Blood

1. Chapter 19 Blood

2. Components Formed elements Living blood cells Plasma Non-living fluid matrix

3. Physical characteristics& volume pH = 7.35-7.45 with high viscosity T = 100.4 (slightly higher than body T) Approx. 7% of total body weight 5-6-L volume in adult male (1.5 Gal) 4-5 L in adult female

4. Functions Distribution Oxygen/nutrients, waste, hormones Regulation T, pH (protein buffers), fluid volume (electrolytes) Protection Clotting (prevent blood loss), preventing infection (WBCs, antibodies)

5. Blood Plasma Blood plasma contains 90% water & over 100 solutes, including: Proteins – albumin, globulins, clotting proteins, and others..plasma proteins ~8% plasma volume Albumin is 60% of plasma protein Transport, buffer, osmotic pressure Nonprotein nitrogenous substances – lactic acid, urea, creatinine Organic nutrients – glucose, carbohydrates, amino acids Electrolytes – sodium, potassium, calcium, chloride, bicarbonate Respiratory gases – oxygen and carbon dioxide

6. Fluid compartments

7. Plasma

8. Formed elements Erythrocytes – anucleate Leukocytes – only complete cells Platelets – cell fragments

9. Hematocrit-packed cell volume (PCV) Percentage of RBC’s in a sample of blood Males – 47% +/-5 Females – 42% +/-5 Fractionation= the process of separating whole blood for clinical anaylsis

10. Erythrocytes Biconcave discs (doughnuts) High surface-to-volume ratio Predominately hemoglobin (transport of gases) Lack nuclei (anucleate), mitochondria and ribosomes 2.5 trillion in average adult 4-6 million/mm3 Too little = anemia Too much = polycythemia

11. RBC function Dedicated solely to respiratory gas transport Hemoglobin binds easily and reversibly w/ O2 Expressed as grams/100ml of whole blood (normal is 12-18g/dl) HEME is a red pigment/GLOBIN is a protein Each hemoglobin can bind to 4 molecules of O2 A single RBC contains ~250 million hemoglobin molecules…each RBC carries ~1 billion molecules of O2 ~20% CO2 transported in the blood combines w/hemoglobin 10% dissolves in plasma/70% converts to bicarbonate ions and is transported in plasma

12. Structure of Hemoglobin Oxyhemoglobin – Hb bound to oxygen Oxygen loading takes place in the lungs Deoxyhemoglobin – Hb after oxygen diffuses into tissues (reduced Hb) Carbaminohemoglobin – Hb bound to carbon dioxide Carbon dioxide loading takes place in the tissues

13. Hemopoiesis Occurs in red bone marrow (myeloid tissue) Adults- axial skeleton (ilium/sternum), proximal humerus/femur Marrow turns out ~1 ounce of blood every day (100 billion cells…> 2-3 million/second) All formed elements arise from the same cell (hemocytoblast) before differentiating Myeloid stem cells?become RBC’s & some WBC’s Lymphoid stem cells?become lymphocytes

14. Production/maturation of Erythrocytes: Erythropoiesis

15. Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction Too few red blood cells leads to tissue hypoxia Too many red blood cells causes undesirable blood viscosity Immature RBC’s are called reticulocytes Reticulocyte counts are used to assess RBC rates of production Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins (especially B12, B6, and folic acid) Regulation and Requirements for Erythropoiesis

16. Hormonal control Erythropoietin (EPO) is the primary stimulus for RBC production Liver produces minimal amount Some circulates in blood at all times Primary production in kidneys Hypoxic kidney cells release EPO

17. Key point to remember… Erythropoiesis is not controlled by the amount of erythrocytes but by their oxygen carrying ability! Decrease # of RBC’s Reduced availabilty of O2 (altitude/disease) Increase tissue demand for O2 (exercise)

18. Life Cycle of Red Blood Cells

19. RBC fate & destruction Life span of 100-120 days Anucleate…cannot grow, divide, or synthesize proteins Lose flexibility and become trapped in small circulatory channels…often the spleen (~1% RBC’s wear out/day) Heme splits from globin?forms biliverdin (Fe stored for re-use) Biliverdin (green pigment) degrades to bilirubin (yellow ) Bilirubin binds to albumin for transport to liver Liver cells pick up and secrete it (in bile) into intestines?feces Globin broken down into AA’s & released into circulation

20. RBC disorders Anemias Low # Hemorrhagic/hemolytic/aplastic Low hemoglobin content Iron deficiency/pernicious (B12) Abnormal hemoglobin Thalassemia (mediterranean descent) sickle cell (black population…1/400 U.S. newborns) Polycythemia (primary/secondary) Blood doping

21. RBC Tests

22. RBC membranes have glycoprotein antigens on their external surfaces These antigens are: Unique to the individual Recognized as foreign if transfused into another individual Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups Human Blood Groups

23. The ABO blood groups consists of: Two antigens (A and B) on the surface of the RBCs Two antibodies in the plasma (anti-A and anti-B) An individual with ABO blood may have various types of antigens and spontaneously preformed antibodies Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions ABO Blood Groups

24. ABO Blood Groups

25. Presence of the Rh agglutinogens on RBCs is indicated as Rh+ Also called D antigen Anti-Rh antibodies are not spontaneously formed in Rh– individuals However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form A second exposure to Rh+ blood will result in a typical transfusion reaction Rh Blood Groups

26. Hemolytic disease of the newborn – Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby Rh– mother becomes sensitized when Rh+ blood (from a previous pregnancy of an Rh+ baby or a Rh+ transfusion) causes her body to synthesis Rh+ antibodies The drug RhoGAM can prevent the Rh– mother from becoming sensitized Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth Hemolytic Disease of the Newborn

27. Transfusion Reactions Transfusion reactions occur when mismatched blood is infused Donor’s cells are attacked by the recipient’s plasma agglutinins causing: Diminished oxygen-carrying capacity Clumped cells that impede blood flow Ruptured RBCs that release free hemoglobin into the bloodstream Circulating hemoglobin precipitates in the kidneys and causes renal failure

28. Blood Typing When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens Positive reactions indicate agglutination

29. Blood Typing Test Determines blood type and compatibility

30. Leukocytes 6,000-9,000/mm3 blood <1% of total blood volume Not confined to blood stream Diapedesis = slip out of capillaries & move by amoeboid motion thru tissue spaces (loose CT/ lymphoid tissue) following chemical trail left by damaged cells or other WBC’s called positive chemotaxis Leukocytosis…good or bad? >11,000

31. Never Let Monkeys Eat Bananas Leukocytes from greatest [ ] to least Neutrophils Lymphocytes Monocytes Eosinophils Basophils

32. Leukocytes, cont. Granulocytes Staining granules present Roughly spherical Lobed nuclei Are all phagocytic cells Neutrophils Eosinophils Basophils Agranulocytes No noticeable staining granules Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei Lymphocytes Monocytes

33. Neutrophils Lobulated nucleus Polymorphonuclear cells (PMNs) Most numerous WBC (50-70% of WBC population) Granules have lysosomal enzymes & bactericides Chemically attracted to sites of inflammation & are active phagocytes Release prostaglandins/leukotrienes Bacteria slayers…increased w/bacterial infections

34. Eosinophils 2-4% of all WBCs Function against parasitic worms too large to be phagocytized by other immune cells Lessen the severity of allergies with enzymes that counteract inflammatory effects of neutrophils and mast cells

35. Basophils 0.5% total WBCs Are functionally similar to mast cells Cells produce histamine (vasodilator) Bind to IgE w/allergic reactions Initiate inflammation Cells also contain heparin (anticoagulant)

36. Lymphocytes 2nd in WBC population 20-30% of WBC’s Some in blood/most in “lymph” T Lymphocytes – vs virus/tumor cells B Lymphocytes – produce antibodies to be released to blood Give rise to plasma cells NK (natural killer) Cells – immune surveillance

37. Monocytes 2-8% of WBCs Largest in size of all WBCs Differentiate into macrophages Increase w/ chronic infections, viruses, and some bacterial parasites Activate lymphocytes to mount immune response Secrete substances that attract immune system cells and fibroblasts to injured area

38. Leukopoiesis Hormonally regulated by cytokines – 2 types Interleukins & colony stimulating factors (CSFs) Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes) Macrophages & T lymphocytes are most important source (agranulocytes) Released in response to specific chemical signals Granulocyte:erythrocyte production = 3:1 Granulocytes live 0.5-9days

39. WBC disorders Leukopenias vs leukemias Leukemia or leukocytosis? Good or bad? Normal or abnormal?

40. Leukemia refers to cancerous conditions involving white blood cells Leukemias are named according to the abnormal white blood cells involved Myelocytic leukemia – involves myeloblasts Lymphocytic leukemia – involves lymphocytes Acute leukemia involves blast-type cells and primarily affects children Chronic leukemia is more prevalent in older people Leukocytes Disorders: Leukemias

41. Immature white blood cells are found in the bloodstream in all leukemias Bone marrow becomes totally occupied with cancerous leukocytes The white blood cells produced, though numerous, are not functional Death is caused by internal hemorrhage and overwhelming infections Treatments include irradiation, antileukemic drugs, and bone marrow transplants Leukemia

42. Platelets Cell fragments from large cells called megakaryocytes 1 megakarycyte ~ 4000 platelets Essential for clotting process Sometimes incorrectly called thrombocytes Degenerate in ~9-12 days Formation regulated by hormone called thrombopoietin (made in liver) 150,000-500,000/mm3 blood

43. Summary of Formed Elements

44. Hemostasis = “blood stoppage” Blood will flow unimpeded thru intact endothelium of blood vessel walls If a wall is damaged…fast, localized, controlled response to plug hole 3 phases of hemostasis: 1. Vascular spasm 2. Platelet plug formation 3. Coagulation

45. 1. Vascular spasm 3 stimuli to cause vasospasm 1-direct injury to vascular smooth muscle 2-chemicals released by endothelial cells & platelets 3-reflexes initiated by local pain receptors Spasm becomes more efficient with an increase in tissue damage.

46. 2. Platelet plug formation Platelets do not stick to themselves or to the smooth endothelial lining of BVs Platelets swell & form spikes once exposed to damaged endothelium and underlying exposed collagen Platelets become sticky and adhere to the collagen Then they release several chemicals like serotonin (to enhance vascular spasm), ADP (to attract more platelets), and some others. The platelet plug is limited to the immediate area of injury by prostacyclin (released by endothelial cells)

47. Platelet plug phase Begins within 15 seconds after injury

48. 3. Coagulation Transforms blood from a liquid to a gel Begins 30 seconds or more after the injury

49. Involves 3 steps: 3. Coagulation

50. Detailed Events of Coagulation

51. Step 1. 2 pathways to prothrombinase: (extrinsic/intrinsic) Intrinsic can happen outside the body (test tube) Only uses components found within blood itself Extrinsic happens within body tissues Uses TF (tissue factor) found outside the blood Ionic Ca activates a series of procoagulants that act as an enzyme to stimulate the next procoagulant in the series until production of the intermediate factor X Factor X combines w/ Ca to form prothrombinase Clot forms within 30 seconds

52. Step 2. Common pathway to thrombin Prothrombinase causes transformation of the plasma protein prothrombin to the active enzyme thrombin

53. Step 3. Common pathway to fibrin mesh Thrombin catalyzes polymerization of fibrinogen (plasma protein made in liver) Fibrinogen molecules line up into hairlike, insoluble fibrin Plasma becomes gel-like and traps formed elements as they try to pass through W/ Ca, thrombin activates factor XIII (fibrin stabilizing factor) to bind fibrin tight and strengthen the clot W/ rapid, extrinsic pathway…clot formation can occur w/in 30 seconds

54. Clot retraction & repair Clot retraction occurs w/in 30-60 minutes Platelets contain actin & myosin and contract in much the same way as mm cells Platelets pull on surrounding fibrin strand & squeezes serum out of the mass Serum = plasma minus clotting proteins As clot is compacted fibroblasts (stimulated by platelet-derived growth factor -PDGF) rebuild the wall while endothelial cells (stimulated by vascular endothelial growth factor -VEGF) multiply to restore the lining

55. Fibrinolysis Plasmin (fibrin-digesting enzyme) is made from activating plasminogen (blood protein) Presence of the clot causes endothelial cells to release tissue plasminogen activator Fibrinolysis begins w/in 2 days and continues slowly over several days until the clot is dissolved

56. Factors limiting clot growth 1. Swift removal of clotting factors 2. Inhibition of activated clotting factors Fibrin acts as an anticoagulant by binding thrombin and preventing its: Positive feedback effects of coagulation Ability to speed up the production of prothrombin activator Acceleration of the intrinsic pathway by activating platelets Heparin – a natural anticoagulant found in the granules of basophils and mast cells and is produced by endothelial cells thereby inhibiting thrombin Secreted in small amounts into plasma

57. Substances used to prevent undesirable clots include: Aspirin – an antiprostaglandin that inhibits thromboxane A2 Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care Warfarin – used for those prone to atrial fibrillation Prevention of Undesirable Clots

58. Thrombus – a clot that develops and persists in an unbroken blood vessel Thrombi can block circulation, resulting in tissue death Coronary thrombosis – thrombus in blood vessel of the heart Embolus – a thrombus freely floating in the blood stream Pulmonary emboli can impair the ability of the body to obtain oxygen Cerebral emboli can cause strokes Hemostasis Disorders:Thromboembolytic Conditions

59. Thrombocytopenia – condition where the number of circulating platelets is deficient Patients show petechiae (small purple blotches on the skin) due to spontaneous, widespread hemorrhage Caused by suppression or destruction of bone marrow (e.g., malignancy, radiation) Platelet counts less than 50,000/mm3 is diagnostic for this condition Treated with whole blood transfusions Hemostasis/Bleeding Disorders

60. Inability to synthesize procoagulants by the liver results in severe bleeding disorders Causes can range from vitamin K deficiency to hepatitis and cirrhosis Inability to absorb fat can lead to vitamin K deficiencies as it is a fat-soluble substance and is absorbed along with fat Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption Hemostasis/Bleeding Disorders

61. Hemophilias – hereditary bleeding disorders caused by lack of clotting factors Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII Hemophilia B – results from a deficiency of factor IX Hemophilia C – mild type, caused by a deficiency of factor XI Symptoms include prolonged bleeding and painful and disabled joints Treatment is with blood transfusions and the injection of missing factors Hemostasis/Bleeding Disorders

62. Laboratory examination of blood can assess an individual’s state of health Microscopic examination: Variations in size and shape of RBCs – predictions of anemias Type and number of WBCs – diagnostic of various diseases CBC & Differential Count Chemical analysis can provide a comprehensive picture of one’s general health status in relation to normal values Diagnostic Blood Tests

63. Before birth, blood cell formation takes place in the fetal yolk sac, liver, and spleen By the seventh month, red bone marrow is the primary hematopoietic area The fetus forms HbF, which has a higher affinity for oxygen than adult hemoglobin Age-related blood problems result from disorders of the heart, blood vessels, and the immune system Increased leukemias are thought to be due to the waning deficiency of the immune system Abnormal thrombus and embolus formation reflects the progress of atherosclerosis Developmental Aspects