Anatomy And Physiology


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Anatomy And Physiology

  1. 1. Anatomy and Physiology Chapter 12 Blood
  2. 2. Introduction to Blood <ul><li>Blood signifies life </li></ul><ul><li>The blood, heart, and blood vessels form the cardiovascular system and link the body’s internal and external environments. </li></ul><ul><li>Type of connective tissue whose cells are suspended in a liquid material </li></ul><ul><li>Complex mixture of cells, cell fragments, and dissolved biochemicals </li></ul><ul><li>Vital in transporting substances between body cells and the external environment thereby promoting homeostasis. </li></ul>
  3. 3. Vital Functions <ul><li>Transports nutrients, O 2 , wastes and hormones. </li></ul><ul><li>Helps maintain the stability of the interstitial fluid. </li></ul><ul><li>Distributes heat. </li></ul><ul><li>Provides protection against infection (white blood cells) </li></ul><ul><li>Promotes clotting (platelets) </li></ul>
  4. 4. Blood Substitutes <ul><li>Early efforts have focused on filling missing fluid volume and reproduce O 2 carrying role. </li></ul><ul><li>The search for a blood substitute intensified: </li></ul><ul><ul><li>After each word war - injured soldiers needed transfusions </li></ul></ul><ul><ul><li>AIDS pandemic made transfusions dangerous unless blood was screened. </li></ul></ul>
  5. 5. <ul><li>Substitutes must meet several requirements: </li></ul><ul><ul><li>Carry O 2 and give it up to tissues </li></ul></ul><ul><ul><li>Be non-toxic </li></ul></ul><ul><ul><li>Storeable </li></ul></ul><ul><ul><li>Function until the body can take over </li></ul></ul><ul><ul><li>Not provoke an immune response </li></ul></ul>
  6. 6. <ul><li>RBC substitutes currently in clinical trials are of two types: </li></ul><ul><ul><li>Perfluorocarbons: synthetic chemicals that carry dissolved O 2 . Developed in 1960’s Famous photo of mouse breathing in liquid. </li></ul></ul><ul><ul><li>Substitutes that dismantle RBC’s and isolate the O 2 -carrying hemoglobin and links them in various ways. Starting material usually cow’s blood or old stored human blood. </li></ul></ul>
  7. 7. <ul><li>RBC substitutes used in the past have included wine, ale, plant resins, urine, and opium </li></ul>
  8. 8. Blood and Blood Cells <ul><li>Whole blood is slightly heavier and 3-4x more viscous than water. </li></ul><ul><li>Red blood cells and white blood cells form in red bone marrow. </li></ul><ul><li>Platelets are cellular fragments. </li></ul><ul><li>Formed Elements: cellular portion; RBC’s, WBC’s and platelets </li></ul><ul><li>Liquid portion: plasma </li></ul>
  9. 9. Blood Volume <ul><li>Volume varies with body size, changes in fluid and electrolyte concentrations, and the amount of adipose tissue. </li></ul><ul><li>Average-sized adult has blood volume of 5.3 quarts or 5 liters. </li></ul><ul><ul><li>Men (1.500 gal) generally have more blood than women (0.875 gal) </li></ul></ul>
  10. 10. Composition of a Blood Sample <ul><li>Hemocrit (HCT): 45% by volume. Includes cells – mostly RBC’s and much smaller numbers of WBC’s and platelets </li></ul><ul><li>Plasma: clear, straw-colored liquid which is a complex mixture of water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes. </li></ul>
  11. 11. Blood consists of a liquid portion (plasma) and a solid portion (RBC’s, WBC’s, platelets). When blood separates, the WBC’s and platelets form a thin layer called the “buffy coat” between the plasma and the RBC’s .
  12. 12. Red Blood Cells / Erythrocytes <ul><li>Biconcave discs </li></ul><ul><ul><li>Shape is an adaptation for transporting gases </li></ul></ul><ul><ul><li>Increases surface area through which gases can diffuse. The combined surface area of all RBC’s in human body is roughly 2000x greater than the body’s external surface </li></ul></ul><ul><ul><li>Places the cell membrane closer to the O 2 -carrying hemoglobin within the cell. </li></ul></ul><ul><li>Hemoglobin </li></ul><ul><ul><li>1/3 of the cell by volume </li></ul></ul><ul><ul><li>Protein responsible for the color of blood </li></ul></ul><ul><ul><li>When hemoglobin combines with O 2 (oxyhemoglobin) = bright red; When O 2 released (deoxyhemoglobin)=darker color </li></ul></ul>
  13. 13. Red Blood Cells. A.) The biconcave shape of a red blood cell makes possible its function. B.) Scanning electron micrograph of human RBC’s. (colored)
  14. 14. <ul><li>Hypoxia: prolonged O 2 deficiency </li></ul><ul><li>Cyanotic: </li></ul><ul><ul><li>Skin and mucous membranes appear bluish due to high concentration of deoxyhemoglobin. </li></ul></ul><ul><ul><li>Can be due to hypoxia or exposure to low temperatures which cause superficial vessels to constrict slowing blood flow which removes more O 2 than usual from blood. </li></ul></ul>
  15. 15. <ul><li>RBC’s have nuclei during early stages of development but extrude them as they mature. </li></ul><ul><ul><li>More space for hemoglobin </li></ul></ul><ul><ul><li>Cannot synthesize proteins or divide </li></ul></ul>
  16. 16. RBC Counts <ul><li>The number of RBC’s in 1 mm 3 of blood. </li></ul><ul><li>RBCC, RCC </li></ul><ul><li>Typical range </li></ul><ul><ul><li>Adult males: 4,600,000 – 6,200,000/mm 3 </li></ul></ul><ul><ul><li>Adult females: 4,200,000 – 5,400,000/mm 3 </li></ul></ul><ul><li>Increasing the number of circulating RBC’s increases the bloods O 2 -carrying capacity. </li></ul><ul><li>Change in RBCC may affect health – routinely consulted to help diagnose and evaluate the courses of various diseases. </li></ul>
  17. 17. Hemopoiesis <ul><li>RBC formation </li></ul><ul><li>Initially occurs in the yolk sac, liver and spleen </li></ul><ul><li>After birth – RBC’s produced almost exclusively in tissue lining the spaces in bones and red bone marrow </li></ul>
  18. 18. <ul><li>Average life span of RBC is 120 days </li></ul><ul><li>Many are removed from circulation each day but the number of cells circulating remains relatively stable. </li></ul><ul><ul><li>Suggests homeostatic control of the rate of hemopoiesis. </li></ul></ul>
  19. 19. <ul><li>Negative feedback mechanism </li></ul><ul><ul><li>A hormone, erythropoietin controls the rate of hemopoiesis </li></ul></ul><ul><ul><li>Kidneys and to a lesser extent the liver release erythropoietin in response to prolonged O 2 deficiency. </li></ul></ul><ul><ul><ul><li>Ex. High altitudes where % of O 2 in air is reduced stimulate the release of hormone and RBC production. When O 2 level in air returns to normal, hormone decreased and rate of hemopoiesis returns to normal. </li></ul></ul></ul>
  20. 20. Low blood oxygen causes the kidneys and liver to release erythropoietin, which stimulates the production of red blood cells that carry oxygen to tissues.
  21. 21. Origin and development of blood cells from hemocytoblasts (stem cells) in bone marrow.
  22. 22. Dietary Factors Affecting RBC Production <ul><li>B-complex vitamins (B12 and folic acid) </li></ul><ul><ul><li>Necessary for DNA synthesis, so all cells with nuclei require them to grow and divide. </li></ul></ul><ul><ul><li>Cell division occurs frequently in hemopoietic tissue </li></ul></ul><ul><li>Iron </li></ul><ul><ul><li>Required for hemoglobin synthesis and normal RBC production. </li></ul></ul><ul><ul><li>Small intestines absorb iron slowly from food </li></ul></ul><ul><ul><li>Body reuses much of iron released during decomposition of hemoglobin from damaged RBC’s so diet needs only include small quantities of iron </li></ul></ul>
  23. 23. Anemia <ul><li>Too few RBC’s or too little hemoglobin leads to reduced O 2 -carrying capacity </li></ul><ul><li>Person appears pale, lacks energy. </li></ul><ul><li>Pregnant women may become anemic if she doesn’t eat iron-rich foods. </li></ul><ul><ul><li>Her blood volume increases due to fluid retention to accommodate the requirements of the fetus. </li></ul></ul><ul><ul><li>Increased blood volume  decrease in hemocrit </li></ul></ul>
  24. 24. Sickle Cell Disease <ul><li>Single DNA base change causing an incorrect amino acid to be incorporated into globin causing hemoglobin to crystallize in a low-O 2 environment bending RBC containing hemoglobin into a sickle-shape </li></ul><ul><li>Blocks circulation in small vessels causing excruciating joint pain and damaging organs. </li></ul><ul><li>Infections are more likely. RBC’s are abnormally short-lived, spleen works harder to recycle. </li></ul><ul><li>Children diagnosed at birth. Receive antibiotics daily for years to prevent infections. </li></ul>
  25. 26. <ul><li>Hospitalization for transfusions: sickling crises of blocked circulation. </li></ul><ul><li>Bone marrow transplant: complete cure but 15% risk of death. </li></ul><ul><li>New treatment: old drug used to treat cancer, hydroxyurea. Activates slightly different form of hemoglobin in fetus. Sickle hemoglobin cannot crystallize as quickly. Sickling is delayed and enables RBC’s carrying sickled hemoglobin to more quickly reach lungs where fresh O 2 restores normal shape. </li></ul>
  26. 27. Destruction of RBC’s <ul><li>RBC’s elastic and flexible. Bend easily as they pass through small blood vessels </li></ul><ul><li>Become more fragile with age and are frequently damaged passing through capillaries in active muscles. </li></ul><ul><li>Macrophages phagocytize and destroy damaged RBC in the spleen and liver. </li></ul>
  27. 28. <ul><li>Hemoglobin molecules liberated from RBC’s broken down into heme (iron-containing portion) and globin (a protein) </li></ul><ul><ul><li>Heme further decomposes into iron and biliverdin (greenish pigment) </li></ul></ul><ul><ul><li>Biliverin is converted to an orange pigment called bilirubin. Both pigments are excreted in bile. </li></ul></ul><ul><li>Blood transports iron and protein to hemopoietic tissue in red bone marrow to be reused in synthesizing new hemoglobin or the liver stores the iron-protein complex </li></ul>
  28. 29. Life cycle of a red blood cell. 1.) Small intestine absorbs essential nutrients. 2.) Blood transports nutrients to red bone marrow. 3.) In the marrow, RBC’s arise from the division of less specialized cells. 4.) Mature RBC’s are released into the bloodstream, where they circulate for about 120 days. 5.)Macrophages destroy damaged RBC’s in the spleen and liver. 6.) Hemoglobin liberated from RBC’s is broken down into heme and globin. 7.) Iron from heme returns to red bone marrow and is reused. 8.) Biliverdin and bilirubin are excreted in bile.
  29. 30. Physiologic Jaundice <ul><li>Seen in newborns a few days after birth </li></ul><ul><li>Along with other forms of jaundice (icterus) are characterized by an accumulation of bilirubin which turns skin and eyes yellowish. </li></ul><ul><li>May be result of immature liver cells that ineffectively excrete bilirubin into bile. </li></ul>
  30. 31. <ul><li>Treatment: </li></ul><ul><ul><li>Bili lights discovered in 1950’s: (Nurse notes improvement after exposure to sunlight, except in diaper area) Exposure to fluorescent light breaks down bilirubin in tissues. </li></ul></ul><ul><ul><li>Feedings to promote bowel movements to remove wastes. </li></ul></ul>
  31. 32. White Blood Cells / Leukocytes <ul><li>Function to protect against infection in various ways: </li></ul><ul><ul><li>Phagocytize bacterial cells in the body </li></ul></ul><ul><ul><li>Produce proteins (antibodies) that destroy or disable foreign particles </li></ul></ul><ul><li>Develop from hemocytoblasts in response to hormones – interleukins and colony-stimulating factors (CSF’s) </li></ul>
  32. 33. Diapedesis <ul><li>Blood transports WBC’s to sites of infection where they can squeeze between cells that form blood vessel walls. </li></ul><ul><li>Allows WBC’s to leave blood circulation and move through interstitial spaces using amoeboid motion (self-propulsion) </li></ul>
  33. 34. Types of WBC’s <ul><li>Differ in size, nature of their cytoplasm, shape of the nucleus, and staining characteristics. </li></ul>
  34. 35. Granulocytes <ul><li>Leukocytes with granular cytoplasm </li></ul><ul><li>2x the size of RBC’s </li></ul><ul><li>Develop in the red bone marrow (as do RBC’s) </li></ul><ul><li>Life span – ave. 12 hours </li></ul><ul><li>Members of group include </li></ul><ul><ul><li>Neutrophils </li></ul></ul><ul><ul><li>Eosinophils </li></ul></ul><ul><ul><li>Basophils </li></ul></ul>
  35. 36. Neutrophils <ul><li>Fine granules, stain light purple in neutral stain. nucleus with 2-5 lobes </li></ul><ul><li>54-62% of leukocytes in adults </li></ul><ul><li>One of most mobile and active phagocyte of small particles </li></ul><ul><ul><li>Contain many lysosomes which are organelles filled with digestive enzymes that break down organic molecules in captured bacteria </li></ul></ul><ul><ul><li>Often become so engorged with digestive products and bacterial toxins that they die. </li></ul></ul>The neutrophil has a lobed nucleus with 2-5 components
  36. 37. Eosinophils <ul><li>Coarse, uniformly-sized granules that stain deep red in acid stain. Bi-lobed nucleus </li></ul><ul><li>1-3% of leukocytes </li></ul><ul><li>Only weakly phagocytic, but do attack and kill certain parasites </li></ul><ul><li>Helps control inflammation and allergic reactions by removing biochemicals associated with these reactions. </li></ul>The eosinophil has red-staining cytoplasmic granules.
  37. 38. Basophils <ul><li>Bi-lobed nucleus, Grannules stain deep blue in basic stain </li></ul><ul><li>1% of leukocytes </li></ul><ul><li>Releases heparin, a blood-clot inhibiting substance that helps prevent intravascular blood clot formation. </li></ul><ul><li>Releases histamine which increases blood flow to injured tissues. </li></ul><ul><li>Play a major role in certain allergic reactions. (more in Ch 14) </li></ul>The basophil has cytoplasmic granules that stain deep blue.
  38. 39. Agranulocytes <ul><li>Monocytes </li></ul><ul><li>Lymphocytes </li></ul>
  39. 40. Monocytes <ul><li>Arise from red bone marrow </li></ul><ul><li>Largest blood cells. 2-3X diameter of RBC’s </li></ul><ul><li>Nuclei vary in shape (round, kidney-shaped, oval, lobed) </li></ul><ul><li>3-9% of leukocytes </li></ul><ul><li>Live several weeks or months </li></ul><ul><li>One of most mobile and active phagocytic leukocyte of larger particles. </li></ul>A monocyte may leave the bloodstream and become a macrophage.
  40. 41. Lymphocytes <ul><li>Formed in organs of lymphatic system and in red bone marrow </li></ul><ul><li>Only slightly large than RBC’s </li></ul><ul><li>Large, round nucleus with thin rim of cytoplasm </li></ul><ul><li>25-33% of leukocytes </li></ul><ul><li>Live for years. </li></ul><ul><li>Important in immunity. Some produce antibodies that attack specific foreign substances that enter the body (more in Ch 14) </li></ul>The lymphocyte contains a large, round nucleus.
  41. 42. White Blood Cell Counts (WBCC) <ul><li># of WBC’s in mm 3 of human blood </li></ul><ul><li>5,000-10,000 cells/mm 3 </li></ul><ul><li>May change in response to abnormal conditions </li></ul><ul><ul><li>Rise in number may indicate infection </li></ul></ul><ul><ul><li>Exceeding 10,000 / mm 3 = leukocytosis and indicates an acute infection such as appendicitis </li></ul></ul><ul><ul><li>Below 5,000/mm 3 = leukopenia. May accompany typhoid fever, influenza, measles, mumps, chicken pox, AIDS, poliomyelitis </li></ul></ul>
  42. 43. <ul><li>Differential White Blood Cell Count (DIFF) </li></ul><ul><ul><li>Lists percent of types of leukocytes in blood sample </li></ul></ul><ul><ul><li>Relative proportions may change in particular diseases </li></ul></ul><ul><ul><ul><li>Neutrophils increase during bacterial infections </li></ul></ul></ul><ul><ul><ul><li>Eosinophils increase during certain parasitic infections and allergic reactions </li></ul></ul></ul><ul><ul><ul><li>A certain type of lymphocyte drops sharply in AIDS </li></ul></ul></ul>
  43. 44. Blood Platelets / Thrombocytes <ul><li>Not complete cells </li></ul><ul><li>Arise from very large cells in red bone marrow (megakaryocytes) that fragment like a shattered plate and release small sections of cytoplasm (platelets) into circulation </li></ul><ul><li>Megakaryocytes develop from hemocytoblasts in response to the hormone thrombopoietin </li></ul>
  44. 45. <ul><li>Lacks nucleus </li></ul><ul><li>Less than ½ size of RBC </li></ul><ul><li>Amoeboid movement </li></ul><ul><li>Circulate for about 10 days </li></ul><ul><li>Varies from 130,000 – 360,000 / mm 3 in normal blood </li></ul><ul><li>Help close breaks in damaged blood vessels and initiate formation of blood clots (more later) </li></ul>
  45. 46. Leukemia <ul><li>“ Cancer of the WBC” </li></ul><ul><li>Symptoms: </li></ul><ul><ul><li>Fatigue Headaches </li></ul></ul><ul><ul><li>Frequent colds Fever </li></ul></ul><ul><ul><li>Chills Sweats </li></ul></ul><ul><ul><li>Bruises Bone pain </li></ul></ul><ul><ul><li>Slow clotting </li></ul></ul><ul><li>Blood Test: Too few RBC’s and platelets. Too many WBC’s. </li></ul>
  46. 47. Leukemia and blood cells. A.) Normal blood cells. B.) Blood cells from a person with granulocytic leukemia, a type of myeloid leukemia. Note the increased number of leukocytes.
  47. 48. Myeloid Leukemia <ul><li>Red bone marrow produces too many granulocytes but they are immature and unable to fight infection. </li></ul><ul><li>Leukemic cells crowd out RBC’s and their precursors in the red marrow causing anemia and fatigue. </li></ul><ul><li>Thrombocytopenia (platelet deficiency) </li></ul><ul><li>Spread of cancer cells outside of marrow weakens surrounding bone. </li></ul>
  48. 49. Lymphoid Leukemia <ul><li>Distinguished by source of cancer cells – lymphocytes produced in lymph nodes </li></ul><ul><li>Similar symptoms to myeloid leukemia </li></ul><ul><li>Sometimes no symptoms and is detected by a routine blood test. </li></ul>
  49. 50. Classification <ul><li>Acute: </li></ul><ul><ul><li>Appears suddenly. </li></ul></ul><ul><ul><li>Progresses rapidly. </li></ul></ul><ul><ul><li>Without treatment – death within a few months. </li></ul></ul><ul><li>Chronic: </li></ul><ul><ul><li>Begins slow and remains undetected for months or years. </li></ul></ul><ul><ul><li>Without treatment – life expectancy 3 years. </li></ul></ul><ul><ul><li>With treatment 50-80% of patients enter remission. </li></ul></ul><ul><ul><li>Chemotherapy increases chances of long remission </li></ul></ul>
  50. 51. Treatment <ul><li>Correction of symptoms </li></ul><ul><li>Blood transfusions, treating infections, drugs that kill cancer cells </li></ul><ul><li>New drug – Gleevec has had success </li></ul><ul><li>Bone marrow transplants can cure leukemia but procedure is risky. </li></ul><ul><li>Stem cell transplants using donated umbilical cord blood can also cure leukemia. </li></ul>
  51. 52. Origin and development of blood cells from hemocytoblasts (stem cells) in bone marrow.
  52. 54. Blood Plasma <ul><li>Clear, straw-colored, liquid portion in which the cells and platelets are suspended. </li></ul><ul><li>Approximately 92% water </li></ul><ul><li>Contains complex mixture of organic and inorganic biochemicals. </li></ul>
  53. 55. Functions <ul><li>Transports nutrients, gases, and vitamins </li></ul><ul><li>Helps regulate fluid and electrolyte balance </li></ul><ul><li>Maintains favorable pH </li></ul>
  54. 56. Plasma Proteins <ul><li>Most abundant of dissolved substances (solutes) in plasma </li></ul><ul><ul><li>Remain in blood and interstitial fluid </li></ul></ul><ul><ul><li>Ordinarily not used as energy sources </li></ul></ul><ul><li>3 main groups that differ in chemical composition and physiological function </li></ul><ul><ul><li>Albumins </li></ul></ul><ul><ul><li>Globulin </li></ul></ul><ul><ul><li>Fibrinogen </li></ul></ul>
  55. 57. Albumins <ul><li>Smallest </li></ul><ul><li>60% by weight </li></ul><ul><li>Synthesized by the liver </li></ul><ul><li>Important determinant of colloid osmotic pressure of the plasma </li></ul><ul><ul><li>Helps to regulate water movement and control blood volume. </li></ul></ul><ul><ul><li>Too large to cross capillary walls so water diffuses towards it. </li></ul></ul><ul><ul><li>Acts opposite blood pressure that tends to force water out of capillaries by filtration </li></ul></ul>
  56. 58. Edema <ul><li>Tissues swell if concentration of plasma proteins falls. </li></ul><ul><ul><li>May result from starvation or a protein-deficient diet (requires the body to use protein for energy) </li></ul></ul><ul><ul><li>May result from an impaired liver that cannot synthesize plasma proteins. </li></ul></ul><ul><li>As concentration of proteins drops, so does osmotic pressure sending fluids into intercellular spaces. </li></ul>
  57. 59. Globulins <ul><li>36% by weight </li></ul><ul><li>3 types </li></ul><ul><ul><li>Alpha: synthesized by liver. Function to transport lipids and fat-soluble vitamins </li></ul></ul><ul><ul><li>Beta: same as alpha </li></ul></ul><ul><ul><li>Gamma: Produced by lymphatic tissues. Type of antibodies </li></ul></ul>
  58. 60. Fibrinogen <ul><li>4% by weight </li></ul><ul><li>Largest in size </li></ul><ul><li>Functions in blood coagulation. (more later) </li></ul><ul><li>Synthesized in liver. </li></ul>
  59. 62. Blood Gases <ul><li>Most important are oxygen and CO 2 </li></ul><ul><li>Blood contains a considerable amount of nitrogen gas </li></ul><ul><li>(More in Ch16) </li></ul>
  60. 63. Blood Nutrients <ul><li>Amino acids, simple sugars, nucleotides, and lipids are absorbed from the digestive tract </li></ul><ul><li>Plasma transports glucose from small intestine to liver where it is stored as glycogen or converted to fat </li></ul><ul><li>Amino acids are transported to the liver to manufacture proteins or are used as an energy source. </li></ul>
  61. 64. <ul><li>Lipoprotein complexes: lipids combine with proteins and become water-soluble </li></ul><ul><ul><li>Plasma lipids include: triglycerides (fats), phospholipids, and cholesterol </li></ul></ul><ul><ul><li>Apoproteins on the outer layer of these large molecules can combine with receptors on the membranes of specific target cells. </li></ul></ul><ul><ul><li>Vary in density by the proportions of their lipids and proteins. </li></ul></ul><ul><ul><li>Help to transport dietary fats between the liver and muscle and adipose tissue </li></ul></ul>
  62. 66. Non-protein Nitrogenous Substances <ul><li>Molecules that contain nitrogen atoms but are not proteins. </li></ul><ul><li>Amino acids enter plasma from protein digestion and from absorption </li></ul><ul><li>Urea and uric acid are products of protein and nucleic acid catabolism. Excreted as urine. </li></ul>
  63. 67. Plasma Electrolytes <ul><li>A variety of electrolytes are absorbed from the intestine or are released as by-products of cellular metabolism. </li></ul><ul><li>Sodium and chloride ions are most abundant. Other ions include calcium, magnesium, bicarbonate, phosphate, and sulfate. </li></ul><ul><li>Bicarbonate ions are important in maintaining osmotic pressure and pH of plasma </li></ul><ul><li>Regulated so that concentrations remain relatively stable. </li></ul>
  64. 68. Hemostasis <ul><li>The stoppage of bleeding </li></ul><ul><li>Following injury, several actions may help limit or prevent blood loss </li></ul><ul><ul><li>Blood vessel spasm </li></ul></ul><ul><ul><li>Platelet plug formation </li></ul></ul><ul><ul><li>Blood coagulation </li></ul></ul>
  65. 69. Blood Vessel Spasm <ul><li>Vasospasm: </li></ul><ul><ul><li>Cutting or breaking smaller vessels stimulates the smooth muscles in its walls to contract. May close completely. </li></ul></ul><ul><ul><li>Effects last only a few minutes to 30 minutes. </li></ul></ul><ul><li>Platelets release serotonin which stimulates vasoconstriction and helps maintain vessel spasm. </li></ul>
  66. 70. Platelet Plug Formation <ul><li>Platelets adhere to each other and collagen underlying the endothelial lining at injury sites forming plugs in broken vessels. </li></ul><ul><li>May control blood loss from a small break, but larger break may require a blood clot to halt bleeding. </li></ul>Link to animation
  67. 71. Steps in platelet plug formation
  68. 72. Blood Coagulation <ul><li>Most effective hemostatic mechanism </li></ul><ul><li>Causes formation of a blood clot </li></ul><ul><li>Clotting factors: </li></ul><ul><ul><li>Biochemicals that promote or inhibit coagulation </li></ul></ul><ul><ul><li>Whether or not blood coagulates depends on the balance between 2 groups of factors. </li></ul></ul><ul><ul><ul><li>Normally, anticoagulants prevail = no clots </li></ul></ul></ul><ul><ul><ul><li>Following injury, biochemicals that favor coagulation may increase and blood coagulates. </li></ul></ul></ul>
  69. 73. <ul><li>The major event in blood clot formation is the conversion of soluble fibrinogen (a plasma protein) into insoluble threads of fibrin </li></ul><ul><li>Biochemicals that promote clotting: </li></ul><ul><ul><li>Prothrombin activator: damaged tissue signals this to be produced. </li></ul></ul><ul><ul><li>Prothrombin: alpha globulin continuously produced by the liver. It is converted to thrombin by prothrombin activator and calcium ions. </li></ul></ul><ul><ul><li>Thrombin catalyzes a reaction that fragments fibrinogen. </li></ul></ul><ul><ul><li>Long fibrin threads stick to exposed surfaces of damaged blood vessels creating a meshwork that entraps blood cells and platelets </li></ul></ul><ul><ul><li>Resulting mass is a blood clot which may block a vascular break and prevent further blood loss </li></ul></ul>
  70. 74. A scanning electron micrograph of fibrin threads.
  71. 75. <ul><li>Serum: clear, yellow fluid that remains after clot. Same as plasma, minus the clotting factors. </li></ul>
  72. 76. <ul><li>Works as a positive feedback system </li></ul><ul><ul><li>The original action stimulates more of the same type of action. Promotes unstable conditions only operates for a short time (life depends on maintenance of stable internal conditions) </li></ul></ul><ul><ul><li>The amount of prothrombin activator in blood is directly proportional to the degree of tissue damage. </li></ul></ul><ul><ul><li>Once clot begins to form, it promotes more clotting because thrombin also acts directly on blood clotting factors. </li></ul></ul>
  73. 77. <ul><li>Normally: </li></ul><ul><ul><li>Blood flow prevents massive clot formation within the cardiovascular system by rapidly carrying excess thrombin away, keeping its concentration too low to enhance further clotting. </li></ul></ul><ul><ul><li>Blood coagulation is usually limited to blood standing still or moving slowly. Clotting ceases where clot contacts circulating blood. </li></ul></ul>
  74. 78. <ul><li>Lab tests used to evaluate blood coagulation mechanisms include: prothrombin time (PT) and partial thromboplastin time (PPT). Both measure the time for fibrin threads to form in a sample of plasma. </li></ul>
  75. 79. Fibroblasts <ul><li>Invade blood clots formed in ruptured vessels. </li></ul><ul><li>Produce connective tissue with fibers throughout clots. </li></ul><ul><li>Help strengthen and seal vascular breaks. </li></ul>
  76. 80. Clots Dissolve with Time <ul><li>Depends on action of a plasma protein that can digest fibrin threads and other proteins associated with clots. </li></ul><ul><li>Clots that fill large blood vessels are seldom removed naturally. </li></ul>
  77. 81. Abnormal Clot Formations <ul><li>Thrombus: a clot abnormally forming in a vessel </li></ul><ul><li>Embolus: </li></ul><ul><ul><li>If a clot dislodges or if a fragment of it breaks loose and is carried away by blood flow. </li></ul></ul><ul><ul><li>Continues to move until it reaches narrow place in vessel where it may lodge and block flow. </li></ul></ul>
  78. 82. <ul><li>Often associated with conditions that change endothelial lining of vessels. Ex. Atherosclerosis = accumulations of fatty deposits. </li></ul>Artery cross sections. A.) Light micrograph of a normal artery. B.) The inner wall of this artery changed as a result of atherosclerosis.
  79. 83. <ul><li>Coronary thrombosis: blood clot forming in vessel that supplies the heart </li></ul><ul><li>Cerebral thrombosis: blood clot forming in vessel that supplies the brain. </li></ul><ul><li>Infarction: Clot that blocks and kills tissues the vessel serves. </li></ul><ul><li>Pulmonary embolism: clot that travels and blocks vessel that supplies the lungs. Affects portion of organ the blocked vessel supplies. </li></ul>
  80. 84. Tissue Plasminogen Activators (tPA) <ul><li>Break up abnormal blood clots and are used to treat heart attacks and strokes. </li></ul>
  81. 85. Coagulation Disorders <ul><li>Hemophilia </li></ul><ul><li>Von Willebrand Disease </li></ul>
  82. 86. Hemophilia <ul><li>Inherited clotting disorder </li></ul><ul><li>Abnormalities of different clotting factors cause different forms of hemophilia </li></ul><ul><li>Hemophilia A: missing factor VIII. Most common. </li></ul><ul><li>Symptoms include severe hemorrhage following minor injuries. Frequent nosebleeds, large muscular hematomas (blood leakage in tissues), and blood in urine </li></ul>
  83. 87. Von Willebrand Disease <ul><li>Tendency to bleed and bruise easily </li></ul><ul><li>Inherited clotting disorder </li></ul><ul><li>Less severe than hemophilia </li></ul><ul><li>Lack a plasma protein, von Willebrand factor, secreted by endothelial cells lining blood vessel walls which enables platelets to adhere to damaged blood vessel walls, a key step preceding actual clotting. </li></ul><ul><li>Sometimes causes spontaneous bleeding from mucous membranes or gastrointestinal and urinary tracts. </li></ul>
  84. 88. Blood vessel spasm, platelet plug formation, and blood coagulation provide homeostasis following tissue damage.
  85. 89. Blood Groups and Transfusions <ul><li>Early attempts at transfusions produced a variety of results. </li></ul><ul><ul><li>Some people recovered, others suffered a blood reaction in which RBC’s clumped obstructing vessels, causing pain and organ damage. </li></ul></ul><ul><ul><li>Scientists determined that blood is of different types. Only certain combinations are compatible. Blood typing procedures were developed. </li></ul></ul>
  86. 90. Antigens and Antibodies <ul><li>Agglutination: </li></ul><ul><ul><li>The clumping of RBC’s following a transfusion reaction </li></ul></ul><ul><ul><li>Due to a reaction between RBC surface molecules called antigens and protein antibodies (formerly called agglutinogens and agglutinins) </li></ul></ul><ul><ul><li>Only a few of the many antigens on RBC membrane produce serious transfusion reactions. Ex. ABC group and Rh group </li></ul></ul>
  87. 91. <ul><li>Mismatched Transfusion </li></ul><ul><ul><li>Symptoms include: anxiety, breathing difficulty, facial flushing, headache, severe pain in neck, chest, and lumbar area </li></ul></ul><ul><ul><li>RBC’s burst releasing free hemoglobin </li></ul></ul><ul><ul><li>Macrophages phagocytize the hemoglobin converting it to bilirubin (which accumulates to cause jaundice) </li></ul></ul><ul><ul><li>Free hemoglobin in the kidneys may cause them to fail </li></ul></ul>
  88. 92. ABO Blood Group <ul><li>Based on the presence or absence of 2 major antigens on RBC membranes </li></ul><ul><li>A person’s erythrocytes have 1-4 antigen combinations on their surface as a result of inheritence: A, B, AB, or neither (O) </li></ul><ul><li>The most common ABO blood types are O=47%, A=41%, B=9%, AB=3% </li></ul>
  89. 93. Different combinations of antigens and antibodies distinguish blood types. (Cells and antibodies not drawn to scale)
  90. 95. <ul><li>After birth (2-8 months) antibodies are synthesized in the plasma. </li></ul><ul><ul><li>When antigen A is absent in RBC’s an antibidy called anti-A is produced, etc. </li></ul></ul><ul><li>Anti-A and Anti-B are large and do not cross the placenta </li></ul><ul><ul><li>Pregnant woman and fetus may be of different ABO blood types. Agglutination in fetus does not occur. </li></ul></ul>
  91. 96. <ul><li>An antibody of one type will react with an antigen of the same type and clump RBC’s. This must be avoided during transfusions. </li></ul><ul><li>Universal Recipients : type AB persons lack both antibodies. Can receive any type blood but AB is still best match because donated A blood still has some anti-B in it. </li></ul>
  92. 97. <ul><li>Universal Donor : lacks antigens A and B. Could be transfused into persons of any blood type. Does contain anti-A and anti-B so it must be transfused slowly so persons larger blood volume dilutes it minimizing chance of reaction. </li></ul>
  93. 98. Agglutination. A.) If RBC’s with antigen A are added to blood containing antibody anti-A, B.) the antibodies react with the antigens, causing clumping (agglutination). C.) Nonagglutinated blood. D.) Agglutinated blood.
  94. 99. Rh Blood Group <ul><li>Named after the rhesus monkey in which it was first studied. </li></ul><ul><li>Inherited trait </li></ul><ul><ul><li>If antigen D and other Rh antigens are present on RBC membrane = Rh+ </li></ul></ul><ul><ul><li>If RBC lacks Rh antigens = Rh- </li></ul></ul><ul><ul><li>15% of U.S. population is Rh-, therefore AB- is rarest and O+ is most common. </li></ul></ul>
  95. 100. <ul><li>Antibodies for Rh (anti-Rh) do not appear spontaneously. Only form in Rh- person in response to special stimulation </li></ul>
  96. 101. Rh- person recieves transfusion of Rh+ blood <ul><li>The Rh antigens stimulate the recipient’s antibody-producing cells to begin producing anti-Rh antibodies. </li></ul><ul><li>Generally initial transfusion has no serious consequences, but Rh- person is now “sensitized” to Rh+ blood. </li></ul><ul><li>Agglutination will occur if second transfusion with Rh+ occurs. </li></ul>
  97. 102. Rh- woman pregnant with Rh+ fetus <ul><li>First time is uneventful but during birth or miscarriage, some infant blood may enter maternal circulation and “sensitize” the woman causing her to begin producing anti-Rh antibodies. </li></ul><ul><li>During second pregnancy with Rh+ fetus, anti-Rh antibodies (called hemolysins) cross placental membrane and destroy fetal RBC’s. </li></ul><ul><li>Fetus then develops erythroblastosis fetalis </li></ul>
  98. 103. If a man who is Rh positive and a woman who is Rh negative conceive a child who is Rh positive, the woman’s body may manufacture antibodies that attack future Rh-positive offspring.
  99. 104. <ul><li>Extremely rare today because physicians carefully track Rh status. </li></ul><ul><ul><li>Woman who might carry Rh+ fetus is given an injection of RhoGAM composed of anti-Rh antibodies which bind to and shield and Rh+ fetal cells that might contact the woman’s cells and sensitize her immune system. </li></ul></ul><ul><ul><li>RhoGAM must be given within 72 hours of possible contact with Rh+ cells including giving birth, terminating pregnancy, miscarrying, amniocentesis. </li></ul></ul>
  100. 105. Clinical Terms Related to the Blood
  101. 106. Anisocytosis <ul><li>Abnormal variation in size of erythrocytes </li></ul>
  102. 107. Antihemophilic plasma <ul><li>Normal blood plasma that has been processed to preserve an antihemophilic factor. </li></ul>Used to temporarily relieve dysfunction of the hemostatic mechanism in hemophilia
  103. 108. Citrated Whole Blood <ul><li>Normal blood to which a solution of acid citrate has been added to prevent coagulation </li></ul>
  104. 109. Dried plasma <ul><li>Normal blood plasma that has been vacuum-dried to prevent growth of microorganisms </li></ul>Dried plasma was developed and first used during WWII . Prior to the United States involvement in the war, liquid plasma and whole blood were used. The &quot;Blood for Britain&quot; program during the early 1940s was quite successful (and popular stateside). Nonetheless the decision was made to develop a dried plasma package for the armed forces because it reduced breakage and made transport, packaging, and storage much simpler. [2] The resulting Army-Navy dried plasma package came in two tin cans containing 400 cc bottles. One bottle contained enough distilled water to completely reconstitute the dried plasma contained in the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. [3] By the end of the war the American Red Cross had provided enough blood for over six million plasma packages. Most of the surplus plasma was returned stateside for civilian use. Serum albumin replaced dried plasma for combat use during the Korean War
  105. 110. Hemorrhagic telangiectasia <ul><li>Inherited tendency to bleed from localized lesions of capillaries. </li></ul>Patients lose capillary network connects between veins and arteries. Most affected areas are lips, tongue, nasal mucosa, finger tips, lungs, brain, liver, and gastrointestinal tract. Treatments include, iron supplements, laser cautery, antifibrinolytic agents, transfusions
  106. 111. Heparinized whole blood <ul><li>Normal blood to which a solution of heparin has been added to prevent coagulation </li></ul>
  107. 112. Macrocytosis <ul><li>Abnormally large erythrocytes </li></ul>Larger than 9 micrometers in diameter. Found in folate and B 12 deficiencies and liver disease.
  108. 113. Microcytosis <ul><li>Abnormally small erythrocytes </li></ul>Smaller than 7 micrometers in diameter. Lymphocyte (blue, 8 micrometers) used as a guide. Found in anemia, thalassaemia, and lead poisoning.
  109. 114. Neutrophilia <ul><li>Increase in the number of circulating neutrophils </li></ul>Shift or transient neutrophilia is generally a very short-lived condition, often lasting less than sixty minutes. This increase in actively circulating neutrophils is usually associated with vigorous exercise, but can also develop following an injection of epinephrine, a seizure, or an intense emotive response, such as fear or rage. All of the neutrophils in circulation are fully mature since they simply have been transferred from the marginal pool, which in a normal adult is comprised of cells that have already fully developed in the bone marrow. When true neutrophilia occurs, however, some of the neutrophils observed in the blood may be immature forms that were released by the bone marrow before their development was complete due to an insufficient number of mature cells to meet the demands of the body. Typically this excessive demand is related to a bacterial infection, which results in the release of chemoattractants that bind to certain neutrophil receptors and initiate their activity so that they can aid in the body’s immune response.
  110. 115. Packed red cells <ul><li>Concentrated suspension of red blood cells from which the plasma has been removed. </li></ul>Leukocyte depleting filters. Packed red blood cells, the most commonly transfused blood component, can restore the blood's oxygen-carrying capacity. This component may be given to a person who is bleeding or who has severe anemia. The red blood cells are separated from the fluid component of the blood (plasma) and from the other cellular and cell-like components. After this step, the red blood cells are concentrated so that they occupy less space, thus the term &quot;packed.&quot; Red blood cells can be refrigerated for up to 42 days. In special circumstances—for instance, to preserve a rare type of blood—red blood cells can be frozen for up to 10 years. Transfusing only selected blood components allows the treatment to be specific, reduces the risks of side effects, and can efficiently use the different components from a single unit of blood to treat several people.
  111. 116. Pancytopenia <ul><li>Abnormal depression of all the cellular components of blood </li></ul>This peripheral blood picture is from an anemic patient with a low white cell count, and a low platelet count. A reduction in all the formed elements of the blood is called a 'pancytopenia'. It often indicates bone marrow failure (leukemia), but can also occur from peripheral destruction of cells, as in hypersplenism (overactive spleen). Also occurs in people with AIDS.
  112. 117. Poikilocytosis <ul><li>Irregularly shaped erythrocytes </li></ul>Lowers blood’s oxygen carrying capacity causing anemia. In all cases, the treatment of poikilocytosis depends on its cause. For example, poikilocytosis can be caused by a vitamin deficiency, in which case the treatment is to take Vitamin B12 or folic acid. It can be caused by a digestive disease, such as celiac disease , in which case the solution may lay in treating the underlying celiac disease so that nutrients can be properly absorbed.
  113. 118. Purpura <ul><li>Spontaneous bleeding into the tissues through the mucous membranes </li></ul>Common in typhus and meningitis and in old age when blood vessels damage more easily. Also a symptom of a variety of other disorders.
  114. 119. Septicemia <ul><li>Presence of disease-causing microorganisms or their toxins in the blood. </li></ul>Septicemia is a serious, life-threatening infection that gets worse very quickly. It can arise from infections throughout the body, including infections in the lungs, abdomen, and urinary tract. It may come before or at the same time as infections of the bone ( osteomyelitis ), central nervous system ( meningitis ), or other tissues. Septicemia can rapidly lead to septic shock and death. Septicemia associated with some organisms (germs) such as meningococci can lead to shock , adrenal collapse, and disseminated intravascular coagulopathy , a condition called Waterhouse- Friderichsen syndrome . Septicemia can begin with spiking fevers and chills, rapid breathing and heart rate, the outward appearance of being seriously ill (toxic) and a feeling of impending doom. These symptoms rapidly progress to shock with decreased body temperature (hypothermia), falling blood pressure, confusion or other changes in mental status, and blood-clotting abnormalities evidenced by a specific type of red spots on the skin (petechiae and ecchymosis). The Pope died from septic shock April 2005
  115. 120. Spherocytosis <ul><li>Hemolytic anemia caused by defective proteins supporting cell membranes of red blood cells. </li></ul><ul><li>The cells are abnormally spherical. </li></ul>Though the spherocytes have a smaller surface area through which oxygen and carbon dioxide can be exchanged, they in themselves perform adequately to maintain healthy oxygen supplies. The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cycle whereby the body destroys its own blood supply (auto- hemolysis ).
  116. 121. Thalassemia <ul><li>Group of hereditary hemolytic anemias resulting from very thin, fragile erythrocytes. </li></ul>The genetic defect results in synthesis of an abnormal hemoglobin molecule. The blood cells are vulnerable to mechanical injury and die easily. To survive, many people with thalassemia need blood transfusions at regular intervals.
  117. 122. <ul><li>See Clinical connection on Thrombotic thrombocytopenic purpura (TTP) p324. </li></ul>