Blood cells

1. Blood cells

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

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

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)

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

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

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

8. Bone marrow Yolk sac Vertebra Liver Sternum Rib Spleen Femur Tibia 20 3 1 ADULT FETAL MONTHS

9. 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

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)

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

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

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

14. Regulation of RBC production • Erythropoetin • Rapid production • Maximum within 24 hours after hypoxia • Stimulates proerythroblast production from stem cells • Increased rate of differentiation

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

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

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

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

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

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

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

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

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

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

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

26. Defense against infection • Leukocytes • White blood cells • Tissue cells • Methods • Phagocytosis • Physical destruction • Antibody production and lymphocyte sensitization

27. Leukocytes • Bone marrow • Granulocytes • Monocytes • Lymphocytes • Lymph tissue • Lymphocytes • Plasma cells • Mobile unit of defense system

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

29. Types • Monocytes (5 %) • Lymphocytes (30 %) • Plasma cells • Platelets • Fragments of megakaryocytes

30. Granulocytes and monocytes • Phagocytosis • Lymphocytes and plasma cells • Connection with immune system • Platelets • Blood clotting

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

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

33. Neutrophils and macrophages • Initial defense against infection • neutrophils • Active in blood • Macrophage • Exist as monocytes in circulation

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

36. Phagocytosis • Neutrophils • Mature cells • Phagocytize 3-20 bacteria per cell • No regeneration • Macrophage • Mature monocyte • Must enter the tissue • Phagocytize 100 bacteria/cell

37. Production of bactericidal agents • Oxidizing agents • Superoxide • Hydrogen peroxide • Hydroxyl ion • Hypochlorite (chloride plus hydrogen peroxide)

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

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

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

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

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

43. Feedback system

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

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

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