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 ADULT

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 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