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Blood cells Types of blood cells • Red blood cells • Macrophage system • Lymphatic system Red blood cells • Functions – Transport of hemoglobin • Oxygen • Free hemoglobin can be filtered into the urine by kidney in higher animals – Must be in the cell – Formation of carbonic acid • Carbonic anhydrase (water plus CO2) • Faster clearance of CO2 from the body • Biological buffer • Shape and size of RBC – Flexible bag • Passing through the capillary • No membrane stretching – Greater membrane to volume ratio • Concentrations – 5,200,000/ml in men and 4,700,000/ml in women (300,000 give or take) • Hemoglobin concentration – 34g/100ml cell (no plasma) • Upper metabolic limit • Almost always around the maximum – Hematocrit (% cell in blood) • 40-45% • 15g/100 ml blood in male and 14g/100 ml blood in female • Each g hemoglobin can carry 1.34 ml oxygen – 20ml O2/100 ml blood in men and 19ml O2/100 ml blood in women RBC production • Areas of body – Fetal stage • Yolk sac during embryonic development • Liver during middle trimester – Spleen and lymph nodes – Postnatal stage • Bone marrow – Switch during the last month of gestation RBC production • Areas of body – Adult • Membranous bones • Ability decreases as one ages Bone marrow Yolk sac Vertebra Liver Sternum Rib Spleen Femur Tibia 1 3 FETAL MONTHS 20 ADULT • Generation of blood cells – Pluripotent hematopoetic stem cells • Reservoir • Committed hematopoetic stem cells – Committed stem cells • Erythrocyte – Derived from colony forming uniterythrocytes (CFU-E) • Granulecytes and monocytes – Derived from CFUGM • Growth and differentiation of stem cells – Growth inducers – Differentiation inducers • Commitment of stem cells to differentiate – Production controlled by external factor • Low blood O2 • Infection (WBC) • Stages of differentiation – Proerythroblast – Basophil erythroblast • Stain with basic dye – Increased % hemoglobin as the stage progresses – Condensation and loss of nucleus and other organelles Regulation of RBC production • Total mass of RBC in circulation – Narrow range • Adequate # of RBC for O2 transport • No impact on blood flow • Oxygenation of tissue – Most essential regulator • Loss of RBC/loss of O2 carrying capacity Regulation of RBC production • Erythropoetin – Stimulates RBC production when low O2 states – Kidney • Main source (90%) • Stimulated by low oxygen availability to tubular cells • Production signaled by other parts of body Regulation of RBC production • Erythropoetin – Rapid production • Maximum within 24 hours after hypoxia – Stimulates proerythroblast production from stem cells – Increased rate of differentiation RBC maturation • RBC – Most rapidly growing and reproducing cells • Vitamins – Vitamin B12 and folic acid • Synthesis of TTP • Essential for nuclear maturation and cell division • Formation of macrocytes (low O2 carrying capacity) when low • Pernicious anemia – Poor vitamin B12 absorption • Atrophy of GI nucosa that causes loss of intrinsic factor for vitamin B12 absorption – Susceptible to digestion – No interaction with blush border in ileum – Reduced B12 being carried in blood • Needs 3-4 years before the symptom appears – Stored in liver • Anemia caused by folic acid deficiency – Spruce • Small intestine disease that reduce folic acid and vitamin absorption Hemoglobin formation • Stages – Formation of succinyl-CoA • Krebs cycle – Combination of succinyl-CoA with glycine • Pyrrole – Formation of protoporophyrin • Four pryrroles – Formation of heme • protoporophyrin plus iron – Combination of heme with globulin protein • Types of hemoglobin chains – Four types • Alpha, beta, gamma, and delta • Hemoglobin A = two alpha plus two beta chains – Determines oxygen binding affinity • Sickle cell anemia – Amino acid substitution in beta chains • Combination of O2 with hemoglobin – Loose interaction with coordination bonds of iron atom • Reversible – Carried as O2 rather than oxygen ion Iron metabolism • Total iron quantity – 4-5 g • 65 % in hemoglobin • Transport and storage – Bound to plasma proteins after absorption – Bound to ferritin in the cell • Storage • Released when plasma concentrations are low • Daily iron loss – 0.6 mg per day – 1.3 mg/day during menstruation • Absorption of iron – Small intestine • Bound to apotransferrin (bile product) to form transferrin • Regulation of total body iron Life span of RBC • Average life span – 120 days – Metabolically active • Enzymes – – – – Pliability Iron transport Iron maintenance Oxidation prevention • Become fragile – Loss of metabolism • Destruction of RBC – Spleen • Self-destruction through narrower passageway – Structural trabecule of red pulp – Hemoglobin • Phagocytosis (macrophage) – Kupffer cells in liver and spleen • Iron – Recycled • Porphyrin – Converted to bilirubin Anemia • Hemoglobin deficiency – Blood loss • Very small RBC (microcytic, hypochromic) – Bone marrow aplasia (loss of function) – Vitamin deficiency • Abnormally large RBC (megaloblastic) – Abnormality of RBC (hereditary) • Sickle cell anemia • Erythroblastosis fatalis Polycythemia • Excess RBC – Hypoxia • Physiologic polycythemia – Low O2 content due to high altitude – Polycythemia Vera • genetic aberration – Increase in blood viscosity • Increased arterial pressure Defense against infection • Leukocytes – White blood cells – Tissue cells • Methods – Phagocytosis • Physical destruction – Antibody production and lymphocyte sensitization Leukocytes • Bone marrow – Granulocytes – Monocytes – Lymphocytes • Lymph tissue – Lymphocytes – Plasma cells • Mobile unit of defense system • Types – Granular appearance (granulocytes, 65% of total WBC) – Multiple nucleus • Polymorphonuclear neutrophils • Polymorphonuclear eosinophils • Polymorphonuclear basophils • Types – Monocytes (5 %) – Lymphocytes (30 %) – Plasma cells • Platelets – Fragments of megakaryocytes • Granulocytes and monocytes – Phagocytosis • Lymphocytes and plasma cells – Connection with immune system • Platelets – Blood clotting Genesis of WBC • Pluripotent hematopoietic stem cell – Two lineage for WBC • Myelocytic (myeloblast) • Lymphocytic (lymphoblast) – Site of generation • Bone marrow – Granulocytes and monocytes • Lymph system • Life span – Granulocytes • 4-8 hours after being released in circulation • 4-5 days in tissue – Monocytes • 10-20 hours in circulation • Up to months in tissue – Transformed into macrophage • Neutrophils and macrophages – Initial defense against infection – neutrophils • Active in blood – Macrophage • Exist as monocytes in circulation • Movement of WBC between circulation and tissue – Initiated by chemotaxis • Toxins • Chemicals released from damaged/infected tissue • Complement complex – Diapedesis • Sliding through the pore – Ameboid motion Phagocytosis • Neutrophils – Mature cells • Phagocytize 3-20 bacteria per cell • No regeneration • Macrophage – Mature monocyte • Must enter the tissue • Phagocytize 100 bacteria/cell • Production of bactericidal agents – Oxidizing agents • • • • Superoxide Hydrogen peroxide Hydroxyl ion Hypochlorite (chloride plus hydrogen peroxide) Monocyte-macrophage cell system • Present in all tissues – – – – – Skin Lymph nodes Lung aleveoli (giant cells) Liver (Kupffer cells) Spleen • Composition – Monocytes, mobile macrophage, and fixed macrophage Inflammation • Change of tissues due to injury – Surrounding area by chemicals • • • • • Vasodilation (excess local blood flow) Increased capillary permeability Clot formation Granulocyte and monocyte migration Cell swelling • Removal of damaged tissue by macrophage – Activated by chemical signals • Injuring living tissue by macrophage • Walling off the injured area – Fibrinigen clot to separate injured area from healthy tissue – Intensity of inflammation • Degree of tissue damage Neutrophil and macrophage response • Tissue macrophage – First line of defense • Enlargement • Mobilization • Migration of neutrophils – Initiated by chemotaxis • Margination (increased stickiness of endotherial surface) • Diapedesis • Increased production of neutrophils – Neutrophilia • Chemical signals • Migration of macrophage – Migration of monocytes • Increased production of granulocytes and monocytes • Formation of pus – Necrotic tissue – Dead neutrophhils and macrophages – Tissue fluid Feedback system Eosinophils • Weak phagocytes – Small portion of total leukocytes (2 %) – High in people with parasite infection • Attach themselves onto the parasite and produce chemicals to eliminate paracites • Collect in tissues with allergic reaction – Chemicals from other cells – Prevent spread of allergic inflammation Basophils • Similar to tissue mast cells – Liberate heparin (anticoagulant) – Release histamine • Small amount of serotonin and bradykinin • Allergic reaction – IgE attach to mast cell/basophils Abnormalities • Leukopenia – Production of low leukocytes by bone marrow – Very acute – Radiation and drugs • Leukemia – Uncontrolled leukocyte production – Lymphotic or myelogenous leukemia • Release of undifferentiated cells