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

Yolk sac

Liver

Spleen

Bone marrow

Tibia

Vertebra

Sternum

Rib

Femur

FETAL MONTHS ADULT1 3 20

• 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

• 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