CHAPTER 8 ■ Blood and Hemopoiesis		135
Erythropoiesis
Figure 8-10A	Proerythroblasts
Figure 8-10B	Basophilic Erythroblasts
Figure 8-10C	Polychromatophilic Erythroblasts
Figure 8-11A	Orthochromatophilic Erythroblasts
Figure 8-11B	Reticulocytes
Figure 8-11C	Clinical Correlation: Reticulocytosis
Thrombopoiesis
Figure 8-12A	Promegakaryocytes
Figure 8-12B	Megakaryocytes
Figure 8-12C	Clinical Correlation: Essential Thrombocytosis
Granulocytopoiesis
Figure 8-13A	A Representation of Granulocytopoiesis
Figure 8-13B	Overview of Stages of Granulocytes in Development
Figure 8-14A–C	Promyelocytes, Myelocytes, and Metamyelocytes
Figure 8-15A–C	Stab (Band) Cells, Bone Marrow Cells, and Bone Marrow
Figure 8-16	Developing Blood Cells in the Hematopoietic Compartment
Synopsis 8-2	Hematopoiesis
Synopsis 8-3	Pathological and Clinical Terms for Mature and Developing Blood Cells

Peripheral Blood Cells

Introduction and Key Concepts for

Peripheral Blood Cells

Blood smears are prepared so that the morphology of the formed elements can be assessed and the relative numbers of the leukocytes can be calculated (differential leukocyte count). If a person is anemic, examination of erythrocyte morphology can help classify the type of anemia. If a person has an elevated leukocyte count, a differential white cell count can provide valuable information toward determining what kind of infection or leukemia the person has. All formed elements serve critically important functions. Erythrocytes function in transport of respiratory gases, platelets function mainly in hemostasis, and leukocytes function in various ways to protect from infection by a wide variety of potential pathogenic organisms.

ERYTHROCYTES deliver oxygen from the lungs to all the tissues of the body, although they are also involved in carbon dioxide transport and pH regulation. Because erythrocytes are anucleate and lack membrane-bounded organelles, their internal structure is homogeneous. An erythrocyte is essentially a plasmalemma bag containing a highly concentrated (30%) hemoglobin solution. In addition, erythrocytes have a membrane-associated complex of cytoskeletal proteins that renders the biconcave disk shape (Figs. 8-2A to 8-3B).

PLATELETS (thrombocytes) are small fragments of cytoplasm with a complex and highly organized structure. They normally range in number from 200,000 to 400,000/μL. If the platelet number falls below 60,000/μL (“thrombocytopenia”), the integrity of the smallest blood vessels is compromised. Platelets function to minimize loss of blood when there is a breach in the circulatory system (Fig. 8-2B).

LEUKOCYTES are much less abundant than erythrocytes, 4,500 to 11,000/μL in contrast to about 5 million/μL. However, white cell numbers can increase markedly in some circumstances, such as infection or leukemia. Leukocytes have a wide range of life spans—from a few days (neutrophils) to years (some lymphocytes). All leukocytes are involved in defense against microorganisms and other foreign agents and in tissue responses to injury. Usually, they perform their functions only after leaving the blood stream and entering the conventional connective tissue through processes of attachment to endothelial cells and active movement through gaps in the endothelium (diapedesis). Leukocytes are constantly released from the bone marrow to be delivered by the cardiovascular system to the vascular beds of all peripheral tissues. Leukocytes are classified as either nongranular (agranular) or granular depending on whether specific cytoplasmic granules are evident when the cells are stained with Romanowsky-type stains like Wright stain. The three types of granulocytes—basophils, eosinophils, and neutrophils—are named and identified by the staining reaction of their specific granules. The two types of nongranular leukocytes, lymphocytes and monocytes, also have granules, but the granules are only nonspecific granules (lysosomes). All granulocytes are terminal cells; that is, they will never again divide because they have lost that capacity during differentiation. Monocytes and lymphocytes have the potential for further division.

Lymphocytes are the second most abundant leukocyte, amounting to about 25% to 33% of leukocytes. These are the cells that mediate specific immunity against foreign molecules and organisms. B lymphocytes produce immunoglobulins, and their derivatives, plasma cells, are specialized to secrete soluble antibodies. T lymphocytes are the agents of cell-mediated specific immune responses, and they comprise several types. Among these, cytotoxic T cells function to kill virus-infected

136 UNIT 2 ■ Basic Tissues

host cells, and helper T cells and suppressor T cells regulate	reactive oxygen compounds in a process termed the respiratory
immune responses (Fig. 8-4 A,C). For null cells, see Chapter	burst (Figs. 8-5 to 8-6).
10, “Lymphoid System.”
	Eosinophils amount to about 1% to 3% of circulating leuko-
Monocytes, the largest of the leukocytes, constitute about	cytes, and, like basophils, their numbers tend to rise in response
3% to 7% of circulating white blood cells. Monocytes are not	to parasitic infections and allergic reactions. The functions of
functionally or structurally mature when they are circulating in	eosinophils are not fully understood, but they clearly function
blood. Rather, they are an intermediate form of a cell lineage	in defense against infection by parasitic worms such as schisto-
that starts differentiation in the bone marrow (like all blood	somes. Eosinophils are recruited to sites of parasitic infection,
cells) but does not fully complete differentiation until arrival in a	and some of their granule contents (e.g., major basic proteins)
peripheral tissue. There are several functional cell types that are	are highly toxic to parasites. They also appear to function in
derived from monocytes, including tissue macrophages, Kupffer	dampening and limiting inflammation at sites of allergic reac-
cells, microglial cells, osteoclasts, and antigen-presenting cells	tions (Fig. 8-7A).
(Fig. 8-4B).
	Basophils are the least numerous (<1%) of the leukocytes.
Neutrophils are by far the most abundant leukocytes. Typi-	Basophils are functionally similar to the mast cells found in
cally 54% to 62% of leukocytes are mature neutrophils, and an	connective tissue. Neither cell type functions by phagocytosis,
additional 3% to 5% of leukocytes are immature (band) forms.	so they are quite unlike neutrophils. Instead, their functions in
Neutrophils are the main cellular weapon for destroying bac-	defense against microbial invasion are indirect. When activated,
teria, and the total number of circulating neutrophils can rise	they secrete (or exocytose) a variety of inflammatory media-
sharply in response to bacterial infections. Once a neutrophil	tors from their granules and synthesize and release a number of
makes contact with a bacterium, the neutrophil attaches to the	arachidonic acid derivatives, such as leukotrienes and prosta-
bacterium and engulfs it (phagocytosis) within a phagosome.	glandins. These signaling molecules intensify inflammation by
The primary and secondary granules of the neutrophil fuse with	(1) increasing local blood flow, (2) enhancing leakage of plasma
the phagosome, thereby exposing the bacterium to an array	proteins from blood, (3) promoting recruitment of other leuko-
of bactericidal compounds and enzymes. Another bacteria-	cytes to a site of infection, and (4) enhancing the activity of the
killing mechanism employed by neutrophils is the generation of	other leukocytes (Fig. 8-7).

CHAPTER 8 ■ Blood and Hemopoiesis

137

Erythrocytes Platelets

	D. Cui		D. Cui

Agranulocytes			Granulocytes
Lymphocytes	Monocytes	Neutrophils	Eosinophils	Basophils

D. Cui		D. Cui		D. Cui		D. Cui		D. Cui

Figure 8-1. Overview of peripheral blood cell types (mature blood cells), blood smear. Wright stain, 1,569

Blood is a specialized connective tissue composed of blood cells suspended in intercellular fluid (or plasma). Blood cells include erythrocytes (red blood cells), platelets (thrombocytes), and leukocytes (white blood cells). Erythrocytes are the most numerous. They are biconcave disk–shaped cells without nuclei and are important in transportation of gases. Platelets are very tiny cell fragments that have no nuclei, cannot reproduce, and come from huge cells called megakaryocytes (Figs. 8-9B and 8-12). Platelets play an important role in hemostasis. Leukocytes can be classified as either agranulocytes or granulocytes based on the absence or presence of specific granules in their cytoplasm. Granulocytes are also called polymorphonuclear leukocytes because of the multiple lobes of their nuclei, but the term is often used specifically for neutrophils. (1) Agranulocytes lack specific cytoplasmic granules but have the ability to divide. Lymphocytes and monocytes fall into this category. Lymphocytes are the smallest cells in the leukocyte series. Each has a round nucleus and a small amount of cytoplasm. They can be found outside of the blood stream in lymphoid organs and connective tissues. Lymphocytes can be classified as T lymphocytes, B lymphocytes, and null cells. They are associated with immunological defense functions. B lymphocytes can further differentiate into plasma cells (see Figs. 4-2B and 4-3A,B). Monocytes are the largest cells in the leukocyte series. They have large, elongated, and often kidney-shaped nuclei. They can differentiate into phagocytes, including macrophages, Kupffer cells, microglia, and osteoclasts. (2) Granulocytes contain specific granules in their cytoplasm, and their nuclei are segmented. They are terminal cells without the capability to divide further. Granulocytes include neutrophils, eosinophils, and basophils. Neutrophils are the most abundant leukocytes in circulating blood. Each cell has a multilobed nucleus and a pale pink cytoplasm that contains primary and secondary (specific) granules. Neutrophils play an important role in defense against bacterial infection. Eosinophils contain large, specific granules that stain red with eosin dye. They usually have a bilobed, or occasionally a trilobed, nucleus. Eosinophils function in controlling allergic reactions and in combating parasitic infections. Basophils are the rarest of the leukocytes (<1%). They contain large, specific granules that are deep violet with a Wright stain. Each basophil has a nucleus with two to three lobes that are not completely separated. Basophils, along with mast cells, are instigators of allergic reactions (see the introduction to this chapter).

138 UNIT 2 ■ Basic Tissues

Erythrocytes and Platelets

A		Erythrocyte

Erythrocytes

D. Cui

Figure 8-2A. Erythrocytes (red blood cells), blood smear.

Wright stain, 1,576

Erythrocytes are the most abundant cells in blood. They have a unique biconcave disk appearance (Fig. 8-3), are anucleate (without nuclei), and have no organelles after they mature. Here, red blood cells are seen as pink circles with pale centers in a Wright stain. Erythrocytes are produced in the red bone marrow and are transported into the blood circulation through the walls of sinusoidal capillaries in the marrow. Their life span is about 120 days. Aged erythrocytes are destroyed by macrophages in the spleen, liver, and bone marrow. Erythrocytes contain highly concentrated hemoglobin (Hb). They appear bright red in color when oxygen content is high and are more purple when they are depleted of oxygen. Their function is to transport oxygen to peripheral tissues and carry carbon dioxide out of tissues. Hemoglobin binds with oxygen to form oxyhemoglobin when the O2 level is high (lung) and binds with CO2 to form carbaminohemoglobin when the CO2 level is high (tissue).

B

Hyalomere

Granulomere

Platelets

Platelets

D. Cui

Figure 8-2B. Platelets (thrombocytes), blood smear. Wright stain, 1,576; inset 1,570

Platelets, also called thrombocytes, are very small, lens-shaped fragments of cells. They have some functional characteristics of whole cells, even though they do not have nuclei. Each platelet has a surface membrane covering cytoplasm that contains microtubules, microfilaments, mitochondria, and several types of granules. The central region where granules stain purple is termed the granulomere; the peripheral region, which stains light blue, is called the hyalomere. The two main types of granules in platelets are alpha granules and delta granules (dense bodies). These play a role in the adhesion and aggregation of platelets in blood coagulation. If damage occurs to the vascular endothelium, platelets adhere to the vessel wall, releasing granules and aggregating to stop bleeding.

The absence of alpha granules can cause gray platelet syndrome, whereas reduced numbers or absence of delta granules will lead to storage pool deficiency.

CLINICAL CORRELATION

C

Normal red blood cell

Sickle-shaped

red blood cells

Inmature red blood cell

Figure 8-2C. Sickle Cell Anemia, Blood Smear. Wright stain, 1,035

Sickle cell anemia is an autosomal recessive disorder characterized by the production of defective hemoglobins, which aggregate and polymerize when deoxygenated. The red blood cells become longer and curved, similar to a “sickle.” Sickle cells block blood vessels, causing ischemia of the tissues and severe pain. Symptoms and signs, which start in early childhood, include anemia, vasoocclusive complications, and chronic hyperbilirubinemia. This disease is more common in people of African, Turkish, Arabian, and Mediterranean ancestry. Dehydration, infection, hypertonicity, and decreased pH can trigger an onset. In a sickle cell patient, the average life span of red blood cells is 17 days, as compared to 120 days in normal persons. Bone marrow transplants can cure a small number of people. Normal and sickle cell forms are shown here.

CHAPTER 8 ■ Blood and Hemopoiesis				139
A		Figure 8-3A.	Erythrocytes, small artery.
		SEM, 1,140

Erythrocytes

This scanning electron micrograph demonstrates the various shapes of the blood cells contained in the lumen of a small artery. The erythrocytes appear as biconcave disks; that is, “doughnuts” with thin diaphragms across the holes. By contrast, the leukocytes are spherical, and the different types cannot be distinguished. No platelets are visible in this view. The inner layer of the artery wall is tunica intima, composed mainly of endothelium and a thin internal elastic lamina.

Endothelium of small artery

Leukocytes

Internal elastic lamina

B

Capillary endothelial cell

Platelet

Erythrocytes

Figure 8-3B. Erythrocytes and a platelet in a small blood vessel. EM, 10,000

The lumen of this capillary (or venule) contains profiles of several erythrocytes and a platelet. The erythrocytes in this thin section present a variety of profile shapes owing to two effects: the random orientation of the plane of section and the flexibility that allows the cells to bend in compliance with surrounding pressures. The platelet here is cut transversely through its biconvex shape, which is maintained by microtubules arranged as a hoop at the edge of the disk. The magnification of this view is not quite sufficient to reveal the microtubules. It can be seen here that the platelet contains a variety of granules and tubules.

140 UNIT 2 ■ Basic Tissues

Leukocytes: Agranulocytes

A

Lymphocyte

Lymphocyte

D. Cui

Neutrophil

Figure 8-4A. Lymphocytes, blood smear. Wright stain, 754; inset 1,569

Most lymphocytes in the blood are small to medium-sized cells. Each has a relatively large, round nucleus with a thin rim of cytoplasm (which is often crescent shaped). Lymphocytes originate in the bone marrow and thymus and circulate throughout the body in the blood and lymph circulation systems. Lymphocytes are motile and play an important role in immunological defense. They can be classified into B lymphocytes, T lymphocytes, and null cells based on their immunologic functions. B lymphocytes are responsible for the humoral immune response, in which immunoglobulins are secreted after they differentiate into plasma cells. T lymphocytes are responsible for the cellular immune response. T and B lymphocytes are morphologically indistinguishable in blood smears. Null cells are large cells that are morphologically similar to other lymphocytes but lack the characteristic surface markers of the B and T cells (see Chapter 10, “Lymphoid System”).

B

Monocyte

D. Cui

Neutrophil

Monocyte

Lymphocyte

Figure 8-4B. Monocytes, blood smear. Wright stain, 754; inset 1,569

Monocytes are the largest agranular cells in the peripheral blood. Each cell has a large, elongated nucleus, often assuming kidney or horseshoe shapes. The cytoplasm of monocytes is blue-gray and contains a variable number of dark blue-purple granules that are called azurophilic granules, so named because they attract azure (bluepurple) dyes in stains used for blood smears. Azurophilic granules are lysosomes, so they are nonspecific granules present in the cytoplasm of both agranular and granular leukocytes. They are distinct from the specific granules found in granular leukocytes. Monocytes originate from the bone marrow and remain in the blood circulation in an immature (precursor) state for 1 to 2 days. They then enter peripheral tissues to complete their differentiation. They become macrophages (tissue phagocytes) in connective tissue, Kupffer cells in the liver, microglia in the nervous system, and osteoclasts in bones.

CLINICAL CORRELATION

C

Smudge cell

CLL

lymphocytes

Neutrophil

Smudge cell

Figure 8-4C. Chronic Lymphocytic Leukemia, Blood Smear. Wright stain, 736

Chronic lymphocytic leukemia (CLL) is a type of blood cancer characterized by abnormally high numbers of mature lymphocytes in certain tissues and peripheral blood. Lymphocytes infiltrate the liver, spleen, lymph nodes, and the bone marrow. Signs and symptoms include petechiae (“pinpoint” hemorrhages) in the skin and soft palate; enlargement of the liver, spleen, and lymph nodes; anemia; fever; infections; bone pain; and weight loss. In some patients, CLL will transform into an aggressive lymphoma. The cause of CLL is not clear, but it may be associated with chromosomal disorders, radiation, benzene exposure, and chemotherapy. CLL progresses slowly but is not considered curable. Treatment includes chemotherapy and bone marrow transplant. In the peripheral blood, CLL cells are small lymphocytes with clumped chromatin and little cytoplasm. Smudge cells, although not specific for CLL, are commonly seen on peripheral blood smears.

CHAPTER 8 ■ Blood and Hemopoiesis

141

Leukocytes: Granulocytes

	A					Figure 8-5A.	Neutrophils, blood smear. Wright
						stain, 754; inset 1,569
					Neutrophils are the most abundant cells in the leu-
					kocyte series. They have a multilobed (two to five
					interconnected lobes) nucleus and pale pink cyto-
			Neutrophils		plasm with many granules (or vesicles). There are
					two main types of granules in neutrophils: primary
					(nonspecific) and secondary (specific) granules.
					Primary granules are azurophilic granules, which
					are modified lysosomes. The neutrophils’ primary
				Neutrophil	granules are larger and less numerous than specific
			Neutrophilic		granules. Secondary granules (specific or neutro-
					philic granules) are more numerous than primary
			stab (band)
					granules, and they contain a variety of antibacterial
			cell
					compounds. They stain lavender or salmon-pink
					with Wright stain, but they are difficult to distin-
			Lymphocyte		guish because of their small size. Like other granular
					leukocytes, neutrophils are terminally differentiated
	D. Cui
					cells unable to divide. They play a primary role in
					defense against bacterial and fungal infections.

B

Lobes of nucleus

Neutrophilic granules

Capillary endothelium

Figure 8-5B. Neutrophil in a capillary. EM, 11,000

This leukocyte fills the lumen of the capillary in which it resides. Although the thickness of the section is only about one two-hundredth of the diameter of the cell, the features of the neutrophil are readily apparent. Profiles of three lobes of the nucleus can be seen, and the cytoplasm has an abundance of small granules that vary in electron density. The shapes of the granules also vary from spherical to rice shaped. It is difficult to unequivocally distinguish the two main types of granules strictly on the basis of morphology. However, the smallest and most numerous granules are specific (neutrophilic, secondary) granules, and the largest granules are nonspecific (azurophilic, primary) granules. The neutrophilic granules are difficult to discern in the light microscope because their size is close to the limit of resolution of light microscopy.

142 UNIT 2 ■ Basic Tissues

Neutrophils 1. Recognition 2. Receptor binding 3. Pseudopod extension

D.Cui

7.Cell death

	Antibody
	of IgG
Fc receptor	Bacterium

6. Formation of	5. Killing and digestion
residual body	of bacterium

Pseudopod

4. Formation of phagosome

D. Cui

Residual body	Phagosome

Figure 8-6. A representation of neutrophil phagocytosis of bacteria.

Neutrophils play a central role in cellular defense against bacterial and fungal infections. They are highly motile cells and respond quickly to inflammation in cases of microbial invasion. Acute inflammation, one of the body’s defense mechanisms, occurs in the very early stage of tissue response to injuring agents, such as bacteria and fungi. During acute inflammation, microvessels dilate, and their permeability increases as a result of histamine and other inflammatory chemicals, which are released into the connective tissue by mast cells (see Chapter 4, “Connective Tissue”). Neutrophils quickly enter tissues from the blood circulation by adhering to activated endothelial cells of capillaries and venules at the site of the inflammation. Bacteria are neutralized by several mechanisms, which include the complement system and antibodies. Neutrophil phagocytosis of bacteria occurs in several steps: (1) Recognition: The process begins with recognition of the bacterium by opsonins (IgG and complement C3b fragments) that coat the bacterium and render it more susceptible to phagocytes. (2) Receptor binding: Fc receptors of neutrophils recognize and bind IgG that has bound to the bacterium, or complement C3b receptors bind C3b fragments on the surface of the bacterium. (3) Pseudopod extension: Pseudopods are slender cytoplasmic processes of neutrophils, which engulf (or “phagocytose”) the bacterium that has been recognized and bound by receptors. (4) Formation of phagosome: The engulfment of the bacterium sequesters it in a membrane-bound vesicle, the phagosome (food vacuole). (5) Killing and digestion of bacterium: Immediately after or even during formation of the phagosome, the proton pumps in the membrane of the phagosome generate an acidic pH; both primary and secondary neutrophil granules fuse with the phagosome and release their components into the phagosome to kill the bacterium and break down the constituents (proteins, carbohydrates, nucleic acids) of the bacterium. Lysosomal enzymes and other products may leak into the extracellular space, causing damage to endothelial cells and nearby tissues. (6) Formation of the residual body: Most of the remaining digested materials form residual bodies (vesicles containing leftover products of indigestible materials after fusion with the contents of a lysosome) inside the cells. (7) Cell death: Soon after neutrophils have finished their job of killing and digesting bacteria, they die. The dead neutrophils may be phagocytosed by macrophages, or they may accumulate locally with tissue debris and fluid to form pus.

Neutrophils use oxidative and nonoxidative mechanisms in killing bacteria and destroying other microbes. The oxidative mechanism, also known as respiratory burst or oxygen-dependent mechanism, involves generation of hydrogen peroxide by the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase system and generation of hypochlorous acid by myeloperoxidase (components of primary granules). The nonoxidative mechanism is involved in phagocytosis in the following manner: Primary and secondary granules fuse with the phagosome, and their granule components are released directly onto the microbe (see above steps 4 and 5). These components include defensins, neutral serine protease, and lysozyme from the primary granules as well as lactoferrin and lysozyme from the secondary granules. They perform their antimicrobial function by disrupting the phagosomal membrane, degrading bacterial membranes, breaking down the protein and carbohydrate of the bacterium, and binding iron (which is needed for bacterial growth) to prevent bacterial growth. Both oxidative and nonoxidative mechanisms work in concert to facilitate killing of the microbes.

A pathologic condition known as myeloperoxidase deficiency is caused by a defect in the NADPH oxidase complex. This condition results in the inability to produce “superoxides” in neutrophils and other phagocytic cells. Affected individuals are unable to kill invading microbes that are normally engulfed by these phagocytic cells. People with this defect can have frequent and prolonged bacterial and fungal infections.

CHAPTER 8 ■ Blood and Hemopoiesis

143

A		Neutrophil	Eosinophil		Figure 8-7A.	Eosinophil, blood smear. Wright stain,
				754; inset 1,569
				Eosinophils have a twoto three-lobed (segmented) nucleus,
				numerous specific (eosinophilic) granules, and a few azuro-
				philic granules in the cytoplasm. Specific granules contain
			D. Cui	acid hydrolases, peroxidase, histaminase, basic protein and
					eosinophil cationic proteins, which have antihelminthic
					properties. Azurophilic granules contain mainly lysosomal
					enzymes. Normally, the bone marrow contains a large
					reserve pool of eosinophils (and other granulocytes) ready
		Eosinophil			for deployment on demand. Eosinophils have a life span of
					a few days in circulating blood, although they can survive

longer in the tissues. They are commonly found in the connective tissue of the digestive tract. Some of the granules in eosinophils are highly toxic to parasitic worms such as schistosomes. Eosinophils also play a role in moderating inflammation resulting from an allergic reaction. They selectively ingest and degrade antigen-antibody complexes and also degrade histamine, therefore limiting inflammation.

B

Basophil

Neutrophil

D. Cui

Neutrophil	Basophil

Figure 8-7B. Basophil, blood smear. Wright stain,

754; inset 1,569

Basophils are the least numerous in the blood circulation, comprising less than 1% of the leukocytes. It is therefore difficult to find them in normal blood smears. They have a twoto three-lobed nucleus and large granules in the cytoplasm. These granules stain deep violet with Wright stain and are distributed unevenly in the cytoplasm. Specific granules in basophils contain heparin, histamine, peroxidase, and eosinophil and neutrophil chemotactic factors (attracts eosinophils and neutrophils to the site). Azurophilic granules are also present in basophils. Basophils have a similar function to mast cells in connective tissue. They contribute to allergic reactions by releasing histamine and heparin to produce inflammation at the allergic reaction site. (For details, see Fig. 4-4B).

SYNOPSIS 8 - 1 Life Spans, Counts, and Sizes of Blood Cells

■Leukocytes: Total number count is 4,500 to 11,000/mm3.

■Erythrocytes: Life span is about 120 days, count is 4,200,000 to 5,900,000/mm3 (male 4,500,000–5,900,000/mm3; female 4,200,000–5,400,000/mm3); size is 7 to 8 μm (in diameter).

■Platelets (thrombocytes): Life span is 8 to 12 days, count is 150,000 to 400, 000/mm3; size is 1 to 4 μm.

■Monocytes: Duration in circulation is a few hours to a few days before differentiating (a macrophage’s life span is up to several months); count is 200 to 900/mm3; size is 12 to 15 μm.

■Lymphocytes: Life span is a few days to years; count is 1,000 to 4,000/mm3; size is 6 to 12 μm.

■Neutrophils: Duration in circulation is a few hours, life span is about 8 days; count is 3,500 to 7,000/mm3; size is 9 to 12 μm.

■Eosinophils: Life span is uncertain, likely a few days; count is 50 to 450/mm3; size is 9 to 14 μm.

■Basophils: Life span is uncertain, likely a few days; count is 0 to 200/mm3; size is 8 to 10 μm.

■Clinical lab blood counts measure total number count of white blood cells ([WBCs] leukocytes/mm3) and differential counts (percent of each type of leukocyte [Table 8-1]). Absolute numbers of WBCs can be calculated by multiplying total number/mm3 times percent of each type of leukocyte.

■Shift to left: Increase in number of immature leukocytes (especially neutrophils in band forms), which suggests high demand because of infection or acute inflammation (normal range of band leukocyte is 2%–6%).

■Shift to right: Absence of immature leukocytes in differential count of leukocytes.

144 UNIT 2 ■ Basic Tissues

Internum (crystalloid) in eosinophilic granules

Lobes of nucleus

Figure 8-8. Eosinophil in connective tissue. EM, 12,000

The irregular surface contours of this cell suggest that it was in motion at the time the specimen was obtained. The two lobes typical of the nucleus of an eosinophil are present in the section, and the relatively large specific granules have the features that are characteristic of eosinophilic granules. The profiles of the granules have twodimensional shapes that are consistent with a biconvex three-dimensional shape. Each granule has a crystalline core (internum) composed of a major basic protein, one of the cationic proteins sequestered within eosinophilic granules.

TABLE 8 - 1 Leukocytes

Types of	Approximate %	Nucleus	Granules in Cytoplasm	Main Functions
Leukocytes	of WBCs
Lymphocyte	25%–33%	Round, relatively large	If present, only a few azurophilic	Play important role in
		compared to cell size	granules	immune defense
Monocyte	3%–7%	Large, kidney shaped	Azurophilic granules only (lysozyme,	Phagocytosis of any
		or horseshoe shaped;	endogenous pyrogens/IL-1)	recognizable nonself
		nonsegmented		agents after becoming
				mature tissue phagocytes
Neutrophil	54%–62%	Multilobed (five or	Azurophilic (primary) granules contain	Defend against bacterial
		more);	lysosome, myeloperoxidase, and	and fungal infection
		segmented	superoxide; small, salmon-pink, specific
			(secondary) granules contain major
			basic proteins, lactoferrin, lysozyme,
			collagenase, and proteases
Eosinophil	1%–3%	two to three lobes;	Azurophilic granules; large red,	Defend against infection
		segmented	specific granules contain major basic	by parasitic worms;
			proteins, acid phosphatase, peroxidase,	moderate inflammation
			arylsulfatase, and β-glucuronidase	in allergic reaction; fight
				viral infection
Basophil	<1%	two to three lobes;	Azurophilic granules; large violet (or	Involved with
		segmented	purple-blue), specific granules contain	inflammation and
			histamine, heparin, peroxidase, eosino-	allergic reactions (similar
			phil/neutrophil chemotactic factor	to mast cells)