Blood Cardiovascular System Blood Functions 1. Transports • Dissolved gasses • Nutrients • Waste products to lungs and kidneys • Enzymes • Hormones from endocrine organs 2. Regulates • pH • Electrolyte concentration of body fluids • Body temperature 3. Restricts fluid loss 4. Defends pathogens and toxins Blood Composition 1. Formed elements • Erythrocytes • Leukocytes • Platelets 2. Plasma Overview of Blood Circulation • Blood leaves the heart via arteries that branch repeatedly until they become capillaries • Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues • Carbon dioxide (CO2) and wastes move from tissues into the blood • Oxygen-deficient blood leaves the capillaries and flows in veins to the heart • This blood flows to the lungs where it releases CO2 and picks up O2 • The oxygen-rich blood returns to the heart Blood Physical Characteristics and Volume Sticky, opaque fluid with a metallic taste • Color varies from scarlet (oxygen-rich) to dark red (oxygen-poor) • pH of blood is 7.35–7.45 • Temperature is 38C, slightly higher than “normal” body temperature • Blood accounts for approximately 8% of body weight • Average volume of blood is 5–6 L for males, and 4–5 L for females Plasma • Plasma accounts for 55 % of the volume of whole blood. • 92% of plasma is water, the rest consists of electrolytes and dissolved organic compounds. Blood plasma contains over 100 solutes, including: • Proteins – albumin, globulins, clotting proteins, etc… • Non-protein nitrogenous substances – lactic acid, urea, creatinine • Organic nutrients – glucose, carbohydrates, amino acids • Electrolytes – sodium (Na+), potassium (K+), calcium (Ca++), chloride (Cl-), bicarbonate (HCO3-) • Respiratory gases – oxygen and carbon dioxide Plasma Proteins • Albumin 1. Contributes to the osmotic pressure of the blood 2. Provides a transport mechanism for specific insoluble or valuable materials in the blood. • Globular proteins 1. Binding and transporting hormones, lipids (lipoproteins), and metal ions. 2. The immunoglobulins (antibodies) are proteins that attack foreign proteins and pathogens. • Fibrinogen molecules aggregate to form large insoluble strands of fibrin that establish the basis for a blood clot. Erythrocytes • Biconcave discs • RBCs have no nuclei or organelles (anucleate) allow for a huge surface area to volume ratio • Hematocrit – % of RBCs out of the total blood volume. (Ave) 46 adult men & 42 adult women. • There are roughly 5 million RBCs in each microliter of blood • Erythrocytes are unable to perform normal maintenance operations and usually degenerate after about 120 days in the circulation. Hemoglobin • Hemoglobin (Hgb), a globular protein formed from four subunits. • Heme molecules bind to oxygen when plasma concentrations are high; the oxygen is released when plasma concentrations decline. • Carbon dioxide molecules can be bound to the globin portion of the hemoglobin molecule. Hemoglobin Composed of: • The protein globin, made up of two alpha and two beta chains, each bound to a heme group • Each heme group bears an atom of iron, which can bind one to oxygen molecule • Each hemoglobin molecule can transport four molecules of oxygen Oxyhemoglobin – hemoglobin bound to oxygen • Oxygen loading takes place in the lungs Deoxyhemoglobin- hemoglobin after oxygen diffuses into tissues (reduced Hgb) Carboxyhemoglobin – hemoglobin bound to carbon dioxide • Carbon dioxide loading takes place in the tissues • The fetus forms HbF, which has a higher affinity for oxygen than adult hemoglobin What happens to old RBC’S? • Damaged or expired red blood cells are recycled by phagocytes. • Proteins are disassembled into amino acids • Iron gets bound to transferrin for transport to the bone marrow and liver • Heme units are not recycled, but removed from the circulation by the liver Fate and Destruction of Erythrocytes • The life span of an erythrocyte is 100–120 days • Dying erythrocytes are engulfed by macrophages • Heme & globin are separated and the iron is salvaged for reuse Fate of Hemoglobin • Heme is degraded to a yellow pigment called bilirubin • The liver secretes bilirubin into the intestines as bile • The intestines metabolize it into urobilinogen • This degraded pigment leaves the body in feces, in a pigment called stercobilin or as urobilinogen in urine • Globin is metabolized into amino acids and is released into the circulation Iron transport Blood Types • Agglutinogens A, B, and D (Rh) on the exposed surfaces of the red blood cells determine an individual's blood type. • Anti-Rh agglutinins are only synthesized after an Rh-negative individual becomes sensitized to the Rh agglutinogen. (During pregnancy) • Testing for compatibility involves the determination of blood type and a cross-match test. • Standard blood typing detects the A, B, and D (Rh) agglutinogens. The most common blood type used for transfusion is O-negative (universal donor – NO ANTIGENS). AB-positive (Universal recipient – NO ANTIBODIES) Blood Rh Type Percent Type A B AB O + 34 % - 6 % + 9 % - 2 % + 3 % - 1 % + 38 % - 7 % Erythroblastosis Fetalis Hemolytic Disease of the Newborn (Erythroblastosis fetalis) • Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby • Rh– mother become 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 • Production of Blood Cells • Hematopoiesis – blood cell formation • Hematopoiesis occurs in the red bone marrow of the: - Axial skeleton and girdles - Epiphyses of the humerus and femur Hemocytoblasts give rise to all formed elements • Circulating stem cells give rise to embryonic blood cells which migrate into the liver, spleen, thymus, and bone marrow. Erythropoiesis • Occurs within red marrow of the sternum, vertebrae, skull, scapulae, pelvis, and proximal limb bones. • Red blood cell formation increases under erythropoietin stimulation. This hormone is released from the kidneys when they are not receiving adequate supplies of oxygen. • Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins • Reticulocytes (immature RBC’s) usually account for 0.8 percent of circulating red blood cells. Erythropoietin Erythropoietin (EPO) release by the kidneys is triggered by: • Hypoxia due to decreased RBCs • Decreased oxygen availability • Increased tissue demand for oxygen Erythropoiesis increases the: • RBC count in circulating blood • Oxygen carrying ability of the blood increases Erythropoiesis requirement • Proteins, lipids, and carbohydrates • Iron, vitamin B12, and folic acid The body stores iron in Hgb (65%), the liver, spleen, and bone marrow Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin Circulating iron is loosely bound to the transport protein transferrin Erythrocyte pathophysiology Anemia – blood has abnormally low oxygencarrying capacity • Blood oxygen levels cannot support normal metabolism • Signs/symptoms include fatigue, paleness, shortness of breath, increased heartrate, low blood pressure, and chills Anemia: Insufficient Erythrocytes • Hemorrhagic anemia – result of acute or chronic loss of blood (e.g.Trauma & Menstruation) • Hemolytic anemia – prematurely ruptured erythrocytes • Aplastic anemia – destruction or inhibition of red bone marrow • Sickle cell anemia Anemia: Decreased Hemoglobin Content Iron-deficiency anemia results from: • A secondary result of hemorrhagic anemia • Inadequate intake of iron-containing foods • Impaired iron absorption Pernicious anemia results from: • Deficiency of vitamin B12 • Often caused by lack of intrinsic factor needed for absorption of B12 Pernicious Anemia Anemia: Abnormal Hemoglobin Thalassemias – absent or faulty globin chain in hemoglobin • Erythrocytes are thin, delicate, & deficient in hemoglobin Sickle-cell anemia – results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS) Polycythemia • Excess RBCs that increase blood viscosity • Blood doping in athletics Leukocytes • White blood cells are components of the immune system that defends the body against pathogens, toxins, wastes, and abnormal or damaged cells and tissues. • There are 6,000-9,000 white blood cells in each microliter of whole blood Leukocytes • Normal response to bacterial or viral invasion • Move through tissue spaces • Granular leukocytes include neutrophils, eosinophils , and basophils. • Neutrophils are abundant, highly mobile phagocytes. • Eosinophils are attracted to foreign compounds coated with antibodies. • Basophils migrate into damaged tissues and release histamine, aiding in the inflammation response. • Monocytes migrating into peripheral tissues become free macrophages. • Lymphocytes, cells of the lymphatic system, include T cells and B cells. T cells migrate to peripheral tissues and attack foreign or abnormal cells; B cells produce antibodies. Leukopoiesis • Granulocytes and monocytes are produced by stem cells in the bone marrow • Lymphocytes are produced in bone marrow, thymus, & spleen Granulocytes Which WBC’s are granulocytes? Neutrophils (Polymorphonuclear) • 60-70% of WBC’s Neutrophils have two types of granules that: • Take up both acidic and basic dyes • Give the cytoplasm a lilac color • Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins) Neutrophils are our body’s bacterial slayers Lifespan : 1 day in blood; 1-2 days in tissue Eosinophils • 1-4% of WBC’s • Have red-staining, bi-lobed nuclei connected via a broad band of nuclear material • Lead the body’s counterattack against parasitic worms • Lessen the severity of allergies by phagocytizing immune complexes • Lifespan: 1 day in blood; weeks in tissue Basophils • 0.5-1% of WBC’s • Have large, purplish-black (basophilic) granules that contain histamine • Histamine – inflammatory chemical that acts as a vasodilator & attracts other WBCs • Lifespan: 1 day in blood; hours in tissue Agranulocytes Which WBC’s are agranulocytes? Lymphocytes • 20-25% of WBC’s • Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm • Found mostly enmeshed in lymphoid tissue (some circulate in the blood) • There are two types of lymphocytes: T cells and B cells • T cells function in the immune response • B cells give rise to plasma cells, which produce antibodies • Lifespan: Years Monocytes • 3-8% of WBC’s • They are the largest leukocytes • They have abundant pale-blue cytoplasms • They have purple staining, U- or kidney-shaped nuclei • They leave the circulation, enter tissue, and differentiate into macrophages • Lifespan: Days in blood; years in tissue Leukocyte pathophysiology • Leukemia refer to cancerous conditions involving white blood cells • 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 • Acute leukemia involves blast-type cells and primarily affects children • Chronic leukemia is more prevalent in older people Leukemia Common symptoms of leukemia: • Anemia • Fever • Weakness and fatigue • Frequent infections • Loss of appetite and/or weight • Swollen or tender lymph nodes, liver, or spleen • Easy bleeding or bruising • Tiny red spots (called petechiae) under the skin • Swollen or bleeding gums • Sweating, especially at night • Bone or joint pain. Thrombocytes • Platelets • Megakaryocytes in the bone marrow release packets of cytoplasm, called platelets, into the circulating blood. There are 150,000-500,000 platelets in each microliter of whole blood. • Platelet granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF) • Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels Blood clotting Cascade Blood clotting • The coagulation process requires calcium ions, and Vitamin K must be available for the synthesis of five of the clotting factors. Hemostasis Pathophysiology • Thromboembolytic Disorders Thrombus – a clot that develops and persist in an unbroken blood vessel Embolus – a thrombus freely floating in the blood stream Thrombocytopenia – condition where the number of circulating platelets is deficient Hemophilias – hereditary bleeding disorders caused by lack of clotting factors Hemophilia 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 Hemophilia after injection Prevention of undesirable clots Substances used to prevent undesirable clots include: • Aspirin • Heparin • Warfarin (Coumadin) • Flavonoids – substances found in tea, red wine, and grape juice that have natural anticoagulant activity Leukocyte Differential Practice Are we done yet?