Cui Dongmei. Atlas of Histology: with functional and clinical correlations. 1st ed

Подождите немного. Документ загружается.

CHAPTER 8

■

Blood and Hemopoiesis

145

Hemopoiesis

Introduction and Key Concepts

for Hemopoiesis

All formed elements, with the exception of some lymphocytes,

have a ﬁ nite life span in circulation, so there must be an ongoing

replacement throughout the life of an individual. The magnitude

of the task for a given cell type can be appreciated if the approxi-

mate required daily production rate is calculated from estimates

of the total number in circulation and the rate of turnover for the

cell type. For erythrocytes, with a life span of about 120 days,

the daily production rate is roughly 250 billion, for neutrophils,

with a time in circulation of less than a day, the daily production

rate is normally roughly 60 billion, and for platelets, with a life

span of about 10 days, the daily production rate is approximately

150 billion. The development of each type of blood cell involves

numerous cell divisions and a series of differentiation steps so that

a small number of completely undifferentiated stem cells pro-

duce enormous numbers of cells that have the speciﬁ c equipment

necessary for the particular mature cell to perform its functions.

Although all blood cells originate from a common pluripotential

hemopoietic stem cell, each blood cell type has its own lineage of

cell generations committed to proliferate and, at the same time,

differentiate only into that cell type. Cells that can be recognized

morphologically as undertaking differentiation into a particular

blood cell are called precursor cells. Precursor cells are produced

by cells that are committed to a speciﬁ c lineage (i.e., they are

determined to give rise to, e.g., only erythrocytes) but show no

morphological signs of differentiation. These are called progenitor

cells. Some progenitor cells are not restricted in potential to just

one blood cell lineage but rather to two lineages. Progenitor cells

are also termed colony-forming cells (CFCs). A commonly used

abbreviation system for designating speciﬁ c progenitor cells uses

the ﬁ rst letter of the blood cell name after the letters CFC, for

example, CFC-E for erythrocyte colony–forming cell and CFC-B

for basophil colony–forming cell. Development of blood cells

occurs mostly in the specialized environment of the bone marrow.

Because extensive cell proliferation is required, the process is very

vulnerable to irradiation, so protection within the cores of bones

is clearly advantageous. The development of each type of blood

cell involves a series of precursor cells that can be recognized in

smears of the red bone marrow that have been stained with the

same procedures used for peripheral blood smears. Lymphocytes

and monocytes are little differentiated, so the morphological

appearance of their precursors (lymphoblasts and promonocytes,

respectively) is not easily distinguished. By contrast, the precursors

of erythrocytes, granulocytes, and platelets exhibit relatively dis-

tinct features as they differentiate in a series of steps that involve

predictable changes and identiﬁ able stages. The red bone marrow

is a hemopoietic compartment where blood cells (except lympho-

cytes) develop and mature (Fig. 8-15C).

ERYTHROCYTE DEVELOPMENT is called erythropoiesis.

The appearances of the precursors of erythrocytes reﬂ ect the pro-

cesses that must take place to generate, from an undifferentiated

cell, a cell that is essentially a plasmalemma bag of hemoglobin. In

the initial stage, the proerythroblast, the main event is generation of

free ribosomes that will be needed to synthesize the globin that will

combine with heme to form hemoglobin. Therefore, the intense

basophilic staining of the cytoplasm in the next stage, the basophilic

erythroblast, results from a peak concentration of free ribosomes

that begin translation of globin mRNAs. In the polychromatophilic

erythroblast, enough hemoglobin has accumulated to confer some

eosinophilia to the cytoplasm, whereas the concentration of ribo-

somes has decreased from dilution that accompanies cell division.

Continuation of cell division, dilution of ribosomes, and accumu-

lation of more hemoglobin account for the strong eosinophilic

staining of the cytoplasm in the orthochromatophilic erythroblast

(

normoblast). Concurrent with the successive changes in staining of

the cytoplasm during erythrocyte development in the cytoplasm are

changes in the appearance of the nucleus. Production of ribosomes

and transcription of mRNA for globin and other proteins are man-

ifested by a large euchromatic nucleus with prominent nucleoli in

the proerythroblast; subsequent stages have progressively smaller,

less active nuclei, and the nucleus is ultimately extruded at the end

of the orthochromatophilic erythroblast stage. The mitochondrion,

another key organelle, is required to synthesize protoporphyrin and

combine it with iron to form the heme of hemoglobin (Figs. 8-9A

and 8-10A to 8-11C).

PLATELET DEVELOPMENT is called thrombopoiesis.

Although platelets are small (2–4 μm in greatest diameter) frag-

ments of highly organized cytoplasm, they are produced by

very large cells called megakaryocytes. These cells measure up

to 100 μm or more in diameter. Megakaryocytes develop from

precursor cells (called megakaryoblasts) through a series of

incomplete cell cycles (endomitosis) that do not include division

of the nucleus or cytoplasm. The result is that the nucleus of a

mature megakaryocyte has up to 64N chromosomes, instead

of the usual 2N chromosomes. The nucleus is large and lobu-

lar, but it remains one nucleus. The cytoplasm develops numer-

ous mitochondria, a variety of granules, and microﬁ laments

and microtubules. As the megakaryocyte reaches maturity, its

cytoplasm becomes cordoned off by an elaborate system of

membranes, called demarcation membranes or channels, which

subdivide the cytoplasm into platelet zones—like perforations

in a sheet of stamps (Figs. 8-9B and 8-12A–C).

GRANULOCYTE DEVELOPMENT (GRANULOCYTOPOI-

ESIS) proceeds through an orderly sequence of events that

result in cytoplasm that is packed with granules containing a

wide variety of substances related to inﬂ ammation and destruc-

tion of pathogenic organisms. As is the case with erythrocyte

development, the initial discernible event is generation of com-

ponents (ribosomes and RNA) needed for protein synthesis,

but in granulocyte development, the proteins will be packaged

in vesicles (granules). Accordingly, packaging of the proteins

requires development of an extensive endoplasmic reticulum

and Golgi complex. These events are prominent in the myelo-

blast and promyelocyte stages, both of which have relatively

large, active nuclei with nucleoli and cytoplasm that is baso-

philic owing to its content of ribosomes. Granule generation

occurs sequentially, the nonspeciﬁ c (lysosomal) granules ﬁ rst,

in the promyelocyte stage, and the speciﬁ c granules second, in

the myelocyte stage. Because speciﬁ c granules ﬁ rst appear in the

myelocyte stage, this is the earliest stage at which the precur-

sors of the three granulocytes can be distinguished from each

other. Other notable changes during granulocyte maturation are

progressive condensation, elongation, and segmentation of the

nucleus (Figs. 8-13A to 8-15B).

CUI_Chap08.indd 145 6/17/2010 10:20:04 AM

146

UNIT 2

■

Basic Tissues

Figure 8-9A. A representation of erythropoiesis (red blood cell formation), bone marrow. Wright stain, 1,569

Erythrocyte formation includes several stages of cell changes during differentiation. Erythrocytes derive from progenitor cells (CFC-Es)

that give rise to the ﬁ rst recognizable erythrocyte precursor, the proerythroblast. The proerythroblast is a large cell, which has a large

active nucleus with nucleoli. Each proerythroblast divides into two basophilic erythroblasts. Each basophilic erythroblast divides into

two polychromatophilic erythroblasts, each of which then divides to form orthochromatophilic erythroblasts, which do not divide.

These, in turn, differentiate into reticulocytes (Fig. 8-11B,C), which ﬁ nally become erythrocytes. There are some general tendencies

accompanying differentiation of erythrocytes: (1) the overall size of the cells decreases, (2) the nucleus size decreases and the condensa-

tion of the chromatin increases, (3) nucleoli disappear, and (4) the color of the cytoplasm changes from blue to gray to pink because

of a reduction of ribosomes and an increase of hemoglobin. When the ribosomes are diluted by cell division and the hemoglobin

concentration rises to a near mature level, the cell becomes an orthochromatophilic erythroblast (or normoblast). When the nucleus

is extruded and only a few organelles (polyribosomes and mitochondria) remain in the cytoplasm, the cell is called a reticulocyte. The

reticulocyte completes maturation and enters the blood circulation to become a mature erythrocyte (red blood corpuscle).

D. Cui

Proerythroblast

Basophilic

erythroblast

Basophilic

erythroblast

Polychromatophilic

erythroblast

Polychromatophilic

erythroblast

Erythrocytes

Orthochromatophilic

erythroblast (normoblast)

Orthochromatophilic

erythroblast

(normoblast)

Reticulocyte

D. Cui

Platelets

Megakaryocyte

Promegakaryocyte

Megakaryoblast

Figure 8-9B. Thrombopoiesis (platelet formation process), bone marrow. Wright stain, 843, 586, and 1,570 (from left to

right)

Platelets are very small fragments of cells that have no nuclei. They are also called thrombocytes. Their differentiation from a large

cell, the megakaryocyte, takes place in the bone marrow. Megakaryoblasts are the precursor cells. They have a large, round nucleus,

undergo mitosis, and become promegakaryocytes. These cells have a large, round nucleus and develop through growth and a series

of endomitoses into megakaryocytes. A megakaryocyte has a large, multilobed nucleus with a huge amount of cytoplasm containing

numerous granules. The maturation process includes the development of a demarcation membrane system and the subdivision of

the cytoplasm to form platelets (Fig. 8-12A,B).

CUI_Chap08.indd 146 6/17/2010 10:20:04 AM

CHAPTER 8

■

Blood and Hemopoiesis

147

Erythropoiesis

Figure 8-10A. Proerythroblasts, bone marrow smear.

Wright stain, 710; inset 1,569

The proerythroblast is a relatively large cell with a

large, round nucleus containing two to three nucleoli.

The cytoplasm appears basophilic (blue) because of the

presence of a large number of ribosomes. At this stage,

the cell is beginning to accumulate the necessary com-

ponents for the production of hemoglobin. Proeryth-

roblasts are precursor cells, which develop from two

functionally identiﬁ able progenitor cells: burst-forming

unit–erythroid (BFU-E) cells, which take about a week

to mature to become colony-forming unit–erythroid

(CFU-E) cells and another week to become proerythro-

blasts. Proerythroblasts undergo mitosis to produce two

daughter cells that will develop the features of basophilic

erythroblasts.

D. Cui

Proerythroblast

PoE

Proerythroblast

Nucleoli

Proerythroblast

D. Cui

Basophilic

erythroblast

Basophilic

erythroblast

Basophilic

erythroblast

Basophilic

erythroblast

Basophilic

erythroblast

PoE

Figure 8-10B. Basophilic erythroblasts, bone mar-

row smear. Wright stain, 710; inset 1,569

The basophilic erythroblast is smaller than the pro-

erythroblast, and its cytoplasm is deep blue because

of a high content of tightly packed ribosomes. Com-

pared to proerythroblasts, basophilic erythroblasts have

smaller nuclei with a coarser texture because most of

the chromatin is in the heterochromatin form. At this

stage, nuclei are less active than in proerythroblasts, and

their nucleoli disappear. These cells undergo mitosis and

divide into daughter cells, which mature to become poly-

chromatophilic erythroblasts. (OE, orthochromatohilic

erythroblast; PoE, polychromatophilic erythroblast; BE,

basophilic erythroblast.)

D. Cui

Basophilic

erythroblast

Polychromatophilic

erythroblast

Polychromatophilic

erythroblast

Polychromatophilic

erythroblast

Polychromatophilic

erythroblasts

Orthochromatophilic

erythroblast

Figure 8-10C. Polychromatophilic erythroblasts, bone

marrow smear. Wright stain, 710; inset 1,569

The polychromatophilic erythroblast is smaller than

its parent cell (basophilic erythroblast). The nucleus is

smaller and it has no nucleoli. The condensed nucleus is

densely stained, and it displays a patchy pattern because

of condensation of chromatin. The cytoplasm of the cell

is usually grayish in overall color because, at this stage,

signiﬁ cant amounts of hemoglobin have been produced

and accumulated in the cytoplasm, so that the staining

of the cytoplasm reﬂ ects the presence of both ribosomes

(basophilic) and hemoglobin (eosinophilic). Therefore,

the cytoplasm is mottled with mixed patches of blue and

pink (polychromatophilic means “attracting multiple

colors”). Polychromatophilic erythroblasts undergo

mitosis and divide into daughter cells that develop into

orthochromatophilic erythroblasts.

CUI_Chap08.indd 147 6/17/2010 10:20:07 AM

148

UNIT 2

■

Basic Tissues

Figure 8-11A. Orthochromatophilic erythroblasts, bone

marrow smear. Wright stain, 710; inset 1,569

The orthochromatophilic erythroblast, also called a

normoblast, is a very small cell, close to the size of an

erythrocyte. The nucleus is small and so condensed that

it looks like a dark dot because of the extreme condensa-

tion of the chromatin. The cytoplasm appears pinker than

that of the polychromatophilic erythroblast. Hemoglobin

production and accumulation are almost complete, with

few ribosomes left in the cytoplasm. At this stage, the cell

is unable to divide. Orthochromatophilic erythroblasts

become reticulocytes (Fig. 8-11B) after losing their nuclei.

D. Cui

Orthochromatophilic

erythroblast

Proerythroblast

PoE

Orthochromatophilic

erythroblast

CLINICAL CORRELATION

Figure 8-11C.

Reticulocytosis, Peripheral Blood

Smear

. New methylene blue stain, 1,020

Reticulocytosis is a condition characterized by an

increased number of reticulocytes. Reticulocytes are

premature red blood cells. The normal percentage of

reticulocytes is 0.5% to 1.5%. Hemolytic anemia usu-

ally increases erythropoietin production, which in turn

causes the bone marrow to produce more red blood

cells, resulting in a reticulocyte percentage of above

4% to 5%. An increased number of reticulocytes in

peripheral blood is an important indication of hemo-

lysis (red blood cell rupture) or bleeding. It can also

be the consequence of treating the anemia of chronic

kidney disease with erythropoietin. This illustration

shows the increased number of reticulocytes with new

methylene blue stain after hemolytic anemia.

Erythrocyte

Reticulocytes

D. Cui

Capillaries

Mature

erythrocyte

(inside of capillary)

Reticulocyte

Orthochromatophilic

erythroblast

(normoblast)

Figure 8-11B. Reticulocytes: the ﬁ nal step of erythro-

cyte formation.

Orthochromatophilic erythroblasts have small and highly

condensed nuclei. In the next stage, the nucleus is extruded

and phagocytosed by macrophages. Although the cells

loose their nuclei, they retain some polyribosomes in their

cytoplasm. When stained supravitally with cresyl blue or

new methylene blue, the ribosomes aggregate into a blue

reticular network; therefore, the cells are called reticulo-

cytes. Reticular cells appear the same as mature erythro-

cytes with Wright stain (Fig. 8-11C). Reticulocytes enter

the blood circulation through the bone marrow sinusoidal

capillaries and become mature erythrocytes in one or two

days. Mature erythrocytes have neither nuclei nor organ-

elles and appear as a biconcave disk.

CUI_Chap08.indd 148 6/17/2010 10:20:12 AM

CHAPTER 8

■

Blood and Hemopoiesis

149

Thrombopoiesis

Figure 8-12A. Promegakaryocytes (immature megakaryo-

cytes), bone marrow smear. Wright stain, 754; inset 1,605

Promegakaryocytes develop from megakaryoblasts in the bone

marrow. Megakaryoblasts lose their ability to undergo cytokine-

sis but undergo a series of incomplete cell cycles called “endomi-

tosis” that results in replication of DNA up to 64N without

division of nuclei or cytoplasm. Each megakaryoblast has a

large nucleus, multiple nucleoli, and basophilic cytoplasm (Fig.

8-9B). Promegakaryocytes can be recognized by their large size,

round (or oval) nuclei, and large amount of cytoplasm. Devel-

opment of a demarcation membrane system is an important

feature of thrombopoiesis and begins at a very early stage. The

demarcation membrane system is produced by the invagination

of plasma membranes to form branched interconnected chan-

nels through the cytoplasm. This system may play an important

role in later subdivision of the cytoplasm into platelet zones.

Megakaryoblast

CLINICAL CORRELATION

Figure 8-12C.

Essential Thrombocytosis, Bone

Marrow

Smear. Wright stain, 304

Essential thrombocytosis, also called essential throm-

bocythemia, is one of the myeloproliferative disorders,

characterized by overproduction of platelets by mega-

karyocytes in the bone marrow without an identiﬁ able

cause. The platelet counts exceed 600,000/μL, but the

platelets do not function properly. Symptoms and signs

include headache; bleeding from gums, nose, and gas-

trointestinal tract; throbbing and burning pain of the

hands and feet caused by thrombosis of small arteri-

oles; and splenomegaly (enlarged spleen). Treatment

includes using low-dose aspirin to control headache

and other vasomotor symptoms and anticancer agents

such as hydroxyurea to maintain proper platelet count.

Bone marrow smears show increased numbers of mega-

karyocytes. Large platelets, similar in size to red blood

cells, may be found in the peripheral blood.

Megakaryocytes

Megakaryocyte

Nucleus of the

megakaryocyte

Incipient

platelets

Neutrophils

Figure 8-12B. Megakaryocytes, bone marrow smear. Wright

stain, 754; inset 2,827

Because of their very large size, megakaryocytes are sometimes

called giant cells. They have a large indented (partially lobulated)

nucleus and an extremely voluminous cytoplasm containing a

variety of granules. In this stage, the demarcation membrane

system is complete, and the megakaryocytes are ready to release

platelets. Megakaryocytes tend to move toward and attach to

the marrow sinusoids (capillaries in the bone marrow) after

they become mature. The platelets are released into the blood

circulation through the wall of the marrow sinusoids. Note the

neutrophils on the surface of the megakaryocyte for size com-

parison. The inset shows incipient platelets (fragments of cyto-

plasm beginning to become platelets) in the surface region of the

megakaryocyte that are ready to be released. Thrombopoietin,

a humoral factor produced in the liver, is believed to regulate

megakaryocytes and the production of platelets.

CUI_Chap08.indd 149 6/17/2010 10:20:16 AM

150

UNIT 2

■

Basic Tissues

Promyelocyte

Eosinophilic

myelocyte

Eosinophilic

metamyelocyte

Eosinophil

Eosinophilic

stab cell

Neutrophil

Neutrophilic

myelocyte

Neutrophilic

metamyelocyte

Neutrophilic

stab cell

Figure 8-13B. Overview of stages of granulocytes in development, bone marrow smear. Wright stain, 1,569

These are examples of microphotographs that show various stages of granulocyte maturation in the neutrophilic and eosinophilic series.

Granulocytopoiesis

D. Cui

Neutrophilic

myelocyte

Neutrophilic

metamyelocyte

Neutrophilic

stab cell

Mature

neutrophil

Eosinophilic

myelocyte

Eosinophilic

metamyelocyte

Mature

eosinophil

Eosinophilic

stab cell

Basophilic

myelocyte

Basophilic

metamyelocyte

Mature

basophil

Basophilic

stab cell

Myeloblast

Promyelocyte

Figure 8-13A. A representation of granulocytopoiesis.

In addition to erythropoiesis, leukopoiesis also occurs in the bone marrow. Here are examples of the development of granular

leukocytes (granulocytopoiesis). The myeloblast is the earliest morphologically recognizable precursor cell. Cell division occurs in

myeloblasts, promyelocytes, and myelocytes. The myelocyte is the last stage that is capable of dividing. The generation of nonspe-

ciﬁ c granules occurs in the promyelocyte stage and speciﬁ c granules in the myelocyte stage. Maturation of granulocytes follows

this sequence: myeloblasts, promyelocytes, myelocytes, metamyelocytes, and stab (band) cells. The following morphologic changes

occur during granulocyte maturation: (1) nucleoli are present only before and during the promyelocyte stage; (2) the nucleus takes

the following shapes in different developmental stages: oval, elongated, indented, arched, and then segmented (lobed); and (3) spe-

ciﬁ c granules are ﬁ rst present at the myelocyte stage.

CUI_Chap08.indd 150 6/17/2010 10:20:23 AM

CHAPTER 8

■

Blood and Hemopoiesis

151

Figure 8-14A. Promyelocytes, bone marrow smear. Wright

stain, 710; inset 1,569

Promyelocytes (also called progranulocytes) have a round

or oval-shaped nucleus with one to three nucleoli. The cyto-

plasm is light blue, containing some dark purple granules

(azurophilic granules). At this stage, speciﬁ c granules have

not been produced. Promyelocytes vary in size and are pro-

duced by the division of myeloblasts. Their nuclei have a

smooth, ﬁ ne texture because of the fact that most of the

chromatin is euchromatin, which is delicately dispersed.

Promyelocytes divide to form myelocytes.

D. Cui

Promyelocyte

D. Cui

Neutrophilic

myelocyte

Neutrophilic

myelocyte

Eosinophilic

myelocyte

Eosinophilic

myelocyte

Neutrophilic

myelocyte

Neutrophilic

myelocyte

Eosinophilic

myelocyte

Eosinophilic

myelocyte

Neutrophilic myelocyte

Eosinophilic myelocyte

Figure 8-14B. Myelocytes, bone marrow smear. Wright

stain, 710; inset 1,569

The myelocyte has an oval or kidney-shaped nucleus that

has no nuclei and a coarse texture because of increasing

heterochromatin content. The cytoplasm contains azuro-

philic granules and speciﬁ c granules. In this stage, the cell

has stopped producing azurophilic granules. In addition,

these granules have also been diluted during cell division,

so they are not as prominent as in the promyelocyte stage.

At the same time, the cell has begun to make and accumu-

late speciﬁ c granules so that the cytoplasm starts to take

the characteristic appearance of a mature granulocyte. The

speciﬁ c granules in neutrophilic myelocytes are small and

appear pinkish, granules in eosinophilic myelocytes are large

and stain red, and granules in basophilic myelocytes are

blue-purple. Basophilic myelocytes are least numerous and,

therefore, difﬁ cult to ﬁ nd. In general, myelocytes are smaller

than promyelocytes, and their nuclear shape and size may

vary. This stage is the longest in granulocytopoiesis.

D. Cui

Eosinophilic

metamyelocyte

Neutrophilic

metamyelocyte

Neutrophilic

metamyelocyte

Eosinophilic

metamyelocyte

Eosinophilic

metamyelocyte

Eosinophilic

metamyelocyte

Neutrophilic

metamyelocyte

Neutrophilic

metamyelocyte

Neutrophilic

metamyelocyte

Figure 8-14C. Metamyelocytes, bone marrow smear.

Wright stain, 710; inset 1,569

Metamyelocytes are small cells. They have condensed

nuclei, which are elongated with various degrees of inden-

tation and contain clumped chromatin. Metamyelocytes

are unable to divide (myelocytes are the last stage in cell

division). The cytoplasm of metamyelocytes contains both

types of granules. Their cytoplasm and granules are similar

to those of mature granulocytes. At this stage, cells have

their distinguishing features, but their nuclei have not yet

become segmented.

CUI_Chap08.indd 151 6/17/2010 10:20:26 AM

152

UNIT 2

■

Basic Tissues

D. Cui

Neutrophilic

stab cell

Eosinophilic

stab cell

Basophilic

erythroblast

Neutrophilic

stab cell

Eosinophilic

myelocyte

Eosinophilic

metamyelocyte

Neutrophilic

stab cell

Neutrophilic

stab cell

Eosinophilic

myelocyte

Eosinophilic

stab cell

Basophilic

erythroblast

Eosinophilic

metamyelocyte

Neutrophilic

myelocyte

Neutrophilic

myelocyte

Neutrophilic

stab cell

Neutrophilic

stab cell

Neutrophilic stab cells

Figure 8-15A. Stab (band) cells, bone marrow smear. Wright

stain, 710; insets 1,569

Granular metamyelocytes mature to become stab cells, which

are also called band cells. The stab cells (mainly neutrophilic

stab cells) can be found in both the bone marrow and the

peripheral blood. Their nuclei are elongated and become band

and arch (or “C”) shaped, and the cytoplasm is the same as

that of mature neutrophils. These cells are the last stage of

granulocyte maturation without division, and in function and

structure, they are very close to mature neutrophils. The nuclei

of mature neutrophils become multilobulated (segmented),

contain dense heterochromatin, and often are described as

polymorphonuclear (or segmented) neutrophils.

Proerythroblast

Neutrophil

Neutrophilic

stab cell

Neutrophilic

stab cell

Neutrophilic

metamyelocyte

Neutrophilic

metamyelocyte

Polychromatophilic

erythroblasts

Polychromatophilic

erythroblasts

Orthochromatophilic

erythroblast

Orthochromatophilic

erythroblast

Eosinophil

Figure 8-15B. Bone marrow cells, bone marrow smear. Wright

stain, 710

This is an example of blood cells at various stages of develop-

ment in the bone marrow, which includes both the erythro-

cyte and the granulocyte series. These cells, at various stages

of development, are densely packed together and can be found

randomly distributed in the bone marrow. During the matura-

tion process, the cell size becomes smaller and nuclei become

denser. In the erythropoiesis series, the cytoplasm of cells

becomes light blue and then more pink, and nuclei become

much denser and smaller and ﬁ nally disappear. In the granu-

locytopoiesis series, the cytoplasm becomes less blue, primary

(nonspeciﬁ c) granules are produced, and then speciﬁ c granules

are produced and are present in myelocytes, which gives these

cells the appearance characteristic of their identity as a neutro-

phil, eosinophil, or basophil. In other changes, nuclei become

progressively denser, and the shape changes from round to

oval, elongated, indented, and then lobed (segmented).

Reticular tissue

Adipocyte

spaces

Adipocyte

spaces

Blood cells

Figure 8-15C. Bone marrow, bone marrow smear. Wright

stain, 35; inset 184

Bone marrow is a specialized example of a reticular connec-

tive tissue, a loose connective tissue in which numerous cells are

supported by a delicate network of reticular ﬁ bers. It resides in

cavities within bones (see Figs. 5-8, 5-10, and 5-11). Bone mar-

row can be categorized into red bone marrow and yellow bone

marrow. The term red bone marrow denotes active hematopoi-

esis; yellow bone marrow refers to a marrow composed chieﬂ y

of adipocytes (fat cells). Pictured is a smear of red bone marrow,

which contains many developing blood cells, a few adipocytes,

and some thin-walled blood vessels (sinusoidal capillaries). The

red bone marrow is organized into a hemopoietic compartment

and a vascular compartment. The hemopoietic compartment is a

network of reticular ﬁ bers in which immature and mature blood

cells are suspended. The vascular compartment is composed of

mainly sinusoidal capillaries, which allow mature blood cells to

enter the blood circulation.

CUI_Chap08.indd 152 6/17/2010 10:20:33 AM

CHAPTER 8

■

Blood and Hemopoiesis

153

Hematopoietic

compartment

Hematopoietic

compartment

Sinusoidal

capillary

Hematopoietic

compartment

Hematopoietic

compartment

Sinusoidal

capillary

Leukocyte granules

Mature neutrophili

or neutrophilic

metamyelocyte

Leukocyte precursors

Endothelial cell

Sinusoidal

capillary

Sinusoidal

capillary

Figure 8-16. Developing blood cells in the bone marrow. EM, 5,000

The two compartments of the red (hematopoietically active) bone marrow can be distinguished here. The vascular compartment is

composed of sinusoidal capillaries, which in this view contain numerous mature erythrocytes. The hematopoietic compartment is

composed of blood cells and the precursors and progenitors of blood cells suspended in a loose network of support cells and reticu-

lar ﬁ bers. The cells seen in the hematopoietic compartment here appear to be mostly developing or mature granulocytes. The exact

stage of differentiation of individual cells is not as clear here as it is in a bone marrow smear.

CUI_Chap08.indd 153 6/17/2010 10:20:41 AM

154

UNIT 2

■

Basic Tissues

SYNOPSIS 8-2 Hematopoiesis

Stem, Progenitor, and Precursor cells

Stem cells

■ are capable of differentiating into multiple cell lineages and can undergo proliferation indeﬁ nitely.

Progenitor cells

■ are only capable of differentiating into a single cell lineage (restricted to one or two blood cell types) and

are morphologically undifferentiated.

Precursor cells

■ can be recognized morphologically as undergoing differentiation along a particular blood cell lineage.

Erythropoiesis

Cytoplasm

■ becomes progressively less basophilic because of dilution of ribosomes during the erythropoiesis process.

Nucleus size

■ progressively decreases because of increased condensation of chromatin.

Cell size

■ progressively decreases during the erythroid differentiation.

Cytoplasm

■ becomes progressively more eosinophilic because of increased accumulation of hemoglobin.

The nucleus

■ retains a round shape and no indentation occurs before it disappears.

Granulocytopoiesis

Cell size

■ decreases and nucleus becomes more condensed as in erythropoiesis.

Nucleus shape

■ changes from round or oval (promyeloblasts) to kidney shaped/slightly indented (myelocytes) and then

changes from deeply indented (metamyelocytes) to band shaped (band cells) and ﬁ nally to lobed (mature granulocytes).

Promyelocytes

■ do not have speciﬁ c granules (only azurophilic granules); at this stage, it is too early to tell which granular

leukocytes they will become.

Myelocytes

■ are the last developmental stage capable of dividing; speciﬁ c granules accumulate in this stage.

SYNOPSIS 8-3 Pathological and Clinical Terms for Mature and Developing Blood Cells

Gray platelet syndrome ■ : This condition is characterized by a deﬁ ciency or absence of the alpha granules and contents in

blood platelets, giving platelets a gray appearance in a Wright stain smear (Fig. 8-2B).

Platelet storage pool deﬁ ciency

■ : Disorder caused by a decrease or absence of platelet delta granules (dense bodies),

which normally store and release adenine nucleotides and 5HT. “Platelet-type” bleeding is common with this deﬁ ciency

(Fig. 8-2B).

Petechiae

■ : Minute red or purple spots on the skin or mucous membranes caused by capillary hemorrhage; common causes

include physical trauma and decreased platelets (thrombocytopenia).

Smudge cell

■ : Damaged lymphocytes seen on a peripheral blood smear caused by mechanical stress in the process of

producing the smear; although nonspeciﬁ c, smudge cells are encountered more frequently on blood smears of patients with

chronic lymphocytic leukemia (Fig. 8-4C).

Reticulocytosis

■ : Increased reticulocytes in the blood, often in response to blood loss, stimulation by erythropoietin treat-

ment, or treatment of iron deﬁ ciency anemia with iron supplementation (Fig. 8-11C).

Thrombocytosis

■ : Increased platelet count in the blood, which may be reactive or neoplastic, as in the disease essential

thrombocytosis (Fig. 8-12C).

CUI_Chap08.indd 154 6/17/2010 10:20:44 AM