1. Formed elements include red blood cells (erythrocytes), platelets, and white blood cells (leukocytes).

2. In the hematocrit, erythrocytes make up 45% of the total volume, leukocytes and platelets comprise the narrow buffy coat, and plasma makes up nearly 55% of the volume.

3. Table 18.2 (p. 642) gives the general properties of whole blood. Two especially notable properties are the viscosity of blood (4.5 to 5.5 times as viscous as water), and its osmolarity (which regulates the passage of materials into and out of the blood).

1. If the proteins are removed from the plasma, the serum is all that remains.

2. The three major types of plasma proteins play a variety of roles, including defense, clotting, and transport.

3. Albumins are the smallest and most abundant of the plasma proteins. They make major contributions to viscosity and osmolarity, and changes in their abundance can influence blood pressure, flow, and fluid balance.

4. There are alpha, beta, and gamma globulins.

5. Fibrinogen is the soluble precursor of fibrin, a protein involved in clotting.

6. The liver produces all plasma proteins with the exception of gamma globulin, which is produced by cells of the immune system.

1. Nonprotein nitrogenous substances in the blood are the amino acids from the digestive tract, and nitrogenous wastes, the toxic end products of catabolism.

1. Various nutrients coming from the digestive tract are transported by plasma.

1. Plasma transports a portion of the carbon dioxide and oxygen circulated by the blood, plus carries dissolved nitrogen.

1. The plasma electrolytes, and their concentrations, are listed in Table 18.3, p. 644. Of these, sodium exerts a major influence of the osmolarity of the blood.

1. Hemopoiesis begins in the embryonic yolk sac. Here, primitive stem cells are produced that colonize fetal bone marrow, spleen, thymus, and liver tissue and begin the production of blood cells.

2. Beyond infancy, almost all formed elements are produced by myeloid hemopoiesis in the red bone marrow, and lymphocytes are produced in lymphoid organs by lymphoid hemopoiesis.

3. All hemopoiesis begins with hemocytoblasts. They are pluripotent, and differentiation is determined by production of the various hormone receptors (now committed cells).

1. Erythropoiesis produces erythrocytes at the rate of 2.5 million cells per second. The proerythroblast (a committed cell) receives erythropoietin, which stimulates it to become an erythroblast.

2. Erythroblasts multiply and synthesize hemoglobin, their nuclei degenerate and the cells are now reticulocytes.

3. Once reticulocytes leave the bone marrow and the remaining ER disappears, they are considered to be mature erythrocytes.

4. Hypoxia in tissues or hypoxemia trigger secretion of more erythropoietin from the kidneys, and red blood cell production increases. In certain instances, like emphysema, polycythemia can result.

5. One of the nutritional requirements for erythropoiesis is iron, which can only be absorbed in its ferrous (Fe²⁺) state in the small intestine. Ferrous ions bind to gastroferritin, produced by the stomach, and travel to the small intestine. They are absorbed into the blood and bound to a plasma protein called transferrin.

6. Transferrin carries the iron to bone marrow, liver, and other tissues. Bone marrow uses the iron to make hemoglobin, muscle cells use it for myoglobin, and other cells use it to make cytochromes.

7. The liver stores excess iron in the form of ferritin.

8. Other nutrient requirements include folic acid and vitamin B₁₂ for DNA synthesis, and copper and vitamin C that serve as cofactors for some of the enzymes that synthesize hemoglobin.

1. Leukopoiesis is the production of white blood cells, which begins with hemocytoblasts. Once committed, these precursors are one of three kinds: B progenitors, T progenitors, or granulocyte-macrophage colony-forming units. A variety of hormones stimulate the production of specific types of leukocytes in response to specific needs of the body.

2. Granulocytes and monocytes are stored in red bone marrow and released when needed. Lymphocytes begin developing in bone marrow, then migrate to lymphoid tissue to mature.

1. Platelet production (thrombopoiesis) begins when a hemocytoblast becomes a megakaryoblast. In response to thrombopoietin, the megakaryoblast develops into a huge megakaryocyte. This large cell fragments, which eventually become functional platelets.

1. Erythrocytes (RBCs) function to carry oxygen from the lungs to the tissues, and to return carbon dioxide from the tissues to the lungs.

2. RBCs are disc-shaped with exterior glycoproteins and glycolipids, conferring blood type, and interior peripheral proteins to impart elasticity to the cell.

3. During development, RBCs lose most of their organelles and use some of the oxygen they are meant to transmit elsewhere. They can also carry on anaerobic fermentation indefinitely.

4. About one-third of the cytoplasm of an RBC consists of hemoglobin, which carries most of the oxygen and carbon dioxide transported by the blood.

5. The shape of the RBCs allows the rapid diffusion of gases throughout the cell.

1. Hemoglobin consists of four protein chains called globins. Two are alpha chains, and two are beta chains. Each chain is conjugated with a nonprotein heme group that binds oxygen to a ferrous ion at its center.

2. Carbon dioxide is transported bound to the globin portion of the hemoglobin.

3. Hemoglobin exists in several forms that differ in their structure and oxygen-carrying capacity. Fetal hemoglobin has a higher oxygen-binding capacity than adult hemoglobin, and thus can extract oxygen from the mother's blood.

1. The number of RBCs is of clinical interest because it indicates the oxygen-carrying capacity of the blood.

2. The hemoglobin concentration is 13-8 g/dL in men, and 12-16 g/dL in women. The RBC count is also higher in men, with 4.6 to 6.2 million RBCs per mm³ in men and 4.2 to 5.4 million per mm³ in women.

3. Reasons for this difference between the sexes is because male androgens stimulate RBC production, women have menstrual cycles, and hematocrit is inversely proportional to body fat, which is usually higher in women.

1. Erythrocytes circulate for 120 days. As they age, their membranes become more fragile and can no longer squeeze through tiny capillaries undamaged.

2. The spleen traps and destroys old cells. Hemolysis is the rupture of RBCs, which releases hemoglobin.

3. The globin portion of hemoglobin is hydrolyzed to amino acids. The heme portion has its iron removed and transported using transferrin. The remainder of the heme becomes the greenish pigment biliverdin that is further modified into bilirubin. These two pigments are added to bile by the liver, and are responsible for the color of feces.

1. Polycythemia (p. 653)

2. Anemia (p. 654; Table 18.6)

3. Sickle-Cell Anemia and Thalassemia (p. 654; Fig. 18.12)

1. The ABO blood group was discovered in 1900 by Karl Landsteiner.

2. Surfaces of blood and body cells possess antigens that are capable of stimulating an immune response in another person. The antigens of RBCs that determine blood type are called agglutinogens because of their role in agglutination during mismatched blood transfusions. Plasma antibodies that react against agglutinogens are agglutinins.

3. The ABO blood group consists of blood types A, B, AB, and O. The presence of ABO agglutinogens determine the person's blood type, as determined by genetics.

4. Type A blood has type A agglutinogens on the surface of its RBCs, and anti-B agglutinins in its plasma. Type B blood has type B agglutinogens and anti-A agglutinins. Type AB has both agglutinogens but no agglutinins, while type O has no agglutinogens, but both anti-A and anti-B agglutinins.

5. Mismatching blood types can lead to clumping of the blood in a transfusion reaction. Death can follow within a week or two due to kidney failure.

1. The RH blood group is so-called because of the rhesus monkey from which it was first discovered.

2. If any of the Rh agglutinogens is present on the RBCs, the person is Rh positive. If none are present, the person is Rh negative.

3. Anti-Rh agglutinins are normally absent, unlike the situation for the ABO blood groups.

4. Problems arise when an Rh- person receives a transfusion from an Rh+ person, and they begin to produce antibodies against the Rh factor. The next time Rh+ blood is received, the recipient's plasma agglutinins would agglutinate the donor's RBCs.

5. A similar situation occurs when an Rh- woman is carrying an Rh+ fetus. The first fetus will go unharmed, but when a second Rh+ begins to grow, the mother's anti-Rh antibodies will cause a severe anemia in the infant, called hemolytic disease of the newborn. This can be prevented by administration of an anti-Rh gamma globulin injection called RhoGAM to the mother shortly after the first, and subsequent, Rh+ babies are delivered.

1. At least 300 other blood groups are known, but most do not cause transfusion reactions.

1. The five types of leukocytes are easily distinguished using the microscope. Some are called granulocytes (the neutrophils, eosinophils, and basophils) because of their granular appearance. Agranulocytes (lymphocytes and monocytes) do not appear granular.

1. The types of leukocytes and their traits are summarized in Fig. 18.17, p. 661.

2. Granulocytes (p. 660)

3. Agranulocytes (p. 660)

1. Total WBC count is usually 5,000-10,000 per mm³. A count less than this (leukopenia) can result from toxic chemicals, drugs, or certain diseases.

2. A higher than average count (leukocytosis) indicates an infection, allergy, dehydration, or emotional disturbance.

3. A more useful count is a differential WBC count, which identifies the relative abundance of each type of white cell. A high neutrophil count indicates a bacterial infection, such as might occur with appendicitis, for example. Numerous eosinophils indicate allergies or parasites.

4. An extraordinarily high number of WBCs is characteristic of leukemia, or cancer of the hemopoietic tissues. Myelocytic leukemia shows uncontrolled granulocyte production, while production of lymphocytes goes unchecked in lymphocytic leukemia. Acute leukemia progresses rapidly after a sudden onset. Chronic leukemia develops and progresses more slowly. Death from leukemia is usually due to bleeding or opportunistic infection as the cancerous tissue crowds out other blood-forming tissues.

1. Hemostasis is the stoppage of bleeding, the mechanisms for which are most effective in the smaller vessels. Platelets play multiple roles in hemostasis.

2. Platelets are cell fragments that have pseudopods enabling amoeboid motion. They are also phagocytic. Normal counts range from 130,000 - 400,000 per mm³.

3. Platelets secrete growth factors that stimulate mitosis in fibroblasts and smooth muscle, and help maintain linings of blood vessels.

4. Platelets secrete vasoconstrictors that cause vascular spasms in broken vessels.

5. They phagocytize and destroy bacteria, and secrete chemicals that attract neutrophils and monocytes to inflamed areas.

6. They dissolve blood clots that have outlasted their usefulness.

1. The prompt constriction of a broken vessel is triggered by nervous impulses (pain pathway), by injury to the smooth muscle within the vessel wall, and by serotonin (a vasoconstrictor) from platelets.

2. Vascular spasm can usually be maintained long enough for platelet plug formation and coagulation to have an effect.

1. When a vessel is injured, collage fibers in its wall are exposed, causing platelets to stick to them. Platelets extend spiny pseudopods that adhere to the broken vessel; these contract and draw the walls of the vessel together.

2. As more platelets join in, a platelet plug forms which can stop minor bleeding.

3. Platelets undergo degranulation as they aggregate, releasing substances that promote hemostasis.

1. Coagulation is the most effective method of hemostasis, and the most complex, involving over 30 chemical reactions.

2. The objective of coagulation is to convert soluble fibrinogen into insoluble fibrin. As this occurs, blood cells and platelets get stuck in the net of fibrin, stopping blood loss.

3. The two reaction pathways to coagulation are the extrinsic mechanism, initiated by chemicals released from damaged tissue, and the intrinsic mechanism, initiated by factors, such as clots, within the vessel itself.

2. Clotting factors are called procoagulants, and are produced in the liver. They normally circulate with the plasma in inactive form.

3. One factor activates the next, which in turn activates another factor, and so on, in a reaction cascade.

4. Initiation of Coagulation (p. 665; Fig. 18.22; Transp. 358)

5. Completion of Coagulation (p. 666)

1. After a clot forms, it undergoes clot retraction within 30 minutes.

2. Platelets and endothelial cells secrete a stimulant causing fibroblasts and smooth muscle cells to multiply and repair the damaged vessel. Fibroblasts invade and strengthen the clot.

3. When tissue repair is completed, the clot is dissolved by fibrinolysis. This process involves a cascade of reactions, ending in the production of plasmin, a fibrin-dissolving enzyme.

1. Controls are required to prevent unnecessary coagulation. These include platelet repulsion, dilution, and anticoagulants, such as antithrombin and heparin.

1. Radiation, drugs, poisons, or leukemia can lead to thrombocytopenia, or low platelet count. People with this condition bruise easily.

2. A deficiency in one clotting factor can shut off the coagulation mechanism, as is the case in hemophilia.

3. Lack of factor VIII causes hemophilia A (from Queen Victoria, affecting 1 out of 5,000 males), which accounts for 83% of hemophilia cases. Lack of factor IX causes hemophilia B (1 out of 30,000 males). Factor VIII is now produced by transgenic bacteria.

4. Most coagulation disorders are in the form of an unwanted blood clot (thrombosis). If it begins to travel, it is an embolus. Clots arising in the arms and legs (from patient inactivity) commonly lodge in the lungs, causing pulmonary embolism.