BLOOD PHYSIOLOGY BLOOD PHYSIOLOGY Blood consists of a liquid portion (plasma) and a solid portion Transports nutrients, O 2, wastes and hormones. Helps maintain the stability of the interstitial fluid. Distributes heat. Provides protection against infection (white blood cells) Promotes clotting (platelets) Composition of the Blood Whole blood is slightly heavier and 3-4x more viscous than water. Formed Elements: cellular portion; RBCs, WBCs and platelets Hemocrit (HCT): 45% by volume. Includes cells mostly RBCs and much smaller numbers of WBCs and platelets Liquid portion: plasma Plasma: clear, straw-colored liquid which is a complex mixture of water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes. RBC formation Initially occurs in the yolk sac, liver and spleen After birth RBCs produced almost exclusively in tissue lining the spaces in bones and red bone marrow Relative rates of red blood cell production in the bone marrow of different bones at different ages. RBC formation Initially occurs in the yolk sac, liver and spleen After birth RBCs produced almost exclusively in tissue lining the spaces in bones and red bone marrow Blood cells Formation of the multiple different blood cells from the original pluripotent hematopoietic stem cell (PHSC) in the bone marrow. Control of bone marrow production of blood cells in response to multiple growth factors Erythropoiesis Genesis of normal red blood cells (RBCs) and characteristics of RBCs in different types of anemias Red Blood Cells / Erythrocytes Biconcave discs Shape is an adaptation for transporting gases Increases surface area through which gases can diffuse. The combined surface area of all RBCs in human body is roughly 2000x greater than the bodys external surface Hemoglobin 1/3 (33-34%) of the cell by volume Protein responsible for the color of blood When hemoglobin combines with O 2 (oxyhemoglobin) = bright red; When O 2 released (deoxyhemoglobin)=darker color Hematocrit The ratio of blood cells to total blood volume, normally (men) and 0, (women) RBC Counts and Hemopoiesis Typical range Adult males: 4,600,000 6,200,000/mm 3 Adult females: 4,200,000 5,400,000/mm 3 Erythrocytes RBC Diameter; 1-2 * 7 M S/V & Flexibility & Deformability Dry Hb %95 Hct %45 Normal Hb gr/dl 1 gr Hb 1.39 mlO2 14 16 1.39 = ml O2/ dl M C V 85 M3 M C H 30 Pg M C H C %34 Red cell mass Destruction of RBC RBCs elastic and flexible. Bend easily as they pass through small blood vessels Become more fragile with age and are frequently damaged passing through capillaries in active muscles. Macrophages phagocytize and destroy damaged RBC in the spleen and liver. Cycle of RCM Low blood oxygen causes the kidneys and liver to release erythropoietin, which stimulates the production of red blood cells that carry oxygen to tissues. Average life span of RBC is 120 days Many are removed from circulation each day but the number of cells circulating remains relatively stable. Kidneys and to a lesser extent the liver release erythropoietin in response to prolonged O 2 deficiency. Regulation of erythropoiesis Erythropoietin: produced by the kidneys when O 2 levels drop. 5min to 5 days Function of the erythropoietin mechanism to increase production of red blood cells when tissue oxygenation decreases. Dietary Factors Affecting RBC Production B-complex vitamins (B12 and folic acid) Necessary for DNA synthesis, so all cells with nuclei require them to grow and divide. Cell division occurs frequently in hemopoietic tissue Iron Required for hemoglobin synthesis and normal RBC production. Small intestines absorb iron slowly from food Body reuses much of iron released during decomposition of hemoglobin from damaged RBCs so diet needs only include small quantities of iron Hemoglobin: 4 protein chains (globins) 2 alpha chains 2 beta chains 4 heme groups site where O 2 molecules bind Formation of hemoglobin. Basic structure of the hemoglobin molecule This showing one of the four heme chains that bind together to form the hemoglobin molecule. Hemoglobin molecule Hemoglobin liberated from RBCs is broken down into heme and globin Biliverdin and bilirubin are excreted in bile. Hemoglobin heme chains that bind together to form the hemoglobin molecule Iron transport and metabolism End of Chapter 32 White Blood Cells & Genesis Origin and development of blood cells from hemocytoblasts (stem cells) in bone marrow RBC / WBC Counts & Genesis Chemotaxis Movement of neutrophils by diapedesis through capillary pores and by chemotaxis toward an area of tissue damage. Neutrohpil & Macrophages Defensive properties Diapedesis Ameboid motion Chemotaxis: Bacterial Toxins Products of degeneration Complement complex Clotting factors Phagocytosis: Rough surface No protective coats Opsonization Phagozomes Digestion : (Lysosoms) 1) Proteolytic Enzyme 2) Lipase (Macrophage) Destraction (killing) 1) Proxisome { Superoxide O2-, Hydrogen proxide H2O2, Hydroxyl OH- } 2) Lysosome { Myeloproxidase> Hypochlorite Lysosyme } Monocyte-Macrophage or Reticuloendothelial System Skin: Histiocytes Lymph nods: Macrophages Alveolar walls: Macrophages Hepatic sinusoids : Kupffer cells Spleen & Bone Marrow: Macrophages Functional structures of the spleen Kupffer cells lining the liver sinusoids, showing phagocytosis of India ink particles into the cytoplasm of the Kupffer cells. Inflammation Mediators: 1)Histamine 2) Bradykinine 3) Serotonin 4) Prostoglandine 5) Lymphokine Inflammation is Characterized by: 1) Vasodilatation 2) Capillary permeability 3) Interstitial Coagulation 4) Leukocyte migration 5) Tissue swelling Response of body defence system : 1) First line Tissue macrophage 2) Second line Neutrophil 3) Third line Macro. Invasion 4) Fourth line Granol. Mono production Control of bone marrow production of blood cells in response to multiple growth factors Production of granulocytes and monocyte-macrophages Control of bone marrow production of granulocytes and monocyte- macrophages in response to multiple growth factors released from activated macrophages in an inflamed tissue. G-CSF, granulocyte colony- stimulating factor; GM- CSF, granulocyte- monocyte colony- stimulating factor; IL-1, interleukin-1; M-CSF, monocyte colony- stimulating factor; TNF, tumor necrosis factor. White Blood Cell Counts (WBCC) # of WBCs in mm 3 of human blood 5,000-10,000 cells/mm 3 May change in response to abnormal conditions Rise in number may indicate infection Exceeding 10,000 / mm 3 = leukocytosis and indicates an acute infection such as appendicitis Below 5,000/mm 3 = leukopenia. May accompany typhoid fever, influenza, measles, mumps, chicken pox, AIDS, poliomyelitis Eosinophils Coarse, uniformly-sized granules that stain deep red in acid stain. Bi-lobed nucleus 1-3% of leukocytes Only weakly phagocytic, but do attack and kill certain parasites Helps control inflammation and allergic reactions by removing biochemicals associated with these reactions. The eosinophil has red-staining cytoplasmic granules. Basophils Bi-lobed nucleus, Grannules stain deep blue in basic stain 1% of leukocytes Releases heparin, a blood-clot inhibiting substance that helps prevent intravascular blood clot formation. Releases histamine which increases blood flow to injured tissues. Play a major role in certain allergic reactions. The basophil has cytoplasmic granules that stain deep blue. Blood Plasma Clear, straw-colored, liquid portion in which the cells and platelets are suspended. Approximately 92% water Contains complex mixture of organic and inorganic biochemical's. Plasma Functions Transports nutrients, gases, and vitamins Helps regulate fluid and electrolyte balance Maintains favorable pH Plasma Proteins 3 main groups that differ in chemical composition and physiological function Most abundant of dissolved substances (solutes) in plasma Remain in blood and interstitial fluid Ordinarily not used as energy sources Albumins Globulin Fibrinogen End of Chapter 33 Hemostasis The stoppage of bleeding Following injury, several actions may help limit or prevent blood loss Blood vessel spasm Platelet plug formation Blood coagulation Blood Vessel Spasm Vasospasm injury Cutting or breaking smaller vessels stimulates the smooth muscles in its walls to contract. May close completely. Effects last only a few minutes to 30 minutes. Platelets release TAX2 & serotonin which stimulates vasoconstriction and helps maintain vessel spasm. Pain & Reflex 1 Platelet Plug Formation Platelets adhere to each other and collagen underlying the endothelial lining at injury sites forming plugs in broken vessels. May control blood loss from a small break, but larger break may require a blood clot to halt bleeding. 2 Physical and Chemical Characteristics of Platelets Platelets -discs 1 to 4 micrometers 150,000 and 300,000 per microliter Platelets : they do not have nuclei Cytoplasm : (1) actin and myosin molecules, and thrombosthenin, that can cause the platelets to contract; (2) endoplasmic reticulum and the Golgi apparatus that synthesize various enzymes and calcium ions; (3) mitochondria : forming (ATP) and (ADP); (4) enzyme systems that synthesize prostaglandins, (5) an important protein called fibrin- stabilizing factorand (6) a growth factor that causes vascular endothelial cells, vascular smooth muscle cells, and fibroblasts to multiply and grow 2 Mechanism of the Platelet Plug When platelets come in contact with a damaged vascular surface, especially with collagen fibers in the vascular wall, the platelets themselves immediately change their own characteristics drastically. They begin to swell; they assume irregular forms with numerous irradiating pseudopods protruding from their surfaces; their contractile proteins contract forcefully and cause the release of granules that contain multiple active factors; they become sticky so that they adhere to collagen in the tissues and to a protein called von Willebrand factor that leaks into the traumatized tissue from the plasma; they secrete large quantities of ADP; and their enzymes form thromboxane A 2. The ADP and thromboxane in turn act on nearby platelets to activate them as well, and the stickiness of these additional platelets causes them to adhere to the original activated platelets. Importance of the Platelet Mechanism for Closing Vascular Holes. Blood vessel spasm, platelet plug formation, and blood coagulation provide homeostasis following tissue damage. 3 Blood Coagulation Most effective hemostatic mechanism Causes formation of a blood clot Clotting factors: Biochemicals that promote or inhibit coagulation Whether or not blood coagulates depends on the balance between 2 groups of factors. Normally, anticoagulants prevail = no clots Following injury, biochemicals that favor coagulation may increase and blood coagulates. Schema for conversion of prothrombin to thrombin and polymerization of fibrinogen to form fibrin fibers. Downloaded from: StudentConsult (on 19 September :02 PM) 2005 Elsevier Clotting process in a traumatized blood & Clot retraction A scanning electron micrograph of fibrin threads. Blood coagulation Coagulation the formation of fibrin two pathways intrinsic mechanism extrinsic mechanism 3 Extrinsic pathway for initiating blood clotting Intrinsic pathway for initiating blood clotting Fibroblasts Invade blood clots formed in ruptured vessels. Produce connective tissue with fibers throughout clots. Help strengthen and seal vascular breaks. 3 Anti-clotting systems Anti-clotting systems Blood does not normally clot in undamaged blood vessels of the body. This is partly due to mechanisms that tend to stop clotting and partly to mechanisms that break up and clots that do form. Clots Dissolve with Time Depends on action of a plasma protein that can digest fibrin threads and other proteins associated with clots. Clots that fill large blood vessels are seldom removed naturally. Fibrinolysis The process of liquefaction of fibrin is known as fibrinolysis End of the Chapter 36 Types of WBC Differ in size, nature of their cytoplasm, shape of the nucleus, and staining characteristics. Neutrophils Fine granules, stain light purple in neutral stain. nucleus with 2-5 lobes 54-62% of leukocytes in adults One of most mobile and active phagocyte of small particles Contain many lysosomes which are organelles filled with digestive enzymes that break down organic molecules in captured bacteria The neutrophil has a lobed nucleus with 2-5 components Monocytes Arise from red bone marrow Largest blood cells. 2- 3X diameter of RBCs Nuclei vary in shape (round, kidney-shaped, oval, lobed) 3-9% of leukocytes Live several weeks or months One of most mobile and active phagocytic leukocyte of larger particles. A monocyte may leave the bloodstream and become a macrophage. Lymphocytes Formed in organs of lymphatic system and in red bone marrow Only slightly large than RBCs Large, round nucleus with thin rim of cytoplasm 25-33% of leukocytes Live for years. Important in immunity. Some produce antibodies that attack specific foreign substances that enter the body. The lymphocyte contains a large, round nucleus. Genesis of white blood cells The different cells of the myelocyte series are 1, myeloblast; 2, promyelocyte; 3, megakaryocyte; 4, neutrophil myelocyte; 5, young neutrophil metamyelocyte; 6, "band" neutrophil metamyelocyte; 7, polymorphonuclear neutrophil; 8, eosinophil myelocyte; 9, eosinophil metamyelocyte; 10, polymorphonuclear eosinophil; 11, basophil myelocyte; 12, polymorphonuclear basophil; 13-16, stages of monocyte formation. Plasma proteins Albumins (60%), globuliins & fibrinogen (40%) Electrophoresis is classical method to separate proteins See biochemistry course Coagulation stages