The circulatory system proper includes the heart, arteries, veins, and capillaries that circulate blood, and the lymphatic system, which includes lymphatic vessels and lymphatic organs (lymph nodes) that circulate lymph. As you will see, these two circulations parallel, interconnect with, and complement one another.
The substance that courses through the arteries, veins, and capillaries is whole blood, a liquid connective tissue consisting of blood cells (formed elements) suspended in plasma. One can see these two components with the naked eye when a tube of unclotted blood is allowed to sit or is spun in a centrifuge. The cells’ density causes them to settle into an opaque layer at the bottom of the tube, leaving the plasma, a clear, yellowish fluid, on top (figure 1). Serum is essentially the same as plasma, except it is the clear fluid from clotted blood, so it lacks the clotting proteins that plasma contains. Serum is often used in immune testing and therapy.
Fig1. The macroscopic composition of whole blood. (a) When uncoagulated blood sits in a tube, it stratifies into a clear layer of plasma, a thin layer of off-white material called the buffy coat (which contains the white blood cells), and a layer of red blood cells in the bottom. (b) Serum is the clear fluid that separates from clotted blood. Clotting causes the red and white cells to clump in the bottom of the tube in a single mass. Source: National Cancer Institute; Created by; Bruce Wetzel and Harry Schaefer (Photographers)
Fundamental Characteristics of Plasma Plasma contains hundreds of different chemicals produced by the liver, white blood cells, endocrine glands, and nervous system and absorbed from the digestive tract. The main component of this fluid is water (92%), and the remainder consists of proteins such as albumin and globulins (including antibodies); other immunochemicals; fibrinogen and other clotting factors; hormones; nutrients; ions and electrolytes; dissolved gases (O2 and CO2); and waste products (urea). These substances support the normal physiological functions of nutrition, development, protection, homeostasis, and immunity.
A Survey of Blood Cells The production of blood cells, known as hemopoiesis or hematopoiesis, begins early in embryonic development in the yolk sac (an embryonic membrane). Later it is taken over by the liver and lymphatic organs, and it is finally assumed entirely and permanently by the red bone mar row. Although much of a newborn’s red marrow is devoted to hematopoietic function, the active marrow sites gradually recede, and by the age of 4 years, only the ribs, sternum, pelvic girdle, flat bones of the skull and spinal column, and proximal portions of the humerus and femur are devoted to blood cell production.
The relatively short life of blood cells demands a rapid turnover that is continuous throughout a human life span. The primary pre cursor of new blood cells is a pool of undifferentiated cells called pluripotential stem cells1 maintained in the marrow. During development, these stem cells proliferate and differentiate—meaning that immature or unspecialized cells develop the specialized form and function of mature cells. The primary lines of cells that arise from this process produce red blood cells (RBCs), white blood cells (WBCs, or leukocytes), and platelets (thrombocytes). The white blood cell lines are programmed to develop into several secondary lines of cells during the final process of differentiation (figure 2). These committed lines of WBCs are largely responsible for immune function.
Fig2. Simplified diagram of blood cell and platelet development. The details of several intermediate steps have been omitted. Undifferentiated stem cells in the red marrow give rise to several different cell lines that become increasingly specialized until mature cells are released into circulation.
The leukocytes traditionally are evaluated by their reactions with a hematologic stain that contains a mixture of dyes and can differentiate cells by color and morphology. When this stain is used on blood smears and evaluated using the light microscope, the leukocytes appear either with or without noticeable colored granules in the cytoplasm; on that basis they are divided into two groups: granulocytes and agranulocytes. Greater magnification reveals that even the agranulocytes have tiny granules in their cytoplasm, so some hematologists also use the appearance of the nucleus to distinguish them. Granulocytes have a lobed nucleus, and agranulocytes have an unlobed, rounded nucleus (figure 2).
Granulocytes The types of granular leukocytes present in the bloodstream are neutrophils, eosinophils, and basophils. All three are known for prominent cytoplasmic granules that stain with some combination of acidic dye (eosin) or basic dye (methylene blue). Although these granules are useful diagnostically, they also function in numerous physiological events.
Neutrophils* are distinguished from other leukocytes by their conspicuous lobed nuclei and their fine, pale lavender granules. In cells newly released from the bone marrow, the nuclei are horseshoe shaped, but as they age, they form multiple lobes (up to five). These cells, also called polymorphonuclear neutrophils (PMNs), make up 55% to 90% of the circulating leukocytes—about 25 billion cells in the circulation at any given moment. The main work of the neutrophils is in phagocytosis. Their high numbers in both the blood and the tissues suggest that there is a constant challenge from resident microbiota and environmental sources. Most of the cytoplasmic granules carry digestive enzymes and other chemicals that degrade the phagocytosed materials. The average neutrophil lives only about 2 days, spending much of this time in the tissues and only about 4 to 10 hours in circulation.
Eosinophils are readily distinguished in a stain preparation by their larger, orange to red (eosinophilic) granules and bilobed nucleus. They are much more numerous in the bone marrow and the spleen than in the circulation, contributing only 1% to 3% of the total WBC count. Their granules contain peroxidase, lysozyme, and other digestive enzymes, as well as toxic proteins and inflammatory chemicals.
The main protective action of eosinophils is their ability to attack and destroy large eukaryotic pathogens. They are also involved in inflammation and allergic reactions. Among their most important targets are the larval forms of worm parasites that cause ascariasis, filariasis, and schistosomiasis. The binding of eosinophils to the larval surface and the release of toxic compounds into their cells causes disintegration of the larvae. Eosinophils are among the earliest cells to accumulate near sites of inflammation and allergic reactions, where they attract other leukocytes and release chemical mediators.
Basophils are characterized by pale stained, two-lobed nuclei and very prominent dark blue to black granules. They are the scarcest type of leukocyte, making up less than 0.5% of the total circulating WBCs in a normal individual. Basophils share some morphological and functional similarities with widely distributed tissue cells called mast* cells. Mast cells are nonmotile elements bound to connective tissue around blood vessels, nerves, and epithelia, and basophils are motile elements that migrate within and between compartments. Both cell types originate from the same bone marrow stem cell line.
Basophils parallel eosinophils in many of their actions, because they also contain granules with potent chemical mediators. These mediators act on other cells and tissues of the body. For ex ample, they may attract white blood cells toward the site of an infection or cause blood vessels to dilate in response to an injury. Mast cells are first-line defenders against the local invasion of pathogens; they recruit other inflammatory cells; and they are directly responsible for the release of histamine and other allergic stimulants during immediate allergies.
