Slide 1

Blood cells


Slide 2

Types of blood cells
• Red blood cells
• Macrophage system
• Lymphatic system


Slide 3

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


Slide 4

• 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)


Slide 5

• 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


Slide 6

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


Slide 7

RBC production
• Areas of body
– Adult
• Membranous bones
• Ability decreases as one ages


Slide 8

Bone marrow

Yolk sac

Vertebra
Liver
Sternum

Rib
Spleen
Femur
Tibia

1

3
FETAL MONTHS

20
ADULT


Slide 9

• 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


Slide 10

• 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)


Slide 11

• Stages of
differentiation
– Proerythroblast
– Basophil erythroblast
• Stain with basic dye

– Increased %
hemoglobin as the
stage progresses
– Condensation and loss
of nucleus and other
organelles


Slide 12

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


Slide 13

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


Slide 14

Regulation of RBC production
• Erythropoetin
– Rapid production
• Maximum within 24
hours after hypoxia

– Stimulates
proerythroblast
production from stem
cells
– Increased rate of
differentiation


Slide 15

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


Slide 16

• 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


Slide 17

• Anemia caused by folic acid deficiency
– Spruce
• Small intestine disease that reduce folic acid and
vitamin absorption


Slide 18

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


Slide 19

• 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


Slide 20

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


Slide 21

• 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


Slide 22

Life span of RBC
• Average life span
– 120 days
– Metabolically active
• Enzymes
–
–
–
–

Pliability
Iron transport
Iron maintenance
Oxidation prevention

• Become fragile
– Loss of metabolism


Slide 23

• 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


Slide 24

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


Slide 25

Polycythemia
• Excess RBC
– Hypoxia
• Physiologic polycythemia
– Low O2 content due to high altitude

– Polycythemia Vera
• genetic aberration

– Increase in blood viscosity
• Increased arterial pressure


Slide 26

Defense against infection
• Leukocytes
– White blood cells
– Tissue cells

• Methods
– Phagocytosis
• Physical destruction

– Antibody production and lymphocyte
sensitization


Slide 27

Leukocytes
• Bone marrow
– Granulocytes
– Monocytes
– Lymphocytes

• Lymph tissue
– Lymphocytes
– Plasma cells

• Mobile unit of defense system


Slide 28

• Types
– Granular appearance
(granulocytes, 65% of
total WBC)
– Multiple nucleus
• Polymorphonuclear
neutrophils
• Polymorphonuclear
eosinophils
• Polymorphonuclear
basophils


Slide 29

• Types
– Monocytes (5 %)
– Lymphocytes (30 %)
– Plasma cells

• Platelets
– Fragments of
megakaryocytes


Slide 30

• Granulocytes and monocytes
– Phagocytosis

• Lymphocytes and plasma cells
– Connection with immune system

• Platelets
– Blood clotting


Slide 31

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


Slide 32

• 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


Slide 33

• Neutrophils and macrophages
– Initial defense against infection
– neutrophils
• Active in blood

– Macrophage
• Exist as monocytes in circulation


Slide 34

• 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


Slide 35


Slide 36

Phagocytosis
• Neutrophils
– Mature cells
• Phagocytize 3-20 bacteria per cell
• No regeneration

• Macrophage
– Mature monocyte
• Must enter the tissue
• Phagocytize 100 bacteria/cell


Slide 37

• Production of bactericidal agents
– Oxidizing agents
•
•
•
•

Superoxide
Hydrogen peroxide
Hydroxyl ion
Hypochlorite (chloride plus hydrogen peroxide)


Slide 38

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


Slide 39

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


Slide 40

• 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


Slide 41

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


Slide 42

• 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


Slide 43

Feedback system


Slide 44

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


Slide 45

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


Slide 46

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