Transcript Blood cells

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
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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
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Superoxide
Hydrogen peroxide
Hydroxyl ion
Hypochlorite (chloride plus hydrogen peroxide)
Monocyte-macrophage cell
system
• Present in all tissues
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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
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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