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Blood Composition and Volume  Blood tissue components ➢ ➢  Liquid fraction of whole blood (extracellular part) called plasma Cellular components suspended in the plasma make up the formed elements Normal volumes of blood ➢ ➢ ➢ Plasma: 2.6 L Formed elements: 2.4 L Whole blood: 4 to 6 L averag...

Blood Composition and Volume  Blood tissue components ➢ ➢  Liquid fraction of whole blood (extracellular part) called plasma Cellular components suspended in the plasma make up the formed elements Normal volumes of blood ➢ ➢ ➢ Plasma: 2.6 L Formed elements: 2.4 L Whole blood: 4 to 6 L average or 7% to 9% of total body weight Copyright © 2017, Elsevier Inc. All Rights Reserved. 4 Components of Blood Courtesy Barbara Cousins. Copyright © 2017, Elsevier Inc. All Rights Reserved. 5 Blood pH and Donation  Blood pH ➢ ➢  Blood is alkaline: pH 7.35 to pH 7.45 Blood pH decreased toward neutral creates a condition called acidosis Blood donations ➢ ➢ ➢ Approximately 14 million units donated annually Plasma volume expanders (such as albumin) can only maintain blood volume after hemorrhage for short periods Storage of donated blood limited to 6 weeks Copyright © 2017, Elsevier Inc. All Rights Reserved. 6 Blood Plasma   Liquid fraction of whole blood minus formed elements Composition ➢ Water containing many dissolved substances, including: • • • Nutrients, salts About 3% of total O2 transported in blood About 5% of total CO2 Copyright © 2017, Elsevier Inc. All Rights Reserved. 7 Composition of Blood Plasma  Composition ➢ Most abundant solutes dissolved in plasma are plasma proteins • • • •  Albumins Globulins Fibrinogen Prothrombin Plasma minus clotting factors called serum ➢ ➢ Serum is liquid remaining after whole blood clots Serum contains antibodies Copyright © 2017, Elsevier Inc. All Rights Reserved. 8 Formed Elements of Blood  Types ➢ ➢ RBCs (erythrocytes) WBCs (leukocytes) • Granular leukocytes  • Agranular leukocytes  • Neutrophils, eosinophils, and basophils Lymphocytes and monocytes Platelets; also called thrombocytes Copyright © 2017, Elsevier Inc. All Rights Reserved. 9 Formed Elements of Blood (Cont.)  Numbers ➢ ➢ ➢  RBCs: 4.2 to 6.2 million/mm3 of blood WBCs: 5000 to 10,000/mm3 of blood Platelets: 150,000 to 400,000/mm3 of blood Formation ➢ ➢ Red bone marrow (myeloid tissue) forms all blood cells except some lymphocytes and monocytes Most other cells formed by lymphoid tissue in the lymph nodes, thymus, and spleen Copyright © 2017, Elsevier Inc. All Rights Reserved. 10 Classes of Blood Cells Copyright © 2017, Elsevier Inc. All Rights Reserved. 11 Mechanisms of Blood Disease   Most blood diseases result from failure of myeloid and lymphoid tissues Causes include toxic chemicals, radiation, inherited defects, nutritional deficiencies, and cancers, including leukemia Copyright © 2017, Elsevier Inc. All Rights Reserved. 12 Aspiration Biopsy Cytology (ABC)   Aspiration biopsy cytology (ABC) permits examination of blood-forming tissues to assist in diagnosis of blood diseases, if bone marrow failure is suspected Bone marrow, cord blood, and hematopoietic stem cell transplants may be used to replace diseased or destroyed blood-forming tissues Copyright © 2017, Elsevier Inc. All Rights Reserved. 13 Red Blood Cells (Erythrocytes or RBCs)  Excellent example of how structural adaptation affects biologic function ➢ ➢ ➢ Tough and flexible plasma membrane deforms easily, allowing RBCs to pass through smalldiameter capillaries Biconcave disk (thin center and thicker edges) results in large cellular surface area Absence of nucleus and cytoplasmic organelles limits life span to about 120 days but provides more cellular space for red pigment called hemoglobin (Hb) Copyright © 2017, Elsevier Inc. All Rights Reserved. 14 RBCs Copyright © 2017, Elsevier Inc. All Rights Reserved. 15 General Functions of RBCs  Transport of respiratory gases (O 2 and CO2) ➢ ➢ ➢ ➢  Combined with hemoglobin Oxyhemoglobin (Hb + O2) Carbaminohemoglobin (Hb + CO2) CO2 converted to bicarbonate by the RBCs Important role in homeostasis of acid-base balance Copyright © 2017, Elsevier Inc. All Rights Reserved. 16 RBC Count  Complete blood cell count (CBC) ➢  Battery of laboratory tests used to measure the amounts or levels of many blood constituents Hematocrit (also called packed cell volume, or PCV) is the percentage of whole blood that is RBCs Copyright © 2017, Elsevier Inc. All Rights Reserved. 17 Hematocrit Test From Bevelander G, Ramalay JA: Essentials of histology, ed 8, St Louis, 1979, Mosby. Copyright © 2017, Elsevier Inc. All Rights Reserved. 18 The Hemoglobin (Hb) Molecule Copyright © 2017, Elsevier Inc. All Rights Reserved. 19 RBC Abnormalities  Named according to size ➢ ➢ ➢  Normocytes: Normal size (about 8 to 9 μm in diameter) Microcytic: Small size Macrocytic: Large size Named according to hemoglobin content of cell ➢ ➢ ➢ Normochromic: Normal Hb content Hypochromic: Low Hb content Hyperchromic: High Hb content Copyright © 2017, Elsevier Inc. All Rights Reserved. 20 RBC Abnormalities From Carr J, Rodak B: Clinical hematology atlas, ed 2, St Louis, 2004, Elsevier. Copyright © 2017, Elsevier Inc. All Rights Reserved. 21 Blood Types  ABO system ➢ ➢ ➢ ➢ Type A blood: Type A antigens in RBCs; anti-B type antibodies in plasma Type B blood: Type B antigens in RBCs; anti-A type antibodies in plasma Type AB blood: Type A and type B antigens in RBCs; no anti-A or anti-B antibodies in plasma; called universal recipient blood Type O blood: No type A or type B antigens in RBCs; both anti-A and anti-B antibodies in plasma; called universal donor blood Copyright © 2017, Elsevier Inc. All Rights Reserved. 22 Blood Typing Photos from Belcher AE: Blood disorders, St Louis, 1993, Mosby. Copyright © 2017, Elsevier Inc. All Rights Reserved. 23 Rh System  Rh-positive blood ➢  Rh-negative blood ➢  Rh factor antigen present in RBCs No Rh factor present in RBCs; no anti-Rh antibodies present naturally in plasma; anti-Rh antibodies, however, appear in the plasma of Rh-negative persons if Rh-positive RBCs have been introduced into their bodies Erythroblastosis fetalis ➢ May occur when Rh-negative mother carries a second Rh-positive fetus; caused by mother’s Rh antibodies reacting with baby’s Rh-positive cells Copyright © 2017, Elsevier Inc. All Rights Reserved. 24 Erythroblastosis Fetalis Copyright © 2017, Elsevier Inc. All Rights Reserved. 25 Blood Typing (Cont.) Adapted from Pagana KD, Pagana TJ: Mosby’s manual of diagnostic and laboratory tests, ed 5, St Louis, 2014, Mosby. Copyright © 2017, Elsevier Inc. All Rights Reserved. 26 Red Blood Cell Disorders   Most often related to either overproduction of RBCs, called polycythemia; or to low oxygencarrying capacity of blood, called anemia Polycythemia ➢ ➢ Cause is generally cancerous transformation of red bone marrow Dramatic increase in RBC numbers: Often in excess of 10 million/mm3 of blood; hematocrit may reach 60% Copyright © 2017, Elsevier Inc. All Rights Reserved. 27 Polycythemia  Signs and symptoms include: ➢ ➢ ➢ ➢ Increased blood viscosity or thickness Slow blood flow and coagulation problems Frequent hemorrhages Distention of blood vessels and hypertension Copyright © 2017, Elsevier Inc. All Rights Reserved. 28 Treatment of Polycythemia   Blood removal Irradiation and chemotherapy to suppress RBC production Copyright © 2017, Elsevier Inc. All Rights Reserved. 29 Anemia  Caused by low numbers or abnormal RBCs or by low levels or defective types of hemoglobin ➢ ➢ Normal Hb levels 12 to 14 g/100 mL of blood Low Hb level (below 9 g/100 mL of blood) classified as anemia Copyright © 2017, Elsevier Inc. All Rights Reserved. 30 Clinical Signs of Anemia  Majority of clinical signs of anemia related to low tissue oxygen levels ➢ ➢ ➢ Fatigue; skin pallor Weakness; faintness; headache Compensation results in increased heart and respiratory rates Copyright © 2017, Elsevier Inc. All Rights Reserved. 31 Types of Anemia  Hemorrhagic anemia ➢ ➢  Acute: Blood loss is immediate (e.g., surgery or trauma) Chronic: Blood loss occurs over time (e.g., ulcers or cancer) Aplastic anemia ➢ ➢ Characterized by low RBC numbers and destruction of bone marrow Often caused by toxic chemicals, irradiation, or certain drugs Copyright © 2017, Elsevier Inc. All Rights Reserved. 32 Deficiency Anemias  Caused by inadequate supply of some substance needed for RBC or hemoglobin production ➢ Pernicious anemia • • • • • • Caused by vitamin B12 deficiency Genetic-related autoimmune disease Decreased RBC, WBC, and platelet numbers RBCs are macrocytic Classic symptoms of anemia coupled with CNS impairment Treatment is repeated vitamin B12 injections Copyright © 2017, Elsevier Inc. All Rights Reserved. 33 Folate Deficiency Anemia    Caused by folate (vitamin B 9) deficiency Decreased RBC count Common in alcoholism and malnutrition Copyright © 2017, Elsevier Inc. All Rights Reserved. 34 Iron Deficiency Anemia     Caused by deficiency of or inability to absorb iron needed for Hb synthesis (dietary iron deficiency is common worldwide) RBCs are microcytic and hypochromic Hematocrit is decreased Treatment is oral administration of iron compounds Copyright © 2017, Elsevier Inc. All Rights Reserved. 35 Hemolytic Anemias   Caused by decreased RBC life span or increased RBC rate of destruction Symptoms, such as jaundice, swelling of spleen, gallstone formation, and tissue iron deposits, are related to retention of RBC breakdown products Copyright © 2017, Elsevier Inc. All Rights Reserved. 36 Sickle Cell Anemia       Genetic disease resulting in formation of abnormal hemoglobin (HbS); primarily found in African-Americans RBCs become fragile and assume sickled shape when blood oxygen levels decrease Mild sickle cell trait—result of one defective gene More severe sickle cell disease—result of two defective genes; causes blood stasis, clotting, and episodes called crises that may be fatal Affects 1 in every 600 African-American babies A hemolytic anemia Copyright © 2017, Elsevier Inc. All Rights Reserved. 37 Sickle Cell Dennis Strete Copyright © 2017, Elsevier Inc. All Rights Reserved. 38 Thalassemia     Group of inherited hemolytic anemias occurring primarily in people of Mediterranean descent RBCs microcytic and short lived Present as mild thalassemia trait and severe thalassemia major Hb levels often fall below 7 g/100 mL of blood in thalassemia major Copyright © 2017, Elsevier Inc. All Rights Reserved. 39 Symptoms and Treatment for Thalassemia   Classic symptoms of anemia coupled with skeletal deformities and swelling of spleen and liver Marrow and stem cell transplantation needed for long-term treatment success Copyright © 2017, Elsevier Inc. All Rights Reserved. 40 Hemolytic Disease of Newborn and Erythroblastosis Fetalis    Caused by blood ABO or Rh factor incompatibility during pregnancy between developing baby and mother Maternal antibodies against “foreign” fetal RBCs or Rh factor can cross placenta, enter the fetal circulation, and destroy the unborn baby’s red cells Symptoms in developing fetus related to decline in RBC numbers and Hb levels; jaundice, intravascular coagulation, and heart and lung damage are common Copyright © 2017, Elsevier Inc. All Rights Reserved. 41 Hemolytic Disease of Newborn and Erythroblastosis Fetalis (Cont.)  Treatment and prevention ➢ ➢ Treatment may include in utero blood transfusions and premature delivery of the baby Prevention of Rh factor incompatibility now possible by administration of RhoGAM to Rhnegative mothers Copyright © 2017, Elsevier Inc. All Rights Reserved. 42 Learning Objectives Lesson 13.2: WBCs and Blood Clotting 6. 7. 8. 9. Describe the structure and function of white blood cells. State the purpose of performing a WBC count, and identify WBC types. Identify and discuss common white blood cell disorders. Explain the steps involved in blood clotting and describe clotting disorders. Copyright © 2017, Elsevier Inc. All Rights Reserved. 43 Leukocytes or White Blood Cells (WBCs)    Categorized by presence of granules (granulocytes) or absence of granules (agranulocytes) WBC count: Normal range is 5000 to 10,000/mm3 of blood Leukopenia: Abnormally low WBC count (below 5000/mm3 of blood) ➢ ➢ Occurs infrequently May occur with malfunction of blood-forming tissues or diseases affecting immune system, such as AIDS Copyright © 2017, Elsevier Inc. All Rights Reserved. 44 WBC Count  Leukocytosis: Abnormally high WBC count (over 10,000/mm3 of blood) ➢ ➢  Frequent finding in bacterial infections Classic sign in blood cancers (leukemia) Differential WBC count: Component test in CBC; measures proportions of each type of WBC in blood sample Copyright © 2017, Elsevier Inc. All Rights Reserved. 45 Leukocyte Types and Functions  Granulocytes ➢ Neutrophils • • ➢ Eosinophils • • • ➢ Most numerous type of phagocyte Numbers increase in bacterial infections Weak phagocyte Active against parasites and parasitic worms Involved in allergic reactions Basophils • • • Related to mast cells in tissue spaces Both mast cells and basophils secrete histamine (related to inflammation) Basophils also secrete heparin (an anticoagulant) Copyright © 2017, Elsevier Inc. All Rights Reserved. 46 Phagocytosis Copyright © 2017, Elsevier Inc. All Rights Reserved. 47 Agranular Leukocytes  Agranulocytes: Monocytes in peripheral blood (macrophages in tissues); lymphocytes—B lymphocytes (plasma cells) and T lymphocytes ➢ Monocytes • • • Largest leukocytes Aggressive phagocytes: Capable of engulfing larger bacteria and cancer cells Develop into much larger cells called macrophages after leaving blood to enter tissue spaces Copyright © 2017, Elsevier Inc. All Rights Reserved. 48 Agranulocytes  Lymphocytes ➢ ➢ ➢ B lymphocytes involved in immunity against disease by secretion of antibodies Mature B lymphocytes called plasma cells T lymphocytes involved in direct attack on bacteria or cancer cells (not antibody production) Copyright © 2017, Elsevier Inc. All Rights Reserved. 49 White Blood Cell Disorders  Two major types of WBC cancers or neoplasms ➢ ➢ Lymphoid neoplasms result from B and T lymphocyte precursor cells or their descendent cell types Myeloid neoplasms result from malignant transformation of precursor cells of granulocytic WBCs, monocytes, RBCs, and platelets Copyright © 2017, Elsevier Inc. All Rights Reserved. 50 Multiple Myeloma    Cancer of B lymphocytes called plasma cells Most deadly blood cancer in people older than age 65 Causes bone marrow dysfunction and production of defective antibodies Copyright © 2017, Elsevier Inc. All Rights Reserved. 51 Multiple Myeloma (Cont.)  Characterized by: ➢ ➢  Recurrent infections and anemia Destruction and fracture of bones Treatment includes chemotherapy, drug and antibody therapy, and marrow and stem cell transplantation Copyright © 2017, Elsevier Inc. All Rights Reserved. 52 Multiple Myeloma (Cont.) From Kumar V: Robbins basic pathology, ed 9, Philadelphia, 2013, Saunders. Copyright © 2017, Elsevier Inc. All Rights Reserved. 53 Leukemia  Leukemias: WBC-related blood cancers ➢ ➢ Characterized by marked leukocytosis Identified as: • Acute  • Chronic  • Slow development of symptoms Lymphocytic  • Rapid development of symptoms Affects lymphocytes Myeloid  Affects granular leukocytes as they develop in the red bone marrow Copyright © 2017, Elsevier Inc. All Rights Reserved. 54 Common Types of Leukemia  Chronic lymphocytic leukemia (CLL) ➢ ➢ ➢ ➢ ➢ ➢ Average age of onset is 65; rare before age 30 More common in men than in women Often diagnosed unexpectedly in routine physical exams with discovery of marked B lymphocytic leukocytosis Generally mild symptoms include anemia, fatigue, and enlarged—often painless—lymph nodes Most patients live many years following diagnosis Treatment of severe cases involves chemotherapy and irradiation Copyright © 2017, Elsevier Inc. All Rights Reserved. 55 Chronic Lymphocytic Leukemia Courtesy Dr. JV Melo. Copyright © 2017, Elsevier Inc. All Rights Reserved. 56 Acute Lymphocytic Leukemia (ALL)      Primarily a disease of children 3 to 7 years of age; 80% of children who develop leukemia have this form of the disease Highly curable in children but less so in adults Onset is sudden; marked by fever, leukocytosis, bone pain, and increases in infections Lymph node, spleen, and liver enlargement is common Treatment includes chemotherapy, irradiation, and bone marrow or stem cell transplantation Copyright © 2017, Elsevier Inc. All Rights Reserved. 57 ALL (Cont.) Courtesy of Dr. Robert W McKenna, Department of Pathology, University of Texas Southw estern Medical School, Dallas, TX. In Kumar V et al: Robbins basic pathology, ed 9, Philadelphia, 2013, Saunders. Copyright © 2017, Elsevier Inc. All Rights Reserved. 58 Chronic Myeloid Leukemia (CML)     Accounts for about 20% of all cases of leukemia Occurs most often in adults 25 to 60 years of age Caused by cancerous transformation of granulocytic precursor cells in the bone marrow Onset and progression of disease are slow, with symptoms of fatigue, weight loss, and weakness Copyright © 2017, Elsevier Inc. All Rights Reserved. 59 CML (Cont.)   Diagnosis often made by discovery of marked granulocytic leukocytosis and extreme spleen enlargement Treatment by new “designer drug” Gleevec or bone marrow transplants is curative in over 70% of cases Copyright © 2017, Elsevier Inc. All Rights Reserved. 60 CML (Cont.) From Hoffbrand AV, Pettit JE: Clinical haematology illustrated, Edinburgh/London, 1987, Churchill Livingstone/Gow er Medical Publisher. Copyright © 2017, Elsevier Inc. All Rights Reserved. 61 Acute Myeloid Leukemia (AML)      Accounts for 80% of all cases of acute leukemia in adults and 20% of acute leukemia in children Sudden onset and rapid progression Symptoms include leukocytosis, fatigue, bone and joint pain, spongy bleeding gums, anemia, and recurrent infections Prognosis is poor, with only about 50% of children and 30% of adults achieving long-term survival Bone marrow and stem cell transplantation has increased cure rates in selected patients Copyright © 2017, Elsevier Inc. All Rights Reserved. 62 Infectious Mononucleosis     Noncancerous WBC disorder Highest incidence between 15 and 25 years of age Caused by virus present in saliva of infected individuals Leukocytosis of atypical lymphocytes with abundant cytoplasm and large nuclei Copyright © 2017, Elsevier Inc. All Rights Reserved. 63 Infectious Mononucleosis (Cont.)   Symptoms include fever, severe fatigue, sore throat, rash, and enlargement of lymph nodes and spleen Generally self-limited and resolves without complications in about 4 to 6 weeks Copyright © 2017, Elsevier Inc. All Rights Reserved. 64 Atypical Lymphocyte From Kumar V: Robbins basic pathology, ed 9, Philadelphia, 2013, Saunders. Copyright © 2017, Elsevier Inc. All Rights Reserved. 65 Platelets and Blood Clotting  Platelets play essential role in blood clotting ➢ ➢ ➢ Blood vessel damage causes platelets to become sticky and form a “platelet plug” Accumulated platelets release additional clotting factors that enter into the clotting mechanism Platelets ultimately become a part of the clot itself Copyright © 2017, Elsevier Inc. All Rights Reserved. 66 Clotting Mechanism     Damaged tissue cells release clotting factors leading to formation of prothrombin activator, which combines with platelet-produced prothrombin activator Prothrombin activator and calcium convert prothrombin to thrombin Thrombin reacts with fibrinogen to form fibrin Fibrin threads form a tangle to trap RBCs (and other formed elements) to produce a blood clot Copyright © 2017, Elsevier Inc. All Rights Reserved. 67 Blood Clotting B copyright Dennis Kunkel Microscopy, Inc. Copyright © 2017, Elsevier Inc. All Rights Reserved. 68 Altering the Blood-Clotting Mechanism    Application of gauze (rough surface) to wound causes platelet aggregation and release of clotting factors Administration of vitamin K increases synthesis of prothrombin Coumadin delays clotting by inhibiting prothrombin synthesis Copyright © 2017, Elsevier Inc. All Rights Reserved. 69 Altering the Blood-Clotting Mechanism (Cont.)   Heparin delays clotting by inhibiting conversion of prothrombin to thrombin Drug called tissue plasminogen activator (TPA or tPA) used to dissolve clots that have already formed Copyright © 2017, Elsevier Inc. All Rights Reserved. 70 Prothrombin Time Test     Used to regulate dosage of anticoagulant drugs Calcium and thromboplastin added to a tube of patient’s plasma and a tube of control solution Timed to see how long clotting takes and compared to see if drug dosage needs to be adjusted Highly variable results among labs have required the use of the INR (International Normalized Ratio) system, which uses a calculation to standardize measurements Copyright © 2017, Elsevier Inc. All Rights Reserved. 71 Clotting Disorders   Thrombus: Stationary blood clot Embolus: Circulating blood clot (TPA used to dissolve clots that have already formed) Copyright © 2017, Elsevier Inc. All Rights Reserved. 72 Pulmonary Embolism From Kumar V, Abbas AK, Fausto N: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Elsevier. Copyright © 2017, Elsevier Inc. All Rights Reserved. 73 Hemophilia  X-linked inherited disorder that results from inability to produce factor VIII (a plasma protein) responsible for blood clotting ➢ ➢ ➢ Most serious “bleeding disease” worldwide; hemophilia A most common form Characterized by easy bruising, deep muscle hemorrhage, blood in urine, and repeated episodes of bleeding into joints causing pain and deformity Treatment includes administration of factor VIII, injury prevention, and avoiding drugs such as aspirin that alter the clotting mechanism Copyright © 2017, Elsevier Inc. All Rights Reserved. 74 Thrombocytopenia      Caused by reduced platelet counts Characterized by bleeding from small blood vessels, most visibly as purpura (purplish spots) in the skin and mucous membranes Platelet count below 20,000/mm3 may cause catastrophic bleeding (normal platelet count 150,000 to 400,000/mm3) Most common cause is bone marrow destruction by drugs, chemicals, radiation, and diseases such as cancer, lupus, and HIV/AIDS Treatment may involve transfusion of platelets, corticosteroid-type drugs, or removal of the spleen Copyright © 2017, Elsevier Inc. All Rights Reserved. 75 Vitamin K Deficiency    Necessary to make several clotting factors Vitamin K mostly produced by bacteria in intestines, where it is absorbed into bloodstream Infants may lack bacteria to produce enough vitamin K for normal clotting Copyright © 2017, Elsevier Inc. All Rights Reserved. 76 Questions? Copyright © 2017, Elsevier Inc. All Rights Reserved. 77

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