Overview – Blood
Plate 4-1. The Red Blood Cell
Plate 4-2. White Blood Cells: The Granulocytes
Plate 4-3. White Blood Cells: The Agranulocytes
Human beings are exquisitely constructed communities of cells held together by a network of connective tissues. For a human being to live, the cells must live. To do so, each cell must exchange gases with the atmosphere, receive nutrients, and dispose of its waste products. Many cells are deeply hidden in nearly inaccessible recesses. Such cells receive the stuff of life from blood.
Blood may be thought of as a kind of liquid connective tissue. In addition to coursing through your vessels, blood permeates the extravascular connective tissue spaces between all cells, tissues, and organs; it is in the extravascular, intercellular spaces that much of its work is done. Blood consists of two major parts each quite different from the other: a liquid phase, the Plasma, and a mixed population of cells, the formed elements of the blood. Blood Plasma is an extremely complex fluid, containing among other things, proteins, fats, sugars, hormones, nitrogenous wastes, antibodies, and salts, most of which are invisible by conventional light and electron microscopy. This chapter focuses on the formed elements of the blood – the cells and platelets most frequently observed in the general circulation.
The Formed Elements of the Blood, shown in Figure 4-1, include red blood cells, called erythrocytes, white blood cells, called leukocytes, and platelets. Platelets are a class unto themselves. Active in the process of clot formation, they are fragments of enormous cells call megakaryocytes.
Red blood cells are the most familiar of the formed elements and are the most numerous of the circulating blood cells. Filled with Hemoglobin and concerned with oxygen transport, erythrocytes give the blood its characteristic red color. White blood cells, which differ radically from red blood cells, tend to be the most frequently misunderstood of the formed elements. Confusion commonly results from the fact that, although leukocytes are called blood cells, they really are not blood cells at all, but connective tissue cells. Leukocytes are found in blood samples because they use the circulatory system as a means of transportation from their birthplace to their functional station in the connective tissues. White blood cells are primarily concerned with fighting infection; they destroy invasive microorganisms and fireign antigens. The relative population of leukocytes, which can reflect the status of one’s health, is usually determined by blood samples taken in the clinic because white blood cells use blood to carry them to their destinations and because, of all tissues, blood is the easiest on which to perform biopsy. The five morphologically distinct types of white blood cells are neutophils, eosinophils, basophils, lymphocytes, and monocytes. There are two magor categories of white blood cells; those that have intracellular granules (the granulocytes) and those that do not (the agranulocytes). The granulocytes include the neutrolphils, eosinophils, and basophils; the agranulocytes include the lymphocytes and monocytes. The classes of blood cells are represented diagrammatically in Figure 4-1. The light and electron microscopy of red and white blood cells is illustrated in the following plates of this chapter.
The Red Blood Cell
Red blood cells (erythrocytes) carry oxygen. The red blood cell, which is dedicated to the performance of that single function, provides an excellent example of the intimate interrelationship between structure and function.
The unique shape of the red blood cell is best appreciated when viewed by scanning electron microscopy. Figure A is a striking scanning electron micrograph that catches a white blood cell (L) in the act of phagocytosing an Erythrocyte (E). In this micrograph, the shape of the Erythrocyte is a biconcave disk – a three-dimensional structure that, in some ways, resembles an automobile tire wrapped up in a plastic bag. This peculiar shape, central to the proper functioning of the Erythrocyte, must fulfill three functional requirements that seem somewhat at odds with one another. First, the red cell must bind and hold all the oxygen it can. This requirement means it must maximize its contained volume of Hemoglobin, the oxygen-binding protein. Second, it must accept oxygen in the lungs and give it up to other tissues quickly, which means the cell must have a large surface area to facilitate gas exchange. Third, the red blood cell must be flexible enough to squeeze through tiny, tortuous capillaries – some narrower than the width of a single Erythrocyte – at very high speed. A biconcave disk will perform all of these functions.
In sectioned material, a red blood cell can present a number of different images, depending on the plane in which the cell is cut. In Figure B, a transmission electron micrograph of the lung, red cells are caught in a variety of planes of section as they wend their way through pulmonary capillaries. When cut in frontal section slightly off-center, they resemble doughnuts. When cut in perfect cross section, they look like figure eights. Some obliquely sectioned red cells look like scimitars; others, twisted as they round a tight bend in a capillary, resemble small sausages. Figure B illustrates another important characteristic of red blood cells: they exist in very high numbers. Between 40 and 50% of the volume of human blood is taken up by erythrocytes. Given that fact, the total number of red blood cells becomes staggering. There are, for example, on the order of 4.5 million red cells/cubic millimeter of blood. This translates to 4.5 billion red cells/Cubic centimeter or 4.5 trillion red cells/L of blood. The average 150-lb person has a blood volume of 7 L , supporting (or rather supported by) a total population of 31.5 trillion red blood cells.
To maintain this tremendous population of red blood cells is no mean feat. Given that each Erythrocyte has a life span of 120 days, bone marrow generates some 26 billion red blood cells every day, or 182 million every minute. During the time it took you to read this page, you have, for example, manufactured upwards of a half-billion red blood cells.
In addition to erythrocytes, blood contains white blood cells and platelets. The white blood cells are illustrated on the Plate 4-2.
Plate 4-1, Figure A. Scanning electron micrograph of a red blood cell being phagocytosed by a white blood cell. E, Erythrocyte; L, Leukocyte. (Micrograph courtesy of Dr. Keith R. Porter.) 9,000 X
Figure B. Transmission electron micrograph of blood cells circulating through capillaries in the lung of the macaque. AS, alveolar (air) space; C, capillary; E, Erythrocyte; E’, Erythrocyte that escaped into air space during tissue preparation. 3,750 X
White Blood Cells: The Granulocytes
In the circulating blood, red blood cells outnumber white blood cells by a very wide margin. White cells are found in an average concentration of 7,000/cubic millimeter of blood. For every 500 to 1,000 red cells observed there is only one white blood cell. This disparity occurs, in part, because white cells, being connective tissue cells, spend on the average only one day of their lifespan in the general circulation.
The three classes of Granulocyte – the Neutrophil, Eosinophil, and basophil – are illustrated in Figures A through E at right. The Granulocyte most commonly seen in circulating blood is the Neutrophil (Figures A and B). Known by such names as polymorphonuclear Leukocyte, PMN, or poly, the Neutrophil has small cytoplasmic granules (G) and a complex, multilobed Nucleus (N). The various names come from the images presented by neutrophils in blood smears, in which the granules take a neutral (purple) color with Romanovsky’s stains and the complicated Nucleus displays many shapes. Figure A shows a typical Neutrophilin a light micrograph of a blood smear. Another Neutrophil, this time fixed in situ in a capillary, is shown by electron microscopy in Figure B.
Chemotactically attracted to bacteria, neutrophils exit the general circulation at sites of infection or inflammation, whereupon they become actively phagocytic. Their granules become lysosomes, capable of enzymatically digesting a broad spectrum of macromolecules. Neutrophils often destroy themselves along with ingested foreign matter and aggregate to form pus.
Eosinophils, less common in the bloodstream than neutrophils, are primarily concerned with the Phagocytosis of Antigen–Antibody complexes formed in the immune response. They perform their function in connective tissue, not blood, and frequently inhabit the Lamina Propria of the gut. In blood smears (Figure C), eosinophils are characterized by a dumbbell-shaped Nucleus (N) and large, prominent, red (eosinophilic) granules (G). When viewed by electron microscopy, as in Figure D, these granules – called specific granules (G) – contain electron-dense crystals. The specific granules are thought to be lysosomes.
Basophils are the rarest of all granulocytes found in blood. Only I in 1,000 white blood cells is a basophil. A typical basophil in a blood smear is shown in Figure E. The basophil is a large cell filled with prominent blue (basophilic) granules (G). These large granules contain Heparin, an anticoagulant, and Histamine, which increases the permeability of capillary walls. Although the precise function of basophils is uncertain, it is generally thought that they leave the bloodstream, enter the connective tissues, and become mast cells. Mast cells, such as the one depicted by electron microscopy in Figure F, are connective tissue cells that, like basophils, contain large granules (G) filled with Heparin and Histamine. At sites of local injury or infection, mast cells degranulate and discharge their contents, which not only seem to cause capillaries to become leaky but also appear to impede blood clot formation.
Figure E. Light micrograph of basophil in human blood smear. G, granule. 8,000 X Figure F. Electron micrograph of Mast Cell in human connective tissue. G, prominent cytoplasmic granules; N, Nucleus. 8,000 X
White Blood Cells: The Agranulocytes
The agranulocytes include lymphocytes and monocytes. Of these two classes of white blood cell, lymphocytes are far more common than monocytes. A typical blood smear shows ten lymphocytes for every Monocyte. Like the granulocytes described earlier, the agranulocytes are connective tissue cells.
Lymphocytes are readily identifiable in the light microscope. As shown in Figure A, they are small, spherical cells with large, round nuclei (N). The Nucleusoccupies most of the volume of the cell, leaving only a thin crescent of Cytoplasm(C) around part of the perimeter. These features facilitate the easy recognition of lymphocytes in electron micrographs. In Figure B, an electron micrograph of a blood-filled capillary, a Lymphocyte is evident right next to the capillary wall (Ca). Here again, the Nucleus (N) fills most of the cell, whereas the scanty Cytoplasmcontains a few Mitochondria (M), a bit of Endoplasmic Reticulum, a Golgi Complex (G), and a prominent Centriole (arrow).
Monocytes, larger and scarcer than lymphocytes, are readily identifiable in blood smears by their lack of granules and a large, horseshoe-shaped Nucleus (N) (Figures C and D). When monocytes leave the bloodstream, they enter the connective tissues to become macrophages, large cells that participate in the immune response and actively phagocytose unwanted foreign matter and cellular debris. Monocytes, then, may be thought of as the transport form of macrophages. Although lymphocytes, too, participate in the immune response, they do so differently from monocytes. There are two classes of lymphocytes, not distinguishable by light microscopy: T-lymphocytes, derived from the Thymus, and B-lymphocytes, born in the bone marrow. Although similar in appearance, T- and B-lymphocytes differ in function. While they both participate in the immune response and perform their functions outside of the bloodstream in the connective tissues, B-lymphocytes differentiate and mature to become Plasma cells. Plasmacells manufacture and release antibodies, which are heavyweight proteins that bind to and inactivate foreign antigens, thereby defending the body from harmful bacteria, viruses, toxins, and the like.
Plasma cells have a distinct appearance. When viewed by light microscopy, as in Figure E, the Plasma cell has a characteristic cartwheel Nucleus (N) surrounded by a dense, highly basophilic Cytoplasm (C). In Figure F, the electron microscope demonstrates the ultrastructure of the Plasma cell. The cartwheel appearance of the Nucleus is due to the presence of large, peripheral clumps of Heterochromatin. The dense basophilia observed in the light microscope takes its origin in the abundant rough Endoplasmic Reticulum, whose parallel Ribosome-studded Cisternae pack the Cytoplasm of the cell. The tremendous amount of rough Endoplasmic Reticulum, evident in the electron micrograph in Figure F, betrays the Plasma cell’s primary function: the production of protein, in the form of antibodies, for export.
Histology Atlas 4-3