Components of Blood

Blood is composed of two portions: 45 percent of its volume is composed of formed elements (cells and cell fragments), and 55 percent is plasma (liquid containing dissolved substances). (Figure 14-1).

*per cubic millimeter

Formed Elements

The formed elements of the blood are (Figure 14-1):

I. Erythocytes (red blood cells)

II. Leucocytes (white blood cells)

A, Granular leucocytes (granulocytes)

1. Neutrophils

2. Eosinophils

3. Basophils

B. Agranular Leucocytes (Agranulocytes)

1. Lymphocytes

2. Monocytes

C. Thrombocytes (platelets)

Origin

The process by which blood cells are formed is called hemopoiesis. In the adult, hemopoiesis takes place in the red bone marrow of the humerus and femur, sternum, ribs, vertebrae, pelvis, and lymphoid tissue. Red blood cells, granular leucocytes, and platelets are produced in red bone marrow. Agranular leucocytes arise from red bone marrow and lymphoid tissue in the spleen, tonsils, and lymph nodes.

All blood cells originate from hemocytoblasts, immature cells that undergo differentiation into five types of cells from which the major types of blood cells develop (Figure 14-2).

The blood, heart, and blood vessels together make up the cardiovascular system. In this reading, we will consider blood. The heart and blood vessels will be discussed in this unit as well. A closely related system, the lymphatic system, will be discussed with the immune system after this unit.

The cardiovascular system is designed to transport blood to all cells of the body. Blood contains all the nutrients and oxygen required by cells, therefore, it must reach virtually every cell in the body. This is accomplished by the heart, which serves as a pump, and blood vessels, which take blood from the heart to body cells.

The substance that bathes cells is called interstitial fluid. Interstitial fluid, in turn, is serviced by blood and lymph. Blood picks up oxygen from the lungs, nutrients from the gastrointestinal tract, hormones from endocrine glands, and enzymes from still other parts of the body. It transports these substances to all the tissues, where they diffuse from microscopic blood vessels into interstitial fluid. From the interstitial fluid, these substances enter the cells and wastes from the cells enter the blood.

The blood carries carbon dioxide and metabolic waste to the lungs, kidneys, and sweat glands for elimination from the body. Some wastes must be processed by the liver before they can be excreted.

Sometimes, disease-causing organisms (pathogens) are able to invade the blood and interstitial fluid. The way in which the lymphatic system filters body fluids to prevent the spread of pathogens throughout the body will also be discussed with the immune system.

Blood inside blood vessels, interstitial fluid around body cells, and lymph inside lymph vessels constitute the body’s internal environment. Because body cells are too specialized to adjust to more than very limited changes in their environment, the internal environment must be kept within normal physiological limits. This condition is called homeostasis. In preceding units, we have discussed how the internal environment is kept in homeostasis. Now we will look at that environment itself, beginning with blood.

The branch of science concerned with the study of blood and blood forming tissues and disorders associated with them is called hematology (hem = blood; logos = study of).

FUNCTIONS OF BLOOD

Blood is a liquid connective tissue that performs a number of critical functions.

1. It transports: oxygen from the lungs to the cells of the body; carbon dioxide from the cells to the lungs; nutrients from the digestive organs to the cells; waste products from the cells to the kidneys, lungs, and sweat glands; hormones from endocrine glands to cells; heat from various cells.

2. It regulates: pH through buffers; normal body temperature through the heat absorbing and coolant properties of its water content; the water content of cells, principally through dissolved sodium ions (Na +).

3. It protects against: blood loss through the clotting mechanism; foreign microbes and toxins through phagocytic white blood cells or specialized plasma proteins such as antibodies.

PHYSICAL CHARACTERISTICS OF BLOOD

Blood is a viscous fluid: it is heavier, thicker, and more viscous than water. The viscosity (adhesiveness or stickiness), or blood, may be felt by touching it. Its temperature is about 38 degrees C (100.4 degrees F), its pH range is 7.35 to 7.45 (slightly alkaline), and its salt (NaCl) concentration is 0.90 percent. The blood volume of an average-sized male constitutes about 8 percent of the total body weight.

ERYTHROCYTES (RED BLOOD CELLS)

Structure: Erythrocytes or red blood cells (RBC’s) are biconcave discs averaging about 8 micrometers (ųm) in diameter (Figure 14-3a). Mature red blood cells are quite simple in structure. They have no nucleus or other organelles and cannot divide or carry on extensive metabolic activities. Essentially, they consist of a selectively permeable plasma membrane, cytoplasm, and a red pigment called hemoglobin. Hemoglobin carries oxygen to body cells and is responsible for the red color of blood. Normal values for hemoglobin are 14 to 20 g/100 mL of blood in infants, 12 to 15g/100 mL in adult females, and 14 to 16.5g/100 mL of blood in adult males. As you will see later, certain proteins (antigens) on the surfaces of red blood cells are responsible for the various blood groups such as ABO and Rh groups.

Functions: The hemoglobin in erythrocytes combines with oxygen and with carbon dioxide in order to then transport them through blood vessels. The hemoglobin molecule consists of four identical proteins called globins and four non-protein pigments called hemes, each of which is attached to a protein and contains iron (Figure 14-3b). As the erythrocytes pass though the lungs, each of the four iron atoms in the hemoglobin molecules combines with a molecule of oxygen to from oxyhemoglobin. The oxygen is transported as oxyhemoglobin to other tissues of the body. In the tissues, the iron-oxygen reaction reverses, and the oxygen is released to diffuse into the interstitial fluid and cells. On the return trip, the globin portion combines with carbon dioxide from the interstitial fluid to form carbaminohemoglobin, which is transported to the lungs, where the carbon dioxide is released and then exhaled. Although some carbon dioxide is transported by hemoglobin, the greater portion is transported in blood plasma. Since erythrocytes lack a nucleus, their capacity for carrying oxygen is increased greatly. Moreover, since they lack mitochondria and generate ATP anaerobically, they do not consume any of the oxygen that they transport.

Life Span and Number: Red blood cells live only about 120 days because of wear and tear on the fragile plasma membranes as the squeeze through blood capillaries. Worn-out red blood cells are phagocytized by macrophages in the spleen, liver, and bone marrow. The red blood cell’s hemoglobin is subsequently recycled (Figure 14-4). The globin is split from the heme portions and broken down into amino acids that may be reused by other cells for protein synthesis. The heme is broken down into iron and biliverdin. The iron is stored in the liver in two forms: ferritin and hemosiderin. Ferritin consists of iron bound to a protein in the liver called apoferritin. Hemosiderin is an extremely insoluble form of iron. Iron is transported in the blood by combining with a protein called transferrin. Transferrin combines with iron that has been absorbed from the gastrointestinal tract or iron released from storage and transports it to bone marrow to be reused for hemoglobin synthesis. Transferrin also transports iron to the liver for storage. The non-iron portion of heme is converted into biliverdin, a greenish pigment, and then into bilirubin. Bilirubin is released into plasma and is transported to the liver to be excreted in bile, which passes from the liver to the small intestine. In the large intestine, bilirubin is converted by bacteria into urobilinogen, most of which is eliminated in feces in the form of a brown pigment (stercobilin), which gives feces its characteristic color.

Production: The process by which erythrocytes are formed is called erythropoiesis. It takes place in red bone marrow. Normally, erythropoiesis and red blood cell destruction proceed at the same pace. A healthy male has about 5.4 million red blood cells per cubic millimeter of blood, and a healthy female about 4.8 million. The higher value in the male is caused by higher levels of testosterone, which stimulate the production of red blood cells. To maintain normal quantities of erythrocytes, the body must produce new mature cells at the astonishing rate of 2 million per second. If the body suddenly needs more erythrocytes or if erythropoiesis is not keeping up with red blood cell destruction, a

homeostatic mechanism steps up production (Figure 14-5). The

mechanism is triggered by the reduced supply of oxygen for the body

cells, called hypoxia. If certain kidney (or liver) cells become oxygen-

deficient, they release an enzyme called renal erythropoietic factor

(REF) that converts a plasma protein into the hormone

erythropoietin (poiem = to make). This hormone travels to the red

bone marrow where it stimulates production of red blood cells. One

medical use of erythropoietin is to increase the amount of blood that

can be collected by individuals who choose to donate their own blood

before surgery. Erythropoiesis increases at high altitudes where the air

Fig 14-5

contains less oxygen and as a result of disease conditions that produce hypoxia, such as pneumonia or the anemias (discussed later).

In order for the bone marrow to produce adequate numbers of healthy red blood cells, individuals must consume adequate amounts of iron, protein, folic acid, and vitamin B-12, and produce enough intrinsic factor (IF) in the stomach to absorb the vitamin B-12. Regular aerobic exercise also increases erythropoiesis.

The rate of erythropoiesis is measured by a procedure called a reticulocyte count. Reticulocytes are an intermediate cell in the development of a mature red blood cell (see Figure 14-2). Some reticulocytes are normally released in the bloodstream before they become mature red blood cells. The percentage of reticulocytes in a blood sample should range from 0.5 to 1.5. A hematocrit (Hct) is the percentage of blood made up of the RBCs. In adult males the average is 40 to 54 percent; in females it is 38 to 46 percent (athletes may have somewhat higher values). The results of a hematocrit test help a doctor to determine the rate of hemopoiesis.

LEUCOCYTES (WHITE BLOOD CELLS)

Structure and types: Unlike red blood cells, leucocytes or white blood cells (WBCs) have nuclei and do not contain hemoglobin (see figure 14-2). Leucocytes fall into two major groups. The first is granular leucocytes. They have large characteristic granules in their cytoplasm and possess lobed nuclei. The three kinds of granular leucocytes are identified on the basis of their specific granules and are called neutrophils (10 –12 micrometers in diameter), eosinophils (10-12 micrometers in diameter), and basophiles (8-10 micrometers in diameter).

The second group is called Agranular leucocytes because the cytoplasmic granules do not stain easily and cannot be seen with an ordinary light microscope. Lymphocytes (7-15 micrometers in diameter) and Monocytes (14-19 micrometers in diameter) are the two types in this group.

Just as red blood cells have surface proteins, so do white blood cells and all other nucleated cells in the body. These proteins, called HLA (human leucocyte associated) antigens, are unique for each person (except for identical twins) and can be used to identify a tissue. If an incompatible tissue is transplanted, it will be rejected by the recipient as foreign, due, in part to differences in donor and recipient HLA antigens. The HLA antigens are used to type tissues and help prevent rejection.

Functions: The skin and mucus membranes of the body are continuously exposed to microbes and their toxins. Some of the microbes are capable of invading deeper tissues to cause diseases. Once they enter the body, it is the function of leucocytes to combat them by phagocytosis or antibody production. Neutrophils and Monocytes are actively phagocytotic- they can ingest bacteria and dispose of dead cells. Neutrophils respond first to bacterial invasion, carrying on phagocytosis and releasing the enzyme lysozyme, which destroys the bacteria. Monocytes take longer to reach the site of infection than do Neutrophils, but once they arrive, they do so in larger numbers and destroy more microbes. Monocytes that have migrated to infected tissues are called wandering (tissue) microphages. They clean up cellular debris following an infection. Most leucocytes possess, to some degree, the ability to crawl through minute spaces between the cells that form the walls of capillaries and through connective and epithelial tissue. This movement, like that of amoebas, is called diapedesis.

Eosinophils are believed to release enzymes, such as histaminase, that combat the effects of inflammation, allergic reactions, and certain parasitic worms. Thus, a high eosinophil count frequently indicates an allergic condition or a parasitic infection. Eosinophils also phagocytize antigen-antibody complexes (to be explained shortly).

Basophils are also believed to be involved in allergic reactions. Once they leave the capillaries and enter the tissues, they are known as mast cells and function to liberate heparin, histamine, and serotonin, substances that intensify the inflammatory reaction.

Some lymphocytes develop into cells that produce antibodies. Antibodies are proteins that inactivate antigens. An antigen is any substance that stimulates the production of antibodies and is capable of reacting specifically with the antibody. Most antigens are proteins, and most are not synthesized by the body. Rather, the antigens make up the cell structures and enzymes of bacteria. They also make up the toxins released by bacteria. When antigens enter the body, they stimulate certain lymphocytes, called B-cells, to become plasma cells (Figure 14-6). The plasma cells then produce antibodies, globulin-type proteins that attach to antigens and inactivate them. This is called the antigen-antibody response. Eosinophils destroy the antigen-antibody complexes.

Other lymphocytes are called T-Cells. One group of T-cells, called cytotoxic (killer) T cells, is activated by certain antigens and reacts by destroying them directly or indirectly by recruiting other lymphocytes and macrophages (Fig 14-7). T-cells are especially effective against bacteria, viruses, fungi, transplanted cells, and cancer cells.

The antigen-antibody response helps us combat infection and gives us immunity to some diseases. It is also responsible for blood types, allergies, and the body’s rejection of organs transplanted from an individual with a different genetic make-up.

An increase in the number of white blood cells present in the blood usually indicates an inflammation or infection. Because each type of white cell plays a different role, determining the percentage of each type in the blood assists in diagnosing a condition. A differential white blood cell count is the number of each kind of white cell in 100 white blood cells. A normal differential blood count falls within the following percentages:

Neutrophils60-70%

Eosinophils2-4%

Basophils0.5-1%

Lymphocytes20-25%

Monocytes3-8%

100%

Particular attention is paid to the Neutrophils in a differential white blood cell count. A high neutrophil count usually indicates a response to invading bacteria. A high monocyte count generally indicates a chronic infection. Eosinophils and basophils are elevated during allergic reactions. High lymphocyte counts indicate antigen-antibody reactions.

Life Span and Number: Bacteria exist everywhere in the environment and have continuous access to the body through the mouth, nose, and pores of the skin. Furthermore, any cells, especially those of the epithelial tissue, age and die daily, and their remains must be removed by leucocytes that actively ingest bacteria and cellular debris. However, a leucocyte can phagocytize only a certain number of substances before they interfere with its own metabolic activities and bring on its death. Consequently, the life span of most leucocytes is only a few days. During a period of infection the may only live a few hours.

Leucocytes are far less numerous that red blood cells, averaging from 5000 to 10,000 cells per cubic millimeter of blood. Red blood cells, therefore, outnumber white blood cells about 700 to 1. The term leucocytes refer to an increase in the number of white blood cells. If the increase exceeds 10,000/ mm3, a pathological condition is usually indicated. An abnormally low level of white blood cells (below 5000/mm3) is termed leucopenia.

Production: Granular leucocytes are produced in red bone marrow and lymphoid tissue; agranular leucocytes are also produced in bone marrow. The developmental sequences for the five types of leucocytes are show in Figure 14-2. White blood cells develop under the influence of substances called colony-stimulation factors (CSF). In addition to stimulating the development of various white blood cells, CSFs also enhance their functions in fighting infection and inflammation. CSFs also play a role in immunity and are now being tested to evaluate their effectiveness in treating AIDS, cancer, and bone marrow suppression.

THROMBOCYTES (Platelets)