Blood and its components


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Blood and its components

  3. 3. Fluids of the Body • Cells of the body are serviced by 2 fluids – blood • composed of plasma and a variety of cells • transports nutrients and wastes – interstitial fluid • bathes the cells of the body • Nutrients and oxygen diffuse from the blood into the interstitial fluid & then into the cells • Wastes move in the reverse direction • Hematology is study of blood and blood disorders
  4. 4. Physical Characteristics of Blood • Thicker (more viscous) than water and flows more slowly than water • Temperature of 100.4 degrees F • pH 7.4 (7.35-7.45) • 8 % of total body weight • Blood volume – 5 to 6 liters in average male – 4 to 5 liters in average female – hormonal negative feedback systems maintain constant blood volume and osmotic pressure
  5. 5. Functions of Blood • Transportation – O2, CO2, metabolic wastes, nutrients, heat & hormones • Regulation – helps regulate pH through buffers – helps regulate body temperature • coolant properties of water • vasodilatation of surface vessels dump heat – helps regulate water content of cells by interactions with dissolved ions and proteins • Protection from disease & loss of blood
  6. 6. Blood components • 55% plasma: 7 to 8% dissolved substances (sugars, amino acids, lipids & vitamins), ions, dissolved gases, hormones – most of the proteins are plasma proteins: provide a role in balancing osmotic pressure and water flow between the blood and extracellular fluid/tissues – loss of plasma proteins from blood – decreases osmotic pressure in blood and results in water flow out of blood into tissues – swelling – most common plasma proteins: albumin, globulins, clotting proteins (fibrin)
  7. 7. Blood: Cellular elements • 45% of blood is the cellular elements or formed elements • 99% of this (44.55% of total blood) is erythrocytes or RBCs – formed by differentiation of hematopoietic stem cells (HSCs) in the red bone marrow of long bones and pelvis – makes about 2 million per second! – most numerous cell type in the body – 4 to 6 million per ul blood – as they mature in the marrow they lose most organelles and its nucleus – lack mitochondria and cannot use the oxygen they transport for ATP synthesis – lives only about 120 days – destroyed by the liver and spleen – liver degrades the hemoglobin to its globin component and the heme is degraded to a pigment called bilirubin - bile – Iron(Fe+3) • transported in blood attached to transferrin protein • stored in liver, muscle or spleen • attached to ferritin or hemosiderin protein • in bone marrow being used for hemoglobin synthesis
  8. 8. • 1% found in the Buffy coat : – -leukocytes (WBCs) and platelets (thromobocytes) – -neutrophils: phagocytic properties – -release lysozymes which destroy/digest bacteria – -release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them – -release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria – - releases cytokines that attract other neutrophils – -eosinophils: parasitic defense cells – -also involved in the allergic response – -release histaminase – slows down inflammation caused by – basophils – -basophils: heparin, histamine & serotonin – -heighten the inflammatory response and account for hypersensitivity (allergic) reaction – -monocytes: enter various tissues and – differentiate into phagocytic macrophages – -lymphocytes: T and B cells
  9. 9. Blood Plasma  Composed of approximately 90 percent water  Includes many dissolved substances Nutrients, Salts (metal ions) Respiratory gases Hormones Proteins, Waste products
  10. 10. FORMED ELEMENTS OF BLOOD • Red blood cells ( erythrocytes ) • White blood cells ( leukocytes ) – granular leukocytes • neutrophils • eosinophils • basophils – agranular leukocytes • lymphocytes = T cells, B cells, and natural killer cells • monocytes • Platelets (special cell fragments)
  11. 11. Erythrocytes (Red Blood Cells)  The main function is to carry oxygen  Anatomy of circulating erythrocytes Biconcave disks Essentially bags of hemoglobin Anucleate (no nucleus) Contain very few organelles  Outnumber white blood cells 1000:1
  12. 12. • Contain oxygen-carrying protein hemoglobin that gives blood its red color – 1/3 of cell’s weight is hemoglobin • Biconcave disk 8 microns in diameter – increased surface area/volume ratio – flexible shape for narrow passages – no nucleus or other organelles • no cell division or mitochondrial ATP formation • Normal RBC count – male 5.4 million/drop ---- female 4.8 million/drop – new RBCs enter circulation at 2 million/second
  14. 14.  Iron-containing protein  Binds strongly, but reversibly, to oxygen  Each hemoglobin molecule has four oxygen binding sites  Each erythrocyte has 250 million hemoglobin molecules • Globin protein consisting of 4 polypeptide chains • One heme pigment attached to each polypeptide chain – each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule
  15. 15. • Each hemoglobin molecule can carry 4 oxygen molecules from lungs to tissue cells • Hemoglobin transports 23% of total CO2 waste from tissue cells to lungs for release – combines with amino acids in globin portion of Hb • Hemoglobin transports nitric oxide & super nitric oxide helping to regulate BP – iron ions pick up nitric oxide (NO) & super nitric oxide (SNO)& transport it to & from the lungs – NO causing vasoconstriction is released in the lungs – SNO causing vasodilation is picked up in the lungs
  16. 16. • Production of abnormal hemoglobin can result in serious blood disorders such as thalassemia and sickle cell anemia. • The blood test, hemoglobin A1c, can be used to monitor blood glucose levels in diabetics
  17. 17. Hematocrit • Percentage of blood occupied by cells – female normal range • 38 - 46% (average of 42%) – male normal range • 40 - 54% (average of 46%) • testosterone • Anemia – not enough RBCs or not enough hemoglobin • Polycythemia – too many RBCs (over 65%) – dehydration, tissue hypoxia, blood doping in athletes
  18. 18. Erythropoiesis: Production of RBCs • Erythrocyte formation, called erythropoiesis, occurs in adult red bone marrow of certain bones. • The main stimulus for erythropoiesis is hypoxia. • Proerythroblast starts to produce hemoglobin • Many steps later, nucleus is ejected & a reticulocyte is formed – orange in color with traces of visible rough ER • Reticulocytes escape from bone marrow into the blood • In 1-2 days, they eject the remaining organelles to become a mature RBC
  19. 19. ANEMIA • Symptoms – oxygen-carrying capacity of blood is reduced – fatigue, cold intolerance & paleness • lack of O2 for ATP & heat production • Types of anemia – iron-deficiency = lack of absorption or loss of iron • type of nutritional anemia • failure to take in essential raw ingredients not made by the body – pernicious = lack of intrinsic factor for vitamin B12 absorption from the digestive tract • B12 is essential for normal RBC formation and maturation • binding of B12 to intrinsic factor allows its absorption • intrinsic factor – synthesized by the small intestine
  20. 20. – hemorrhagic = loss of RBCs due to bleeding (ulcer) – hemolytic = defects in cell membranes cause rupture • rupture of too many RBCs by external factors such as malaria (normal RBCs) or genetic disorders like sickle cell anemia (defective RBCs) – thalassemia = hereditary deficiency of hemoglobin – aplastic = destruction of bone marrow (radiation/toxins) • failure of the bone marrow to produce enough RBCs • may selectively destroy the ability to produce RBCs only • but may also destroy the myeloid stem cells – affect WBCs and platelets
  21. 21. WHITE BLOOD CELLS • Leukocytes (white blood cells or WBCs) are nucleated cells and do not contain hemoglobin. Two principal types are granular (neutrophils, eosinophils, basophils) and agranular (lymphocytes and monocytes). – Granular leukocytes include eosinophils, basophils, and neutrophils based on the straining of the granules. – Agranular leukocytes do not have cytoplasmic granules and include the lymphocytes and monocytes, which differentiate into macrophages (fixed and wandering). • Leukocytes have surface proteins, as do erythrocytes. They are called major histocompatibility antigens (MHC), are unique for each person (except for identical siblings), and can be used to identify a tissue.
  22. 22. • Less numerous than RBCs – 5000 to 10,000 cells per drop of blood – 1 WBC for every 700 RBC • Leukocytosis is a high white blood cell count – microbes, strenuous exercise, anesthesia or surgery • Leukopenia is low white blood cell count – radiation, shock or chemotherapy • Only 2% of total WBC population is in circulating blood at any given time – rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen
  23. 23. • WBCs leave the blood stream by emigration. • Some WBCs, particularly neutrophils and macrophages, are active in phagocytosis. • The chemical attraction of WBCs to a disease or injury site is termed chemotaxis.
  24. 24. • WBCs roll along endothelium, stick to it & squeeze between cells. – adhesion molecules (selectins) help WBCs stick to endothelium • displayed near site of injury – molecules (integrins) found on neutrophils assist in movement through wall • Neutrophils & macrophages phagocytize bacteria & debris – chemotaxis of both • kinins from injury site & toxins
  25. 25. Types of Leukocytes  Granulocytes  Granules in their cytoplasm can be stained  Include neutrophils, eosinophils, and basophils  Agranulocytes  Lack visible cytoplasmic granules  Include lymphocytes and monocytes
  26. 26. Granulocytes  Neutrophils Multilobed nucleus with fine granules Act as phagocytes at active sites of infection • Fastest response of all WBC to bacteria • Direct actions against bacteria – release lysozymes which destroy/digest bacteria – release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them – release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria
  27. 27.  Eosinophils Large brick-red cytoplasmic granules Found in repsonse to allergies and parasitic worms • Leave capillaries to enter tissue fluid • Release histaminase – slows down inflammation caused by basophils • Attack parasitic worms • Phagocytize antibody-antigen complexes
  28. 28.  Basophils Have histamine-containing granules Initiate inflammation • Involved in inflammatory and allergy reactions • Leave capillaries & enter connective tissue as mast cells • Release heparin, histamine & serotonin – heighten the inflammatory response and account for hypersensitivity (allergic) reaction
  29. 29. Agranulocytes  Monocytes  Largest of the white blood cells  Function as macrophages  Important in fighting chronic infection • Take longer to get to site of infection, but arrive in larger numbers • Become wandering macrophages, once they leave the capillaries • Destroy microbes and clean up dead tissue following an infection
  30. 30.  Lymphocytes  Nucleus fills most of the cell  Play an important role in the immune response • B cells – destroy bacteria and their toxins – turn into plasma cells that produces antibodies • T cells – attack viruses, fungi, transplanted organs, cancer cells & some bacteria • Natural killer cells – attack many different microbes & some tumor cells – destroy foreign invaders by direct attack
  31. 31. Platelets  Derived from ruptured multinucleate cells (megakaryocytes)  Needed for the clotting process  Normal platelet count = 300,000/mm3
  32. 32. • Thrombopoietin stimulates myeloid stem cells to produce platelets. • Myeloid stem cells develop into megakaryocyte-colony- forming cells that develop into megakaryoblasts. • Megakaryoblasts transform into megakaryocytes which fragment. • Each fragment, enclosed by a piece of cell membrane, is a platelet (thrombocyte). • Normal blood contains 250,000 to 400,000 platelets/mm3. Platelets have a life span of only 5 to 9 days; aged and dead platelets are removed by fixed macrophages in the spleen and liver.
  33. 33. • Disc-shaped, 2 - 4 micron cell fragment with no nucleus • Normal platelet count is 150,000- 400,000/drop of blood • Other blood cell counts – 5 million red & 5-10,000 white blood cells
  34. 34. HEMOSTASIS • A clot is a gel consisting of a network of insoluble protein fibers (fibrin) in which formed elements of blood are trapped. • The chemicals involved in clotting are known as coagulation (clotting) factors; most are in blood plasma, some are released by platelets, and one is released from damaged tissue cells. • Blood clotting involves a cascade of reactions that may be divided into three stages: formation of prothrombinase (prothrombin activator), conversion of prothrombin into thrombin, and conversion of soluble fibrinogen into insoluble fibrin.
  35. 35. • Stoppage of bleeding in a quick & localized fashion when blood vessels are damaged • Prevents hemorrhage (loss of a large amount of blood) • Methods utilized – vascular spasm – platelet plug formation – blood clotting (coagulation = formation of fibrin threads)
  36. 36. Platelet Plug Formation • Platelets store a lot of chemicals in granules needed for platelet plug formation – alpha granules • clotting factors • platelet-derived growth factor – cause proliferation of vascular endothelial cells, smooth muscle & fibroblasts to repair damaged vessels – dense granules • ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2 • Steps in the process – (1) platelet adhesion (2) platelet release reaction (3) platelet aggregation
  37. 37. Blood Clotting • Blood drawn from the body thickens into a gel – gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped • If clotting occurs in an unbroken vessel is called a thrombosis • Substances required for clotting are Ca+2, enzymes synthesized by liver cells and substances released by platelets or damaged tissues • Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads – prothrombinase & Ca+2 convert prothrombin into thrombin – thrombin converts fibrinogen into fibrin threads
  38. 38. • Prothrombinase is formed by either the intrinsic or extrinsic pathway • Final common pathway produces fibrin threads
  39. 39. Extrinsic Pathway • Damaged tissues leak tissue factor (thromboplastin) into bloodstream • Prothrombinase forms in seconds • In the presence of Ca+2, clotting factor X combines with V to form prothrombinase
  40. 40. Intrinsic Pathway • Activation occurs – endothelium is damaged & platelets come in contact with collagen of blood vessel wall – platelets damaged & release phospholipids • Requires several minutes for reaction to occur • Substances involved: Ca+2 and clotting factors XII, X and V
  41. 41. Final Common Pathway • Prothrombinase and Ca+2 – catalyze the conversion of prothrombin to thrombin • Thrombin – in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads – activates fibrin stabilizing factor XIII – positive feedback effects of thrombin • accelerates formation of prothrombinase • activates platelets to release phospholipids
  42. 42. Anticoagulants and Thrombolytic Agents • Anticoagulants suppress or prevent blood clotting – heparin • administered during hemodialysis and surgery – warfarin (Coumadin) • antagonist to vitamin K so blocks synthesis of clotting factors • slower than heparin – stored blood in blood banks treated with citrate phosphate dextrose (CPD) that removes Ca+2 • Thrombolytic agents are injected to dissolve clots – directly or indirectly activate plasminogen – streptokinase or tissue plasminogen activator (t-PA)