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Blood

Blood. Chapter 17. Review: What is Blood?. Only fluid connective tissue Plasma Formed elements Erythrocytes (RBC’s) Leukocytes (WBC’s) Thrombocytes ( platelets ) Hematocrit is % of RBC’s out of total blood volume. 2. Centrifuge. Plasma (55% of whole blood).

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Blood

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  1. Blood Chapter 17

  2. Review: What is Blood? • Only fluid connective tissue • Plasma • Formed elements • Erythrocytes (RBC’s) • Leukocytes (WBC’s) • Thrombocytes(platelets) • Hematocrit is % of RBC’s out of total blood volume 2 Centrifuge Plasma(55% of whole blood) Buffy coat:leukocyctes and platelets(<1% of whole blood) Formed elements Withdraw blood and place in tube Erythrocytes(45% of whole blood) 1 Figure 17.1

  3. Physical Characteristics • pH 7.35 – 7.45 • Temperature about 38°C (normal 37°C) • Approximately 8% body weight • Males: 5 – 6 L • Females: 4 – 5 L • Human blood is NEVER blue • Scarlet (oxygen-rich) • Dark red (oxygen-poor)

  4. Functions • Distribution • O2 and nutrients in • CO2 and wastes out • Hormones to target cells • Regulation • Body temp • Absorb/distribute heat • pH • Buffer systems • Bicarbonate atoms • Fluid volumes • Salts and proteins • Protection • Prevent blood loss • Clot formation • Platelets and proteins • Prevent infection • Fight foreign invaders • Antibodies, WBC’s, and complement proteins

  5. Plasma • 90% water • 100+ dissolved solutes • Proteins • Albumin: osmotic pressure • Globulin: antibodies and transport proteins • Fibrinogen: role in clotting • Nutrients: fuel from digestive tract • Electrolytes: osmotic pressure and pH • Gases: O2 and bicarbonate ions bound to hemoglobin • Hormones

  6. Formed Elements • ‘Cell’ types • WBC’s are complete cells • RBC’s without nuclei or organelles • Platelets are cell fragments • Live only a few days • Don’t divide, but are renewable • Where does hematopoiesis occur?

  7. Erythrocytes (RBC’s) • Biconcave shape • Large SA to small volume • Flexibility to pass through vessels • Primarily composed of hemoglobin • Readily binds/transports O2 and CO2 • Generate ATP anaerobically • Means what? • No mitochondria

  8. Hemoglobin (Hb) • Transports respiratory gases • Globin protein bound to 4hemescontaining iron • 1 RBC about 250 million Hb molecules = 1billion O2 • Normal values • 14-20g/100ml infants • 13-18g/100ml males • 12-16g/100ml females • Specific types • Oxyhemoglobin • Deoxyhemoglobin • Carbaminoglobin (binds amine groups)

  9. Hematopoiesis • Hemocytoblasts (stem cells) commit to a formed element • Unchangeable after • Growth factors and hormones ‘push’ to specialize • Erythropoiesis 15 days (+ 2 to mature) • Leukopoiesis discussed later

  10. Hormonal Control of Erythropoiesis • Erythropoietin (EPO) release by kidneys • Decreased RBC numbers (trauma) • Decreased O2 availability (altitude) • Increased O2 demand (exercise) • Insufficient hemoglobin (iron deficiency) • EPO inhibited by high O2 or RBC count • Type of feedback? • Kidney fails = no EPO = low RBC count • EPO injections • Abuse by athletes to increase hematocrit

  11. Imbalance Start Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2 Imbalance Increases O2-carrying ability of blood Reduces O2 levels in blood Erythropoietin stimulates red bone marrow Kidney (and liver to a smaller extent) releases erythropoietin Enhanced erythropoiesis increases RBC count Erythropoiesis Homeostasis

  12. Dietary Regulation • Iron is key • 65% stored in hemoglobin (Hb) • Free ions are toxic, so stored bound to proteins • Some lost daily • B12 and folic acid • Necessary for DNA synthesis • Roles in mitosis • AA’s, lipids, and carbs too

  13. Life and Death of Erythrocytes • 100 – 120 day • Cells age and Hb degenerates • Engulfed by macrophages • Components of Hb separated • Hemebilirubin urobilinogen • Bilirubin binds albumin and moves to liver • From liver with bile to intestines • Out in feces • Iron saved and bound to protein for storage • Globin metabolized to AA’s and into circulation • See fig. 17.7

  14. Erythrocyte Disorders • Anemias: low O2carrying capacity; sign not disease • Insufficient number of RBC’s • Hemorrhagic anemia: blood loss; acute or chronic • Hemolytic anemia: lysing of RBC’s early from parasites, mismatched blood • Aplastic anemia: disruption/destruction of red bone marrow • Low Hb content • Iron-deficiency anemia: inadequate iron intake • Pernicious anemia: deficiency of B12 in diet • Abnormal Hb • Thalassemia: absent or faulty globin chain • Sickle-cell anemia: defective gene codes for abnormal HB • Polycythemias: high number of RBC’s • Blood doping: remove and replace RBC’s = artificial polycythemia • Secondary polycythemia: EPO increase when O2 levels down (high altitude)

  15. Leukocytes • Not confined to blood vessels • Chemotaxis to locate damage/infection • Working WBC’s increase production of WBC’s • Leukocytosis: high WBC count response to infection • General types • Granulocytes • Agranulocytes

  16. Granulocytes • Characteristics • Larger and shorter-lived than RBC’s • Phagocytic cells with lobed nuclei • Cytoplasmic granules • Types • Neutrophils: body’s 1st phagocytic cells • Eosinophils: fights parasitic worms and lessens allergies by phagocytizing immune complexes • Basophils: release histamine, a vasodilator

  17. Agranulocytes • Characteristics • Spherical or kidney like nuclei • Types • Lymphocytes • T cells: direct action against infected cells • B cells: become cells that produce antibodies • Monocytes • Become macrophages after leaving blood supply • Active phagocytes that also activate lymphocytes

  18. Recognizing Leukocytes

  19. Leukopoiesis • All leukocytes originate from hemocytoblasts • Either myeloid or lymphoid stem cell lines • Myeloid stem cells • Myeloblasts • Monoblasts • Lymphoid stem cells • Lymphoblasts • Similarities to erythropoiesis

  20. Hormonal Control of Leukopoiesis • Interleukins • Numbered (IL – 1, IL – 2, IL – 3, etc.) • Colony-stimulating factors (CSFs) • Named for the WBCs stimulated (granulocyte – CSF) • Hematopoietic factors from red bone marrow and WBCs too • Encourage maturation and division • Used clinically after chemotheraphy, stem cell transplants, or in AIDS patients

  21. Leukocyte Disorders • Leukpenia: abnormal WBC count; usually drug (anticancer) induced • Leukemia: cancerous conditions named for cell type involved • Bone marrow fills with cancerous leukocytes • Numerous, nonfunctional WBCs produced • Myelocytic (myeloblasts) or lymphocytic (lymphocytes) • Acute (blast-type cell) or chronic (later cell stage) • Mononucleosis: epstein-barr virus; excessive agranulocytes

  22. Platelets • Fragments of megakaryocytes • Myeloid stem cell line • Mitotic without cytokinesis • Anucleate, live about 10 days • Thin blue cytoplasm with a few purple granules • Form temporary plugs during the clotting process • Thrombopoietin regulates their production

  23. Hemostasis • Stoppage of bleeding • Platelets, clotting factors, and injured tissues involved • 3 phases • Vascular spasm • Rapid vasoconstriction of damaged vessel • Efficiency increase with damage • Plug formation • Platelets bind to exposed collagen in damaged vessel • Positive feedback of chemical messengers to attract more platelets • Coagulation • Liquid to gel • Endothelial cells (extrinsic) and platelets (intrinsic) factors interact with clotting factors • Fibrous tissue eventually regrows to permanently seal

  24. Coagulation Process • Phase One: prothrombin activator pathways • Intrinsic: factors in blood already • Slower b/c many steps • Extrinsic: tissue factor III (TFIII) outside blood in tissue • Faster b/c skips steps • Phase Two: thrombin activation • Prothrombin activator catalyzes • Prothrombin protein to thrombin enzyme • Phase Three: fibrin mesh produced • Fibrinogen catalyzed to fibrin • Fibrin glues platelets together = clot • Plasma becomes gel-like • Factor XIII strengthens, sealing fibrin together • Fig 17.14 http://www.astrographics.com/cgi-bin/ase/ase.cgi?affiliate=sciam&mode=display&gallery=3&type=medical&color=&keywords=&page=2

  25. Clot Retraction and Repair • Contractile proteins of proteins pull fibrin strands together • Stabilizes clot • Platelet derived growth factor (PDGF) stimulates smooth muscle and fibroblast mitosis to rebuild wall • Fibrinolysis dissolves clots • Beneficial once healed • Prevents build up in vessels

  26. Controlling Clot Formation • Limit growth through constant blood circulation • Keeps [clotting factors] low in given locations • Inhibit thrombin (intrinsic pathway too) • Fibrin binds to prevent spread • Antithrombin III (in plasma) inactivates • Heparin enhances antithrombin III and inhibits pathway • Prevent clotting • Antithrombics (NO) and undamaged vessel tissue prevents platelet adhesion • Blood thinner administration (aspirin, warfarin)

  27. Hemostasis Disorders (Thromboembolytic) • Undesirable clot formation • Thrombus: clot in an unbroken blood vessel • Can block normal blood flow = tissue death • Coronary thrombus may cause heart attack • Embolus: free floating clot • Embolism once blood vessel is obstructed • Pulmonary embolisms inhibit obtaining O2 • Cerebral embolisms may cause strokes

  28. Hemostasis Disorders (Bleeding) • Problems controlling bleeding • Thrombocytopenia: platelet number is low • Spontaneous bleeding all over body from mov’t • Purple blotches on skin signify • Liver can’t produce procoagulants • Vitamin K deficiencies • Other liver diseases • Hemophilia: genetic disorder causing missing clotting factors • Type depends on affected factor

  29. Human Blood Groups • RBC membranes have glycoprotein antigens on external surface • Unique to individuals • Recognized as foreign by other individual bodies • Agglutinogens because they promote agglutination (clumping) • Presence or absence of antigens used to classify blood groups

  30. ABO Blood Groups • Two antigens (A and B) on RBC surface in blood • Blood types: A, B, AB, and O • Two antibodies (anti-A and anti-B) in the plasma • Non-complement to blood type produced • See chart below • Agglutinogens and complement antibodies can’t mix w/o hemolytic reaction • Newborns don’t start development until 2 months after birth; complete between 8 and 10

  31. Rhesus (Rh) Blood Groups • Multiple agglutinogens • C, D, and E most common • Named for monkey first discovered in • Rh+ individuals have the D antigen • Lack anti-Rh antibodies produced in plasma • Can receive Rh+ or Rh- blood • Rh- individuals lack the D antigen • Lack anti-Rh, but can produce w/ Rh+ transfusion • 1st occurrence = sensitization (no reaction), starts production • 2ndoccurrence+ = attack and lysis of donor RBC’s

  32. Transfusions Gone Wrong • Transfusion reactions when mismatched blood is exchanged • Recipient's plasma attacks donor’s RBC’s • Donor’s plasma may attack recipient’s RBC’s, but less serious condition • RBC’s hemolyse or phagocytize • O2 carrying capacity drops • Agglutination clogs small vessels • Hb released into blood  kidney damage possible

  33. Diagnostic Blood Tests • Hematocrit: % of RBC in blood • Differential WBC count: different number of WBC cells • Platelet count: ability of blood to clot • Complete blood count (CBC): number of formed elements, hematocrit, Hb, and RBC size • Hemoglobin: amount in blood

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