The components of blood and their functions are summarized in Figure 10-4. Normal values for blood components are found inside the front cover of this book.

All blood cells originate from the red bone marrow. In the adult, red bone marrow is found in the flat and irregular bones, ribs, vertebrae, sternum, and pelvis. The iliac crest in the pelvic bone is a common site for a bone marrow aspiration for biopsy. The various blood cells develop from a single stem cell (pluripotential hematopoietic stem cell) during the process of hemopoiesis or hematopoiesis (Fig. 10-5). From this basic cell, the differentiation process forms committed stem cells for each type of blood cell. These cells then proliferate and mature, providing the specialized functional cells needed by the body. A pathological condition of the blood that usually refers to disorders involving the cellular components of blood is called dyscrasia. A number of specific blood dyscrasias are addressed later in the chapter.

Erythrocytes or red blood cells (RBCs) are biconcave, flexible discs (like doughnuts but with thin centers rather than holes) that are non-nucleated when mature and contain hemoglobin (Fig. 10-6). The size and structure are essential for easy passage through small capillaries. The hormone erythropoietin, originating from the kidney, stimulates erythrocyte production in the red bone marrow in response to tissue hypoxia, or insufficient oxygen available to cells. Normally RBCs (4.2 to 6.2 million/mm³) constitute most of the cell volume in blood. Adequate RBC production and maturation depend on the availability of many raw materials, including amino acids, iron, vitamin B₁₂, vitamin B₆, and folic acid.

Hemoglobin consists of the globin portion, two pairs of amino acid chains, and four heme groups, each containing a ferrous iron atom, to which the oxygen molecule (O₂) can attach (see Fig. 10-16A). Heme provides the red color associated with hemoglobin. Normally hemoglobin becomes fully saturated with oxygen in the lungs. Oxyhemoglobin is a bright red color, which distinguishes arterial blood from venous blood. As the blood circulates through the body, oxygen dissociates from hemoglobin, depending on local metabolism (see Fig. 13-6). Deoxygenated hemoglobin (deoxyhemoglobin or reduced hemoglobin) is dark or bluish-red in color and is found in venous blood.

Only a small proportion of the carbon dioxide (CO₂) in blood is carried by hemoglobin (carbaminohemoglobin) attached to nitrogen in an amino acid group at a different site from that for oxygen. Most carbon dioxide is transported in blood as bicarbonate ion (in the buffer pair). Oxygen can easily be displaced from hemoglobin by carbon monoxide, which binds tightly to the iron, thus causing a fatal hypoxia (deficit of oxygen). Carbon monoxide poisoning can be recognized by the bright cherry-red color in the lips and face.

The lifespan of a normal RBC is approximately 120 days. As it ages, the cell becomes rigid and fragile and finally succumbs to phagocytosis in the spleen or liver and is broken down into globin and heme (Fig. 10-7). Globin is broken down into amino acids, which can be recycled in the amino acid pool, and the iron can be returned to the bone marrow and liver to be reused in the synthesis of more hemoglobin. Excess iron can be stored as ferritin or hemosiderin in the liver, blood, and other body tissues. A genetic disorder, hemochromatosis, otherwise known as iron overload, results in large amounts of hemosiderin accumulating in the liver, heart, and other organs, causing serious organ damage.

Hematopoiesis

Leukocytes, which number 5 to 10,000/mm³, make up only about 1% of blood volume. They are subdivided into three types of granulocytes and two types of agranulocytes. All types develop and differentiate from the original stem cell in bone marrow (see Fig. 10-5). Leukopoiesis, or production of white blood cells (WBCs), is stimulated by colony-stimulating factors (CSFs) produced by cells such as macrophages and T lymphocytes. For example, granulocyte CSF or multi-CSF (interleukin-3 [IL-3]) may be produced to increase certain types of WBCs during an inflammatory response (see Chapter 5). White blood cells may leave the capillaries and enter the tissues by diapedesis or ameboid action (movement through an intact capillary wall) when they are needed for defensive purposes.

The five types of leukocytes vary in physical characteristics and functions (see Fig. 10-4). Some examples of WBCs are visible as large, nucleated cells (purple stain) in the blood smear in Figure 10-8.

• Lymphocytes make up 30% to 40% of the WBCs. The roles of B and T lymphocytes in the immune response are reviewed in Chapter 7. Some T cells are designated natural killer cells and are significant in immunity.

• Neutrophils (also called polys, segs, or PMNs) are the most common leukocyte, comprising 50% to 60% of WBCs, but they survive only 4 days. They are the first to respond to any tissue damage and commence phagocytosis. An immature neutrophil is called a band or stab, and these are increased in numbers by bacterial infection. The laboratory reports note this as a “shift to the left” in the pattern of leucocytes seen.

• Basophils appear to migrate from the blood and enter tissue to become mast cells that can release histamine and heparin. They may be fixed in tissues or wandering.

• Eosinophils tend to combat the effects of histamine. They are increased by allergic reactions and parasitic infections.

• Monocytes can enter the tissue to become macrophages, which act as phagocytes when tissue damage occurs.

A differential count indicates the proportions of specific types of WBCs in the blood and frequently assists in making a diagnosis. For example, a bacterial infection or inflammatory condition stimulates an increase in neutrophils, whereas allergic reactions or parasitic infections increase the eosinophil count.

Thrombocytes, also called platelets, are an essential part of the blood-clotting process or hemostasis (Fig. 10-9). Thrombocytes are not cells; rather, they are very small, irregularly shaped, non-nucleated fragments from large megakaryocytes (see Fig. 10-8). Platelets stick to damaged tissue as well as to each other to form a platelet plug that seals small breaks in blood vessels, or they can adhere to rough surfaces and foreign material. The common drug ASA (aspirin) reduces this adhesion and can lead to an increased bleeding tendency. Thrombocytes can also initiate the coagulation process.

10-1  

Apply Your Knowledge

Predict three possible problems that could arise in the production of blood and blood cells and explain the cause of each.

Hemostasis consists of three steps.

Clot formation (coagulation) requires a sequence or cascade of events as summarized:

An individual’s blood type (e.g., ABO and Rh groups) is determined by the presence of specific antigens on the cell membranes of that person’s erythrocytes. ABO groups are an inherited characteristic that depends on the presence of type A or B antigens or agglutinogens (Table 10-1). Shortly after birth, antibodies that can react with different antigens on another person’s RBCs form in the blood of the newborn infant. Such an antigen–antibody reaction would occur with, for example, an incompatible blood transfusion, resulting in agglutination (clumping) and hemolysis of the recipient’s RBCs (Fig. 10-11).

Another inherited factor in blood is the Rh factor, which may cause blood incompatibility if the mother is Rh-negative and the fetus is Rh positive (see Fig. 22-2). Rh blood incompatibility between maternal and fetal blood is reviewed in Chapter 22.

Plasma or colloidal volume-expanding solutions can be administered without risk of a reaction because they are free of antigens and antibodies.

The basic diagnostic test for blood is the complete blood count (CBC), which includes total RBCs, WBCs, platelet counts, and morphology (size and shape), a differential count for WBCs, hemoglobin, and hematocrit values (see normal values inside the front cover of this book). These tests are useful screening tools. For example, leukocytosis, an increase in WBCs in the circulation, is often associated with inflammation or infection. Leukopenia, a decrease in leukocytes, occurs with some viral infections as well as with radiation and chemotherapy. An increase in eosinophils is common with allergic responses. The characteristics of the individual cells observed in a blood smear, including size and shape, uniformity, maturity, and amount of hemoglobin, are very important. Different types of anemia are distinguished by the characteristic size and shape of the cell, and presence of a nucleus in the RBC. More specialized tests are available. A summary of the most common diagnostic tests is provided in Ready Reference 5.

The hematocrit shows the percentage of blood volume composed of RBCs and indicates fluid and cell content. It may be an indicator of anemia, a low RBC count. Hemoglobin is measured, and the amount of hemoglobin per cell is shown by the mean corpuscular volume (MCV). MCV indicates the oxygen-carrying capacity of the blood.

Bone marrow function can be assessed by the reticulocyte (immature non-nucleated RBC) count, plus a bone marrow aspiration and biopsy.

Chemical analysis of the blood can determine the serum levels of such components as iron, vitamin B₁₂ and folic acid, cholesterol, urea, glucose, and bilirubin. The results can indicate metabolic disorders and disorders within various other body systems.

Blood-clotting disorders can be differentiated by tests such as bleeding time (measures platelet function—the time to plug a small puncture wound); prothrombin time or INR International Normalized Ratio (measures the extrinsic pathway); and partial thromboplastin time (PTT—intrinsic pathway), which measure the function of various factors in the coagulation process. They are also used to monitor anticoagulant therapy. The reference values for these tests are best established for individual patients based on their health history.