I. Peripheral blood - about 6L, 7% of body weight!- functions: conducting oxygen, nutrients, electrolytes, hormones to tissue!- conducted CO2 to lungs, waste to kidneys and liver!- pathway, regulates T, acid/base =, osmotic balance!- machinery for clotting and blood vessel repair!- Composition!- 45% cells/formed elements: RBCS, platelates, WBCS, agrano-, granulocytes!- Platelets: function in clotting and blood vessel repair, no nucleus - Erythrocytes (RBCS): biconcave disks, 7.2-7.5 microns diameter - Leukocytes (WBCs): go to other tissue to do job - Granucolytes: specific granules + azurophilic granules - Neutrophils: multilobe nucleus, 60-70% of leukos, destruction of pathogens and in inflammatory response - Eosinophils: bilobed nucleus, less that 4% of leukos, eosinphilic granules (hydrolytic enzymes), immune and inflamm response and killing parasite worms - Basophils: lobed nucleus, dark granules w/histamin, heparin, chemotactic factors, hydrolytic enzymes 0.5% of leuks, immune and inflamm response - Agranulocytes: lack specific granules, but have azurophilic granules (lysosomes) - Lymphocytes: 20-25% leuks, B and T cells - Monocytes: largest cells in blood, 3-5% of leukos, differentiate into macrophages, phagocytosis of garbage/foreign material!- 1% buffy coat: WBCs, platelets!- 55% fluid extrracellular matrix: plasma!- solutes that help maintain homeostasis, albumin (colloid osmotic P, carrier protein), globulins (immuno and nonimmune) , fibrinogen (turns into fibrin), complement protein (imp in inflammation)!- Blood smears: Wright's stain (methylene blue= basic dye, azures= basic dye, eosin= acidic dye)!!II. Hemopoiesis (hematopiesis)- blood cell formation!- In adult platelets, erythrocytes and leukocytes continuously formed in bone marrow by multiplication and diff. of precursor cells!- 4 phases in fetus:!- yolk sac: nucleated erthyropoiesis, begins wk 3 - hepatic: liver at wk 6, leukos by wk 8 - splenic: by 2nd trimester, hepatic and spleenic continue thru gestation, normally end after birth - myeloid: bone marrow, by end of 2nd trimester. Liver and spleen keep their potential for this.!- Blood stem cells: all blood cells are from a pluripotent hemopoietic stem cell (has the CD34+ surface marker protein). They divide infrequently.!- Mouse exp. to show this, all new cells derived from a single marked stem cell!- pluropotent stem cell --> multipotent (CFU= colony forming unit) stem cells: CFU-L (for lymphocytes) andCFU-GEMM (for granulocytes, erythrocytes, monocytes, megakaryocytes) --> committed stem cells (diff. one for each type of blood cell) !- CFU-Ly (lymph), CFU-E (erhtyro), CFU-PMN (leuko), CFU-Meg (platelets)!- stem cells stimulated by cytokines (e.g. interleukins act on pleuri's and multi's, other factors act on unipotentials (e.g. erythropoietin, thrombopoietin, and GM-CSF- colony stimulating factors). Bind to cell surface receptors. Can act at multiple steps.!- Bone marrow:!- hemopoiesis takes place in bone marrow: reticular cells for growth factors and sinusoidal circulatory system for a cell to exit from!- inactive bone marrow accumulates brown fat!- Clinical relevance:!- drugs can destroy stem cells and lead to aplastic anemia!- chronic myelogenous leukemia (super high # of cells), can see abnormal Philly chrom in RBC precursors, WBCs, and megakaryocytes (abnormality is in stem cells)!- transplantation to patient w/defective marrow by injecting normal pluripotent stem cells (done at U)!!III. Platelets - limit hemorrhage and repair vascular/endothelial lining after injury/wear and tear!- structure:!- small, periph clear region= hyalomere, dark region= granulomere!- lack nuclei, contain: pm w/glucocalyx (for coag), mitochrondria, golgi, glycogen!- contain lots of granules: alpha (clotting factors/fibrinogen, vW factor-- platelet aggregration, vessel repair), delta (Ca, ATPADTP, serotonin, histamine--platelet agg/adhesion, vasoconstriction), lamda (azurophilic---resorb clots)!- specialized membrane systems: surface-opening tubules (for release and uptake) + dense tubular system like sarcoplasmic retic. because it holds Ca2+!- cytoskel: disc shape maintained by 1 MT coiled many times, high [ ] in cyto of unpolymerized actin and myosin!- function: forms a hemostatic plug!!- platelets just circulate normally, but when vascular endothel is injured/vessels severed --> collagen/CT of basement membrane exposed --> injured cells release factors (seroton, ADP, vW) --> cause platelets to adhere to underlying collagen --> Platelet activation --> release alpha granules --> activates more platelets --> and release delta granules --> platelets stick and form primary hemostatic plug --> stops over hemorrhage/repair small tears --> more factors released --> stimulates thrombin + vasoconstrictor A2 --> rxn cascade catalyzed by glycocalyx --> fibrinogen into fibrin --> form fibrin clot/thrombus/blood clot!- during activation they change shape irreversibly: MT coil depolymerizes, actin polymerizes + help of WASprotein --> filopodia --> platelet changes to octopus shape --> filopodia connect to fibrin fils --> bridge vascular tear!- post clot formation, actin-myosin makes mini-sarcomeres w/in platelets --> filopodia contract --> pull fibrin fils together --> form definitive hemostatic plug - clinical sig:!- thrombocytopenia: lower than normal platelet # (autoimmune usually)!- defective platelets, reduced # due to radiation/chemo --> spont. bleeding!- dysfunctional clotting process ex. hemophilia!- thromboembolisms: spont. clot formations --> pulmonary embolisms, MI's!- Develoment and control:!- in bone marrow: platelets bud from megakaryocytes --> enter blood stream!- low platelet level: thrombopoietin --> CFU-Meg (committed stem cells) to form --> megakaryoblast (one nucleus) --> endomitosis --> promegakaryocyte --> megakaryocyte (has polyploid, multilobed nucleus in one nuclear envelope, highly dev. golgi, RER, mitochron, granules, etc)!- megakaryocyte makes all the components --> packages platelets by subdividing its cytoplasm by membranes called platelet demarcation channels --> megakary has pseudopodia --> go into sinusoids of bone marrow --> platelets bud off --> enter peripheral blood --> form 2 pools: 50/75% circulating in blood + 25/50% stored in splee!- lifespan: less than 2 weeks !!IV. Erythrocytes (RBCs)!- Morphology and function: no membranous organelles !- Cytoplasm only has hemoglobin and some enzymes!- hemoglobin [ ] = 33% = 330 mg/ml!!- protein:
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