinogen to fibrinàntwk that entraps formed elements
§ anticoagulant: densities of elements RBC>platelets, lymphocytes, granulocytes>plasma
II. Morphology and Function of Blood Cells
Erythrocytes (mature RBC)
§ 7-8 mm in diameter
§ anucleate, acidophilic body
§ loses nucleus, golgi, centrioles, ER and most of mitochondria
§ bulk of cytoplasm consists of hemoglobin, few organelles
§ biconcave skisk to achieve max SA to cytoplasmic volume ratio
§ enclosed in fluid bilayer cell membrane, makes flexible and elastic to allow movement thru capillary
§ cup shape in capillary
§ peripheral membrane proteins, spectrin and actin, serve a cytoskeletal function
§ 120 day life span, as ages SA decreases, sphere formation, more rigid and trapped in splenic cords
§ Reticulocyte
Less mature erthrocyte
RBC from bone marrow into circulation considered reticulocytes for 2 days
Contain residual ribonucleoprotein particle which imparts a bluish hue called plychromasia
Make up 1-2% of red cells
Leukocytes (WBC)
Granulocytes (segmented nucleus in mature stage)
Neutrophils
§ 12-15 mm
§ Prominent nucleus segmented into 2-5 lobes joined by fine nuclear strands
§ Most numerous of WBC in adult (more in children)
§ Less mature neutrophils have band-shaped nucleus
§ Specific (secondary) granules- most numerous type, small, stain pink-blue hue
§ Azurophili (primary) granules- less numerous, larger, stain reddish purple; primary lysosomes which contain myeloperoxidase and acid hydrolases characterisic of lysosomes
§ Cytoplasm contains glycogen and filaments and microtubues
§ Band-cell- premature neutrophils with sorseshoe-shaped nucleus
§ 50-75% of WBC, 3-5% band
§ 1-4 day lifespan
§ firstline of defense against microorganisms (bacteria)
§ active phagocytes-particles taken up in vacuole, pH lowered, azurophilic granules fuse, killing and digestion occurs, lysozyme destroys cell wall of gram positive bacteria
§ undergo chemotaxis
§ facilitates phagocytosis
§ bone marrow will release more neutrophils in response to stimuli such as bacterial infection etc
Eosinophils
§ same size as neutrophil 12-15 mm
§ bilobed nucleus
§ cytoplasm has granules that stain bright orange ( granules contain dense filamentous core of major basic protein MBP = crystalloids)
§ MBP kills worms
§ matrix of granules contain lysosomal enzymes
§ 1-3% in peripheral blood
§ high in individuals with allergies or parasitic infections
§ circulates 8 hours
§ chemotaxis- phagocytose antigen-antibody complexes and inactivate mediators of inflammation like leukotrienes
Basophils
§ 9-10 mm
§ 2-3 lobe nucleus
§ metachromatic granules stain deep purple color
§ high concentration of heparain (anticoagulant), histamine (vasodialating agent), serotonin
§ .5-1% in peripheral blood, least numerous granulocyte, least numerous WBC
§ phagocytic function
§ secretrory cell which mediates hypersensitivity reaction
§ bind IgE antibody
Mononuclear Cells
Monocytes
§ 12-15 mm
§ 1.5 days in blood, migrate to tissue to become macrophages
§ largest cell in blood
§ fairly large nucleus- ovoid, kidney shaped often located in an eccentric position
§ cytoplasm is pale and may contain azurophilic granules (lysosomes), pinocytotic vacuoles frequently seen, also RER, free ribosomes, ply robosomes, well developed golgi
§ cell membrane ahs finger-like microvilli
§ 3-8% of peripheral blood
§ 5-8 day lifespan
§ mononuclear-phagocyte system: leave blood and enter tissue differentiating into macrophages
§ phagocytize and remove particles, tissue debris, infectious agents
§ interact with lymphocytes and play essential role with antigen interaction of immunocompetent cells
Lymphocytes
§ spectrum of sizes 6-8 mm to 10-12 mm
§ single, deeply-stained, spherical nucleus
§ nucleus surrounded by thin rim of lightly basophilic cytoplasm
§ cytoplasm contains few non specific granules (lysosomes), few mitochondria, many ribosomes, and golgi
§ T cell lymphocytes- processed by thymus and participatein cell-mediated immunity (graft rejection), elaborate cytotoxic agents, make lymphokines, memory T-cell
§ B-lymphocytes-bursa derived, play role in humoral or antibody mediated immunity, some divide and differentiate into plasma cells in tissue, memory cells, characterized by imunoglobulin on their cell membrane
Plasma cells
§ From B-lymphocytes
§ Eccentrically placed nucleus
§ Contain abundant RER whose cisternae can be filled with antibody, well developed Golgi
§ 20-25% peripheral blood
§ 80% T-cells, 15% B-cells, 5% null, plasma cells not seen in peripheral blood
Platelets (thrombocytes)
§ non nucleated flat, biconvex, round or ovoid disks, derived from megakaryocytes
§ contain pale-blue peripheral hyalomere with system of invagination channels connecting with their membrane, system of electron dense tubules, marginal bundle of circumferential microtubules to maintain disk shape, actin and myosin
§ contain thicker central purple granulomere containing several kinds of granules
§ alpha granules are azurophilic and contain fibrinogen, platelet derived growth factor
§ dense granules contain calcium pyrophosphate, ADP, ATP
§ also sotre serotonin
§ small vesicules contain lysosomal enzymes
§ promote coagulation cascade involing plasma factors- aggregate on damaged endothelium and exposed collagen, release alpha and dense granules
§ clotting process is good to limit hemorrhage but can be life threatening on wall of coronary artery (coronoary thrombosis) or when breaking fee from veins of extremities and going to lungs to cause pulmonary embolism
§ deficiency is called thrombocytopenia- result in bruising or bleeding, caued by immunde destruction by antibodies against it, bone marrow infiltration by cancer.
HEMATOPOETIC SYSTEM I I: BONE MARROW
I. Introduction
§ Bone marrow is highly vascularized connective tissue that produces formed elements
§ Bone marrow is most rapidly replicative tissue in body
II. Blood Cell Renewal
Problem
§ Blood cells have finite and brief life spand and must be renewed
§ Process of renewal isknown as hematopoiesis
§ Hematopoiesis- infection, hemorrhage, tumors and other factors increase or decrease level of heatopoiesis
Hematopoietic tissues
§ Tissue which actively or potentially produce blood cells
§ Myeloid tissues- red marrow of bones
§ Lymphoid tissues- somelymphocytes of peripheral blood arise from proliferation within lymphoid tissues. Elements of larger lymphatic system. Lymphocyte stem cell located in bone marrow.
Hematopoiesis in Utero
§ Embryo and fetus (intrauterine development)
Different tissues serve as major blood cell producers at different gestational ages. Gesational hematpoiesis occurs in three major waves of phases
|
Gestational age |
Phase |
Lacation |
|
2 weeks – 2 months |
Mesoblastic: hematopoiesis begins in yalk sac wall wher small nest of blood cell production can be visualized.. nests are referred to as “blood islands” |
Wall of yolk |
|
6 weeks – birth |
Hepatic: islands of blood cell developmentoccur within liver parenchyma. Although liver is dominant site of hematopoiesis for first half of gestaion, blood cell production also occurs at leser intensity within spleen |
Liver |
|
2.5 months-birth |
Myeloid: hematopoiesis wihin bone marrow begins in clavicle at 2.5 mones activity continues to rise until myelid tissue becomes major sie of hematopoiesis in latter half of gestions. Myelid hematopiesisis centered in most bone marrow during intrauterine life. |
Bone marrow |
§ At birth, myeloid phase predominates in hematopoiesis and occurs in medullary cavities of long bones
§ As a child grows, long bones assume weight bearing function and marrow becomes yellow
§ Site of hematopoiesis shifts to red marrow of axial skeleton (skull, vertebral column, ribs, sternum, shoulder girdle and pelvic girdle)
§ Adults- hematopoiesis resides in red marrow of axial skeleton. Under certain conditions, spleen, liver and yellow marrow can resume hematopoietic activity in adult
III. Theories of Hematopoiesis
§ Dualistic or polyphyletic theory- bleood cell types arise from its own unique stem cell
§ Unitarian or monophyletic theory- all blood cell types arise from common stem cell believed to look like a lymphocyte and travels in blood as null cell.
IV. Red Marrow
§ Composed of network of vascular sinuses situated throughout sponge like network of hematopoietic cells.
§ Sinuses interposed between between arteries and veins and contain peripheral blood.
§ Red marrow is organized into sacs within which hematopoietic cells develop in nests or foci.
§ Reticular cells and reticular fibers form a supportive framework for developing blood cells and sinuses.
§ In red marrow, cells of RBC line develop near sinus wall.
§ Each RBC nest has an associated macrophage which contains iron.
§ Cells of granulocyte series develop away from sinus
§ Megakaryocytes develop next to sinuses.
V. Developmental stages of blood cells
Erythropoiesis (RBC)
§ Pronormoblast-divides
§ Basophilic normoblast-divides
§ Plychromatophilic normoblast-divides
§ Orthochromic normoblast-divides
§ Reticulocyte-no division
§ Erythrocyte-no division
§ Control of erythropoiesis- 16-32 divisions in one week, RBC formation under control of kidney produced hormone known as erythropoeitin, dietary vitamin B12 and folic acid are required for normal maturation of RBCs.
Granulopoiesis
§ Myeloblast- divides
§ Promyelocyte- divides
§ Neutrophilic, eosinophilic or basophilic myelocyte- divides
§ Neutrophilic, eosinophilic or basophilic metamyelocyte- no division
§ Neutrophilic, eosinophilic, basophilic band (stab)- no division
§ Neutrophil, eosinophil, or basophil- no division
§ Control of granulopoiesis- stimulated by CSF, substances released by macrophage/monocyte community. One stimulus for CSF release is increase cell migration into tissues, such as an infection.
§ Total time taken for myeloblast to emerge as mature neutrophil is 11 days
§ Five mitotic divisions occur for myeloblast, promyelocyte and myelocyte
§ Neutrophils pass through several functionally anatomically defined compartments
§ Meduallary formation compartment- subdivide into mitotic compartment and maturation compartment
§ Meduallary storage compartment acts as buffer system, capable of releasing large numbers of mature neutrophils upon demand
§ Medullary storage compartment acts as buffer system capable of releasing large numbers of mature neutrophils upon demand.
§ Circulating compartment consists of neutrophils suspended in plasma and circuating in blood vessels
§ Marginal compartment is composed of neutrophil present in blood but not circulation
§ Marginal and circulating compartments are of equal size, constant interchange of cells. Important for acute bacterial infaction. Neutrophils can be recruited from marginating pool immediately rather than waiting for neutrophils to be formed and released from marrow.
Thrombopoiesis (platelets)
§ Megakaryoblast- large cell with big nucleus (4n) situated close to sinuses
§ Promegakaryocyte- larger than megakaryoblast, contains voluminous plypliod nucleus (8n).
§ Megakaryocyte- giant cell with large polypliod nucleus (32n-64n) platelet demarcation channels distinct, massive protrusion of call penetrates a sinus and fragments into platelets
§ Thrombocyte (platelet)- final end product which circulates inperipheral blood. Responsible for primary hemostasis (clot formation)
§ Control of thrombopoiesis- serm glycoprotein, thrombopoetin stimulates megakaryocytes and platelet production.
Other red marrow cells
§ Macrophages- tissue counterparts of monocytes of peripheral blood. In bone marrow function in phagocytosis andiron storage.
§ Structural cells- include fat cells, reticular cells, endothelial cells
§ Lymphocytes- few lymphocytes and plasma cells are usually present in bone marrow
Tags: active phagocytes, Amino acids, anticoagulant, Azurophili granules, bone marrow, carbohydrates, chemotaxis, cytoplasm, electrolytes, Eosinophils, erythrocytes, Erythropoiesis, fats, Granulopoiesis, heatopoiesis, Hematopoetic System, Hemoglobin, heparain, hormones, leukocytes, Megakaryoblast, metachromatic granule, Neutrophils, peripheraql blood, phagocytic function, plasma proteins, Promegakaryocyte, Thrombopoiesis, vitamins
