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Blood cells
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Types of blood cells
• Red blood cells
• Macrophage system
• Lymphatic system
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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
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• 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)
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• 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
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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
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RBC production
• Areas of body– Adult
• Membranous bones
• Ability decreases as one ages
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Yolk sac
Liver
Spleen
Bone marrow
Tibia
Vertebra
Sternum
Rib
Femur
FETAL MONTHS ADULT1 3 20
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• Generation of blood cells– Pluripotent hematopoetic
stem cells• Reservoir• Committed hematopoetic
stem cells
– Committed stem cells• Erythrocyte
– Derived from colony forming unit-erythrocytes (CFU-E)
• Granulecytes and monocytes– Derived from CFU-GM
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• 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)
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• Stages of differentiation– Proerythroblast– Basophil erythroblast
• Stain with basic dye
– Increased % hemoglobin as the stage progresses
– Condensation and loss of nucleus and other organelles
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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
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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
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Regulation of RBC production
• Erythropoetin– Rapid production
• Maximum within 24 hours after hypoxia
– Stimulates proerythroblast production from stem cells
– Increased rate of differentiation
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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
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• 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
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• Anemia caused by folic acid deficiency– Spruce
• Small intestine disease that reduce folic acid and vitamin absorption
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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
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• 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
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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
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• 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
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Life span of RBC
• Average life span– 120 days– Metabolically active
• Enzymes – Pliability– Iron transport– Iron maintenance– Oxidation prevention
• Become fragile– Loss of metabolism
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• 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
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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
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Polycythemia
• Excess RBC– Hypoxia
• Physiologic polycythemia– Low O2 content due to high altitude
– Polycythemia Vera• genetic aberration
– Increase in blood viscosity• Increased arterial pressure
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Defense against infection
• Leukocytes– White blood cells– Tissue cells
• Methods– Phagocytosis
• Physical destruction
– Antibody production and lymphocyte sensitization
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Leukocytes• Bone marrow
– Granulocytes– Monocytes– Lymphocytes
• Lymph tissue– Lymphocytes– Plasma cells
• Mobile unit of defense system
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• Types– Granular appearance
(granulocytes, 65% of total WBC)
– Multiple nucleus• Polymorphonuclear
neutrophils
• Polymorphonuclear eosinophils
• Polymorphonuclear basophils
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• Types– Monocytes (5 %)
– Lymphocytes (30 %)
– Plasma cells
• Platelets– Fragments of
megakaryocytes
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• Granulocytes and monocytes– Phagocytosis
• Lymphocytes and plasma cells– Connection with immune system
• Platelets– Blood clotting
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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
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• 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
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• Neutrophils and macrophages– Initial defense against infection– neutrophils
• Active in blood
– Macrophage• Exist as monocytes in circulation
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• 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
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Phagocytosis• Neutrophils
– Mature cells• Phagocytize 3-20 bacteria per cell
• No regeneration
• Macrophage– Mature monocyte
• Must enter the tissue
• Phagocytize 100 bacteria/cell
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• Production of bactericidal agents– Oxidizing agents
• Superoxide
• Hydrogen peroxide
• Hydroxyl ion
• Hypochlorite (chloride plus hydrogen peroxide)
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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
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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
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• 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
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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
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• 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
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Feedback system
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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
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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
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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